Losso, Jack N - The Maillard Reaction Reconsidered _ Cooking and Eating for Heal

JACK N.
LOSSO
The Maillard
Reaction
Reconsidered
JACK N. LOSSO
The Maillard
Reaction
Reconsidered
C O O K I N G A N D E ATI N G F O R H E A LTH
Boca Raton London New York
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Version Date: 20151014
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To
My children:
Mariel, Boriss, and MerryJean
My wife:
Jane
For your unconditional love and support
and
My late brothers and sisters:
Hugo, Beatrice, Boniface, Rose, and Diama
For your love and support and not being
around long enough to share with us
Contents
Preface.............................................................................................................................................xxi
Acknowledgments ........................................................................................................................ xxiii
Author ............................................................................................................................................xxv
Part I
The Maillard Reaction and Foods
Chapter 1
Introduction to the Maillard Reaction ...............................................................................................3
1.1 Introduction ............................................................................................................................. 3
1.2 The Maillard Reaction in Food Processing and Cooking.......................................................4
1.2.1 Definition ...................................................................................................................4
1.2.2 Steps and Benefits of the Maillard Reaction in Food Processing and Cooking ........ 4
1.2.3 Desirable Attributes of the Maillard Reaction........................................................... 7
1.2.3.1 Improved Aroma and Flavor of Cooked Foods..........................................7
1.2.3.2 Improved Colors and Increased Palatability .............................................. 7
1.2.4 Undesirable Attributes and Health Significance of the Maillard Reaction ...............7
1.2.4.1 Loss of Color and Darkening of the Final Product .................................... 7
1.2.4.2 Loss of Protein Biological Value ................................................................8
1.2.4.3 Effect on Allergenicity ...............................................................................8
1.2.4.4 Hydrogen Peroxide ..................................................................................... 8
1.2.4.5 Acrylamide ................................................................................................. 8
1.2.4.6 Furans .........................................................................................................9
1.2.4.7 Reactive Dicarbonyl Compounds ............................................................... 9
1.2.4.8 Pyridines and Heterocyclic and Mutagenic Compounds ......................... 10
1.2.4.9 Advanced Glycation End Products ........................................................... 10
1.2.4.10 Insulin Glycation ...................................................................................... 14
1.3 Caramelization ...................................................................................................................... 15
1.4 Current and Future Directions in Maillard Reaction............................................................ 16
References ........................................................................................................................................ 17
Chapter 2
Basic Understanding of Inflammation ............................................................................................. 21
2.1 Introduction ........................................................................................................................... 21
2.2 Inflammation in Health ......................................................................................................... 21
2.3 Inflammation in Disease ....................................................................................................... 22
2.4 Maternal and Utero Inflammation ........................................................................................ 22
2.5 Maillard Reaction Products-Induced Inflammation .............................................................24
References ........................................................................................................................................25
Chapter 3
So Tasty and Yet Proinflammatory .................................................................................................. 29
3.1 Introduction ........................................................................................................................... 29
3.2 Bacon..................................................................................................................................... 29
3.3 Butter and Margarine ............................................................................................................ 31
3.4 Cheese ................................................................................................................................... 31
vii
viii Contents
3.5 Processed Meat ..................................................................................................................... 32

3.6 Grilled Cheese and Processed Meat ..................................................................................... 33
3.7 Pizza ......................................................................................................................................34
3.8 Macaroni and Cheese ............................................................................................................ 36
3.9 Lasagna ................................................................................................................................. 37
3.10 Fried Cheese.......................................................................................................................... 38
3.11 Fried, Stone Baked, Flamed, and Seared Foods ................................................................... 39
3.12 Grilled and Fried Fish ........................................................................................................... 42
3.13 Smoked Meat and Fish .......................................................................................................... 42
3.14 Bagels, Croissants, Rolls, and Cheese Bread ........................................................................ 43
3.15 Roasted Nuts and Nut Butter................................................................................................. 45
3.16 Rice Crispy Cereal Cookie Bar............................................................................................. 48
3.17 Roasted Seeds ....................................................................................................................... 48
3.18 Spinach Dip and Cheese-Rich Dressings.............................................................................. 49
3.19 Sweetened Pies ...................................................................................................................... 50
3.20 Sugar-Rich Dried Fruits ........................................................................................................ 51
3.21 Cereal and Protein Bars ........................................................................................................ 52
3.22 Beverages .............................................................................................................................. 53
3.23 Potential Proinflammatory Effect of Heat-Treated Foods .................................................... 54
References ........................................................................................................................................ 55
Part II
The Maillard Reaction and Health Disorders
Chapter 4
Obesity ............................................................................................................................................. 61
4.1 Definition of Obesity ............................................................................................................. 61
4.2 Social and Economic Significance of Obesity ...................................................................... 61
4.3 Origins and Causes of Obesity.............................................................................................. 61
4.3.1 Lifestyle Choices Including Urbanization and Consumption of Calorie-Dense Diets .... 62
4.3.2 Insufficient Physical Activity ................................................................................... 63
4.3.3 Social Networks ....................................................................................................... 63
4.3.4 Genetics.................................................................................................................... 63
4.3.5 Viral Infections ........................................................................................................64
4.3.6 Economic, Social, and Cultural Factors ..................................................................64
4.4 Health Significance of Obesity .............................................................................................64
4.5 Dietary Approaches to Obesity ............................................................................................. 65
4.5.1 Introduction .............................................................................................................. 65
4.5.2 Government’s Role in the Fight against Obesity ..................................................... 65
4.5.3 The Food Industry ................................................................................................... 65
4.5.3.1 Designing AGE-Less or AGE-Free Food Ingredients .............................66
4.5.3.2 Adding AGE-Breaker Ingredients in Foods.............................................66
4.5.3.3 Designing Anti–Mood Disturbance Ingredients and Foods ....................66
4.5.3.4 Designing Tasty and Healthier AGE-Reduced Lunch and Dinner Meals ...69
4.5.3.5 Designing Tasty and Healthier Ingredients or Meals
with Triglyceride Binders ......................................................................... 70
4.5.3.6 Designing Better, Flavorful, and Healthier Beverages ............................ 70
4.5.3.7 Designing Tasty and Healthier Snacks and Desserts
with Triglyceride Binders ......................................................................... 70
4.5.3.8 Designing Foods That Improve Insulin Sensitivity ................................. 71
Contents ix
4.5.4 Restaurant and Food Service Industry..................................................................... 71

4.5.5 The Consumer .......................................................................................................... 72
4.5.5.1 Replenishing the Pantry and Refrigerator with AGE-Free
or AGE-Less Foods .................................................................................. 72
4.5.5.2 Starting the Day with Tryptophan-Rich Breakfast Foods ....................... 72
4.5.5.3 Eating Small Portions of Nutrient-Balanced Food in Moderation ........... 73
4.5.5.4 Avoiding Intake of AGE-Loaded or AGE-Inducing Foods ..................... 73
4.5.5.5 Consuming High-Calorie Foods before the Evening ............................... 73
4.5.5.6 Reducing Ingestion and Intestinal Absorption of Fat............................... 73
4.5.5.7 Consuming Foods That Inhibit Adipose Tissue Accumulation ............... 74
4.5.5.8 Consuming Foods That Decrease Cholesterol Absorption ...................... 74
4.5.5.9 Consuming Food Rich in Triglyceride Binders ....................................... 74
4.5.5.10 Consuming Foods That Improve Insulin Sensitivity ............................... 75
4.5.5.11 Managing Weight with Physical Activity................................................. 75
References ........................................................................................................................................ 75
Chapter 5
Diabetes Mellitus ............................................................................................................................. 79
5.1 Definition of Diabetes ........................................................................................................... 79
5.2 Social and Economic Significance of Diabetes ....................................................................80
5.3 Risk Factors for Diabetes ......................................................................................................80
5.3.1 Obesity and Overweight...........................................................................................80
5.3.2 Genetic Susceptibility .............................................................................................. 81
5.3.3 Ethnicity ................................................................................................................... 81
5.3.4 Low Levels of “Good” Cholesterol and High Levels of Triglycerides .................... 81
5.3.5 Insulin Resistance .................................................................................................... 81
5.3.6 Age ........................................................................................................................... 82
5.3.7 Glycemic or Fructose Index ..................................................................................... 82
5.3.8 Food Heated at High Temperature in the Absence of Water ................................... 82
5.3.9 Potassium ................................................................................................................. 83
5.3.10 Low Birth Weight .................................................................................................... 83
5.4 Health Risks Associated with Diabetes ................................................................................ 83
5.4.1 Hypertension ............................................................................................................84
5.4.2 Hypotension .............................................................................................................84
5.4.3 Erectile Dysfunction ................................................................................................84
5.4.4 Coronary Artery Disease .........................................................................................84
5.4.5 Atherosclerosis .........................................................................................................84
5.4.6 Cataract and Diabetes Retinopathy ......................................................................... 85
5.4.7 Kidney Disease ........................................................................................................ 85
5.4.8 Nerve Damage ......................................................................................................... 85
5.4.9 Skin Damage ............................................................................................................ 85
5.4.10 Periodontal Disease ................................................................................................. 86
5.4.11 Diabetes and Cognitive Brain Function ................................................................... 86
5.4.12 AGEs–Diabetes–Cancer Axis ................................................................................. 86
5.5 Dietary Approaches to Diabetes Prevention ......................................................................... 87
5.5.1 Dietary Approach to Prevent T1DM Progression .................................................... 87
5.5.2 Dietary Approach to Help Prevent T2DM Progression ........................................... 91
5.5.3 The Family Doctor ...................................................................................................92
5.5.4 Food Industry ........................................................................................................... 93
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5.5.5 The Restaurant Industry ..........................................................................................94

5.5.6 The Consumer .......................................................................................................... 95
5.5.7 Governments and Food Research Institutions .........................................................96
5.6 Dietary Management of T2DM to Prevent Complications ...................................................97
5.6.1 Controlling Hyperglycemia through Caloric Restriction ........................................97
5.6.2 Controlling AGEs in Foods .....................................................................................97
5.6.3 Oxidative Stress and Inflammation.......................................................................... 98
5.6.4 Triglyceride Control/Lipid Abnormalities ............................................................. 102
5.6.5 Insulin Resistance .................................................................................................. 108
5.6.6 Hypertension .......................................................................................................... 108
5.6.7 Angiogenesis or the Formation or Absence of Blood Vessels ............................... 109
5.6.8 Immune Modulation .............................................................................................. 109
5.7 Developing β-Cell-Friendly Beverages for People with Diabetes ...................................... 110
5.8 Trends in Diabetes............................................................................................................... 113
5.8.1 T1DM in Children ................................................................................................. 113
5.8.2 T2DM in Children and Adolescents ...................................................................... 114
5.9 Future Directions ................................................................................................................ 114
References ...................................................................................................................................... 115
Chapter 6
Hypertension .................................................................................................................................. 127
6.1 Definition of Hypertension.................................................................................................. 127
6.2 Risk Factors for Hypertension ............................................................................................ 127
6.2.1 Nonmodifiable Risk Factors for Hypertension ...................................................... 127
6.2.1.1 Age ......................................................................................................... 127
6.2.1.2 Genetics or Family History of HBP ....................................................... 128
6.2.1.3 Low Weight at Birth ............................................................................... 128
6.2.1.4 Gender .................................................................................................... 128
6.2.1.5 Race/Ethnicity ........................................................................................ 128
6.2.1.6 Diabetes .................................................................................................. 129
6.2.2 Modifiable Risk Factors for Hypertension ............................................................. 129
6.2.2.1 Obesity and Hypertension ...................................................................... 129
6.2.2.2 Dietary Salt and Hypertension ............................................................... 129
6.2.2.3 Dietary Sugar and Hypertension ............................................................ 132
6.2.2.4 Caffeine and Tyramine-Rich Foods and Hypertension ......................... 132
6.2.2.5 Heavy Alcohol Consumption and Hypertension .................................... 132
6.2.2.6 Cigarette Smoking and Hypertension .................................................... 133
6.2.2.7 Insulin Resistance .................................................................................. 134
6.2.2.8 Physical Inactivity .................................................................................. 134
6.3 Complications of Hypertension........................................................................................... 134
6.4 Dietary Strategies to Reduce or Prevent Hypertension....................................................... 135
6.4.1 Individual or Consumer ......................................................................................... 135
6.4.1.1 Reducing the Consumption of Sodium- and
Phosphate-Rich Foods ..................................................................136
6.4.1.2 Promoting the Consumption of Food Ingredients and Foods
That Protect against Hypertension ......................................................... 136
6.4.1.3 Adopting the DASH Plan ....................................................................... 137
6.4.1.4 Reducing Weight, Being Physically Active, Consuming Alcohol
in Moderation, and Avoiding Smoking .................................................. 137
Contents xi
6.4.2 The Family Doctor................................................................................................. 137

6.4.3 Food Industry ......................................................................................................... 138
6.4.3.1 Reducing Sodium Levels in Foods......................................................... 138
6.4.3.2 Finding Alternatives to Sodium ............................................................. 139
6.4.3.3 Reducing Sugar Levels in Foods and Beverages.................................... 140
6.4.3.4 Offering Balanced Potassium- and Sodium-Rich Foods and Beverages ... 140
6.4.3.5 International Agencies............................................................................ 140
6.4.3.6 Government and Government-Funded Research Institutions ................ 141
References ...................................................................................................................................... 143
Chapter 7
Atherosclerosis ............................................................................................................................... 149
7.1 Definition ............................................................................................................................ 149
7.2 Risk Factors for Atherosclerosis ......................................................................................... 149
7.2.1 Genetic Risk Factors .............................................................................................. 149
7.2.2 Aging...................................................................................................................... 150
7.2.3 Gender .................................................................................................................... 151
7.2.4 Environmental Risk Factors for Atherosclerosis ................................................... 151
7.2.4.1 Hyperglycemia and Advanced Glycation End Products ........................ 151
7.2.4.2 Obesity.................................................................................................... 151
7.2.4.3 Insulin Resistance .................................................................................. 151
7.2.4.4 Diabetes .................................................................................................. 151
7.2.4.5 Abnormal Lipid Levels........................................................................... 152
7.2.4.6 Hypertension .......................................................................................... 152
7.2.4.7 Smoking ................................................................................................. 152
7.2.4.8 Mitochondrial Dysfunction .................................................................... 152
7.3 Therapeutic Approach to Atherosclerosis ........................................................................... 153
7.4 Dietary Patterns to Prevent Atherosclerosis Development ................................................. 153
7.4.1 Dietary Approach to Stop Hypertension Diet........................................................ 154
7.4.2 Improving Western Dietary Pattern....................................................................... 155
7.4.3 Mediterranean Dietary Pattern .............................................................................. 155
7.4.4 Japanese Dietary Pattern........................................................................................ 157
7.4.5 Vegetable- and Fruit-Rich Diet .............................................................................. 158
7.5 Current Trends .................................................................................................................... 159
References ...................................................................................................................................... 160
Chapter 8
Kidney Inflammation ..................................................................................................................... 163
8.1 Introduction ......................................................................................................................... 163
8.2 AGEs, Free Fatty Acids, and Kidney Inflammation ........................................................... 163
8.3 Association of Other Dietary and Modifiable Factors and Kidney Inflammation ............. 165
8.3.1 Dietary Protein....................................................................................................... 165
8.3.2 Dietary Sodium ...................................................................................................... 166
8.3.3 Inorganic Phosphates ............................................................................................. 166
8.3.4 Indoles .................................................................................................................... 167
8.3.5 Gut Microbiota ....................................................................................................... 168
8.3.6 Physical Inactivity .................................................................................................. 169
xii Contents
8.4 Dietary Approaches to Healthy Kidney .............................................................................. 169

8.4.1 Identification of Proinflammatory Foods or Food Components
That Exacerbate Kidney Inflammation.................................................................. 169
8.4.2 Dietary Sodium Reduction .................................................................................... 170
8.4.3 Low-Oxalate Diet................................................................................................... 170
8.4.4 Dietary Inorganic Phosphate Reduction ................................................................ 170
8.4.5 Adaption of Low-Animal-Protein Diets ................................................................ 171
8.4.6 Adoption of Diet High in Plant Proteins, Vegetables, and Fruits .......................... 172
8.4.7 Targeting the Metabolic Syndrome ....................................................................... 172
8.5 Future Direction .................................................................................................................. 172
References ...................................................................................................................................... 173
Chapter 9
Osteoporosis................................................................................................................................... 177
9.1 Introduction ......................................................................................................................... 177
9.2 Composition of Human Bones ............................................................................................ 177
9.3 Prevalence and Socioeconomic Significance of Osteoporosis............................................ 178
9.4 Risk Factors for Osteoporosis ............................................................................................. 178
9.4.1 Nonmodifiable Risks of Osteoporosis ................................................................... 178
9.4.1.1 Old Age .................................................................................................. 178
9.4.1.2 Gender .................................................................................................... 179
9.4.1.3 Gravida Status ........................................................................................ 179
9.4.1.4 Age at Menarche .................................................................................... 179
9.4.1.5 Small Thin Built ..................................................................................... 180
9.4.1.6 Ethnicity and Race ................................................................................. 180
9.4.1.7 Genetics of Family History of Fractures ................................................ 180
9.4.1.8 Diabetes Mellitus ................................................................................... 180
9.4.2 Modifiable Risk Factors for Osteoporosis ............................................................. 181
9.4.2.1 Low Intake or Bioavailability of Calcium and Vitamin D..................... 181
9.4.2.2 Cigarette Smoking .................................................................................. 181
9.4.2.3 High Intake of Caffeine.......................................................................... 182
9.4.2.4 Protein Intake Deficiency ....................................................................... 183
9.4.2.5 High Intake of Cola Drinks .................................................................... 183
9.4.2.6 High Intake of Dihydrophylloquinone ................................................... 184
9.4.2.7 Vitamin K Deficiency............................................................................. 184
9.4.2.8 B-Vitamin Deficiency ............................................................................. 184
9.4.2.9 Alcohol Consumption............................................................................. 184
9.4.2.10 Sedentary Lifestyle................................................................................. 185
9.4.2.11 Use of Glucocorticoids ........................................................................... 185
9.4.2.12 Medical Conditions That Inhibit Nutrient Absorption ........................... 185
9.4.2.13 Inflammatory Bowel Disease ................................................................. 185
9.5 Therapeutic Approaches to Osteoporosis ........................................................................... 185
9.6 Dietary Approaches to Osteoporosis .................................................................................. 186
9.6.1 Calcium and Vitamin D and Bone Health ............................................................. 186
9.6.2 Mediterranean Diet ................................................................................................ 187
9.6.3 Vegetable Protein and Bone Health ....................................................................... 187
9.6.4 Dairy Foods ........................................................................................................... 188
9.6.5 Prebiotics................................................................................................................ 188
Contents xiii
9.6.6 Reducing Inorganic Phosphate Load in Foods ...................................................... 189

9.6.7 Diet of the Blue Zones ........................................................................................... 189
References ...................................................................................................................................... 191
Chapter 10
Eye Health ...................................................................................................................................... 197
10.1 Introduction ......................................................................................................................... 197
10.2 Dietary Risk Factors for Retina Cell Inflammation ............................................................ 197
10.3 Inflammatory Retinal Diseases of Public Health Significance........................................... 197
10.4 AGE–ALE and Retinal Inflammatory Diseases ................................................................. 198
10.5 Dietary Intervention for Healthy Eye .................................................................................. 198
10.5.1 Foods or Beverages to Avoid or Consume in Moderation ..................................... 198
10.5.2 Foods That Protect against Retinal Inflammation .................................................200
10.5.3 Adopting a Healthy Lifestyle .................................................................................204
References ......................................................................................................................................205
Chapter 11
Multiple Sclerosis ...........................................................................................................................207
11.1 Definition ............................................................................................................................207
11.2 Symptoms of MS.................................................................................................................207
11.3 Risk Factors for MS ............................................................................................................208
11.3.1 Age, Gender, and Race ..........................................................................................208
11.3.2 Environmental Factors and Lifestyle .....................................................................208
11.3.3 Advanced Glycation End Products from Foods.....................................................209
11.3.4 Oxidative and Nitrosative Stress ............................................................................209
11.3.5 Inflammation .......................................................................................................... 210
11.4 Economic Significance of MS............................................................................................. 210
11.5 Therapeutic Approaches to MS........................................................................................... 210
11.6 Potential Contribution of the Food Industry to Preventing MS Development .................... 210
11.6.1 Proinflammatory Ingredients, Foods, or Catalysts for MS.................................... 211
11.6.1.1 Spray-Dried Milk or Milk By-Products ................................................ 212
11.6.1.2 Sweetened Condensed Milk .................................................................. 212
11.6.1.3 Evaporated Milk .................................................................................... 212
11.6.1.4 Spray-Dried Egg Yolk ........................................................................... 212
11.6.1.5 High-Temperature Processing ................................................................ 214
11.6.1.6 Methionine-Rich Foods.......................................................................... 214
11.6.1.7 Butter, Cheese, Margarine, and Other Fat-Rich Foods .......................... 215
11.6.1.8 Palmitate-Rich and Other Cooking Oils ................................................ 215
11.6.2 Gut Microbiota ....................................................................................................... 215
11.6.3 Identifying Antioxidative Foods for Preventing MS Development ....................... 216
11.6.4 Developing Seasonal and Year-Around Foods for Preventing MS Development ....216
11.6.5 Identifying Neuroprotective and Myelin Protective Foods for Preventing MS
Development .......................................................................................................... 216
11.6.6 Developing Good Mood Food for MS Patients ..................................................... 217
11.7 Cooking to Provide Health-Enhancing Foods to MS Patients............................................ 217
11.8 Current Trends .................................................................................................................... 217
References ...................................................................................................................................... 218
xiv Contents
Chapter 12
Erectile Dysfunction ...................................................................................................................... 223
12.1 Definition and Introduction ................................................................................................. 223
12.2 Risk Factors......................................................................................................................... 223
12.2.1 Age ......................................................................................................................... 223
12.2.2 Diabetes .................................................................................................................224
12.2.3 Cyclic Guanosine Monophosphate ........................................................................224
12.2.4 Smoking .................................................................................................................224
12.2.5 Dietary Advanced Glycation End Products ...........................................................224
12.2.6 Obesity ...................................................................................................................224
12.2.7 Hypertension .......................................................................................................... 225
12.2.8 Depression.............................................................................................................. 225
12.2.9 Atherosclerosis ....................................................................................................... 225
12.3 Dietary Approach to Improve Erectile Dysfunction ........................................................... 225
12.3.1 Caloric Restriction ................................................................................................. 226
12.3.2 Mediterranean Diet ................................................................................................ 226
12.3.3 Okinawan Diet ....................................................................................................... 226
12.3.4 Ikarian and Cretan Diets ........................................................................................ 227
12.3.5 Nicoyan’s Diet ........................................................................................................ 227
12.3.6 Seventh Day Adventists’ Diet ................................................................................ 227
12.3.7 Advanced Glycation End Products-Less Diet ........................................................ 227
12.3.8 Food Extracts with Potential for Improving Sexual Dysfunction ......................... 228
12.4 Lifestyles That Improve Erectile Function ......................................................................... 229
References ...................................................................................................................................... 230
Chapter 13
Insomnia and Sleep Disorders ....................................................................................................... 233
13.1 Definitions ........................................................................................................................... 233
13.2 Risk Factors for Insomnia ................................................................................................... 233
13.2.1 Age and Gender ..................................................................................................... 233
13.2.2 Socioeconomic Status ............................................................................................ 234
13.2.3 Work Time Control ................................................................................................ 234
13.2.4 Ethnic Origin ......................................................................................................... 234
13.2.5 Pathological Conditions ......................................................................................... 235
13.2.6 Psychiatric Disorders ............................................................................................. 235
13.2.7 Inflammation and Sleep Disorders ........................................................................ 235
13.2.8 Health, Economic, and Social Significance of Insomnia
and Sleep Disorders ............................................................................................. 235
13.2.8.1 Sleep Disturbance and Infectious Disease ............................................. 236
13.2.8.2 Insomnia and Diabetes ........................................................................... 236
13.2.8.3 Insomnia and Cardiovascular Disease ................................................... 236
13.2.8.4 Insomnia and Obesity............................................................................. 237
13.2.8.5 Insomnia and Depression ....................................................................... 237
13.2.8.6 Insomnia and Suicidal Thoughts ............................................................ 237
13.2.8.7 Insomnia and Obstructive Sleep Apnea ................................................. 237
Contents xv
13.3 Dietary and Aromatheraphy Management of Insomnia ..................................................... 237

13.3.1 Dietary Habits and Lifestyle That Are Counterproductive for Managing Insomnia...... 238
13.3.2 Beverages That May Help Improve Sleep Time and Quality ................................ 239
13.3.3 Aromatherapy ........................................................................................................ 241
13.3.4 Foods That May Help Improve Sleep Time and Quality....................................... 241
13.3.5 Future Direction ..................................................................................................... 243
References ...................................................................................................................................... 243
Chapter 14
Parkinson’s Disease ....................................................................................................................... 249
14.1 Definition, Symptoms, and History of Parkinson’s Disease ............................................... 249
14.2 Prevalence, Incidence, and Economic and Social Impact of Parkinson’s Disease ............. 249
14.3 Risk Factors for Parkinson’s Disease .................................................................................. 250
14.3.1 Nonmodifiable Risk Factors for PD ....................................................................... 250
14.3.1.1 Age and Parkinson’s Disease ................................................................. 250
14.3.1.2 Genetics, Gender, and Parkinson’s Disease ........................................... 250
14.3.2 Modifiable Risk Factors for PD ............................................................................. 250
14.3.2.1 Metabolic Syndrome and Parkinson’s Disease ...................................... 250
14.3.2.2 Dietary Advanced Glycation End Products (AGEs) and PD.................. 251
14.3.2.3 Soursop and Parkinson’s Disease. .......................................................... 252
14.4 Dietary Approaches to Parkinson’s Disease ....................................................................... 252
14.4.1 Introduction ............................................................................................................ 252
14.4.2 Dietary Patterns and Risk of Parkinson’s Disease................................................. 252
14.4.3 Dietary Approached to Reduce the Risk of Parkinson’s Disease .......................... 253
References ...................................................................................................................................... 254
Chapter 15
Cancer ............................................................................................................................................ 259
15.1 Introduction ......................................................................................................................... 259
15.2 Risk Factors for Cancer....................................................................................................... 259
15.3 Characteristics of Cancer Cells ...........................................................................................260
15.3.1 Self-Sufficiency in Growth Signals........................................................................260
15.3.2 Insensitivity to Anti-growth Signals ...................................................................... 261
15.3.3 Evasion of Death .................................................................................................... 262
15.3.4 Unlimited Replicative Potential/Sustained Immortalization................................. 263
15.3.5 Angiogenesis or Ability to Induce the Formation of New Blood Vessels .............264
15.3.6 Addiction to Sugar .................................................................................................266
15.3.7 Mitochondria.......................................................................................................... 268
15.3.8 Immune Escape...................................................................................................... 269
15.3.9 Loss of Cell-to-Cell Communication .................................................................... 269
15.3.10 Tissue Invasion and Metastasis .............................................................................. 269
15.4 Symptoms Common to Cancer Patients.............................................................................. 270
15.4.1 Chronic Inflammation............................................................................................ 270
15.4.2 Cachexia and Fatigue ............................................................................................. 270
15.4.3 Anorexia................................................................................................................. 271
15.4.4 Muscle Wasting ...................................................................................................... 271
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15.4.5 Insulin Resistance .................................................................................................. 272

15.4.6 Weakness and Fatigue............................................................................................ 272
15.4.7 Significance of Advanced Glycation End Products and Cancer ............................ 272
15.5 Dietary Approaches to Cancer ............................................................................................ 272
15.5.1 Dietary Patterns Associated with High Risk of Cancer ........................................ 272
15.5.2 Dietary Patterns Associated with Low Incidence of Cancer ................................. 274
15.5.3 Dietary Approach to Cachexia and Anorexia ........................................................ 276
15.6 Future Prospects.................................................................................................................. 278
References ...................................................................................................................................... 278
Chapter 16
Alzheimer’s Disease ...................................................................................................................... 283
16.1 Introduction ......................................................................................................................... 283
16.2 Prevalence, Incidence, and Social and Economic Impact of Alzheimer’s Disease ............ 283
16.3 Risk Factors for Alzheimer’s Disease ................................................................................. 285
16.3.1 Nonmodifiable Risk Factors for Alzheimer’s Disease ........................................... 285
16.3.1.1 Age ........................................................................................................ 285
16.3.1.2 Genetics ................................................................................................ 285
16.3.1.3 Gender................................................................................................... 286
16.3.1.4 Down Syndrome ................................................................................... 286
16.3.1.5 Traumatic Brain/Head Injury ............................................................... 286
16.3.2 Modifiable Risk Factors for Alzheimer’s Disease ................................................. 286
16.3.2.1 Chronic Oxidative Stress ...................................................................... 287
16.3.2.2 Advanced Glycation End Products ....................................................... 287
16.3.2.3 Chronic Inflammation .......................................................................... 287
16.3.2.4 Midlife Visceral Obesity ...................................................................... 288
16.3.2.5 Insulin Resistance ................................................................................. 288
16.3.2.6 Type 2 Diabetes .................................................................................... 288
16.3.2.7 Midlife Chronic Hypertension.............................................................. 289
16.3.2.8 Hyperlipidemia or “Bad” Cholesterol................................................... 289
16.3.2.9 Elevated Plasma Level of Homocysteine .............................................. 289
16.3.2.10 Estrogens............................................................................................... 289
16.3.2.11 Mitochondrial Dysfunction .................................................................. 290
16.3.2.12 Poor Nutrition or Harmful Dietary Habits ........................................... 290
16.3.2.13 Vitamin Deficiencies ............................................................................ 290
16.3.2.14 Deficiency in Polyunsaturated Fatty Acid ............................................ 290
16.3.2.15 Dairy Products ...................................................................................... 291
16.3.2.16 Meat Products ....................................................................................... 291
16.3.2.17 Energy-Dense Foods ............................................................................. 291
16.3.2.18 Refined and Reducing Sugars ............................................................... 292
16.3.2.19 Lactic Acid and Lactic Acid–Rich Foods............................................. 293
16.3.2.20 Alkaloids in Foods................................................................................ 293
16.3.2.21 Capsaicin .............................................................................................. 294
16.3.2.22 Environmental Lifestyle and Exposure ................................................ 294
16.3.3 Medical Risk Factors ............................................................................................. 295
16.4 Unmodifiable and Modifiable Risk Factor Interactions ...................................................... 295
16.5 Dietary Approach to Alzheimer’s Disease ......................................................................... 296
16.5.1 Introduction ............................................................................................................ 296
16.5.2 Dietary Patterns, Lifestyle, and Risk of Cognitive Dysfunction and AD ............. 296
Contents xvii
16.5.3 Dietary Approach to Alzheimer’s Disease ............................................................ 299

16.5.4 Dietary Bioactives or Supplements with Potentials to Slow Alzheimer’s
Disease Progression ...............................................................................................300
16.5.5 Future Prospects: Designing Foods with Potentials in Alzheimer’s Disease
Development Prevention ........................................................................................ 301
References ......................................................................................................................................302
Part III
Champagne, Caviar, Good Cuisine, and Ice Wine
Chapter 17
Healthy Gut, Healthy Life.............................................................................................................. 315
17.1 Introduction ......................................................................................................................... 315
17.2 Healthy Gut Microbiota and Immune Cells from Birth to Adulthood ............................... 315
17.3 Environmental and Lifestyle Factors That Can Promote Unhealthy Gut Microflora ......... 317
17.4 Gut Microbiota and Chronic Diseases ................................................................................ 318
17.5 Strategies for a Healthy Gut ................................................................................................ 319
17.5.1 Avoiding Proinflammatory Foods and Beverages ................................................. 319
17.5.2 Caloric Restriction and Gut Microflora ................................................................. 320
17.5.3 Enhanced Consumption of Probiotics, Prebiotics, Synbiotics, and High-Fiber Foods ... 320
References ...................................................................................................................................... 327
Chapter 18
Adopting a Diet .............................................................................................................................. 331
18.1 Definition of Diet ................................................................................................................ 331
18.2 Western Diet ........................................................................................................................ 331
18.2.1 Western Dietary Patterns and the Risks of Chronic Diseases ............................... 332
18.2.2 Regions of Longevity in the West .......................................................................... 333
18.2.2.1 Dietary Patterns in Nicoya Peninsula, Costa Rica, and Longevity ...... 334
18.2.2.2 Dietary Patterns of the Seventh-Day Adventists, Loma Linda, CA,
and Longevity ....................................................................................... 334
18.3 Traditional Mediterranean Diet .......................................................................................... 335
18.3.1 Clusters of Longevity in the Mediterranean Region.............................................. 336
18.3.1.1 Traditional Sardinian and Nuoro Dietary Pattern ................................ 336
18.3.1.2 Sicilian Diet .......................................................................................... 337
18.3.1.3 Cretan Diet ............................................................................................ 337
18.3.1.4 Ikarian Diet ........................................................................................... 337
18.3.2 Some Differences between the Western and Mediterranean Diets ....................... 338
18.4 Traditional Okinawan Diet..................................................................................................340
18.5 Comparison of the Dietary Patterns and Longevity in the Blue Zones .............................. 341
18.6 Confusion and Disappointment in the Supermarket ........................................................... 341
18.6.1 Introduction ............................................................................................................ 341
18.6.2 Western Diet, Natural Ingredients, and Organic Foods ........................................ 341
18.6.2.1 Gluten Free ........................................................................................... 342
18.6.2.2 Calorie-Free Water ............................................................................... 345
18.6.2.3 Bread ..................................................................................................... 345
18.6.2.4 Yogurt ................................................................................................... 347
18.6.2.5 Muffins..................................................................................................348
18.6.2.6 Sweetened Beverages............................................................................348
xviii Contents
18.6.2.7 Milk ...................................................................................................... 351

18.6.2.8 Butter and Like-But-Not-Butter ............................................................ 351
18.6.2.9 Cheese ................................................................................................... 352
18.6.2.10 Margarine ............................................................................................. 352
18.6.2.11 Agave, Honey, High-Fructose Corn Syrup, Maple Syrup, Dextrose,
Glucose, Cane Sugar, Cane Juice, or Evaporated Cane Juice .............. 353
18.6.2.12 Pizza...................................................................................................... 354
18.6.2.13 Flamed or Rotisserie Chicken .............................................................. 355
18.6.2.14 Parsley................................................................................................... 355
18.6.2.15 Fish Oil ................................................................................................. 356
18.6.2.16 Fruit Jams ............................................................................................. 356
18.6.2.17 Roasted Nuts ......................................................................................... 356
18.6.2.18 Dried Fruits........................................................................................... 357
18.6.2.19 Milk Chocolate Bars ............................................................................. 357
18.6.2.20 Cookies and Chips ................................................................................ 357
18.6.2.21 Kettle-Baked and Gluten-Free Potato Chips ........................................ 357
18.6.2.22 Sea Salt, Iodized Salt, or Salt ............................................................... 358
18.6.3 Traditional Western-Style Food Stores versus Ethnic Food Stores ....................... 358
18.6.3.1 Traditional Western-Style Food Stores versus Ethnic Food Stores ...... 358
18.6.3.2 Microbial and Other Chemical Safety of Ethnic Food Stores.............. 366
18.6.4 Traditional Western-Style Fast-Food Restaurants and the Westernization of
Ethnic (Fast-Food) Restaurants ............................................................................. 368
18.6.4.1 Westernization of Ethnic Foods, Frying and Grilling in
Ethnic Restaurants ................................................................................ 369
18.7 Conclusion and Future Direction ........................................................................................ 371
References ...................................................................................................................................... 372
Chapter 19
Thinking Outside the Traditional Box and Setting Up and Maintaining a Healthy Pantry,
Refrigerator, and Freezer ............................................................................................................... 381
19.1 Introduction ......................................................................................................................... 381
19.2 Thinking Outside the Traditional Box and Setting Up and Developing a Healthy
Pantry, Refrigerator, and Freezer ........................................................................................ 382
Chapter 20
Food Preparation Techniques and Potential Health Benefits......................................................... 389
20.1 Introduction ......................................................................................................................... 389
20.2 Association of Western Cooking Style and Health ............................................................. 389
20.3 Association of Dietary Biologically Active Compounds and Healthy Living .................... 391
20.4 Association of Traditional Cooking Techniques and Dietary Bioactive Availability......... 391
20.4.1 Steaming ................................................................................................................ 392
20.4.2 Decoction and Boiling ........................................................................................... 394
20.4.3 Stewing .................................................................................................................. 395
20.4.4 Poaching................................................................................................................. 396
20.4.5 Vacuum-Packed Pouch Cooking or Sous-Vide Cooking ....................................... 396
20.4.6 Fermentation .......................................................................................................... 397
20.4.7 Sprouting/Germination .......................................................................................... 398
20.4.8 Baking .................................................................................................................... 398
20.4.9 Frying/Broiling ...................................................................................................... 398
Contents xix
20.4.10 Roasting.................................................................................................................400
20.4.11 Braising .................................................................................................................400
20.4.12 Searing .................................................................................................................. 401
20.4.13 Microwave Cooking ..............................................................................................402
20.4.14 Canning .................................................................................................................402
20.4.15 Double-Sword Nature of Black Pepper .................................................................403
20.5 Future Direction ..................................................................................................................404
References ......................................................................................................................................404
Chapter 21
Addressing Children, Youth, and Consumer Education ................................................................ 411
21.1 Significance of Healthy Eating ........................................................................................... 411
21.2 Addressing Healthy Eating to Children and Youth ............................................................ 412
21.3 Consumer Education ........................................................................................................... 413
References ...................................................................................................................................... 414
Chapter 22
Champagne, Caviar, Good Cuisine, and Ice Wine ........................................................................ 415
22.1 Introduction ......................................................................................................................... 415
22.2 Champagne and Caviar ....................................................................................................... 415
22.3 Antidepressing and Good Mood Foods .............................................................................. 417
22.4 Good Cuisine ...................................................................................................................... 420
22.5 Ice Wine .............................................................................................................................. 422
References ...................................................................................................................................... 424
Preface
Food is health, personal, regional, national, and international security. To defend the ascendant
French Empire, Napoleon Bonaparte turned to food science and technology and offered a monetary
reward to anyone who could invent a process of preserving foods for his soldiers. Nicholas Appert,
a French brewer and Paris chef, spent the next 14 years perfecting canning partridges, vegetables,
and gravies. After he had perfected the process of sealing food in airtight jars, he sent samples to
Napoleon’s army. The soldiers rated the food excellent and fresh. Canning was born, and Napoleon
personally awarded the equivalent of $5000 to Nicolas Appert in 1809. Since that time, processed
and preserved foods have saved billions of lives worldwide.
Globalization has created unprecedented opportunities for the food industry from farm to the
human gut. Restaurants, including fast food and sit-in restaurants or school cafeterias, are bour-
geoning around the world as convenience and world travel have become the way of life. To feed the
world, food has to be processed and preserved. Food scientists and engineers develop processed
foods that fill the world’s food supermarket shelves and are used in restaurants, hospital and school
cafeterias, and at home.
Food is medicine. The food that we consume from breakfast to dinner or at movie times is
metabolized, and the metabolites have an impact on our health, mood, behavior, and performance
throughout our lives. Louis-Camille Maillard (1878–1936), a French chemist and physician, reported
in 1912 that in the human body reactive sugars such as glucose or fructose continuously react with
proteins containing lysine, arginine, or histidine amino acid to produce compounds known as
advanced glycation end products (AGEs) that play a role in the pathogenesis of chronic diseases,
particularly diabetes. It took until the 1970s when scientists began to understand that AGEs mediate
the complications of illnesses such as diabetes and tissue modification during human aging. In the
presence of excess glucose or fructose, the sugar can also auto-oxidize and form reactive dicarbon-
yls, such as methylglyoxal, and the latter reacts with proteins to form AGEs.
Food is a biological material obtained from land animals, birds, fish, vegetables, fruits, or seeds,
after the animal or bird has been slaughtered or the fruit or vegetable has been cut. Beef sirloin is
a cut from a slaughtered cow. Salmon or catfish filet is a cut from a slaughtered salmon or catfish.
Cheese is a by-product of milk fractionation. As such, foods contain variable amounts of carbohy-
drates, lipids, minerals, proteins, vitamins, pigments, and micronutrients and are very susceptible
to biochemical interactions and microbial deterioration. Food scientists and engineers develop pres-
ervation techniques to keep food safe and palatable.
The discovery of fire gave humans the ability to prepare healthy and safe food from raw animal
or agricultural products. Louis Pasteur discovered and demonstrated the ability of heat treatment to
kill microorganisms in food and make food safer. While Pasteur focused on the efficacy of cooking
at low temperature to develop safe and healthy foods, there are several other forms of heat treatment
that can be applied to raw agricultural products to prepare tasty meals.
Cooking food is not only an art, but a combination of art and science such as chemistry, and
involves the interactions of carbohydrates, lipids, proteins, minerals, vitamins, salt, and micronutri-
ents at temperatures that can range from freezing to flame temperatures. According to the French
chemist Antoine Lavoisier, nothing is lost during cooking but matter is transformed. During cook-
ing, new desirable and undesirable chemicals are generated.
In recent years, convenience in many sectors of life has become essential for business. To meet
consumer demand for convenience, thermal and nonthermal techniques have been developed that
deliver food that is tasty and microbiologically safe. At the same time, consumers have been accus-
tomed to an open-ended high temperature and short-time cooking techniques that encompass bak-
ing, frying, grilling, broiling, bricking, microwaving, or searing food as the easy answer to deliver
xxi
xxii PrefaCe
tasty and flavorful foods. Despite warnings by medical doctors and certain media, it has been
reported that the American eating habit worsened in 2013 compared to years before.
According to Lavoisier and Maillard, the application of high temperatures to a biological mix-
ture such as food cannot go without consequences. The Maillard reaction is responsible for the flavor
of baked, barbecued, broiled, grilled, roasted, seared, microwaved, or flamed foods. As the cook-
ing temperature increases, the Maillard reaction generates a mixture of flavorful, often toxic, and
sometime carcinogenic compounds in foods depending on the cooking conditions. Reactive dicar-
bonyls are bioavailable and easily react with proteins or enzymes and disrupt protein or enzyme
functionality. About 10% of ingested AGEs remain inside the body, accumulate in different tissues
over time, and induce oxidative stress. Chronic oxidative stress induces chronic inflammation; and
chronic inflammation is the hallmark of chronic degenerative diseases, including obesity, diabetes,
eye disease, anemia, kidney diseases, hypertension, osteoporosis, sarcopenia, cardiovascular dis-
ease, multiple sclerosis, cancer, and Parkinson’s and Alzheimer’s diseases. Therefore, diet-related
diseases, including obesity and others, and food safety issues cannot be addressed by chefs and
nutritionists alone without the critical involvement of food scientists and engineers.
This book is divided into three parts. Part I describes the Maillard reaction in layman’s terms to
let those in culinary schools and cafeterias understand the chemistry that goes on when food ingre-
dients are mixed in the presence of heat. Inflammation in health and disease focuses on maternal
in utero inflammation as a risk factor for adulthood disease. In Chapter 3, the author presents some
of the tastiest and popular foods ever designed by mankind that are yet rich in inflammatory AGEs.
Part II of the book links the Maillard reaction products to chronic inflammatory degenera-
tive diseases, including obesity, diabetes, hypertension, kidney, atherosclerosis, osteoporosis, eye
health, multiple sclerosis, erectile dysfunction, insomnia, cancer, and Parkinson’s and Alzheimer’s
diseases. Through each chronic disease, the risk factors, including foods, are presented and protec-
tive foods are suggested.
Part III of the book covers champagne, caviar, good cuisine, and ice wine. The gut is the epicen-
ter of healthy life, suggesting that healthy gut is healthy life. The most coveted diets, including the
Western, traditional Mediterranean, and the Okinawan diets, are discussed. However, in between
the West and Japan, there are regions called the “Blue Zones” where centenarians live and are active
members of their communities. The adoption of Japanese and Mediterranean diets has brought
significant confusion in food outlets where consumers are presented westernized variations of the
Japanese or Mediterranean foods that are unfortunately AGEs rich.
Champagne, caviar, good cuisine, and ice wine help develop a healthy pantry both at home and
away from home. Cooking techniques are discussed, including advantages and disadvantages asso-
ciated with each technique. It is suggested that healthy gut and healthy life start with a good cuisine
at or away from home that addresses healthy children’s foods because children represent the future.
The health benefits of champagne and caviar are presented, and ice wine is introduced as the dessert
wine for laisser le bon temps rouler.
Acknowledgments
This book is a compilation of the talents and hard work of many contributors, and I express my
deepest thanks to the numerous friends, colleagues, anonymous reviewers, and students who con-
tributed to the publication of this illustrated book.
I am particularly very grateful to my children, Mariel, Boriss, and MerryJean, and my wife,
Jane. I brainstormed with them, and they guided and critiqued my ideas at home before I wrote
them down. They helped with groceries, meal preparations, and picture taking. They are co-authors.
Special thanks to my friend Judy Blustein of West Bloomfield, Michigan. We first met in 1982
when I attended Wayne State University as a summer student learning English before heading to
college at Washington State University in Pullman, Washington. We have kept in touch since. She
is like a mother to me and my wife and a grandma to our children. We thank her for taking care of
us in many ways.
Special thanks to my friend Dr. Robert Levine, ophthalmologist at Ford Hospital in Dearborn,
Michigan, and his family. We have been friends for decades. Dr. Levine reviewed the book’s table
of contents and drafts of almost every chapter. His interest in and understanding of healthy eating
has always been very encouraging throughout the development of this book. I thank him for the
many face-to-face and phone conversations we had over the last several years on a wide range of
topics. Special thanks to Dr. Levine’s family, including his wife, Naomi, and children, Jeremy and
Alex. We have spent some precious vacation time with the Levines, at or away from their home.
They were among the first who knew about the progress of the book and encouraged its publication.
I thank my friend Marv Finklestein of Bloomfield Hills, Michigan, with whom we have spent
memorable vacation time in Michigan. Marv is a World War II veteran-turned-mechanic. His ser-
vice to the world and friendship to my family are greatly appreciated.
The late Dr. John and Mary Ellen Gorham of Pullman, Washington, were very good friends
of ours and deserve special recognition. Mary Ellen always said, “Jack, I am your mom and your
children are my grandchildren.” John and Mary Ellen were very good to us like dad, mom, and
grandparents for 32 years. We miss you John and Mary Ellen.
Special thanks to our friends Dr. LeRoy Rogers and his wife Jean Rogers, residents of Dallas,
Oregon. We first met the day I arrived in Pullman, Washington, in the summer of 1982. They
became our godparents. Dr. and Mrs. Rogers have been very generous to us since 1982, check on us
regularly, and the friendship keeps rolling.
I thank my friend Kathy Bero from Lebanon, Wisconsin. Kathy is a stage-IV breast and head
cancer survivor. She wanted to learn more about angiogenesis and cancer and the potentials of diet
to inhibit angiogenesis. Kathy and Titus Ford, CEO of Pro Health Care in Waukesha, Wisconsin,
invited me to speak on “Angioprevention with dietary factors” to the corporate executives in
Waukesha on November 18, 2009. After my presentation to the hospital executives, Kathy suggested
that I communicate my views to the laypeople in a book. After several months of thinking back and
forth, I opted to address the “way we cook foods” because it is one of the main reasons many people
are not eating healthy and may not prevent disease development. Kathy worked with others to found
NuGenesis Farm in Oconomowoc, Wisconsin.
My graduate student Jose Daniel Estrada deserves special acknowledgment; he helped shape
this book by arranging the numerous pictures that I had taken over the years so that they could fit
the different chapters correctly. I owe him a debt of gratitude. I also acknowledge my former and
current students, including Benham Keshavarz, Shirin Pourafshar, Adriana Soto, Diana Carvajal-
Diaz, Srikanth Earpina, Phil Gao, Reynaldo Moreno, Kristen Kramer, Kwan Rhea, Kristina Cook,
Marco Toc, Fallon Salinas, Namrata Karki, and Jeimy Menjivar, for technical assistance.
I bear the responsibility for any errors that remain in the text.
xxiii
Author
Jack N. Losso, PhD, is a professor of food science in the School of Nutrition and Food Sciences at
Louisiana State University, Baton Rouge, Louisiana. He received his bachelor degree in chemistry
(cum laude) from the University of Kinshasa, Democratic Republic of Congo, in 1979. He received
his master’s and PhD in food science from Washington State University in 1985 and 1990, respec-
tively. He had the privilege to be trained as a postdoctoral fellow by the late food protein chem-
ist Shuryo Nakai at the University of British Columbia. He also worked as a research scientist at
Canadian Inovatech. He joined Louisiana State University as an assistant professor in 1999 and has
since become a full professor. He teaches food analysis and food protein biotechnology.
His current research interest revolves around functional foods and angiogenesis, macular degen-
eration, and chronic inflammatory diseases. Dr. Losso has published more than 150 peer-reviewed
papers, book chapters, proceedings, and journal/magazine articles. He is a certified food scientist
and professional member of the Institute of Food Technologists, the American Chemical Society, the
American Oil Chemists Society, and the American Association of Cereal Chemists International.
xxv
PArt I
the Maillard reaction and Foods
The Maillard reaction (MR), referred to in honor of the French chemist and medical doctor
Louis Camille Maillard (1878–1936) who first enunciated the process in 1912, is one of the most
important interactions in food systems especially in the restaurant industry. The reaction occurs
between a reactive aldehyde usually a reducing sugar and an amine group and is favored by heat.
The MR affects the aroma, appearance, and flavor of several types of foods including bread crust,
pizza, peanut butter, cheese, condensed sweetened milk, roasted coffee, roasted chicory, grilled
poultry or red meat, dry soups, biscuits, protein and cereal bars, breakfast cereals, beer, and cola.
The MR also affects the nutritional quality of foods that have undergone the reaction.
Chapters 1 and 2 describe the MR and elaborate on the reaction so that we all can understand
why this reaction is very important to all chefs, culinologists, food services, restaurant industry,
school and hospital cafeterias, parents, individuals, and students in culinary schools and culinology.
Caramelization is considered as a special case of the MR and will also be discussed because it is an
important nonenzymatic browning reaction of interest to all groups mentioned earlier.
The MR delivers tasty foods that are very good to the palate. Yet it is being shown that the tasty
foods that billions of individuals crave for around the world are proinflammatory. Books, review
papers, research papers, proceedings, and monographs have been and are being written on both
the positive effects of the MR on gastronomy and the side effects of inflammation. These chapters
concisely address both aspects.
ChAPter 1
Introduction to the Maillard reaction
1.1 INtrODUCtION
This chapter will cover the basic of the Maillard reaction (MR) that students in culinary schools
and culinology, chefs, and individuals in the restaurant industry need to know because they develop
MR regularly in several aspects of their occupation in the kitchen. However, before describing the
MR, a brief introduction on the history of modern restaurant is presented.
The first contemporary restaurant “Le Restaurant Boulanger” opened in Paris, France, in 1765
and was developed by Mr. Boulanger also known as Champ d’Oiseau. Before 1765, Mr. Boulanger
was selling a bouillon made from a meat juice concentrate that he developed to help people restore
strength especially women after labor/childbirth or individuals who were tired. Because he was
using food to restore strength in people, Mr. Boulanger was called a “restaurateur” or the person
who restores strength and health. Unlike the inns that opened for certain hours, where there was no
menu and the food selected by the chef was served to all customers sitting on several joint tables,
Boulanger developed a premise that opened all day and where customers sat on a single table,
ordered from a menu, and were served by a server. He named the venue “restaurant,” meaning a
place to restore strength.
Other businessmen embraced Mr. Boulanger’s idea and started serving bouillons made of meat
and vegetables to the weak and sick. In 1782, Antoine Beauvilliers opened the first high-end con-
temporary restaurant in Paris, named it “Grande Taverne de Londres” and served his customers
foods similar to what was served at Versailles and wine in bottle similar to restaurants in London.
Grande Taverne de Londres remained the best restaurant in Paris for more than 20 years. The
French Revolution contributed to the rise of the restaurant business in France. The revolution left
several chefs unemployed. Many regional leaders moved to Paris leaving their families behind
in the country side. Several restaurants opened in Paris where chefs trained in some of the best
culinary schools found employments and became “restaurateurs.” By 1789, there were hundreds of
restaurants in Paris, and by 1810, the number went up to about 3000.
In the United States, the first French-style restaurant opened in Boston in 1794. Customers sat on
single tables, the food was brought on the table, and customers served themselves. The gold rush in
California (1848–1855) saw the rise of the restaurant industry on the West Coast. Expensive French
food, champagne, and oysters were served to gold prospectors when they “hit it rich.”
The industrial revolution whereby individuals had to perform duties far away from home and
in offices also contributed to the development of the restaurant industry and convenient foods. In
order to run a cost-effective business, the restaurant industry had to rely on cost-effective ingredi-
ents. It turned out that ready-made food ingredients were more cost-effective than make-as-you-go
ingredients. Globalization and the development of middle class in emerging economies in Asia,
Middle East, Africa, and South America are also contributing to the proliferation of restaurants in
every country around the globe.
3
4 tHe MaILLarD reaCtIon reConsIDereD: CooKInG anD eatInG for HeaLtH
At the farm gate, produce can be classified into different categories including (1) produce that
are ready to eat as food such as berries, certain fruits, and nuts and (2) produce that require further
processing including coffee, milk, cereals, eggs, meat, seafood, certain fruits and vegetables, and
oilseeds. However, in some cases, ready-to-eat foods can also be used as ingredients in operations
such as baking or frying.
The food industry uses appropriate technologies including drying at low or high temperature
and precooking at low or high temperature to provide ready-to-use ingredients or foods depending
on applications. For instance, butter can be used as spread (ready-to-eat food) or as ingredient for
making waffles, rolls, potato salad, or frying foods. Similarly, cheese can be used as is on sand-
wiches or added to dough for lasagna or pizza preparation.
Recent studies have shown that several food ingredients or ready-to-eat foods are rich in proin-
flammatory compounds. The following paragraphs first explain how some processing technologies
turn natural produce into proinflammatory food ingredients or ready-to-eat foods. Similarly, the
paragraph shows how cooking in restaurants, school cafeteria, hospital, correction cafeteria, or at
home can also turn healthy produce into proinflammatory compounds for the human body.
1.2 the MAILLArD reACtION IN FOOD PrOCeSSING AND COOKING
1.2.1 Definition
The MR occurs between a reducing sugar (Table 1.1) and available amine group in the amino
acid lysine, guanidino side of the amino acid arginine, or imidazole side of the amino acid histidine
in a protein, an amino acid, peptide, protein hydrolyzate, phospholipid, or nucleic acid (Table 1.2).
Table 1.3 lists some dietary sources of reducing compounds.
1.2.2 Steps and Benefits of the Maillard reaction in Food Processing and Cooking
In 1912, Louis Camille de Maillard, a French chemist and physician, discovered that when a
reducing sugar such as glucose or fructose is in the presence of a long-lived protein such as col-
lagen or lens proteins at body temperature, the sugar binds to the protein and the sugar–protein
complex may play a major role in the development and progression of chronic diseases, particu-
larly diabetes [1]. The reaction between such a protein and carbohydrate has been named “the
Maillard reaction.” The MR occurs as part of normal human aging process but is accelerated
under pathological conditions whereby the body contains unusual and unnecessary high levels
of sugar.
The MR can also rapidly occur in foods during processing or cooking when a protein and
reactive sugar (including lactose, which is the sugar in milk; ribose, which is the sugar in meat;
fructose, which is the sugar in most fruits, honey, or most soft drinks) with or without fats are
heat-treated at temperatures such as 32°C, which is as low as the cheese making temperature.
The reaction is accelerated by heat and is fast forwarded when the protein and sugar react under
dry heating conditions including baking, blackening, braising, broiling, frying, grilling, roasting,
sautéing, or searing.
Since several food products or ingredients contain a mixture of proteins rich in amino acid
lysine, arginine, or histidine and reactive sugar and are processed at a temperature close to or
higher than the body temperature, the MR occurs regularly during cooking. The reaction becomes
complex when nucleic acids (found in baker’s yeast) and/or lipids (fats or oils) are involved in. Food
composition, type of sugar, temperature of cooking, moisture content, acidity of food, and method
of cooking are very critical to the completion of MR. When the reaction occurs in presence of lipids,
yeast, and temperature, more flavorful compounds are formed.
IntroDuCtIon to tHe MaILLarD reaCtIon 5
table 1.1 reducing Sugars and Some of their Dietary Sources

Glucose (dextrose)
Grapes
fruits and vegetables (apple, date, fig, pepper, tomato, onion, and others)
Grain products
fructose
High-fructose corn syrup
Maple syrup
Watermelon
Most fruits
Xylose
Corn cob
Pecan shell
Cottonseed hulls
ribose
Meat
ribose 5-phosphate
Human and mammalian cells
sucrose (hydrolyzes into glucose + fructose during freezing, dehydration, or storage)
sugar cane
Maple syrup
Lactose (hydrolyzes into glucose and galactose)
Human milk
Cow’s milk
Goat milk
Camel milk
Maltose (glucose + glucose)
Malt
Maltose syrup
L-rhamnose
Buckthorn
okra
arabinose
Plant gums
Galactose
Lactose
Pectin
Mucilages
In foods, the MR is best illustrated by the crust on bread or pizza, roasted coffee, peanut or nut
butter, and the dark brown color in beer, on flamed chicken, barbecued beef roast, or many other
foods (Figure 1.1). As the cooking temperature increases, the MR gives food a distinct aroma and
flavor that enhance the palatability of the cooked food. Broiling or grilling meat, grilling cheese,
flaming chicken, frying meat or fish, searing fish or pizza, sautéing food, or roasting nuts with or
without sugar all expose foods to MR.
Once initiated, the speed of the MR increases during most standard food storage conditions
even in food products that contain very little amounts of water. The MR occurs in dry milk powder,
condensed and evaporated milk, and protein and cereal bars during storage. The MR is amplified
when the food product is stored at very high temperature.
table 1.2 reactive Primary or Secondary Amine Groups and Food Sources
ε-amine group of lysine
Guanidino group of arginine
Imidazole group of histidine
Phosphatidylcholine (found in egg yolk and soyabean oil)
Phosphatidylethanolamine (found in egg yolk and soyabean oil)
Phosphatidylserine (found in egg yolk and soyabean oil)
Deoxyribonucleic acid (found in yeast)
ribonucleic acid (found in yeast)
Milk
Cream
Butter
egg whites and yolks
nuts and nut fragments
Cocoa solids
Collagen and gelatin
Cereal flour and starch
oilseed and legumes
Whey
red meat
Poultry
fish
seaweeds
table 1.3 Dietary Sources of and reducing Compounds

Corn starch
Maltodextrins
aldehydes
Ketones
orthophenols
ethanol
fruit juices
ascorbic acid
Figure 1.1 Classical example of Mr.

1.2.3 Desirable Attributes of the Maillard reaction
Since the discovery by Robert Ling on the malt flavor and the relentless pursuit of the MR by
food scientists and engineers, several in food research and industry have doubled down on the MR
for tastier and more flavorful foods. Others have looked at economic and technological consider-
ations and investigated other attributes such as improved organoleptic, antioxidative, and emulsify-
ing properties and even anticarcinogenic properties of the MR. Recent studies are revealing and
challenging. The next paragraphs will briefly delineate some of the desirable attributes such as
aroma, flavor, taste, and color that food scientists and flavorists have been encouraging when pro-
moting the MR in food product development. Bread, biscuit, breakfast cereals, and processed milk
are universal foods and typical examples of food products that draw their worldwide acceptability
because of the MR.
1.2.3.1 Improved Aroma and Flavor of Cooked Foods
The MRs impart desirable aroma to the food and enhance food palatability. Both volatile and non-
volatile flavor compounds are also formed during the MR, and food manufacturers and chefs/cooks need
it to improve and enhance the sensory attributes of heat-treated food. Flavor formation during the MR is
the function of the type of amino acids in the protein, sugar, temperature, pH, time, and moisture content.
Sugar and amino acid composition often dictate the type of flavor compounds formed. For instance, the
interaction between the amino acid cysteine and ribose derived from nucleotide in meat muscle leads to
the formation of sulfur-containing compounds that characterize the flavor of cooked meat. Bread, rice,
and popcorn flavor is mostly associated with the amino acid proline [2]. In roasted coffee, the MR is
associated with the nutty and roasted flavor/aroma, bitter, burnt, and astringent flavor/aroma.
1.2.3.2 Improved Colors and Increased Palatability
Because we eat with our eyes, toasted cereal, roasted red meat and coffee, or brewed beer have
colors that make these foods or beverages very appealing to the eye. The MR imparts desirable
aroma and colors that enhance the color and palatability of the foods mentioned earlier and others
including pizza, lasagna, dark beer, macaroni and cheese, protein and cereal bars, and peanut butter.
The list of foods that are palatable because of the MR is very extensive and can include a wide range
of food products in grocery stores.
1.2.4 Undesirable Attributes and health Significance of the Maillard reaction
As well, several undesirable products are also formed during and depending on the extent of the
MR. The early stage of MR is associated with the formation of small but very reactive molecules
including glyoxal, methylglyoxal, 3-deoxyglucosone, and reductones [3–5]. It is the high chemical
reactivity of these small molecules that drives the MR to the development of several undesirable
molecules including advanced glycation end products (AGEs) and melanoidins. Some of these small
molecules include hydrogen peroxide, acrylamide found in some types of French fries, furans found
in bread crust, dicarbonyls found in some carbonated beverages and AGEs that characterize indi-
viduals with diabetes or high blood sugar, and sugar-bound insulin that cause insulin insensitivity
in individuals who develop insulin resistance.
1.2.4.1 Loss of Color and Darkening of the Final Product
Excessive MR can lead to undesirable product color change. Excessive dark color on barbecued
or roasted meat is a good example of excessive MR. Dark roasted coffee is another good example.
1.2.4.2 Loss of Protein Biological Value
Lysine is an essential amino acid that is in high amount in meat, egg, and fish. During the MR,
the biological value of the lysine is lost. Animal studies have shown that when the MR is formed
between a reducing sugar and a protein rich in lysine, the lysine in the ensuing complexes cannot
be used by animals for growth. This reduction in nutritive value has also been shown in humans.
1.2.4.3 Effect on Allergenicity
Nuts contain allergens that affect more than 1% of the U.S. population, which represents more
than 3 million people [6]. There are specific proteins in nuts that once ingested the consumer devel-
ops an allergic reaction. For instance, Ber e 1 protein is the major allergen in Brazil nut. Ara h 1,
Ara h 2, and Ara h 3 are the major allergens in peanut. Amandin is the major allergen in almond.
During MR, proteins react with sugars, and it has been shown that higher temperature unfolds the
protein and exposes it more than when the nut is not heat-treated. The unfolding exposes more
interaction sites and it has been shown that roasted nuts lead sensitive individuals to develop more
allergic reactions. Therefore, in most cases, the MR does not reduce the allergenicity of nuts. For
instance, Beyer et al. [7] investigated the allergenicity of two US varieties of peanut that were
boiled, fried, or roasted. The allergenicity of Ara h 1, Ara h 2, and Ara h 3 were compared by a
clinical chemistry technique known as immunolabeling using sera from eight patients allergic to
peanut. Boiling and frying peanut reduced the amount of the marker of allergenicity also known as
immunoglobulin E (IgE) bound to Ara h 1, Ara h 2, or Ara h 3. Roasting increased the amount of
IgE bound to Ara h 1, Ara h 2, and Ara h 3 suggesting an increase in protein allergenicity. The aller-
genicity of peanut flour has also been reported in certain individuals [8]. Amandin is not affected
by blanching, roasting, or autoclaving [9,10].
1.2.4.4 Hydrogen Peroxide
Roasted coffee is one the best known MR products. Hydrogen peroxide has been identified as
a major product in MR mixture and coffee such as espresso [11]. In freshly brewed coffee, high
levels of hydrogen peroxide that can stimulate inflammation have been measured [12]. The toxicity
of hydrogen peroxide has been established as this oxidant enters the cell and increases the levels of
oxygen radicals causing inflammation and cell death.
Coffee is such a popular beverage that research has often been controversial on the health
benefits of this dark liquid. While Muscat et al. [12] reported on the high levels and toxicity of per-
oxide in coffee, Boettler et al. [13] analyzed several coffee extracts to identify antioxidant activities
from brewed coffee. Chlorogenic acid is high in coffee. Inside the human body, chlorogenic acid is
metabolized into caffeic acid. However, high levels of caffeic acid in the order of micromolar con-
centration are needed to demonstrate the antioxidative activity of coffee. Paur et al. [14] ascribed the
health benefits of coffee to roasting, the dark roasted coffee being excellent against inflammation.
1.2.4.5 Acrylamide
Acrylamide is a well-known bioavailable neurotoxin [15,16]. Several investigators have docu-

mented in experimental animals and discussed the mutagenic and carcinogenic effects of heterocy-
clic compounds and acrylamide generated during the MR [17–19]. High levels of acrylamide can be
detected on bread crust, in biscuits, coffee, cookies, corn chips, roasted almonds, potato products
including French fries and potato crisps. While the daily intake may be low between 0.3 µg/kg body
weight and 0.6 µg/kg body weight, regular consumption of food containing acrylamide can lead to
organ accumulation of this carcinogen [20].
Since acrylamide was identified in foods by scientists in Europe and the United States, several
studies have been performed in Sweden to determine whether there was an association between
dietary acrylamide and certain types of cancer. The association between acrylamide intake and
colorectal cancer was examined in a population-based prospective cohort of 45,306 Swedish
men [21]. The men were followed for an average of 9.3 years during which 676 men developed
colorectal cancer. It was concluded that there was no evidence that dietary acrylamide in amounts
consumed by Swedish men is a risk factor for colorectal cancer. Mucci et al. [22] also found no
evidence of association between dietary acrylamide consumed in Sweden and cancer of the bladder
(N = 263), large bowel (N = 591), or kidney (N = 133). There was no association between dietary
acrylamide and colorectal cancer in Swedish women [23]. Pelucchi et al. [24] who also carried a
meta-analysis of epidemiological studies and found no association between acrylamide and human
cancer suggested that although epidemiological studies have found no association between dietary
acrylamide and cancer in Sweden further epidemiological studies that enroll large populations with
broad exposure contrasts are warranted. While the epidemiological observations and analyses in
Sweden have shown no association between dicarbonyls and colon cancer, these data cannot be
literally translated to other countries. Rather, studies should be performed in every country where
consumption of acrylamide-rich products such as French fries and roasted almonds are high.
The toxicity of acrylamide on male reproductive system has been demonstrated in animal stud-
ies and involves side effects in sperm nucleus and tail, depletion of antioxidant proteins, and testis
DNA damage [25,26].
1.2.4.6 Furans
The flavor of breakfast cereals, pasta, coffee, commercial baby foods, and some infant formula
is associated with the presence of compounds known as furans. Hydroxymethylfurfural and meth-
ylfurfural, which are prototypes of furans, have been identified in foods mentioned earlier [27].
The genotoxicity of the MR products has also been documented [28–31]. Whereas most coverage
on hydroxymethylfurfural and furfural has been on their flavor-enhancing ability, the effects of
chronic ingestion of these molecules have never been investigated. It may be useful to know the
metabolism of these compounds.
1.2.4.7 Reactive Dicarbonyl Compounds
Flavor generation is one of the hallmarks of the MR. Certain carbonated beverages contain-
ing high-fructose corn syrup contain very reactive molecules known as α-dicarbonyl compounds
including glyoxal, methylglyoxal, and deoxyglucosone. Some of these carbonated beverages also
contain furans such as 5-hydroxymethylfurfural (5-HMF) [32,33]. Methylglyoxal is abundant in
beverages containing high-fructose corn syrup as demonstrated by Tan et al. [33] who measured a
range of 83.19–493.83 µg per serving size (354 mL). Tan et al. also measured methylglyoxal in diet
beverages free of fructose corn syrup and found methylglyoxal at a range of 25.13–111.51 µg per
serving size (354 mL). The highest levels of methylglyoxal per serving size were found in root beer
(269 µg/354 mL or can), decaffeinated coffee (140.7 µg/cup), cola drinks (81.4 µg/354 mL or can),
brewed coffee (75.6 µg/cup) [34], and honey (from as low as 100 mg/kg to as high as 1200 mg/kg)
[35]. Argpyrimidine is a methylglyoxal-derived AGE that is formed by the interaction of methyl-
glyoxal and arginine amino acid of a protein. Argpyrimidine has been detected at levels as high
as 162 ± 9.05 pmol/mg protein in familial amyloidotic polyneuropathy patients and not in healthy
control individuals [36]. Methylglyoxal binds to arginine residue in proteins to form an imidazole
derivative. Methylglyoxal can bind to any short- or long-lived arginine-containing protein such as
protamine P1 that packages sperm DNA in all mammals [37,38]. Binding to arginine may have a
detrimental effect on the vasodilator nitric oxide productivity and efficacy. Nitric oxide is associated
with erectile function. The potential side effects of too much exogenous or dietary dicarbonyls in
diets on erectile function are not known. Reduced nitric oxide levels and activity impairs the car-
diovascular system. Recently, Price and Knight [39] suggested that high levels of methylglyoxal in
diabetes exacerbate the levels of protein-reducing sugar complex also known as AGEs, inflamma-
tion and may account for diabetes complication including immune suppression in diabetes.
1.2.4.8 Pyridines and Heterocyclic and Mutagenic Compounds
Pyridine is a volatile flavor compound in cooked meat as a result of the interaction between
lipids and MR products [40,41]. Pyridines are well-known mutagens.
The presence of reducing sugars, amino acids, and large amount of creatine in meat or fish muscle
creates favorable conditions for the formation of mutagenic heterocyclic amine compounds during
frying-induced MR. The higher the cooking temperature, the faster and higher the levels of mutagens
and carcinogens generated during the MR. Heterocyclic amines are commonly known mutagens. The
level of mutagens formed is always a function of heating temperature suggesting that heating foods
at temperatures below 100°C often leads to nondetectable levels of creatinine or other carcinogens/
mutagens. High levels of pyridine, 3.3 µg/100 g duck meat, were detected when the duck meat was
pan-fried. In charcoal-grilled duck meat up to 17.8 µg of pyridine per 100 g of meat was detected.
Pan-frying and charcoal-grilling of duck meat also showed significant amounts, said 0.42 µg of het-
erocyclic amine formed per 100 g of meat. Heterocyclic amines from cooked meat are mutagens and
carcinogens [42].
1.2.4.9 Advanced Glycation End Products
The MR generates AGEs such as carboxymethyllysine (CML), pyrraline, pentosidine, and

furosine. Chronic exposure to or ingestion of AGE-rich diets (Figure 1.2) can, over time, impair
the functions of cells that regulate the passage of macromolecules and circulating cells from blood
to tissues also known as endothelial cells. Impairment of endothelial cells leads to or accelerates
vascular dysfunction. About 10% of ingested AGEs is bioavailable. Bioavailable AGEs or AGE
metabolites may interact with their receptor also known as RAGE and trigger a cascade of reac-
tions that involve enhanced oxidative stress, inflammation, and the development of a wide range of
Figure 1.2 fried foods combo.

Produce
High temperature and dry conditions
AGEs
Eye disease Stroke

Oxidative Asthma Allergy
stress Kidney Skin disorders
Inflammation
Insulin resistance
Arthritis Cardiovascular
Atherosclerosis Cancer
Inflammatory bowel disease Alzheimer’s Early aging
Multiple sclerosis Parkinson’s
Figure 1.3 Potential effects of aGes on the development of chronic degenerative diseases.
chronic degenerative diseases as shown in Figure 1.3. Because of AGEs association with several
degenerative diseases, its inhibition or reduction in foods has been proposed and pushed by sev-
eral investigators including Paul Thornalley [43–45], Helen Vlassara research group [46–49], and
Thomas Henle [50–54], or discounted by others [55,56].
Recent studies have focused on the fate of dietary AGEs inside the human body. Evaporated
milk, bread crust [57], breakfast cereals [58], infant formulas [59], roasted nuts and seeds [60], bar-
becue sauces [61], fried meat and sausages [57,62], and ice cream [63] are rich sources of CML and
possibly other AGEs. Some have suggested that daily ingestion by humans of foods or beverages rich
in AGEs including CML, or their precursors such as methylglyoxal and fructoselysine, increases the
pool of endogenous AGEs, whereas reduced intake of dietary AGEs reduces endogenous levels of
AGEs [64–66]. In one human study, 21 volunteers on high-AGE diet for 1 week gained weight and
had impaired insulin sensitivity [66]. A clinical study in Taiwan investigated the association of diets
with high or low levels of AGEs (pentosine, CML, and furosine) and serum AGEs (pentosine, CML,
and furosine) and inflammatory markers including interleukin-1 alpha (IL-1α), monochemoattrac-
tant protein-1 (MCP-1), and glycated low-density lipoprotein (LDL) in type 2 diabetic patients [67].
Diabetic patients in two groups, one group (N = 50) on low daily intake of AGEs (≤ 300 µg) and
the other group (N = 68) on high daily intake of AGEs (≥ 300 µg) were compared to control healthy
subjects (N = 74). The study lasted 7 days during which all subjects completed a dietary record. The
results showed that diabetic patients who consumed high-AGE diet had significantly higher plasma
levels of AGEs, HbA1c, glycated LDL, LDL, and LDL cholesterol compared to diabetic patients on
low-AGE diet and control subjects. Similarly, diabetic patients on high-AGE diet had significantly
higher plasma levels of inflammatory biomarkers IL-1α, tumor nuclear factor-alpha (TNF-α), and
MCP-1 compared to diabetic patients on low-AGE diet and control subjects. The activity of the anti-
oxidant enzyme superoxide dismutase was lower in diabetic patients on high-AGE diet than diabetic
patients on low-AGE diet than control subjects.
The rationale of investigating the correlation of dietary intake of AGEs and plasma levels of
AGEs in diabetes patients is threefold: (1) Circulating AGEs is the hallmark that threatens the
lives of diabetic patients, (2) more people are prediabetic or developing diabetes, and (3) the high
medical costs and reduced productivity and life expectancy associated diabetes are causes of
concern.
In the human or vertebrate body, these AGEs accumulate over the years and bind to long-lived
proteins such as the plasma proteins, artery proteins, cholesterol-bound proteins also known as
LDLs, lens proteins, heart proteins, muscle proteins, breast tissue proteins, and penis proteins and
completely alter the functions of these proteins. In the presence of lipids, the latter react with pro-
teins to form advanced lipid oxidation products (ALEs). A reactive sugar can also oxidize to form
very small reactive compounds known as glyoxal or methylglyoxal that can combine with proteins
to form AGEs. Lipids under heat can oxidize and generate glyoxal or methylglyoxal that are prone
to bind to proteins and generate AGEs.
Several research groups have analyzed a variety of foods and reported that very high levels of
AGEs can easily be found in a wide range of ready-to-eat foods or ingredients for humans or pets.
Bacon, cheese, peanut butter, and red and poultry meat contain high levels of AGEs. Butter contains
very high levels of ALEs. For instance, raw milk has undetectable levels of AGEs, but the process-
ing of milk generates a wide range of food ingredients or products that are enriched in AGEs. As
shown in Figure 1.4, from milk we obtain fresh milk, butter, condensed milk, cheese, and powder
milk. Butter is made by churning milk and is highly enriched in saturated fat. Butter is also high in
ALEs. Sweetened condensed milk is made with high levels of sugars allowing the MR to take place
in the presence of milk proteins and the heat treatment used for sterilization. During storage, the
MR proceeds and more AGEs are formed during storage until consumption.
Cheese is produced at a temperature that is warm and AGE formation increases during cheese
ripening and early storage. It has been shown that during prolonged storage, AGE levels decrease,
but it is not known what the by-products of AGEs are. Powder milk is produced by spray drying
liquid milk on a very hot surface to generate dried particles. The high temperature facilitates or
Milk
Homogenized milk Butter Condensed milk Cheese Powder milk

low AGEs high ALEs high AGEs high AGEs high AGEs
Pasta, soups, desserts
Breakfast Snack Lunch Snack Dinner Snack
Figure 1.4 the Mr during milk processing and the domino effect of a food or food ingredient containing high
levels of aGes.
exacerbates the MR giving a resulting milk powder that is very rich in AGEs. Storage of milk pow-
der, whether nonfat or high fat, exacerbates the MR and the formation of more AGEs. Given the
prevalence of butter, cheese, or milk powder in cooking at home or restaurant, a silent killer (AGEs)
gets into food unnoticed and is consumed daily as often as people can consume foods containing
milk products. Even if minute amounts are consumed at every meal, at the end of the day because
these AGEs are present in every piece of food from breakfast to movie theater popcorn, the cumula-
tive effect is that substantial amounts of AGEs are ingested every day. When most individuals rely
on the very same dietary pattern where AGEs are found everywhere, AGEs become part of daily
ingested unhealthy compounds (Figure 1.4).
Peanut butter is full of AGEs and not really health enhancing. Since peanut butter is AGE- and
ALE-rich and can be consumed all day long in different types of foods including bread sandwich,
cracker sandwich, cookies, and cereal bars and other different types of snacks, peanut butter is an
excellent, although perhaps unwelcome, carrier of AGEs and ALEs into the human body (Figure 1.5).
The domino effect of red meat can also be presented. Nowadays, red meat can be consumed
at breakfast, lunch, dinner, and in snacks (Figure 1.6). Due to the omnipresence of AGEs in red
meat, spreading red meat consumption through all the daily meals may not be a good idea for
healthy living.
Fructose is the sweetener in many food products from breakfast foods and beverages to
evening-time beverages and foods. Because fructose is very reactive, fructose is a good pre-
cursor of AGEs. And because fructose is found in almost every food and beverages offered in
commerce, fructose-containing foods are excellent warehouses of AGEs. Consumption of these
foods and beverages leads to body accumulation of AGEs or AGE precursors such as methylg-
lyoxal (Figure 1.7).
Some investigators have argued that there was no evidence that ingested AGEs accumulate
inside the human body [55,68]. Others have reported that AGEs such as CML-modified human
Peanut
Raw low AGEs Roasted high AGEs
Figure 1.5 Peanut butter as an excellent source of aGes and the domino effect of peanut butter as a source
of high levels of aGes.
Red meat or poultry

raw or cooked
high levels of AGEs
Breakfast Lunch Dinner
Figure 1.6 the domino effect of raw or cooked red meat as a source of high levels of aGes.
Corn
Corn flour Corn oil High fructose corn syrup

no AGEs no or low ALEs very reactive
Beverages
Figure 1.7 the domino effect of high-fructose corn syrup in food products.
serum albumin or glycolaldehyde-modified β-lactoglobulin are unable to bind to their receptor

RAGE [69,70]. However, there are more investigators who have pointed out the negative effects of
dietary AGEs on human health [56,71] than those who promote AGEs as health enhancing.
1.2.4.10 Insulin Glycation
Sugar–insulin complex also known as glycated insulin leads to decreased efficacy of insu-
lin overtime (Figure 1.8). Abdel-Wahab et al. [72] were first to report the presence of glycated
insulin in the pancreatic islets of normal animals and elevated levels of glycated insulin and
proinsulin within the pancreas islets in both insulin-dependent and independent diabetic ani-
mal models. The same group injected glycated and nonglycated insulin to mice and observed
that the extent of insulin glycation was inversely related to insulin biological activity and could
Insulin sensitivity
Healthy body
Insulin secretion
Insulin sensitivity
Diseased body
Birth Old age
Figure 1.8 reduced insulin sensitivity due to insulin glycation.
be related to glucose intolerance in diabetes [73]. They also questioned if glycated insulin could
also be identified in humans with diabetes. McKillop et al. [74] demonstrated the presence of
glycated insulin in the plasma and islets of diabetic animals supporting the hypothesis that
glycated insulin plays a role in the pathogenesis of diabetes. McKillop et al. [75] also identi-
fied glycated insulin as a significant proportion of total circulating insulin in both humans
and animals with type 2 diabetes. They suggested that glycated insulin may exhibit impaired
biological activity including glucose clearance compared to native insulin. Finally in 2003,
Lindsay et al. [76] demonstrated the presence of elevated levels of circulating glycated insulin
in type 2 diabetic subjects. Recently, Oliveira et al. [77] showed that methylglyoxal, a precur-
sor of AGEs found in baked foods, honey [78] including manuka honey that has high levels of
methylglyoxal [79], and several soft drinks [33] can modify insulin and impair insulin biologi-
cal activity including glucose regulation. While the antibacterial activity of honey is ascribed
to methylglyoxal, the in vivo health benefits of this molecule are food for thought when honey
is added to foods.
Can the MR products formation be prevented? Yes! Go to Chapter 7, please.
1.3 CArAMeLIZAtION
Caramel is one of the most extensively used colorants by the flavor, drug, carbonated soft
drink, and beverage industries. It is obtained by the process known as caramelization whereby
sugar is heated at temperature higher than 149°C or above its melting point under alkaline
(pH 9) or acidic conditions (pH 3) in absence of a nitrogen-containing compound such as amino
acid, peptide, or protein. Crème brulée and Madeira wine are a delight for many food connois-
seurs around the world. These two products are typical examples of caramelization products.
Caramelization can occur in the presence or absence of water. In the same food, caramelization
and MR may occur simultaneously. For instance during bread baking, starch is degraded into
small reducing sugar molecules and the reducing sugar can be part of both browning reactions.
As the pH of the reaction increases to alkaline region or the acidity decreases, thermal degrada-
tion of fructose generates high levels of reactive carbonyl compounds that polymerize into brown
compounds. The chemical and physical properties of caramel products depend on temperature,
pH, and heating time. Caramel products are a mixture of volatiles and nonvolatiles with a wide
range of molecular size [80].
There are four types of caramels, Type I–IV, obtained when food-grade sugars are heated with
1. Sodium hydroxide (class I)

2. Sodium hydroxide and sulfur dioxide mixture or in the form of sodium sulfite or metabisulfite (class II)
3. Ammonia (class III)
4. Sugar heated with sulfur dioxide and ammonia as is or sugar heated with ammonium sulfite, ammo-
nium hydrogen sulfite, sodium sulfite, sodium hydrogen sulfite, or sodium metabisulfite (class IV)
The only color allowed in vinegar, alcoholic beverages including whisky, beer and liqueur,
soft drink beverages, desserts, ice cream, and malt bread is caramel. Information on the speci-
fications for caramel colors can be obtained in Licht et al. [81]. Caramel I has no net charge,
Caramel Color II and IV carry negative charge, and Caramel III carries a positive charge. Most
soft drinks contain negatively charged tannins derived from plant barks or roots and as a result
most soft drinks are negatively charged. To avoid flocculation/precipitation of the tannins, soft
drink manufacturers select caramels with isoelectric point below the beverage pH. Because
most soft drinks have pH around or below pH 3, class IV caramel, which has a pI between
0.5 and 2.0, is often selected and is stable in citric or phosphoric acid. Non-cola beverages with
pH >3.5 can accommodate and remain stable with class I caramels including DDW #525, 528,
or 570, which are slightly negatively charged. Class III caramel including DDW #301 and 304
has a pI between pH 5.0 and pH 7.0. This class caramel is used for a soft drink commonly used
in Latin America under the name of Malta because this beverage is positively charged and has
a pH around 4.0.
Caramel also protects food or beverage flavor from light deterioration. Caramel can substitute
for gums and be used as emulsifiers in beverage formulations containing essential oils. In soft
drinks caramel dosage varies from lowest in ginger ale (0.002%) and increases in products such
as apple drinks, cream soda, Malta, energy drink, guarana, root beer, and cola (0.45%). Additional
information on the use of caramel single-strength versus caramel double-strength can be found at
www.caramel.com.
1.4 CUrreNt AND FUtUre DIreCtIONS IN MAILLArD reACtION
The MR is as old as human civilization, although it was formally discovered in 1912 and was
right away associated with diabetes. For decades, the food and beverage industries used it to develop
flavorful and tasty food products. Since the 1970s, the association of the MR with chronic diseases
has been investigated in research laboratory and clinics around the world. Despite the plethora
of information on the potential health side effects associated with chronic consumption of MR
product–rich foods, research findings have not completely translated into public warnings sufficient
enough to move the majority away from reducing the consumption of MR product–rich foods.
While several reasons can be put forward to explain the slow progress toward reducing the con-
sumption of MR product–rich foods, it is important to suggest that the majority of people cannot
think out of the box to develop tasty and flavorful foods without using reducing sugars, amino com-
pounds, and high temperatures. However, the next chapters will show that it is possible to eat tasty
and flavorful foods without the MR.
As more and more consumers become aware of the risks over benefits associated with the MR,
there will be less abuse of the reaction as it has been in recent years with increased consumption of
broiled, fried, and roasted foods. At the same time, the culinologists, chefs, and food scientists are
being challenged to develop tasty and flavorful foods and beverages that are either MR product–less
or MR product–free. Knowledge of the factors that affect the reaction is important to guide food
developers into moving away from chronic use of the MR.
reFereNCeS
1. Maillard LC. Action des acidesamines sur les sucres: Formation des melanoidines par voie methodique.
CR Academy of Sciences (Paris) 1912;154:66–68.
2. Van Boekel M. Formation of flavour compounds in the Maillard reaction. Biotechnology Advances
2006;24:230–233.
3. Hodge JE. Dehydrated foods, chemistry of browning reactions in model systems. Journal of Agricultural
and Food Chemistry 1953;1:928–943.
4. Odani H, Shinzato T, Usami J et al. Imidazolium crosslinks derived from reaction of lysine with glyoxal
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ChAPter 2
Basic Understanding of Inflammation
2.1 INtrODUCtION
Inflammation is the body’s response to harmful stimuli to eliminate the injurious agent and
repair the damaged tissue. There are several sources of inflammation including microbial and viral
infections, exposure to allergens, radiation, toxic chemicals, obesity, alcohol consumption, smok-
ing, high-calorie or energy-dense foods, and oxidative stress. There are two forms of inflammation:
acute and chronic.
2.2 INFLAMMAtION IN heALth
Acute inflammation is the body’s initial response, mediated through activation of the immune
system, to ward off the injurious agent. Acute inflammation is initiated by the body’s immune
system and used as a protective mechanism against harmful insults. During acute inflammation,
leukocytes and plasma proteins including antibodies move quickly to the site of injury to eliminate
the stimuli. The morphology of acute inflammation is characterized by the four cardinal signs of
inflammation including redness, swelling, heat, and pain. Acute inflammation lasts until the offend-
ing agent is eliminated and the tissue has been repaired. In the absence of acute inflammation, a
wound or an infection would not heal.
Chronic or persistent inflammation is the second stage of inflammation and sets in only if the
injury-causing agent persists for a long time and/or the ability of the immune system to ward off the
injury has failed. During chronic inflammation, the injury, the injury-causing agent or its associate,
and the body’s defending agents all coexist. Although chronic inflammation is preceded by acute
inflammation, there is indication that chronic inflammation may begin as subtle low-grade inflam-
mation and symptomless disease-specific process. Chronic inflammation is a major risk factor for
age-related health problems and chronic degenerative diseases including inflammatory bowel dis-
ease, obesity, arthritis, asthma, atherosclerosis, diabetes, cardiovascular, insomnia, kidney disease,
lupus, macular degeneration, multiple sclerosis, cancer, Parkinson’s, and Alzheimer’s. Chapters 4
through 16 will elaborate on some of these diseases.
Oxidative stress is generated by the imbalance between excessive formation of highly reactive
species, including reactive oxygen species (ROS) and insufficient levels of antioxidants in the tissue
area of inflammation. However, the production of ROS is not always detrimental to the body; rather
it is an essential component of the body’s response to insults. But excessive levels of ROS have been
implicated in the pathogenesis of a wide range of chronic diseases mentioned earlier.
21
2.3 INFLAMMAtION IN DISeASe
In many chronic diseases, chronic inflammation is first initiated as a beneficial process to pro-
tect cells against stress. However, over time the process turns from a beneficial one to a pathological
one. The first cellular sign of chronic inflammation is the infiltration of the tissue by white blood
cells and their differentiated forms called macrophages. Since the first cellular sign of acute inflam-
mation seems to differ from the first cellular sign of chronic inflammation, it is suggested that the
factors that initiate and regulate chronic inflammation processes differ from those involved in acute
inflammation. Where does chronic inflammation in humans start?
2.4 MAterNAL AND UterO INFLAMMAtION
In 1986, Barker and Osmond introduced the “fetal origins of adult disease” hypothesis or the
“Barker hypothesis” that suggests that adverse intrauterine and early postnatal environment includ-
ing birth weight and body length strongly increase the risk of noncommunicable chronic diseases
such as cardiovascular disease in adulthood [1]. In 1990, Barker wrote that in search of fetal and
infant origins of adult diseases, “the womb may be more important than the home” [2]. This sug-
gestion was based on previous studies done in the United States, Britain, Finland, and Norway that
showed an inverse relationship between adverse living conditions during childhood such as poor
diet and housing and the risk of ischemic heart disease [2]. Since the 1990s several epidemiologi-
cal studies in the United States, Europe, and India and reviews examined the link between several
chronic adult diseases to maternal utero and early postnatal environment [3–7].
The association of low birth weight, which is synonymous of poor fetal growth and nutrition
and adult chronic degenerative diseases seems to be exacerbated by catch-up growth and obesity
[8,9]. Cardiovascular disease later in life was associated more strongly with poor fetal growth and
maternal health and physics than environmental conditions such as overcrowding [10]. A strong
association has been shown between birth weight and the intermediary biomarkers of heart disease
including diabetes, hypertension, cholesterol, and fibrinogen [11]. An increased rate of cardiovascu-
lar disease and insulin-dependent diabetes later in life was associated with low birth weight, thin-
ness, and short body weight at birth [12]. In 2004, Barker extended the hypothesis to suggest that
“growth in infancy and early childhood is linked to later disease” including cardiovascular disease
and type 2 diabetes.
In 2009, Barker et al. [9] reviewed the Helsinki Birth cohort that looked at 13,345 men and
women born in the city between 1934 and 1944 and a cohort of 7086 individuals born between
1924 and 1933. It was concluded that children who grew up slowly during fetal life and infancy
and increased their body masses after childhood developed coronary heart disease and diabetes.
While Barker originally linked low weight at birth to cardiovascular disease late in life, others have
looked at the effect of high weight at birth, which translates into overnutrition and its correlation
with increased risk of a multitude of chronic diseases in mid- or adult life [13,14]. Gluckman et al.
[15], Seckl and Holmes [16], and Rogers and Velten [17] have suggested that there is a correlation
between “maternal health and the intrauterine environment” and cardiovascular disease develop-
ment in adult life. Fetal development is a short but very critical period of life during which organs
develop suggesting that any disturbances in the utero can have a lasting effect on the infant and the
adult. This period has been coined as “developmental plasticity,” a period during which the fetus
receives all the beneficial and dysfunctional metabolic information available from the maternal
environment. Studies have shown that this package of good and bad information becomes the fetus
signature that will help it adapt and grow after birth [17–19].
Numerous prospective and retrospective studies have confirmed Barker’s hypothesis, which
has also been labeled as “fetal programming” and have even suggested that maternal nutritional
BasIC unDerstanDInG of InfLaMMatIon 23
imbalance and metabolic disorders may have persistent effect on the health of the offspring and
across generations. For instance, transgenerational epigenetic effects of food components have been
associated with increased risk of type 2 diabetes in American native Indians [20–23]. Delisle [8]
added that it was more than imperative to improve women nutrition because it enhances the health
and survival of mothers and children and may help prevent the development of chronic disease in
generations to come. There are, however, those who have found the Barker hypothesis to be incon-
clusive [11,24,25].
Maternal inflammation may not always be a threat to the fetus because the growth of the fetus
to an infant is an angiogenic process, a process whereby new blood vessels are formed for fetal
development. This physiological inflammation turns off whenever the tissue or organ has achieved
its growth characteristics. However, while in the womb the fetus is also exposed to maternal inflam-
mation and the pregnant mother is commonly exposed to inflammation from two general sources:
internal endogeneous and external exogenous (Figure 2.1). The internal source includes the genetic
makeup of the mother and all the baggage that may include the woman’s link to metabolic disorders
such as obesity, diabetes, multiple sclerosis, cancer, schizophrenia, autism, and chronic inflam-
mation that can affect the developing fetus and lead to an offspring with preexisting metabolic
dysfunction. The external source includes the mother’s lifestyle such as smoking, regular exposure
to smoking or other chemical toxicants, alcohol consumption, diet, and stress. While the internal
source or the genetic load is inflammatory to start with, the external source may lead to oxidative
stress which in turn induces inflammation in the mother-to-be and the fetus. Prenatal exposure to
energy-dense foods, cigarette smoke, or alcohol can adversely influence fetal development. Stress
may change the pregnant woman’s mood which in turn may affect her food preferences [26,27]. The
latter if associated with the presence of compounds that promote inflammation can only add up to
the inflammation package around and in the fetus because maternal blood transmits almost every-
thing from the mother to the fetus and growing fetus. For instance, several clinical studies have
clearly demonstrated that mothers who fed themselves regularly and extensively on junk food pro-
cessed at high temperature or an unbalanced diet high in pro-inflammatory compounds absorbed a
lot of toxic compounds from the food and transmitted these compounds to the fetus who kept them
until birth and beyond to become obese [28,29]. The fetal origins of adult obesity have been traced
Endogenous sources of Exogenous sources of

maternal inflammation maternal inflammation
Genetics Diet
Health status Lifestyle
Stress and emotions
Oxidative stress Oxidative stress
Maternal inflammation
Figure 2.1 risk factors for maternal inflammation.

to mothers who consumed excessive amounts of energy-dense, high fat, high sugar, and palatable
foods in early pregnancy and before giving birth [30–32]. These foods and beverages cause adverse
insults during intrauterine growth which can result in permanent damage in the physiology and
metabolism of the adult offspring [33].
Similarly, a mother with a child in utero may consume foods devoid of essential nutrients and
thus delivers an infant who is prone to develop metabolic dysfunction [34–36]. To substantiate this,
several studies have consistently shown that mothers who did not take enough folic acid before
and during their pregnancy delivered infants who later developed neural tube defects [37–41].
Maternally transmitted metabolic disorders including pro-inflammatory compounds raise the levels
of pro-inflammatory pool in the newborn.
The combination of internal and external inflammation exacerbates the burden of inflammation
in the mother and fetus. Maternally transmitted malnutrition package, a pro-inflammatory burden
in the infant and, if combined with neonatal exposure to malnutrition and environmental stressors
in infancy, may increase the susceptibility to and incidence of chronic disease in the child’s adult-
hood. Malnutrition is defined here as an unbalanced diet. Studies of women who became pregnant
during famine suggested that metabolic disorders later in the child’s life were dependent on the
timing of nutritional insult during pregnancy.
For instance, mothers who were undernourished or malnourished during the first trimester of
their pregnancy during the 1944–1945 Dutch Hunger delivered infants who later were prone to or
developed cardiovascular disease compared to children born from mothers whose pregnancy was
at the second or third trimester when the famine started [6,35,42]. Recent studies have shown that
while low birth weight is consistently associated with increased risk of type 2 diabetes, hyper-
tension, and ischemic heart disease, the association between low birth weight and these diseases
appears to be mediated by prenatal and postnatal factors [43–46].
Neonatal nutrition also has been linked to health in later life. Both maternal undernutrition and
overnutrition and neonatal undernutrition and overnutrition may induce early aging and affect the
expression of genes involved in the metabolic syndrome including insulin resistance, obesity, type
2 diabetes, dyslipidemia, hypertension, and cardiovascular disease. Maternal overconsumption of
high-fat diet has shown to lead to offspring who developed hepatic insulin sensitivity, nonalcoholic
fatty liver disease, cardiovascular dysfunction, and hypertension [47–49]. Infants exposed to high
fat, high sugar diets often develop a preference for high fat diets [50]. Early postnatal undernutrition
and overnutrition have shown to affect the composition of the gut microbial population also termed
gut microbiota often in favor of the growth of and colonization by harmful bacteria. As a result, a
gut microbiota full of harmful bacteria has been identified as a risk factor for chronic disease in later
life (Chapter 17). Harmful bacteria in the gut are lifelong source of low-grade inflammation because
these bacteria release compounds from their cell walls that enter the blood stream and stimulate the
development of low-grade inflammation characterized by increased concentration of inflammatory
biomarkers (detailed in Chapter 17). The latter, if not counteracted properly, can become chronic
inflammation and lead to the development of chronic degenerative diseases.
However, the origin of adult disease is not necessarily fetal. Individuals who die from work-
related chronic chemical exposure such as those in the construction industry cannot blame it on
their mothers.
2.5 MAILLArD reACtION PrODUCtS-INDUCeD INFLAMMAtION
Foods cooked at very high temperature including baking, broiling, frying, grilling, roasting,
and searing have less available lysine compared to foods cooked in water or steamed. During the
Maillard reaction advanced glycation end and advanced lipoxidation products (AGEs and ALEs)
are formed. These AGEs/ALEs bind to their receptors and trigger adverse health effects in cells,
Alzheimer
Atherosclerosis and Asthma and
Stroke
cardiovascular disease airway disease Cancer
Parkinson’s
Huntington
Other neurological disorders Cataract and
eye disorders
Allergy and Chronic inflammation

Diabetes
autoimmune diseases
Obesity
Skin disorders Kidney diseases
Insomnia Rheumatoid arthritis Erectile dysfunction
Figure 2.2 Potential health risks associated with chronic consumption of Maillard reaction-rich food products.
tissues, and organs. A number of studies conducted in healthy animals and humans with or without
diabetes have shown that individuals who consumed AGEs-rich diets had elevated levels of oxida-
tive stress markers such as 8-isoprostanes and various inflammatory markers including C-reactive
protein compared to individuals who consumed AGEs-poor diets such as steamed foods [51–53].
AGEs-rich diets correlated with high serum levels of AGEs and the studies also showed that the
high serum levels of AGEs were inversely correlated with renal dysfunction. Peppa et al. [54] and
Uribarri et al. [55] showed that there was a positive relationship between intake of dietary AGEs
and levels of plasma inflammatory markers. Intervention studies in AGEs restricted diets, that is,
low-AGEs diets using patients on hemodialysis or peritoneal dialysis showed significant decrease in
plasma inflammatory markers and endothelial dysfunction [54]. Caffeine-free cola drinks contain
high levels of AGEs precursor methylglyoxal. Consumption of caffeine-free cola drink by healthy
and diabetic volunteers showed an increase in plasma inflammatory biomarkers [56]. AGEs-rich
made of egg white cooked with fructose and fed to diabetic patients produced serum levels of AGEs
that were proportional to amounts consumed [57]. The kidneys of diabetic patients or nondiabetics
with kidney disease do not easily excrete the products of degradation of endogenous AGEs.
Isocaloric meals (580 kcal) containing similar ingredients were prepared to generate high AGE
levels by frying or broiling at 230°C for 20 min or low AGE levels by steaming or boiling at 100°C for
10 min [58]. The two meals had identical ingredients, and differed only by the temperature and time
of cooking. When the meals high in AGE were fed to T2DM patients, the patients showed a marked
increase in circulating markers of endothelial dysfunction (VCAM-1 and E-selectin) and decrease in
adiponectin and leptin levels associated with acute postprandial changes in endothelial and adipocyte
function [59]. These effects were prevented when patients consumed the meal containing low levels of
AGE. Absorbed dietary AGEs enhance low-grade inflammation and oxidative stress even in normal
subjects and low-grade inflammation is a hallmark of obesity and one of the perpetuating factors.
Figure 2.2 shows potential health risk associated with chronic consumption of excessive amounts of
Maillard reaction products-rich foods. The risks of inflammation associated with the consumption
of tasty Maillard reaction products-rich foods are discussed in the following chapter.
reFereNCeS
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ChAPter 3
So tasty and Yet Proinflammatory
3.1 INtrODUCtION
Globalization, convenience, and instant gratification have created an unprecedented opportunity

for a successful growth for the food industry and all its branches including the food processing and
the restaurant industries. To meet consumer demand for convenience, hurried lifestyles, “laisser
les bons temps rouler” meaning “Let the good times roll,” quick delivery, and global peace and
prosperity, the food industry, including the ingredient development and the restaurant sections, has
embraced high-temperature short-time (HTST) processing and cooking techniques to provide food
that is tasty and microbiologically safe. For instance, spray drying of milk takes seconds to pro-
vide milk powder that is used in a wide range of food formulations. Ultra-high temperature takes
seconds to provide liquid milk that is shelf stable for months. Baking, broiling, bricking, flaming,
frying, grilling, microwaving, or searing fruits and veggies or ingredients has become the easy and
quick answer to prepare tasty and flavorful foods. Cooking techniques, diets, and recipes are being
promoted freely through the Internet, without scientific scrutiny, promoting flame and high tem-
perature as the best way to develop delicious meals.
The following sections describe some of the tastiest and most flavorful foods and beverages avail-
able to consumers and travelers around the world. While each one of these foods and/or beverages
symbolizes “laisser les bons temps rouler” and offers instant good mouth feel, satiety, gratification, and
energy to perform well in a short-term, regular, and long-term overconsumption of these foods or sim-
ply the cumulative effects of combining these foods throughout the days or years may be a risk factor
for developing chronic inflammation. Methylglyoxal, advanced glycation end products (AGEs), acryl-
amide, heterocyclic amines, polycyclic aromatic hydrocarbons, and diacetyl are some of the proinflam-
matory markers that are commonly found in the foods described later. The list of foods is not exhaustive
but has included foods that are commonly available in restaurants and cafeterias around the world.
3.2 BACON
Bacon contains proteins, sugar, and fat. Frying bacon creates the best conditions for the Maillard
reaction to develop. The resulting fried bacon tastes very good because of the flavor generated by the
special Maillard reaction that involves the protein, sugar, and fat in the meat (Figure 3.1). Therefore,
as a result of this process, bacon contains very high levels of dicarbonyls, AGEs, and advanced lipid
oxidation end products (ALEs) [1]. Bacon is also a very salty product that is not recommended as
healthy for individuals watching their blood pressure.
Fried bacon is known to contain the highest levels of heterocyclic mutagenic compounds [2]
among fried meats, some of which may be bioavailable. Higher consumption of red meat has
been associated with increased levels of C-reactive protein, a biomarker of inflammation in the
plasma [3,4]. Several epidemiological studies have shown that frequent red meat consumption, the
29
Figure 3.1 fried bacon contains very high levels of dicarbonyls, aGes, and aLes.
cooking methods including high temperature associated with barbecuing, frying, grilling, and well-
done meat are a major risk for breast [5,6], prostate [7,8], and colon and pancreatic cancer [9–11].
Heterocyclic amines, benzo(a)pyrene, and polycyclic aromatic hydrocarbons are mutagens that
form in meat during long-time cooking at high temperature and may contribute to the high risk of
cancer associated with frequent red meat consumption [12,13].
Bacon sprinkled with black pepper was developed for improved flavor. Yet combining bacon
and black pepper may be unhealthier than consuming bacon without sprinkling on the black pep-
per (Figure 3.2). The reason is as follows. Black pepper contains a compound called “piperine,”
which is a good antioxidant. However, piperine is also known in research for its ability to enhance
the bioavailability of less bioavailable bioactive compounds in the body to increase their concen-
tration in the blood and other tissues. Consuming fried bacon sprinkled with black pepper in any
form whether in a sandwich, as bits in spinach salad, or a pizza may enhance the bioavailability of
unhealthy heterocyclic compounds and promote unhealthy outcome.
Figure 3.2 addition of black pepper on bacon exacerbates the bioavailability of aGes inside the human body.
so tasty anD yet ProInfLaMMatory 31
3.3 BUtter AND MArGArINe
Butter is tasty yet it is rich in saturated fatty acids mostly palmitic acid from palm oil.
Saturated fatty acid palmitic acid is known for having detrimental effects on cardiovascular
system. Butter is widely used in food formulations. It is used in rolls, baking, frying, grilling, and
stove top cooking. The domino effect of butter can be devastating.
Margarine of course differs from butter. It is made mostly with oils rich in saturated fats.
Palmitic acid makes the major portion of margarine composition. Both butter and margarine are
proinflammatory.
3.4 CheeSe
Cheese is made by precipitating the major milk family of protein known as caseins. The precipi-
tation can be done with rennet (an enzyme found in the calf stomach) to give the rennet-coagulated
cheese or using a food-grade acid to give acid-curd cheese. The resulting casein is blended with salt
and flavoring and aged for some time until consumption. Basically, cheese is a rich coagulate of
milk caseins. The Maillard reaction occurs during cheese making and the stored cheese carries with
it AGEs. Some cheeses are rich in AGEs and some have fewer amounts of AGEs.
Uribarri et al. [1] analyzed 549 food ingredients and products and reported AGEs levels for
a variety of cheeses. Parmesan cheese contained the highest levels of AGEs, followed by Cream
cheese, American White, Greek feta, Brie, Cheddar, Swiss reduced fat, Swiss processed, American
low fat, Cheddar extra sharp, Mozzarella reduced fat, and cottage cheese 1% fat.
Others [14–16] have looked at dairy products or dairy drinks [16] and reported high levels of
AGEs in pasteurized and sterilized milk or dairy drinks suggesting that high levels of AGEs could
be identified in products such as cheese and chocolate-flavored drink mixes that contain pasteur-
ized or sterilized milk as ingredient. Powder cheese (Figure 3.3) and thick and creamy cheese
(Figure 3.4) are also Maillard reaction-rich products or ingredients. The high-temperature drying
that cheese undergoes to turn into powder is conducive to more Maillard reaction and detrimental to
the health of such a product that is preferred and consumed by millions around the world.
Figure 3.3 Cheese powder is processed under a high temperature condition that favors the formation of
more aGes.
Figure 3.4 Creamy cheese is tasty but provides significant amounts of unhealthy aGes to those who
consume it.
3.5 PrOCeSSeD MeAt
Processed red meats including frankfurters, bologna, ham, hot dogs, corned beef, and sau-
sages are naturally rich in AGEs because AGEs form throughout aging in the mammal’s body at
body temperature (Figure 3.5). In processed meat, AGE levels may also increase as a function of
processing temperature and storage conditions. For instance, chicken nuggets contain eight times
more AGEs than ground white raw chicken meat [1]. High levels of AGEs have been measured in
frankfurters, sausages, and hams while low levels have been detected in bologna, although bologna
does contain AGEs [1]. The proinflammatory activity of AGEs was discussed in Chapter 2. Regular
consumption of processed meat is associated with increased risk of inflammatory biomarkers such
as C-reactive protein, type 2 diabetes, and cardiovascular disease [4,17,18]. Processed meat-loaded
sandwiches (Figure 3.6) and processed meat and cheese-loaded sandwiches are AGEs-rich foods.
Figure 3.5 red meat contains residual amount of aGes. Processed meat such as ham contains high levels
of aGes as a result of processing conditions.
Figure 3.6 a combination of processed meat and cheese is tasty, yet it is a combination of two rich sources
of aGes.
3.6 GrILLeD CheeSe AND PrOCeSSeD MeAt
Grilled cheese is a tasty pan/grilled sandwich using two slices of bread, butter, cheese, and
toasted for 2–3 min at 300°F–400°F (Figure 3.7). Bread is rich in carbohydrate and contains meth-
ylglyoxal [1]. Butter is a rich source of ALEs, cheese is rich in methylglyoxal and AGEs, and the
bread crust is a source of AGEs and a small amount of acrylamide. A combination of these ingre-
dients in the presence of heat generates a very flavorful food whose composition is known to con-
tain more AGEs. At 400°F (204°C), butter can form high levels of the reactive methylglyoxal [19].
Methylglyoxal is a precursor of AGEs. Methylglyoxal binds to amino acids that are sometimes
critical to the structure and function of protein, enzyme, and genetic molecules and may suppress
the immune system [20,21].
Figure 3.7 Grilled cheese combines the aGes from bread and aGes from cheese making a tasty yet proin-
flammatory popular food.
At 400°F, high levels of diacetyl are also formed in the butter. Diacetyl is a flavorant used in
popcorn, caramel, coffee, and cream soda. It was recently reported that at concentration found in
the body upon occupational exposure diacetyl enhances amyloid beta toxicity toward neuronal cells,
causes DNA damage and warrants investigation on the potential neurotoxic effect of this widely
used but potential harmful dietary flavorant [22]. Exposure to high levels of diacetyl in popcorn-
flavoring factory has been linked to the development of inflammatory lung disease also known as
bronchiolitis obliterans [23]. AGEs are proinflammatory.
Grilling bread with cheese and processed red meat generates more dicarbonyls and AGEs in the
grilled product. Grilled cheese and bacon has a complex chemical composition because it contains
AGEs, ALEs, and heterocyclic amines from the bacon, all the AGEs and reactive dicarbonyls from
the grilled cheese, and the AGEs being formed between the protein in bacon and cheese and the
carbohydrate in bread. Similarly, grilled cheese and ham is also a combination that has high levels
of AGEs. A routine diet centered on the meals mentioned earlier is a diet rich in proinflammatory
biomarkers.
3.7 PIZZA
For some, pizza is a success in nutrition because it tastes good and is accepted by billions of
people around the world. Pizza is a classic example of a combination of food ingredients that deliver
a very tasty meal but with questionable long-term health benefits (Figure 3.8). Pizza is made by
baking bread dough with cheese, meat, with or without veggies, and tomato paste along with some
oil as flavor enhancer at 450°F for at least 15 min. The Maillard reaction involves the interactions
of protein, sugars, and is exacerbated by temperature and lipids. All the conditions for a successful
Maillard reaction are met when a flat circle or square of pizza is developed. The cheese that goes
on the pizza is a concentrate of casein, the major protein in milk and rich in dicarbonyls and AGEs.
Figure 3.8 Pizza is a popular and tasty food that is also a very good source of Maillard reaction products
known as aGes.
The flour is carbohydrate. The meat topping whether it is bacon, ham, Canadian bacon, pepperoni,
sausage, or salami is a rich source of proteins and AGEs. The oil and tomato improve the flavor of
the cooked pizza. The yeast allows the dough to rise and is also a source of nucleic acids.
The pizza cooking temperature is one of the best and conducive environments for the Maillard
reaction to develop. Recent studies have shown that several heterocyclic amine mutagens were
formed in the pizza toppings such as ham and salami when pizza was baked following the manufac-
turer’s instructions (15 min at 446°F or 230°C) and the levels increased when the baking time was
increased to 18 min [24]. Dietary mutagens such as heterocyclic amines can lead to tissue such as
prostate or breast injury and the development of chronic inflammation that later can lead to cancer
development [25,26].
Diets high in pizza in any of its forms with meat or cheese toppings may be unhealthy. Adding
olive oil may also not enhance health. This is due to the fact that the smoke point may be reached
or exceed 190°C or 374°F. The smoke point of an oil is the temperature at which the oil begins to
break down and form acrolein that is given off as obnoxious gas. Acrolein is a toxic irritant to the
eye, nasal passages, and neurotoxin that inactivates antioxidant glutathione and induces oxidative
stress and inflammation. However, because in the pizza the oil is distributed within the dough, any
small amount of acrolein formed may remain inside the pizza. The tolerable amount of acrolein is
7.5 mg/kg body weight, an amount that is impossible to achieve with about two tablespoons of oil
commonly used in pizza. But it is worth knowing that when baking pizza with oil it is important to
use oil that has a smoke point that is higher than the baking temperature. For pizza baking at 375°F
or 190.5°C, healthier and safer oil is canola, sunflower, or safflower with smoke points that are
above 460°F or 237.8°C. Due to the high temperature at which pizza is baked, adding mushroom or
onion or greens may not enhance the health benefits of pizza because none of these foods contain
AGE breakers.
The combination of pizza and beer (Figure 3.9) or pizza and sugar-sweetened carbonated bever-
age (Figure 3.10) only exacerbates the unhealthy effect of pizza. Diacetyl, glyoxal, and methylgly-
oxal are found in beer [27–29]. Carbonated beverages are good sources of dicarbonyls methylglyoxal
[30,31]. Beer and carbonated beverage in combination with pizza would offer more AGEs to be
ingested. Bread pizza (Figure 3.11) and thin pizza (Figure 3.12) are inexpensive, affordable, and
widely consumed in households across the United States and Canada. These foods that contain large
amounts of cheese with or without meat are good sources of proinflammatory AGEs.
Figure 3.9 Pizza is often consumed with beer. Both are good sources of aGes and in combination would
provide more aGes to the consumer.
Figure 3.10 Pizza can also be consumed with a carbonated beverage and most of these beverages are good
sources of dicarbonyls that are precursors of aGes.
Figure 3.11 Pizza and sausage are good sources of aGes.
3.8 MACArONI AND CheeSe
Similarly to pizza described earlier, oven-baked macaroni and cheese undergo the same steps.
Macaroni is carbohydrate, cheese is protein with AGEs, and in the presence of high temperatures
the Maillard reaction occurs (Figure 3.13). Macaroni and cheese is cooked and eaten in almost every
US and Canadian household at least twice a week. Kids love it; teenagers like it, college students
like it because it is affordable, and adults choose it for the same reasons of flavor and financial
consideration. Former President Thomas Jefferson ate it while visiting France in 1793 and imported
macaroni and Parmesan to develop his own dishes at home. TV celebrities love and talk about it
all day. It is inexpensive and can provide a tasty and flavorful meal to a large number of people at
a fraction of dollar. When macaroni and cheese is baked at 350°F or 176.7°C for at least 15 min,
the Maillard reaction is promoted and makes this tasty food one of the powerhouses of AGEs for
Figure 3.12 thin pizza enriched with cheese and meat contains high levels of aGes.
Figure 3.13 Macaroni and cheese, especially when it is oven-baked, leads to the formation of more aGes.
human consumption. Due to the high content of dicarbonyls and AGEs in cheese, even stove top-
cooked macaroni and cheese is a source of high levels of dicarbonyls or AGEs. However, lower
levels of AGEs are found in stovetop cooked macaroni and cheese than in baked ones. Since cheese
is a good source of AGEs, microwave-cooked macaroni and cheese will contain significant amounts
of AGEs that need to be factored in when looking at the convenient and healthy cooking methods
available to consumers.
3.9 LASAGNA
A favorite in many households, lasagna is a rich mixture of lots of red meat including raw
ground meat and sausages (high in AGEs and creatinine), different types of cheese (making it very
high in AGEs), tomatoes, sugar, lasagna noodle, spices, other ingredients, and baked at 375°F for
Figure 3.14 Lasagna combines refined flour, red meat, cheese, and flavoring ingredients. the refined flour,
the red meat, and the cheese provide each some aGes to the final product making lasagna a
tasty product with high levels of aGes.
45 min or 450°F for at least 15 min (Figure 3.14) until the top of the cheese turns brown. The com-
position of lasagna and the cooking conditions make this food an ideal environment for more AGEs
to form. A serving size of lasagna is very rich in dicarbonyls and AGEs. The tomato and spices
that can be part of the lasagna cannot help reduce the levels of AGEs because at the temperature
lasagna is baked most of the bioactive compounds in the tomato paste spices are either destroyed or
degraded into other compounds.
A large cohort of 300,948 men and women were followed up for several years to identify the
potential mechanism that underlies the association between meat consumption and colorectal can-
cer [32]. During 7 year follow-up, red and processed meat intakes in foods such as lasagna, pizza,
chili, and stew were positively associated with colorectal cancer development. There is no research
that shows that at lasagna baking temperature, the compounds in tomato paste are transformed
into more active compounds. Given the popularity of lasagna, it would be interesting to study the
efficacy of added antioxidants such as curcumin or pepper as AGEs-breakers in lasagna. Black pep-
per in lasagna may have the same unhealthy effects as black pepper on bacon in that it may help
enhance the absorption of unwanted heterocyclic compounds formed during the high-temperature
and long-time baking of lasagna.
3.10 FrIeD CheeSe
Cheese is naturally high in AGEs. Frying cheese in oil adds dicarbonyls and ALEs to existing
AGEs in cheese (Figure 3.15). Most fried cheeses are also very salty, so this food becomes very
unhealthy. Consuming fried cheese with a beverage high in sugar exacerbates the Maillard reaction.
Enjoying fried cheese with alcohol enhances the levels of AGEs and ALEs that can be absorbed
once ingested. Fried cheese is a popular food item in Brazil. Chronic consumption of fried cheese
was among the dietary risk factors associated with the incidence of oral cancer in Brazil [33].
Fried cheese picks up a lot of oil during frying. Figure 3.16 shows fried cheese 1 day later after
refrigeration showing that this food is a carrier of high levels of fried oil. Whether fried cheese is
served in a Mediterranean-style or Western-style restaurant, its remains a fried food and does not
enhance health.
Figure 3.15 fried cheese combines aGes from the cheese and potential aLes that derive from the interaction
of oil and proteins in the cheese.
Figure 3.16 fried cheese absorbs lots of oil during frying making the food a rich source of aGes and aLes.
3.11 FrIeD, StONe BAKeD, FLAMeD, AND SeAreD FOODS
Fried foods (onions, potato, chicken) (Figure 3.17), stone-baked pizza (Figure 3.18) or flamed
or seared chicken (Figure 3.19) contribute significant amounts of methylglyoxal, AGEs, and/or
ALEs per serving size. These foods can be consumed at breakfast, lunch, and/or dinner. The
probability of finding and consuming these foods on a regular basis is very high because they are
convenient, affordable, and readily available. While these foods are good tasting and above all
very convenient, they are prepared at temperatures at which most nutrients cannot survive. The
flamed foods are loaded with smoke. As a result of their good taste and convenience, they may
become addictive over time. Most of these foods are derived from healthy produce or raw meat;
however, the cooking temperature range that most food artists have chosen to prepare food is not
a good one.
Figure 3.17 fried foods combination provides more aGes than individual food products.
Figure 3.18 stone-baked pizza is prepared at high temperature that provides the necessary conditions for the
formation of more aGes than pizza prepared at temperature around 300°f.
Fried potatoes are good sources of methylglyoxal and acrylamide. Potatoes fried with skin
on (Figure 3.20) are tasty but there are compounds in potato skin that may not be good for regu-
lar consumption. Potato contains the amino acid asparagine that reacts with reducing sugar in
potato to undergo the Maillard reaction. The reactivity of asparagine with reducing sugars at
frying temperature generates acrylamide, a neurotoxin and carcinogen [34,35]. Although there
appears to be no increased risk of cancer with consumption of acrylamide-rich foods such as
French fries or beverages such as coffee [36,37], others have cautioned that chronic consump-
tion of acrylamide-rich foods is of human health concern and efforts should made to reduce the
formation of acrylamide in foods [38,39]. The reactivity of methylglyoxal through its ability to
bind lysine residues in proteins is of concern. The frankfurters and breaded chicken are very
good sources of AGEs.
Figure 3.19 seared or flamed chicken from the rotisserie is a source of homocysteine and Maillard reaction
products including aGes.
Figure 3.20 skin-on fried potatoes are a source of acrylamide and methylglyoxal.
Searing involves heating at temperature that can reach 900°F (450°C) under very dry conditions
and exacerbates the formation of AGEs and charred compounds in foods such as flamed chicken or
stone-baked pizza. HTST cooking is not a good approach to healthy eating because the high tem-
perature and dry conditions that surround the cooking generate mutagenic heterocyclic compounds.
The time saved in serving customers faster translates into a loss of needed nutrients. Similarly
unwanted compounds are built in the food. Foods that were intended to provide needed energy and
nutrients end up providing nothing but only calories and high levels of heterocyclic compounds.
When meat, whether poultry or red meat, is cooked over a flame, the juices from the fat and meat
drip onto the hot fire and the reaction between the juice and the flame generates a wide range of
mutagenic polycyclic aromatic hydrocarbons such as benzo(a)pyrene that coat the surface of the
cooked meat [40,41]. The high temperature also catalyzes the formation of inflammatory heterocy-
clic amines from the interactions of creatinine, amino acids, and sugar in the meat [42].
3.12 GrILLeD AND FrIeD FISh
Fish consumption is considered to be healthy. Fish are what they eat. Fish such as wild salmon,
trout, or mackerel that ingest phytoplanktons are good sources of omega-3 fatty acids, also known
as fish oil. Fish fed grains or oilseeds do not offer much fish oil; rather these fish are carriers of the
very same vegetable oils they are fed. Grilled or fried fish (Figure 3.21) is as good as grilled or fried
meat, most of the nutritive value is lost and AGEs such as carboxymethyllysine (CML) and ALEs
are formed in the fish during frying making fried or grilled fish less healthy [43]. Uribarri et al.
measured high levels of methylglyoxal and CML in broiled or pan-fried fish rich in fish oil [1]. Fish
oil is very unstable, and frying fish destroys the health benefits of the oil.
3.13 SMOKeD MeAt AND FISh
Smoking meat including pork, beef, turkey, chicken, fish, crayfish, and shrimp is a worldwide
practice that helps to preserve and add flavor to meat [44–47] (Figures 3.22 and 3.23). Smoking
meat was developed at a time when refrigeration technology was not yet developed. At present,
smoking can be done using liquid smoke or direct smoke from firewood. Smoking is associated with
the development of AGEs that suppress a compound known as sirtuin in the brain and inhibition of
sirtuin has been shown to be associated with brain function decline [48].
Wood smoke or liquid smoke is associated with the incorporation of undetectable to detectable
levels of the carcinogen polycyclic aromatic hydrocarbons (such as benzo[a]anthracene, benzo[b]
fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, and indeno[l,2,3‐c,d]pyrene) [49]. It has been
shown that smoking led to the incorporation of up to 7.4 μg/kg in grilled pork chops while PAH levels
of ≤0.2 μg/kg were found in trout and PAHs range of ≤16.0 μg/kg were measured in salmon.
In Denmark, highest concentrations of PAHs were detected in smoked herring and mackerel and
on average 320 µg PAHs per kg of herring and 235 µg PAHs per kg of mackerel were measured [50].
Visciano et al. detected the following PAHs including anthracene, fluoranthene, pyrene, benz(a)
anthracene, chrysene, benzo(b)fluoranthene, benzo(k)fluoranthene, and benzo(ghi)perylene in liq-
uid smoke [51]. Apple-tree used for smoking generates low levels of PAHs while spruce generates
high levels of PAHs [52] suggesting that the type of wood used for generating smoke determines the
Figure 3.21 aGes such as CML are formed in grilled fish.

Figure 3.22 smoking generates aGes that may inhibit sirtuin.
Figure 3.23 smoked turkey is a good source of methionine and aGes.
levels of PAHs that can infuse in the meat. Liquid smoke obtained from polar wood contained the
highest numbers and concentrations of PAHs [53].
In Estonia, consumption of smoked meat is high [54]. It was estimated that the Estonian chil-
dren (aged 1–16 years old) ingested on an average 16 µg PHA/kg from smoked meat and ham,
19 µg PHA/kg from smoked sausage, and 6.5 µg PHA/kg from smoked chicken [54]. PAH levels in
fish or meat are linearly correlated to fat levels.
3.14 BAGeLS, CrOISSANtS, rOLLS, AND CheeSe BreAD
The ingredients used to make bagels (Figure 3.24) include wheat flour, water, sugar, milk,
yeast, salt, and butter [55]. Oil can be used as a substitute for butter. The ingredients for crois-
sants (Figure 3.25) and wheat bread are similar to the ingredients for bagel except that eggs are
Figure 3.24 Bagel is a bread and a classic example of the Maillard reaction.
Figure 3.25 Croissant is an oily bread that encompasses the formation of aGes and aLes.
also added [55]. Dough fermentation releases significant amounts of amino acids. Butter contains
methylglyoxal that can easily react with the protein or amino acids from fermentation to generate
AGEs. All these bakery products are good sources of methylglyoxal and AGEs by virtue of bread
being the classical example of a Maillard reaction-generated product. Caramelization also occurs
on the bread crust. Cheese is a good source of AGEs and proteins; adding cheese on top of bagels
to enhance bagel flavor and taste is nutritionally unwise because more unknown Maillard reaction
products are formed on the bread crust (Figure 3.26).
The ingredients for cheese bread (Figure 3.27) are refined flour, water, sugar, milk, yeast, eggs,
cheese, salt, and butter or oil. Most oils when heated at 100°C generate methylglyoxal that will be
available for interacting with either amino acids from the dough fermentation or the protein to gen-
erate some Maillard reaction products.
Figure 3.26 the addition of cheese on top of a bagel may add taste but also adds more aGes to the food.
Figure 3.27 Cheese bread increases the content of aGes on the food.
3.15 rOASteD NUtS AND NUt BUtter
Most nuts are roasted at temperature higher than 129°C (264.2°F). Roasted nuts taste very good.
However, the chemical makeup of most nuts, if not all of them, reveals products containing lots of
oil, proteins, asparagine, and reducing sugars. Roasting nuts creates the best environment for the
Maillard reaction to occur. Research by Uribarri et al. [1] has shown that roasted nuts including
almonds (Figure 3.28) contain very high levels of AGEs.
Recent studies have shown that acrylamide, a neurotoxin and probable carcinogen to humans,
is formed in roasted nuts [56,57]. Raw nuts such as raw almond contain no detectable level of
acrylamide [58]. Almonds roasted between 129°C and 180°C contain between 260 and 2000 ng/g
acrylamide [56,58,59]. Roasting almonds within the temperatures that generate simultaneously no
Figure 3.28 almond is rich in protein, carbohydrate, and lipids and roasted almonds under the Maillard reac-
tion generate aGes.
bitterness and the best flavors is always associated with the generation of more acrylamide than any
other nut investigated so far. Roasted peanut and hazelnut contain 66 and 128 ng/g of acrylamide,
respectively [60]. All these nuts are also good sources of AGEs. Roasting nuts with honey makes
these foods very high sources of AGEs (Figures 3.29 and 3.30).
Pine nuts (Figure 3.31) contain on average 31%–68% fat, 31%–34% protein, 10%–14% carbohy-
drate, 5.15%–5.6% moisture, and 4.3%–4.5% ash [61]. Pine nuts can be consumed raw or roasted.
The nuts are a very good source of unsaturated fatty acids [62]. The oil has been reported to sup-
press appetite by inducing the release of satiety hormones including cholecystokinin (CCK-8) and
glucagon-like peptide-I (GLP-1) postprandially while having no effect on other satiety hormones
including ghrelin and peptide YY (PYY).
Figure 3.29 roasting almonds with honey favors the formation of more aGes than roasting almonds without
the sugar.
Figure 3.30 Peanut is a good source of protein, oil, and carbohydrate. roasted peanut is an excellent source of
aGes. the addition of honey to the roasting process develops a product that is very rich in aGes.
Figure 3.31 Pine nuts are rich in oil, proteins, and carbohydrate and can easily undergo the Maillard reaction
during roasting.
Eighteen overweight postmenopausal Korean women received a light breakfast along with cap-
sules of 3 g Korean pine (Pinus koraiensis) nut free fatty acids, 3 g pine nut triglycerides, or 3 g of
olive oil as placebo in a crossover double-blind randomized placebo-controlled intervention [63].
There was a 1-week washout period between interventions. The results showed that over a period
of 4 h, plasma CCK-8 was 60% higher in subjects that consumed nut free fatty acids compared to
placebo (p <0.01); plasma CCK-8 was 22% higher in subjects that consumed pine nut triglycerides
compared to placebo (p <0.01), and GLP-1 levels were 25% in subjects that consumed pine nut free
fatty acids (p <0.05). Pine nut free fatty acids or triglycerides had no effect on ghrelin or PYY.
Roasting pine nut creates a favorable environment for Maillard reaction products including AGE
and ALE generation. Uribarri et al. [1] reported very high levels of AGEs in roasted pine nuts.
Figure 3.32 Brazil nut contains allergens that are proteins, oil, and carbohydrate. roasted brazil nut easily
develops aGes.
Nut butter is made from roasted nut, suggesting that nut butter may contain the same amounts of
acrylamide that can be found in the roasted nut. Peanut butter is the most ancient nut butter known
to mankind. Peanut butter was reported to contain 54 ng/g of acrylamide [60]. The dilemma with
tasty roasted nuts and the most popular peanut butter is that these products are consumed regularly
by most people from pre-school age to adult age. Regular and chronic consumption of peanut butter
in different foods including sandwiches in bread or crackers will lead to small amounts of acryl-
amide accumulating in tissues and the organ tropism of peanut butter AGEs and acrylamide is not
known. However, knowing the neurotoxicity of AGEs and acrylamide one should be inquisitive
about these tasty but neurotoxin-carrier roasted nuts.
Nut allergy is a health problem. More than three million Americans and more than 620,000 of
the people in the United Kingdom are allergic to nuts in general [64]. Nut allergens are proteins. The
allergen in almond is called “amandin.” Peanut has two or three different allergens called “Arah
1, Arah 2, or Arah 3.” Brazil nut (Figure 3.32) allergen is termed “Ber e 1 protein.” Roasting often
increases the allergenicity of the nut. Allergenicity is an inflammatory disease. The best treatment
for nut allergy is to avoid consuming or being in contact with the nut in any form whether as food
or shampoo or else.
3.16 rICe CrISPY CereAL COOKIe BAr
A rice crispy cookie bar (Figure 3.33) is tasty. It is made with lots of butter or margarine both of
them being unhealthy. Gluten-free rice crispy cookie bars are also made with butter or margarine.
While individuals who are gluten-sensitive may think of rice crispy as an healthy food for the gas-
trointestinal condition, butter or margarine are proinflammatory and may not help at all.
3.17 rOASteD SeeDS
Roasting generates excellent flavor in foods and make the foods more palatable.
Sunflower seeds are oily, rich in protein, and do contain some sugar. Roasting sunflower seeds
also generates AGEs and 66 ng/g acrylamide (Figure 3.34) [1,56]. With the high content of oil and
Figure 3.33 rice crispy contains butter, sugar, and proteins and creates an environment conducive for the
formation of aGes.
Figure 3.34 roasted sunflower and other seeds such as pumpkin seeds contain oil, protein, and carbohy-
drates that react during roasting generating the Maillard reaction products.
the presence of asparagine in the sunflower seed, the high roasting temperature used for preparing
roasted sunflower can easily promote acrylamide formation in such seeds [65–67]. Acrylamide is
inflammatory.
3.18 SPINACh DIP AND CheeSe-rICh DreSSINGS
Spinach dip is a favorite of many people because it sets a good tone for the dinner meal that is on
the way (Figure 3.35). Spinach is a good source of chlorophyll, lutein [68], and sulfoquinovosyl diac-
ylglycerol [69], a known anticancer compound. However, spinach dip is prepared with a high content
of butter (rich source of ALEs) or margarine and a high level of cheese (rich source of AGEs) at a
Figure 3.35 spinach dip is prepared with several aGe-rich ingredients making its quality questionable.
temperature that favors more AGE and ALE formation. Most of the dressings that go along with spin-
ach dip are also cheese-loaded. Unfortunately, spinach dip as it is prepared may not be the best food to
start a healthy meal. Similarly, cheese-rich dressings may be good for mouth feel but not for the body.
3.19 SWeeteNeD PIeS
Pies are fruit-based desserts (Figures 3.36 and 3.37). Some pies such as apple and pumpkin
pies are made without the fruit peels. Others such as blueberry or cranberry pies are made with
the whole fruits. Fructose is the natural sugar in fruits. Fructose contribution to inflammation and
several degenerative diseases including cancer is currently a hot topic of research [70,71]. While
fruits such as apples, blueberries, cranberries, or pumpkin are used to make pies, additional sugar
such as table sugar is needed to make pies to comply with our sweet tooth desire. At the end, most
Figure 3.36 Pumpkin pie has less sugar than blueberry pie.
Figure 3.37 Blueberry pie has more sugar than pumpkin pie.
pies have more sugar (fructose from the fruit and added sugar) than really needed for a successful
pie. The amount of sugar added may not add lots of calories, but at the baking temperature table
sugar decomposition occurs. The resulting sugar, if it has not interacted with components of the pie,
will be available for the Maillard reaction once ingested. The kind and concentrations of bioactive
compounds in the fruit skins such as anthocyanins do not inhibit the Maillard reaction and therefore
will not prevent the reaction from occurring.
3.20 SUGAr-rICh DrIeD FrUItS
Sugar-rich dried fruits can be used as snacks. The removal of water in dried fruits leads to
products that concentrate sugars and therefore have high levels of sugar. For instance, a serving size
of dried raisins, pineapple, apricots, or papaya is 40 g (Figures 3.38 and 3.39). Out of the 40 g, the
Figure 3.38 sugar-loaded dried pineapples and papaya.

Figure 3.39 sugar-loaded dried mango.
dried fruits contain 31 g of sugar, which is equivalent to almost 80% of the dried fruit. Most if not
all of this sugar is fructose. The development of the inflammatory nonalcoholic fatty liver disease
(NAFLD) has been associated with the consumption of high-fructose diets [72,73]. NAFLD preva-
lence in the world is increasing at an alarming rate and the disease affects 20%–30% of adults and
10% of children in developed nations [74,75]. The progression of the disease can lead to obesity,
metabolic syndrome, and diabetes. Ghanim et al. [76] showed that fructose at 75 g in a single dose
in the presence of enough flavonoids such as orange juice did not induce inflammatory stress.
However, people who are used to fructose-loaded foods can easily consume 75 g or more of
fructose on a regular basis over a long period of time. To consume 75 g of fructose on a daily basis,
an individual can drink one serving of commercial fruit juice in the morning (25–31 g of fructose)
followed by one can of sweetened soda (38–39 g) and consumption of one cookie (20 g). The idea
that because the sugar in fruits is natural and healthy is only possible when one does not understand
that the sugar in the fruit is fructose and the reactivity of sugars is the same whether it is fructose
from nature or man-made fructose. What happened to sugar whether it is fructose from the fruit or
fructose from corn when ingested? Fructose is fructose and will react under appropriate conditions.
Also, once ingested, the sugar can react with proteins in the human body even at body temperature
and lead to AGEs formation or be converted into lipid in the liver and the lipid may accelerate the
formation of radicals. AGEs formed inside the body deposit at different tissues including the arter-
ies, retinal, and brain cells. Repeated and chronic consumption of foods with high content of AGEs
could over time accelerate vascular cell dysfunction and lead to serious diseases.
3.21 CereAL AND PrOteIN BArS
In 2013, the energy and protein bars were projected to near $8.3 billion by 2016. These products
are made with protein or protein hydrolyzates from animal, marine, or plant sources. The Maillard
reaction browning occurs regularly during the storage of energy bars developed with proteins or
protein hydrolyzates because most of these products are formulated with high-fructose corn syrup
and/or other reducing sugars [77]. While short-term consumption of energy bars has shown that
there is no correlation between cereal bars consumption and obesity or weight gain, chronic con-
sumption of cereal/energy bars designates what may build up in the body.
3.22 BeVerAGeS
This section covers only beverages with potential proinflammatory activities. Sugar-sweetened
beverages include carbonated soft drinks, fruit drinks, cola, diet cola, fruit-flavored soft drinks, and
herb- and root-based beverages, fruitades, energy drinks, water, and vitamin drinks are widely con-
sumed all around the world. High-fructose corn syrup or sucrose is the sweetener used in most soft
drinks. It provides similar metabolic effects [78]. Fructose is used across the board in almost every
food or beverage formulation because it is cost effective. A scientific statement from the American
Heart Association suggests that high fructose levels in food products play a role in the epidemics of
inflammatory diseases including obesity, type 2 diabetes, hypertension, dyslipidemia, and cardio-
vascular disease [79].
Carbonated soft drinks are good sources of methylglyoxal, a well-known reactive carbonyl that
is also an important precursor of AGEs [30]. Thirteen brands of soft drinks obtained from dif-
ferent supermarkets showed methylglyoxal range of 24.24–474.3 µg per serving size [30]. High-
fructose corn syrup has been identified as a major source of methylglyoxal in the soft drinks [30].
Methylglyoxal is toxic to cell and tissues [80,81]. Nakayama et al. [82] reported 7.3 µM of methylg-
lyoxal in cola drinks and 5.8 µM of methylglyoxal in lemon-lime soft drinks. Reactive carbonyl such
as methylglyoxal causes carbonyl stress and the latter plays a pathological role in inflammatory dis-
eases such as hypertension, diabetic complications, and uremia [83–85]. In humans, methylglyoxal
inactivates Cu and Zn superoxide dismutase, forms cross-link fluorescent complexes, and causes the
release of Cu from the enzyme leading to enzyme inactivation [86]. Human subjects who consumed
beverages containing high levels of methylglyoxal showed increased plasma levels of methylglyoxal
within 30 min that returned to basal level within 120 min [82].
Chocolate beverages (Figure 3.40) are popular around the world. They are made from a blend
of alkali-treated cocoa powder and dairy products. While the original cocoa is a very good source
of anti-inflammatory bioactive compounds known as proanthocyanidins and other phenolic com-
pounds, alkali-treated cocoa that undergoes the Dutch process contains significantly less amounts
of the health-enhancing proanthocyanidins [87]. Ultrahigh-temperature (UHT)-treated milk choco-
late drink, sterilized chocolate drinks, and sterilized evaporated milk contain 136 mg CML, 250 mg
CML, and 430 mg CML per kg crude protein, respectively. Chocolate drinks made using UHT or
Figure 3.40 Chocolate beverage made from alkali-treated cocoa.

sterilized milk contain very high levels up to 20 times more CML than chocolate drinks made using
plain milks [88]. The high levels of CML in chocolate drinks and the popularity of these drinks
among adolescents suggest that young people may ingest up to 50% of daily CML intake from choc-
olate drinks. Given the potential health effects associated with AGEs, reducing the levels of AGEs
such as CML in chocolate drinks should be a good option for those involved in producing these
beverages. The oligomeric and polymeric phenolic compounds from chocolate bind to and precipi-
tate milk proteins, a phenomenon that is hardly observed when looking at chocolate milk; however,
the cloudiness generated by the mixture should stir the mind and thinking of a curious individual.
As a result of the interactions between the chocolate phenolics and milk proteins, the purported
health benefits ascribed to chocolate are not achieved. Monomeric phenolics do not bind to milk pro-
teins, and when present in chocolate, these compounds may enter the circulation and provide health
benefits.
Coffee, the third most consumed beverage after water and tea, has been reported to enhance
health, and in some cases, coffee and coffee substitutes obtained by conventional roasting process
have been reported to contain acrylamide [89,90].
3.23 POteNtIAL PrOINFLAMMAtOrY eFFeCt OF heAt-treAteD FOODS
The health risks of chronic consumption of AGEs- and pro-inflammatory-rich foods are
summarized in Figure 3.41.
AGEs + FFA + excessive energy intake
Oxidative stress
Low-grade inflammation
Chronic inflammation
Insulin resistance
(obesity, glucose intolerance, dyslipidemia, hypertension)
Type 2 diabetes, cardiovascular disease, cancer, Alzheimer’s
Figure 3.41 the long term effects of aGes-rich foods on human health.
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PArt II
the Maillard reaction and health Disorders
The Maillard reaction products also known as advanced glycation end products (AGEs) bind to
their receptors and induce oxidative stress that in turn induces low-grade inflammation. Chronic
low-grade inflammation upgrades to inflammation. As a result of chronic inflammation, insulin
resistance develops. Insulin resistance is the common denominator for several chronic inflamma-
tory degenerative diseases including obesity, diabetes, hypertension, kidney, atherosclerosis, osteo-
porosis, eye health, multiple sclerosis, erectile dysfunction, insomnia, Parkinson’s disease, cancer,
and Alzheimer’s disease. Therefore, unhealthy diets link the Maillard reaction products to several
chronic degenerative disease development. Through each chronic disease, the risk factors and the
association or lack of AGEs have been established. Dietary approaches to prevent the development
of the disease are presented and protective foods are suggested.
ChAPter 4
Obesity
4.1 DeFINItION OF OBeSItY
Obesity is a disease of excessive abdominal or subcutaneous body fat mass (Figure 4.1). Obesity
is best measured by waist circumference rather than body mass index (BMI) because waist circum-
ference measures abdominal obesity, whereas BMI measures total body fat. Individuals with high
BMI such as some athletes who are not necessarily obese may also qualify as obese when in reality
they do not necessarily have big waist circumferences.
4.2 SOCIAL AND eCONOMIC SIGNIFICANCe OF OBeSItY
Obesity has been a societal issue since ancient Egypt; however, since the 1980s it has become
a rampant alarming major public health-care and economic problem for world health authorities,
mostly Western health-care providers and officials. In several Western nations, the obesity habitus
has become the new normal [1]. Recent statistics suggest that between 1960 and 2006, the preva-
lence of obesity in the United States increased from about 13% to 35.1%, and there are more than
21 million obese American adults [2–4]. Thirteen percent of American youth is obese. In the world,
there are more than 400 million adults who are obese and the number will increase to more than
700 million people by 2020 [5]. There are more than 134 million U.S. adults 20 years or older who
are overweight or obese. There are already more than 1.6 billion individuals around the world who
are considered overweight.
The United States leads the Western world in obesity ranking; obesity is on the rise in economi-
cally developing countries while Japanese remains the slimmest people on earth. Obesity increases
the chance of taking early retirement and the incidence of disability. Obese women are more suscep-
tible to early retirement and disability than obese men. Obesity is a crisis of esthetics with reduced
quality of life and can contribute to increased tendency to depression and suicide rate.
4.3 OrIGINS AND CAUSeS OF OBeSItY
Obesity is an old disease that goes back to ancient Egypt where obese people could be found
in upper classes, where people had access to abundant food. The causes of obesity are multifacto-
rial and include lifestyle choices, marketing of energy-dense foods, insufficient physical activity,
social networks, economic and cultural determinants, use of medication with undesirable weight
gain side effects, genetic links, viral infection, and the gut microbial population also known as gut
microbiota.
61
Subcutaneous
Retroperitoneal
Visceral
Figure 4.1 subcutaneous, visceral, and retroperitoneal obesity.
4.3.1 Lifestyle Choices Including Urbanization

and Consumption of Calorie-Dense Diets
The industrial revolution brought machinery to do agriculture and produce more foods.
Farming became mechanized and more people moved to cities. In Western nations, processed
foods are cheaper than the raw agricultural products they derived from, easily affordable and
available for any occasion. The Western diet is mostly developed using refined grains, refined
meat or poultry products, refined juices or beverages, and refined everything. Consumption of
such diet leads to increased absorption and accumulation of calories. Foods rich in high-fructose
corn syrup including sweetened soft drinks, sweetened juices, sweetened water, and foods rich in
carbohydrate that are easily digested including croissants, fried starchy foods, pizzas, and pasta
that are served and consumed around the clock are widely recognized as major risks. The recent
introduction of Agave as a better alternative to other sugars is scientifically flawed because Agave
is about 90% fructose and de facto worse than high-fructose corn syrup. The Framingham Heart
Study has indicated that consumption of soft drinks increases obesity in children and adolescents
and is associated with a higher prevalence and incidence of metabolic syndrome in middle-aged
adults [6]. It is not only the beverages that are loaded with sugars; it is almost anything out there
that can go into the mouth except for drinking water. This makes the choice of sugar-free food very
difficult. Therefore, the Western-style diet has become a major risk factor for obesity. In brief, the
rising of obesity in the United States and worldwide has been in part exacerbated by consumption
of processed ingredients, foods, and beverages that are similar in composition whether one dines at
home or away from home. Parents fill the pantry in the house with sweet and salty foods. When the
children start school, they have no option; the cafeterias offer glazed doughnuts, pizzas, lasagna,
pasta, fried foods, fructose-sweetened drinks, and fructose-sweetened dairy shakes and products.
Similarly, the convenience stores as well as the supermarkets offer the same types of foods: fried,
oven-baked, hot and salty, frozen and too sweet, cold and sweet, or glazed and sweet everything.
oBesIty 63
Adults also have less affordable choices among a wide range of foods that are either carbohydrate-
rich or AGE-rich. People are not encouraged to drink water. Children are exposed to inexpensive
AGE-containing or AGE-promoting foods including soft drinks and fried foods 24/7 because most
parents can’t offer fruits and vegetables on a daily basis. Most of these energy-dense foods require
long hours of physical activity to rid the body of the excess energy absorbed as it will be shown in
the following segment.
4.3.2 Insufficient Physical Activity
In poor developing countries, people who eat less unprocessed food, walk more, and balance
their food intake with physical activity. In those same nations, people who can afford the Western
lifestyle or individuals of high socioeconomic status residing in the metropolitan area are very sus-
ceptible to obesity. Obesity is inversely associated with affluence. Children in poor neighborhood
in developing countries spend more time engaging in light physical activities including walking
to school and playing on mud or ground throughout the day while children of similar ages in poor
neighborhood in developed nations do very little physical activity.
In developing economies including Brazil, Argentina, and India, childhood obesity is increasing
at an alarming pace. From 2008 to 2013, the prevalence of childhood obesity was 41.8% in Mexico,
22.1% in Brazil, 22.0% in India, and 19.3% in Argentina [7]. In most of these countries, secular
trends or physical inactivity trends increased at an alarming pace.
In most developed nations, school meals often include one or two slices of pizza, a serving size
of soft drink containing more than 35 g sugar or a serving size of grape juice containing more than
50 g of sugar, a chocolate chip cookie containing 20 g of sugar, and a dessert containing 40 g of
sugar. As a consequence, the mere 1 h physical education activity offered to students is not enough
to burn all the calories ingested in the cafeteria. In large cities where mass transportation is the
norm, obesity tends to be reduced compared to small cities where people drive to work or to the
grocery stores. In a world where the culture of “do it yourself” has been replaced by a culture of
convenience, interest in physical activity has declined over the years among adolescent or teenagers
in all communities and as a result obesity has increased in these groups.
4.3.3 Social Networks
Obesity is a toxic spreadable disease and social contagion [8]. An evaluation of a densely inter-
connected social network of more than 12,000 participants in the Framingham Heart Study sug-
gested that a person’s chances of becoming obese increases by more than 50% if he or she had a
friend who became obese in a given interval; a sibling’s chance of becoming obese increases by
about 40% if he or she had an obese sibling; an obese spouse increases the likelihood of the other
spouse to become obese by 37%; siblings of the same sex have greater chance of both becoming
obese; however, obesity does not seem to spread among neighbors [9]. The Framingham study
results suggest that obesity easily spreads through social ties and networks. The same can be said of
slimness; it spreads through social networks.
4.3.4 Genetics
Obesity has a genetic link [10]. Obesity procreates obesity. The participants from the Framingham
Heart Study were evaluated for the association of parental obesity with offspring BMI. It was found
that for each obese parent BMI was higher in the offspring and increased significantly in the third
generation [11]. Although obesity has a genetic link, in genetically obese individuals multiple genes
must be triggered by environmental factors over time to lead to the phenotype often observed.
Dr. George Bray from the LSU Pennington Biomedical Research Center summed it up very well
when he said “In obesity, the genetic background loads the gun, but the environment pulls the trig-
ger” [12]. Studies have shown that genetic relatives living in different environments can differ in
average BMI suggesting that the environment can be more or less obesogenic. Obesity is inversely
related to education. The Danish Twin Registry survey of 21,522 twins of same-sex pairs showed
negative correlations between education and BMI among men as well as women and showed well-
educated twins were less likely to have high BMIs [13].
4.3.5 Viral Infections
Recently, viral infection by adenovirus 36 (Ad36) has been proposed as a possible cause of the
obesity epidemic based on evidence in various model systems as well as clinical data [14]. Ad36 is a
human adenovirus that was isolated for the first time in Germany in a fecal sample from a girl who
had enteritis. Animal and cell culture studies suggest a fecal–oral route of transmission for Ad36
and infection with Ad36 increases obesity. Ad36 infection is transmissible from infected animals
or humans to their naïve mates. Ad36 is prevalent in obese people (30%) than in nonobese (11%).
Studies in twins have strengthened the possibility that Ad36 causes infectobesity. However, longi-
tudinal studies are missing and very much needed. A meta-analysis of recent studies on Ad36 has
suggested that Ad36 infection is more associated with accumulation of subcutaneous fat than that
of visceral fat [15]. In any event, any excess of subcutaneous fat spills over to increase visceral fat.
4.3.6 economic, Social, and Cultural Factors
Vulnerable populations are susceptible to the contagion of obesity. Individuals in low-income

and urban communities in the Western world, immigrants from developing nations, and migrant
workers who rely on fast foods are very susceptible to diet-derived and physical inactivity–derived
obesity.
In most developing nations, low-income individuals live a life full of involuntary restricted diet
but full of physical activity. As a result, they do not have access to lots of foods; most of their diet is
centered around raw foods, fruits, and vegetables and lots of daily walkings that end up taking care
of whatever fats they may have consumed in their meals. Low-income individuals in rich nations to
the contrary have more access to processed and inexpensive foods and tend to have no reasons to
walk around the block for physical activity. A study conducted to examine the difference in abdomi-
nal visceral adiposity between white and African-American adults concluded that white men and
women had greater abdominal visceral adipose tissue (bad fat) than African-Americans of similar
age. However, after adjustment for covariates, white men and women had significantly lower subcu-
taneous adipose tissue (good fat) than did African-American men and women. The study suggests
that human body fat distribution across racial groups is heterogeneous.
4.4 heALth SIGNIFICANCe OF OBeSItY
Obesity is a risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD).
Obesity increases insulin resistance, but most obese and insulin-resistant individuals do not nec-
essarily progress to type 2 diabetes. Obesity and being overweight increase the lifetime risk of
developing diabetes in people of all ages and races and shifts the onset of diabetes to younger ages.
Regular and excessive consumption of sweetened beverages and fried, roasted, grilled, barbecued,
and melted and cheesy foods are major contributors to the onset and complications of obesity.
Obesity is also a risk factor for gallbladder disease, hypertension, osteoarthritis, sleep apnea,
Alzheimer’s disease (AD), and several types of cancer including esophageal, breast, colon,
oBesIty 65
endometerial, pancreatic, and prostate [16,17]. Obese people are more susceptible to early aging
(biologically and physically), have a shorter lifespan, and are more prone to depression and suicide
[18]. Obese women carry the risk of infertility or pregnancy complications [19]. Abdominal obesity
lends support to increased deposition of white fat, which by itself stores hormones that control appe-
tite and metabolism, by promoting or antagonizing the effects of insulin. Obesity brings significant
morbidity and mortality.
4.5 DIetArY APPrOACheS tO OBeSItY
4.5.1 Introduction
There is no universal approach to obesity management using diet. Obesity is associated with
excessive energy-dense food ingestion and fat absorption with less energy expenditure. The food
industry including the restaurant industry, government, research institutions, and consumer each
can significantly help prevent obesity. The following paragraphs describe what each player can do
to prevent obesity development and complications.
4.5.2 Government’s role in the Fight against Obesity
Governments around the world are to protect citizens against invasion by others as well as
protect their citizens against preventable diseases. In a perfect world, governments should have the
best experts and think tanks that set the tone and monitor the activities of those developing foods
for consumers. Governments should not be followers of the food industry development or catching
up with research findings. Since the mission of the government is to ensure that consumers access
the healthiest foods, governments should develop programs that educate consumers on their food
choices. After all, a government with an increased number of obese citizens will have a less pro-
ductive workforce, reduced revenues, and increased health-care costs. Citizens’ health impacts the
government’s ability to play its role in citizen welfare. Because management of obesity metabolic
complications is difficult due to the biological and environmental factors that promote weight gain
or loss, it is logical to focus on lifestyle changes such as diet and physical activity. Governments can
help in these two areas.
4.5.3 the Food Industry
The industrial revolution moved people from rural areas to metropolitan areas. For instance,
in the United States alone, agriculture farmers represent only 2% of the population compared to
80 years ago (1930s) when 30% of the population was farming. Produce are processed into ingredi-
ents or ready-to-eat foods because consumers have no land and time to farm, process, or cook food
from scratch every day making the food industry a major player in people’s lives. The food industry
also provides ingredients to restaurants. The food industry has helped reduce hunger and malnutri-
tion around the world.
However, the literature is quite well established that processed foods are the major contributors
to exogenous AGEs in the human body because the ingredients are AGE-rich and the processing
technologies such as spray-drying of milk generate AGE-rich ingredients that are used all day long
in a variety of foods and snacks leaving no room to escape the side effects of AGEs (see Chapter 3).
As a result, in most households the pantry, refrigerator, and freezer are all full of AGE-rich foods
or AGE-rich food ingredients because AGE-rich foods or AGE-rich food ingredients are what are
available on the grocery store shelves.
The food industry can design better and healthier food ingredients and foods because the knowl-
edge and technologies to get it done are available. The food industry can help reduce the rise in
obesity by developing
1. AGE-reduced or AGE-free food ingredients

2. AGE-breaker rich ingredients and foods
3. Anti–mood disturbance foods
4. Foods for healthy gut with
a. Less digestible carbohydrate
b. Less fat
5. Foods that improve insulin sensitivity
4.5.3.1 Designing AGE-Less or AGE-Free Food Ingredients
In Chapter 1, it was shown that ingredients such as milk powder, condensed sweetened milk,
or cheese powder find applications in several food products. It is imperative that such ingredients
be AGE-free or AGE-reduced; otherwise there is a domino effect in almost every food and meal.
The use of technologies such as spray-drying that use high temperature to dehydrate food samples
containing reducing sugar and protein containing epsilon amine group should be reduced or tech-
nologies phased out in an effort to reduce the levels of AGE-rich ingredients in food products.
Similarly, adopting technologies that reduce the levels of AGEs in egg yolk or egg white powder can
significantly reduce the levels of AGEs in food products formulated with egg products.
Cereal products such as croutons that are prepared at high temperature also undergo the Maillard
reaction. Because millions of people rely on these products to be used as ingredients in further pro-
cessing or formulations, it is time for food scientists in industry to pay attention to these products.
Butter was prolifically used by the rich French bourgeoisie. Margarine was invented as a butter
substitute for poor French people. Both of these ingredients/products are ALE-rich contributing
significant amounts of exogenous ALEs to consumers who use these products/ingredients regularly.
The time to find healthy substitutes for these two is overdue. The industry has to act because con-
sumers like these products for flavor.
Bacon is a tasty ingredient/food item. Bacon provides extremely high levels of AGEs suggest-
ing that regardless of the portion size consumed, bacon adds to the pool of AGEs inside the body.
Building low-grade inflammation is a lifetime process and anything that contributes to this buildup
may have to be removed from the regular diet.
4.5.3.2 Adding AGE-Breaker Ingredients in Foods
In the event manufacturers cannot quickly upgrade their technologies and equipment, the alter-
native to reduce AGE levels in food is to use compounds that break AGEs. Such compounds exist
and can be used while waiting to phase out AGE-producing technologies and equipment.
4.5.3.3 Designing Anti–Mood Disturbance Ingredients and Foods
Breakfast foods associated with anti–mood disturbance are needed whether people leave home
for work or stay home for the day. In most parts of the world, breakfast meals revolve around cere-
als, pancakes, toast, cereals and fried eggs, sausages, milk, dairy products such as yogurt or cream
cheese, chocolate drinks, coffee, malt drinks, processed fruit juices, occasional fruits, tea, and
water. Most of these foods are either AGE-rich, carbohydrate-rich, or sugar-loaded. Refined carbo-
hydrate contributes to insulin resistance and most people are developing insulin resistance over time
after several years of excessive and refined carbohydrate consumption. Toasting bread, which is a
oBesIty 67
(a) (b)
Figure 4.2 sorghum flour is emerging as a healthy alternative for gluten-free diet. (a) sorghum and
(b) sorghum flour.
product already high in AGEs, only exacerbates the Maillard reaction in bread toast. Whole grain
rich in resistant starch can substitute for all the refined flours being sold for pancakes and other
breakfast meals.
Sorghum (Figure 4.2) is emerging as a natural source of resistant starch that does not need
further processing before uses. The structure of sorghum shows that phenolics surround starch
and create an appropriate mixture that resists digestion thus allowing reduced digestibility of sor-
ghum starch and creating a natural resistance that is good for food applications. Sorghum, which
is widely used around the world, is gluten-free and would be also good for individuals with celiac
disease. Using toaster designed to operate to ≤300°F could also reduce the development of AGEs
in sorghum-based breakfast.
Oatmeal (Figure 4.3) is one of the best foods for breakfast. When prepared as suggested by the
manufacturer, oatmeal is an excellent food for good mood and breakfast. However, there are varia-
tions of oatmeal foods on the market that are overloaded with unnecessary sugar. Due to the sugar
content, these products may no longer offer the benefits of health ascribed to oatmeal.
Fish rich in polyunsaturated fatty acid (PUFA) is a good mood food to start the day with.
Although fish as breakfast looks like an unacceptable idea in some parts of the world, the food
industry can help fight obesity by developing better foods for breakfast and AGE-free fish products
Figure 4.3 oatmeal has health benefits that can help prevent weight gain.
Figure 4.4 fish sticks coated with carbohydrate may not be the answer to the fight against obesity.
could be an excellent choice. Fish sticks (Figure 4.4) as sold in supermarkets nowadays are not the
answer because these products are rich in AGEs.
Tryptophan is the amino acid needed for serotonin and there are several foods that can be used
for creating or contributing to good mood in the morning and throughout the day. Oatmeal is an
excellent source of tryptophan and this explains more why oatmeal is a good breakfast meal. Rice
is a good source of tryptophan. Seaweed (spirulina) contains 739 mg tryptophan per serving size.
Along with rice, this could be a good calming combination food. Egg white is also an excellent
source. Spinach can provide up to 690 mg of tryptophan per serving size. Cow’s milk and soymilk
are good sources of tryptophan and tofu has more because it is a concentrate. Seafood including
tuna fish, halibut, salmon, and sardines can provide more than 590 mg tryptophan per serving size.
Chicken and turkey are excellent sources but tryptophan is destroyed in fried chicken or turkey
suggesting that fried chicken or turkey and fried foods in general may not be good for good mood
breakfast. Cooking at temperature lower than 310°F can protect tryptophan from degradation.
Boiled egg white (Figure 4.5) has fewer AGEs than egg white powder obtained by spray-drying,
making boiled egg white an excellent food for breakfast, good mood, and obesity prevention.
Figure 4.5 Boiled egg white contains fewer aGes and may be ideal for weight loss.
oBesIty 69
Figure 4.6 Liquid yogurt containing pre- and probiotics as a food for weight gain control.
However, more needs to be done for powder egg white to reduce the levels of AGEs because this
product finds applications in a variety of food products.
Yogurts are AGE-free and good for breakfast (Figure 4.6). Yogurt rich in prebiotics includ-
ing oligosaccharides, polydextrose, or resistant starch and/or probiotic bifidobacteria would be also
good for obesity prevention and healthy gut. AGE-free cheese and cream cheese are needed for
incorporation into healthier breakfast.
Fruits rich in tryptophan include avocado, kiwi, persimmons, guava, and cherry. The calming
effect of cherry juice is a topic of recent research interest, and cherry juice is poised to be an excep-
tional juice for the evening that can put people to sleep [20].
4.5.3.4 Designing Tasty and Healthier AGE-Reduced Lunch and Dinner Meals
Vegetables are perfect foods with reduced AGE levels. However, vegetables do not provide
energy for busy people. Carbohydrates are served in different forms including bagels, pizza bread,
cheese-loaded bread sticks, sandwiches loaded with cheese and microwaved, pasta, pizza, and des-
serts. Too much carbohydrate in the human body leads to the pancreas producing too much insulin
around the clock. Too much carbohydrate in the diet may explain the rise of diabetes worldwide
(see Chapter 5).
This is another opportunity for the food industry to design balanced ingredients that can
help provide balanced lunches with reduced AGEs. Pizza is a popular food that needs significant
improvement in its quality. This should start with the ingredients that make pizza followed by the
way pizza is cooked. The food industry’s responsibility is on the ingredients, the cooking equip-
ment, and cooking instructions. Pizza is a mixture of carbohydrate and proteins, but the proteins
(meat or cheese) are AGE-rich and baking pizza at 450°F generates more AGEs. Resistant starch
may help reduce the levels of AGEs in these popular foods. However, although resistant starch
is commercially available, it is not widely used as suggested by food scientists because of cost.
Sorghum-based meals contain enough naturally occurring resistant starch, is inexpensive, and may
help in pizza and pasta formulations provided that the cheese and meat are also AGE-reduced or
AGE-free. Designing equipment that limit cooking at no more than 310°F will improve the health
attributes of pizza and pasta and save lives. In brief, improvement in the quality of carbohydrate
delivered to the restaurant industry should be one of the priorities of the food industry.
4.5.3.5 Designing Tasty and Healthier Ingredients

or Meals with Triglyceride Binders
Triglyceride binders can prevent or reduce fat digestion and absorption. Incorporation of tri-
glyceride binders in commonly consumed foods including pizza, lasagna, macaroni and cheese, or
pasta and cooking these products at temperature less than 310°F will make these products healthier
than they are presently. Incorporation of lemon peel, apple peel, orange peel, or strawberry can pro-
vide excellent sources of dietary fiber that can prevent fat digestion. Asparagus, amaranth, marine
algae, soybean, mushroom, wheat germ and wheat bran, fenugreek, and grape leaves are also good
sources of lipase inhibitors and can help reduce fat digestion and absorption. Developing ingredients
containing these bioactive compounds is an option in the right direction in the fight against obesity.
4.5.3.6 Designing Better, Flavorful, and Healthier Beverages
Beverages are one good option to prevent obesity because consumers are advised to drink lots of
fluids of any kind with their meals or between meals. Beverages that reduce intestinal absorption of
fat without compromising the bioavailability of fat-soluble vitamins are needed. Tea is probably the
most popular beverage in the world. There are several kinds of teas; most of them contain sufficient
amounts of bioactive compounds including saponins, phenolics, and terpenes, which can inhibit the
enzyme lipases that digest fat in the gut. Well brewed hot teas, including black, oolong, green, rose-
mary, mint, sage, fenugreek, cinnamon, ginger, hibiscus, and cardamom tea, contain saponins and
polyphenols that are excellent inhibitors of pancreatic lipase and can be effective when consumed
with meals throughout the day. Lemon peel–rich lemon juice is another good source of lipase inhibi-
tor. The teas that inhibit lipases are also good inhibitors of amylases.
Fruit juices rich in phenolics are needed for healthy living. Because flavonoids and anthocyanins,
which make the most of phenolics in juices for human consumption, are showing to be health-enhancing,
unsweetened juices are what can help consumers be healthy. Cranberry is a very healthy berry that gets
to the dining table almost completely depleted of its health-enhancing bioactives because of the astrin-
gency associated with these bioactives. Raspberry juice is very healthy but no where to be found.
Training children as early as possible to like the taste of raw cranberry or raspberry will lead
to new generations of individuals getting the best and most out of cranberry without the need of
removing the phenolics and replacing it with sugar. Recent work shows that bioactives in cranberry
including quercetin and the anthocyanidins can prevent preadipocyte differentiation into mature
adipocytes that often lead to obesity.
Processed juices are often obtained from concentrates and therefore contain high amounts of
sugar that most people would not consume if they had to squeeze the fruits themselves. It is sug-
gested that juices be processed to contain the same levels of sugar as the single fruit. Cranberry can
be blended with blueberries or pineapple or apples to reduce the astringency. Too much carbohy-
drate consumed throughout the day predisposes to insulin resistance development.
Chocolate beverages contain procyanidins and are healthier when consumed without too much
sugar and AGEs from processed milk that make the majority of cocoa drinks.
4.5.3.7 Designing Tasty and Healthier Snacks and

Desserts with Triglyceride Binders
Most snacks contain dairy ingredients such as milk powder and are therefore overloaded with
AGEs and sugars making snacks significant contributors to the epidemics of obesity. Reducing
sugars regularly used in snack formulations need to be replaced with nonreducing sugars that do
not undergo the Maillard reaction. Fucose from brewer’s yeast, galactomannan from fenugreek,
and polysaccharides from okra can be developed into sugar for snacks. While some of these
oBesIty 71
Figure 4.7 Matzah is rich in dietary fiber and can serve well for weight gain control.
carbohydrates can reduce AGE formation [21–23], triglyceride binders can prevent fat digestion.
The snack matzah (Figure 4.7) is sometimes a fiber-rich food that can help prevent fat digestion
[24,25]. Dark chocolate is rich in flavonoids. Dark chocolate–enriched food products rather than
sugared chocolate or AGE-rich milk-enriched chocolate should be developed because phenolics in
chocolate do not break AGEs or prevent AGEs from binding to its receptors.
The food industry has to readjust to human health reality and offer foods based on both health
and business. It is time for the food industry to sell real health by phasing out reducing sugars found
in many food formulations. Ingredients and processing conditions are the base of health and as long
as ingredients and processing conditions with established links to inflammation are part of what the
food industry offers consumers, there will be no real improvement in the way the food industry is
contributing to disease prevention.
4.5.3.8 Designing Foods That Improve Insulin Sensitivity
Insulin resistance translates into loss of insulin sensitivity. Insulin glycation also contributes to
increased insulin insensitivity. Reducing the levels of reactive reducing sugars in processed foods
will help reduce insulin glycation. Agave, for instance, is full of reducing sugar and not as healthy
as commercialized.
4.5.4 restaurant and Food Service Industry
The restaurant industry, which includes the sit-down fine dining and fast-food restaurants, plays
a major role in providing safe foods to consumers. Restaurants have to be ahead of the healthy eat-
ing habit trends by offering customers their newly created healthy choices, emphasizing that recipes
and menus have changed and been updated. This kind of leadership will be appreciated by custom-
ers if restaurants stand tall and tell customers that certain recipes will never be cooked the way it
used to be in the past.
Due to the fact that food preparation involves the interactions of carbohydrate, protein, lipids,
salts, vitamins, and micronutrients in water at high temperature or under dry conditions, anybody
in this industry should be proficient in food chemistry. The lives of billions of people around the
world are at stake and it is imperative that those who handle food understand the chemistry and
biochemistry of food ingredients. Cooking in restaurants should no longer be an art only; rather an
additional emphasis should be on understanding what happens when ingredients interact at differ-
ent temperatures. If food chemistry, especially the Maillard reaction and all of its side effects, was
taught and extensively explained to students in culinary schools, people in the restaurant business
would be more demanding and inquisitive about the ingredients they purchase from food manufac-
turers. Similarly, with knowledge of the Maillard reaction, pizza would not be seared and cheese
and chicken would not be flamed and sold to people.
4.5.5 the Consumer
The consumer has the ultimate responsibility to make the healthy choice when purchasing food.
However, the consumer is exposed to inexpensive AGE-rich food products all day long. Some have
only seen and consumed AGE-rich food products throughout their lives. This limits the choice the
consumer has when purchasing food or food ingredients. Unfortunately, consumer education is in
the hands of specialists who know little about the Maillard reaction. The following suggestions are
for consumers to make the best out of what is on the market of food products:
1. Replenishing the pantry and refrigerator with AGE-free or AGE-less products

2. Starting the day with tryptophan-rich foods
3. Eating small portions of balanced food in moderation
4. Avoiding intake of AGEs and unnecessary calorie-loaded foods
5. Ingesting calorie-rich foods during daytime
6. Reducing intestinal absorption of fat
7. Inhibiting accumulation of white (bad) fat
8. Decreasing total cholesterol intake
9. Consuming food high in fat binders to promote fat excretion
10. Consuming food that improves insulin sensitivity
11. Engaging in light physical activity for weight management
4.5.5.1 Replenishing the Pantry and Refrigerator with AGE-Free or AGE-Less Foods
In many households, obesity is promoted by what is in the pantry. A look at what is in most
pantries and refrigerators in most households in the West shows the presence of food items includ-
ing ingredients, snacks, and meal items that are rich in AGEs. Cleaning the pantry and freeing it
from AGE-loaded food ingredients or products is one of the first steps in moving away from the
obesity club.
4.5.5.2 Starting the Day with Tryptophan-Rich Breakfast Foods
Recent study suggests that obesity may increase the risk of developing body dissatisfaction and
depressive symptoms [26]. Food can regulate human temperament and emotions. The food we eat
can have a very significant influence on our mood throughout the day and week. Nutrients extracted
from food are used by different tissues in the body including the brain and central nervous system
tissues for growth and development. It is also known that the brain and central nervous system are
the centers of emotion and mood regulations. Therefore, it is important to understand what the brain
and central nervous system need in order to keep the body in a good mood.
The brain needs energy from food. About 30% of PUFAs in the human body are concentrated in
the brain making the brain the largest deposit of PUFA. The PUFAs exist under two different forms:
the ω-3 and ω-6 fatty acids. Most cooking oils are rich in ω-6 fatty acids. With exposure to foods
cooked mostly with ω-6 fatty acids and deficient in ω-3, the levels of ω-3 decrease with aging leav-
ing the brain more concentrated in ω-6 fatty acids. The ω-6 fatty acids promote inflammation while
the ω-3 fatty acids inhibit the production of inflammatory cytokines. Due to the presence of PUFA
oBesIty 73
in the brain, it is simply reasonable that the brain in turn needs enough PUFA and liposoluble anti-
oxidants to protect the PUFA from oxidation and inflammation. The brain also needs vitamins to be
functioning. Serotonin, dopamine, and noradrenaline are neurotransmitters that regulate behavior.
Serotonin, a neurotransmitter obtained from the metabolism of the amino acid tryptophan, plays a
major role in sleep, depression, appetite, mood, anxiety, depression, concentration levels (focusing),
and memory and has a calming effect.
People with low levels of serotonin may suffer from chronic fatigue syndrome. Fatigue syn-
drome can wrongly be temporarily overcome using stimulant beverages. Such dependence on
stimulants can grow, become irreversible, and worsen leaving the individual with an aging body.
Serotonin can be boosted by high intake of food rich in tryptophan but the tryptophan has to be
absorbed and properly metabolized into serotonin.
4.5.5.3 Eating Small Portions of Nutrient-Balanced Food in Moderation
Eating small portions of nutrient-balanced food in moderation and avoiding foods that enhance
appetite is one of the best ways to prevent the development of obesity. Butter, caramel, fat, salt,
and sugar enhance appetite. A habituation to food-rich in these ingredients is a major risk factor
for developing obesity. Eating small portions of nutrient-balanced foods containing carbohydrate,
protein, lipids, and micronutrients is good for obesity prevention.
4.5.5.4 Avoiding Intake of AGE-Loaded or AGE-Inducing Foods
AGE- and empty calorie-rich foods are at the heart of the obesity epidemics in the world.
Avoiding AGE-rich food significantly reduce the accumulation of adipocytes in the body. AGE-
rich foods have been listed in Chapter 3. Daily consumption of beverages including vitamin and
sweetened water, soft drinks, sweetened fruit juices, and fruits rich in sugars that easily undergo the
Maillard reaction is a major risk factor for the development and progression of obesity and obesity-
related health risks.
4.5.5.5 Consuming High-Calorie Foods before the Evening
Consuming a high-calorie meal followed by exercise is one way to maintain body weight
because enough exercise should help diffuse the calories absorbed. In the Mediterranean region,
heavy/high-calorie meals are consumed before 3:00 p.m. to allow the body time to rid itself of
unnecessary calories. Light meals are consumed in the evenings. Adherence to the Mediterranean
diet has been reported to protect against obesity and the development of CVD in children as well
as in adults [27].
4.5.5.6 Reducing Ingestion and Intestinal Absorption of Fat
It is possible to reduce energy intake by (1) reducing fat ingestion and (2) inhibiting fat diges-
tion and absorption without altering homeostasis. Reducing fat trafficking through the gut can pre-
vent excessive fat in the bloodstream. In order for ingested fat to be absorbed, it has to be digested
by lipases. There are three important enzymes involved in the digestion of fat ingested with food:
lingual lipase, gastric lipase, and pancreatic lipase. Fat digestion by lingual lipase involves the
breakdown of the fat molecule at the mouth level when the food is being chewed. Lingual lipase is
secreted by the glands in the mouth and digests about one-third of the fats in the food. The gastric
lipase, located in the stomach, digests approximately 10%–30% of ingested fat. The pancreatic
lipase is the enzyme secreted by the pancreas whose function is to digest ingested fats and convert
it into glycerol and free fatty acids and allows these to enter the bloodstream. The pancreatic lipase
is responsible for the digestion of 50%–70% of ingested fats making pancreatic lipase the major
source of calories from ingested food and an excellent target for obesity prevention or manage-
ment. There are also the hepatic, lipoprotein, and endothelial lipases, which also act on fat inside
the body.
However, lingual, gastric, and mostly the pancreatic lipase account for the abnormal elevation
in blood lipid and low-density lipoproteins and for approximately 60% of CVD worldwide and
4.5 million deaths annually. It is important that fat absorption be reduced at the gut level because the
glycerol and free fatty acids generated by the lingual, gastric, and pancreatic lipases interact with
bile salts, cholesterol, and lysophosphatidic acid to form mixed micelles. The latter are absorbed
and in the bloodstream the original fat that was ingested is reformed and is stored in the adipose
tissue. Excessive fat deposition leads to excessive adipocytes and obesity. Therefore, inhibiting the
activity of phospholipase can curtail excessive calories entering the bloodstream. There are several
foods out there that are natural inhibitors of phospholipase that may help the millions of individuals
around the world who would like or need to lose weight.
Well-brewed hot teas, including black, oolong, green, rosemary, mint, sage, fenugreek, cin-
namon, ginger, hibiscus, and cardamom tea, contain saponins and polyphenols that are excellent
inhibitors of pancreatic lipase and can be effective when consumed with meals. These teas can
significantly reduce white fat in the abdomen. Lemon peel-rich lemon juice is another good source
of lipase inhibitor. Asparagus, amaranth, marine algae, soybean, mushroom, wheat germ and
wheat bran, citrus, fenugreek, ginseng, grape leaves, peanut skin, raspberry, and mistletoe are also
good sources of lipase inhibitors. Although we have all these foods available, the question remains
whether we use them appropriately and in the right amounts and under the right conditions. The
answer to this question is mostly “No!” People in Japan often take their meals with hot green tea.
4.5.5.7 Consuming Foods That Inhibit Adipose Tissue Accumulation
Research has shown that drugs that inhibit angiogenesis can also induce weight loss. Since
obesity is an angiogenic disease whereby angiogenic biomarkers accumulate during the deposition
of adipose tissue, it is possible to identify and use dietary inhibitors of angiogenesis to fight obesity
[28,29]. The following foods when used in moderation and regularly can help prevent obesity. Pectin
in unsweetened marmalade, black seed oil, orange oil, ginger oil in salads, and lemon peel in baked
products can help as anti-angiogenic foods. Ginger oil is an excellent anti-angiogenic functional
food that can be used in several food formulations [30]. Similarly, black seed oil can be used in sev-
eral food formulations [31]. Sweet orange oil is often used in baking, this oil has an excellent flavor
and can be used as anti-angiogenic ingredient in food formulations.
4.5.5.8 Consuming Foods That Decrease Cholesterol Absorption
Cholesterol absorption can be reduced by foods rich in squalene such as amaranth or soluble
dietary fiber. Limonene-rich citrus peel can dissolve cholesterol and reduce its side effect. Grapefruit
pectin is GRAS and has shown to reduce serum cholesterol. Fenugreek also known as “Methi” in
India has cholesterol-lowering properties. Salmon oil rich in omega-3 fatty acids reduce serum cho-
lesterol. Krill oil is also effective.
4.5.5.9 Consuming Food Rich in Triglyceride Binders
Bulk dietary fibers including food such as Israeli matzah (very high in fiber), lemon peel, apple
peel, and strawberry are good candidates for reducing obesity. The food industry can help in the
fight against obesity by developing sugar-free and AGE-free fiber-rich snacks. The consumer can
prepare meals rich in these binders.
oBesIty 75
4.5.5.10 Consuming Foods That Improve Insulin Sensitivity
Insulin sensitivity affects endothelial function and vice versa. Increased insulin sensitivity improves
endothelial function and functional endothelium can help in increasing insulin sensitivity. Soluble dietary
fiber–rich foods containing foods such as fenugreek, lemon peel, orange peel, strawberry, baked and
cooled potato, and baked and cooled sweet potato improve insulin sensitivity. The Okinawa-diet is also
known for its high content of green vegetables, tofu, sweet potato, miso, seaweed, and improved insulin
sensitivity. The Mediterranean diet is also good for improving insulin sensitivity.
4.5.5.11 Managing Weight with Physical Activity
Lack of physical inactivity is a major risk factor for dementia [32]. Physical activity is one of the
best non-pharmaceutical interventions for weight management. Physical activity may not be enough
for obesity prevention or weight reduction and management. However, physical activity increases
energy expenditure and reduces adiposity, regulates fat balance, fat mass, and body sugar levels,
helps keep weight stable and prevents metabolic disorders including hypertension, dyslipidemia,
and impaired glucose tolerance. School-age children, teenagers, adolescents, and adults are encour-
aged to spend at least 1 h of light physical activity a day that may involve playing (and not watching)
sport, walking, or swimming.
Eat less, walk more has been suggested as a way of staying in shape. Physical activity should be
an integral part of human life to prevent and delay the onset of chronic degenerative diseases. The
components of physical activity include strengthening, endurance, and flexibility. The American
College of Sports Medicine recommends a moderate intense physical activity of 150–250 min per
week, which is sufficient to produce modest weight loss and prevent weight regain of >3% in most
adults [33]. It is recommended that individuals who have been physically or have significant comor-
bidity engage in walking for 30 min two or three times a week.
Physical activity also results in improvement of systolic and diastolic blood pressure, resting
heart rate, mood, insulin sensitivity, blood glucose, and blood lipid levels. However, physical activ-
ity as part of weight management often results in <3% weight loss because most people have dif-
ficulty maintaining a regular level of physical activity [33,34].
A 12-week intervention with obese and normal weight children aged 7–15 years showed that
participation in multicomponent physical activity significantly decreased the levels of BMI, skinfold
thickness, and fasting glucose in overweight and obese children [35]. Overweight and obesity in the
reproductive age group women can affect maternal health and the health of the offspring and can
sometimes lead to infertility. Infertility is associated with decreased ovarian reserves [36]. Physical
activity significantly improves ovarian reserve markers in all reproductive age overweighed and
obese women compared to normal weight women [36].
Experiments with rats even at advanced age, regular physical exercise in male obesogenic off-
spring decreased testicular oxidative stress, increased sperm anti-oxidant and sperm quality and
fertility [37]. Obesity is associated with increased levels of proinflammatory biomarkers in the
tendons. Physical activity when performed with caution can help reduce the level of inflammatory
markers in the tendons [38]. Adopting physical activity on a regular basis can help reduce childhood
obesity, which has become a worldwide global problem [39].
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ChAPter 5
Diabetes Mellitus
5.1 DeFINItION OF DIABeteS
Diabetes is a group of metabolic diseases characterized by abnormal high blood sugar levels that
result from defects in the body’s ability to produce and/or use insulin. The disease was discovered
in 1000 BC by an Indian physician, Susruta, but was named “diabetes” in 100 BC by a Greek physi-
cian, Aretaeus, after the Greek word “dia-bainein,” which means “to siphon.”
The presence of sugar in the urine of people with diabetes was first reported by Thomas Willis
in 1650. There are three main types of diabetes: type 1 and type 2 diabetes mellitus (T1DM and
T2DM) and gestational diabetes mellitus (GDM). The term “mellitus” was added to diabetes in
1750 by Cullis.
T1DM or insulin-dependent diabetes mellitus (IDDM) is characterized by insulin deficiency
due to the body’s inability to produce enough insulin as a result of autoimmune destruction of
insulin-producing pancreatic β-cells. As a result, insulin production decreases leading to insuf-
ficient insulin and excessive glucose or hyperglycemia in the body that cannot be used by needed
tissue. The disease is evident in childhood and is often referred to as juvenile diabetes. Individuals
with T1DM are treated with regular insulin injections to help distribute glucose to tissues such as
liver, muscle, and fat tissues. The pancreatic β-cells in general contain very low levels of antioxidant
enzymes and are very sensitive to oxidative stress and attack. In T1DM, pancreatic islets, inflam-
mation induces oxidative stress and the latter activates more inflammatory. The reactive oxygen
radicals and inflammatory markers such as interleukin-1 beta (IL-1β) and nuclear factor-kappa B
(NF-κB) end up destroying the β-cells. Studies have also shown that when the antioxidant defense of
the mitochondria of β-cells is strengthened with exogenous antioxidants, the β-cells become resis-
tant to the action of reactive oxygen species. T1DM is prevalent in Finland [1], the Sardinian region
of Italy, Northern Europe, and North America [2,3].
T2DM is associated with insulin resistance and defective pancreatic β-cells. First, there is the
insulin resistance phenomenon. Then the body tries to respond to the insulin resistance by secreting
more insulin. With time, the pancreas cannot keep up with producing too much insulin, the β-cells
become dysfunctional, and insulin levels become insufficient in peripheral tissues including liver,
adipose tissue, and skeletal muscle. T2DM is that it is a progressive disease with a sustained and
metastasizing cellular dysfunction. The disease is often diagnosed after the metabolic dysfunction has
reached several organs and tissues including the kidney, nerves, coronary arteries, joints, blood, skin,
eye, pancreas, heart, and mouth [4]. The disease often becomes evident in adulthood and is referred to
as adult-onset diabetes. T2DM is often associated with the development of obesity. Diabetes acceler-
ates mortality. T2DM is the most common form of diabetes and affects 90% of diabetic patients.
GDM develops during pregnancy in some, not all, pregnant women. These women have never
been diabetics beforehand, and the disease disappears in 90% of women after pregnancy. However,
a woman who had GDM has about 70% chance of developing the disease during a future pregnancy.
79
A woman who developed GDM is about seven times more likely to develop T2DM compared to a
woman who never developed GDM.
There are several risk factors for developing GDM including genetic predisposition, overweight,
unhealthy diet habits, high cholesterol, smoking, physical inactivity, and hypertension. As an exam-
ple, genetic predisposition can be associated with the prevalence of GDM in the Pima Indians of
Arizona [5]. The mothers in this community are carriers, are at high risk of developing T2DM, and
have daughters who are highly susceptible to be carriers, making the Pima Indians the group with
the highest incidence of GDM in the world [6].
Worldwide, the incidence of GDM is on the rise because of the high incidence of T1DM women
or women who developed GDM. Hyperglycemia in the uterine of T1DM or GDM pregnant women
is a risk factor for future risk of T2DM development in the offsprings. Muslim women who fast dur-
ing the Ramadan are at higher rate of developing GDM compared to women who do not fast during
the Ramadan [7,8].
5.2 SOCIAL AND eCONOMIC SIGNIFICANCe OF DIABeteS
Diabetes is a burden to the individual who has the disease and society because it has no cure.
Diabetes is on the rise in the United States and worldwide. According to the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK), about 29,713 Americans develop diabetes
each year. T1DM accounts for about 5% of all the diabetes cases and the remaining 95% of people
with diabetes are T2DM. There are more than 23 million American adults aged 20 years or older who
are diabetics and these individuals represent close to 13% of the U.S. adult population. The number of
adults with diabetes continues to rise at an alarming rate. The highest prevalence of T2DM is among
the Pima Indians of Arizona. Diabetes is also prevalent in the Hispanic communities.
Diabetes is also on the rise worldwide. There are close to 170 million people worldwide (5% of
the world population) who have diabetes [9]. Compared to other diseases, the prevalence of diabe-
tes, especially T2DM has doubled between 1980 and 2010. China leads the way followed by India,
Pakistan, and Bangladesh [10,11]. World Health authorities estimate that diabetes will affect more
than 360 million individuals worldwide by the year 2030.
Drugs designed to manage the disease without severe side effects are few and the disease appears
to beat every drug with time. As a result, diabetes represents a growing socioeconomic burden and
is likely to be a major public health challenge for generations to come.
Diabetes care is very expensive because it is a lifetime expense and individuals can live with
the disease for decades. In the United States, the per capita medical expenditures total an average
of $3,000 for patients without diabetes compared to an average of $15,000 for patients with dia-
betes. The cost associated with diabetes care is estimated at more than $130 billion a year. These
huge healthcare cost estimates suggest efforts should be made on all fronts to prevent diabetes that
should lead to significant cost savings for the U.S. healthcare system. Similar efforts must be made
by world health authorities and advocates.
5.3 rISK FACtOrS FOr DIABeteS
5.3.1 Obesity and Overweight
Obesity and overweight increase the lifetime risk of developing diabetes in people of all ages
and races. People with a body mass index equal to or more than 25 kg/m2 are at higher risk of devel-
oping obesity and diabetes compared to individuals of similar age and normal weight. Obesity also
DIaBetes MeLLItus 81
shifts the onset of diabetes to younger ages. Obese, diabetic, or prediabetic mothers are more likely
to have children born with prediabetic risk factors. Recent studies have shown that infants of obese,
diabetic, or prediabetic mothers are already predisposed to diabetic risk factors by carrying high
levels of advanced glycation end products (AGEs) in their blood. The rising in obesity worldwide
has been exacerbated by consumption of large portions of AGE-rich foods and beverages including
pizza, all foods with excessive and unnecessary amounts of cheese, meat, and beverages sweetened
with excessive sugar [12,13]. In most affluent nations, school-age children are the most vulnerable
because most schools provide high-calorie meals or highly proinflammatory foods without enough
time devoted to exercise whereby the children could lose some weight [13,14].
5.3.2 Genetic Susceptibility
First-degree relatives with diabetes often are a major risk factor for the development of diabetes
in the family [15]. More than 80% of IDDM patients have no family history of diabetes. Nondiabetic
relatives of T2DM patients carry dysfunctional β-cell as a result of genetic predisposition. In Pima
Indians of Arizona, genetics is related to diabetes prevalence in this society [16].
5.3.3 ethnicity
Low-income Native Americans, Hispanic-Americans, Latinos, African-Americans, Pacific

Islanders, and Asian-Americans are vulnerable groups for diabetes [17,18]. Low-income individuals
in these communities tend to consume inexpensive AGE-rich foods from commercial outlets more
than individuals from other communities [19,20]. Moving from one commercial outlet for breakfast
to another outlet for lunch and finally to a third one for dinner on a single day and regular basis is
common among individuals in these susceptible communities because AGE-rich foods tend to be
inexpensive and tasty. Immigrants adopt Western fast foods in addition to ethnic traditions that may
not provide healthy dietary habits. As a result, obesity develops faster in these communities than
others [21].
5.3.4 Low Levels of “Good” Cholesterol and high Levels of triglycerides
A low level of “good” cholesterol, also called high-density lipoprotein (HDL) cholesterol, is
often accompanied by a high level of “bad” cholesterol or low-density lipoprotein (LDL) choles-
terol. Diabetic patients have an increased number of small dense LDL particles that carry “bad”
cholesterol in the body compared with nondiabetic individuals. Deficiency in “good” cholesterol
levels is a feature of oxidative stress and chronic low-grade inflammation. Fats are composed of
three fatty acid chains linked to a glycerol molecule.
5.3.5 Insulin resistance
Insulin resistance is an environmental factor that can be produced by either insulin insufficiency
or excessive insulin action in different tissues including liver, brain, muscle, or endothelium result-
ing in different disease in the affected tissue. For instance, insulin resistance in skeletal muscle or
brain can lead to obesity or dyslipidemia; insulin resistance in the pancreatic β-cells or liver pro-
duces glucose intolerance and T2DM. Obesity, glucose intolerance, and dyslipidemia can also be
produced by excessive unused insulin in fat while excessive and unused insulin in the liver produces
dyslipidemia. Regardless of which tissue is affected, insulin resistance is a major risk factor for car-
diovascular disease (CVD). Diabetes-derived inflammation and insulin resistance can accelerate the
development and progression of atherosclerosis in patients with diabetes. Diabetes is often preceded
by a prediabetic stage, a period of life during which an individual shows impaired fasting glucose
and/or impaired glucose tolerance. The number of prediabetic individuals in the United States is
alarming: about 30% of U.S. adults are prediabetics.
5.3.6 Age
Individuals aged 40 or older have a higher risk of developing diabetes than younger people.
T2DM is rare in children and adolescents; however, in recent years, it is being diagnosed in children
and adolescents in native Indian, African-American, and Hispanic and Latino American popu-
lations. Regular and excessive consumption of energy-dense foods including fried foods, roasted
foods, grilled foods, and barbecued foods is a major contributor to the development, progression,
rise, and complications of diabetes. Similarly, regular consumption of all sort of sugar-sweetened
beverages that contain unnecessary high levels of sugar including the cola drinks, sweetened water
containing artificial fruit flavors, other soft drinks and all the sweetened fruit drinks is a risk fac-
tor for diabetes. A good diet and lots of exercise can help reduce weight and insulin resistance and
prevent the progression from prediabetes to full-blown diabetes.
5.3.7 Glycemic or Fructose Index
The glycemic control can be evaluated by measuring the levels of sugar-bound hemoglobin
or HbA1c as it is believed to reflect an individual’s glucose level over a period of several months.
Dietary carbohydrate ability to raise blood glucose differs from one type of carbohydrate to another.
The glycemic index provides excellent information on the ability of a dietary carbohydrate to stimu-
late insulin secretion but does not identify foods that stimulate insulin resistance.
Fructose has a low glycemic index and as a result does not increase the concentration of glycated
hemoglobin (HbA1c), a marker of abnormalities in blood sugar level also known as dysglycemia.
However, consumption of less than 50 g of fructose per day shows no significant effect on postprandial
triacylglycerol and consumption of less than 100 g of fructose per day shows no effect on fasting tria-
cylglycerol or body weight. Unfortunately for the millions of people with diabetes, most people who
deal with sugar reactions with proteins also known as the Maillard reaction do not know that fructose
is more reactive than glucose and fructose is probably the worst enemy for individuals with diabetes.
The attention of nutritionists and others may have shifted too much to glucose and glycemic
index to the point that fructose, the silent killer of people with diabetes, has been ignored. According
to Lavoisier, nothing is lost but all is transformed. The fructose that is absorbed, no matter how little
it is, reacts with proteins although slowly but with time its effect can be seen.
5.3.8 Food heated at high temperature in the Absence of Water
Louis Camille Maillard (1878–1936) was a French physician and chemist who studied the
reaction between amino acids containing amine groups and reactive sugars in the human body.
He discovered that at temperature as low as the human body temperature, sugar like ribose (sugar
in mammals), fructose (honey, corn syrup), and galactose (milk) reacts with amino acids like lysine,
arginine, and histidine in long-lived proteins such as collagen to form a complex of carbohydrate–
proteins called AGEs. Individuals with insulin resistance and hyperglycemia are predisposed to
accumulate AGEs in their bodies.
Regular and continuous consumption of energy-dense foods such as pizza, lasagna, macaroni, and
cheese increases the risk of chronic ingestion of high levels of AGEs. At least 10% of the AGEs remain
inside the body and accumulate in long-lived tissues such as the arteries, kidney tissues, and brain.
Accumulated AGEs induce weight gain and oxidative stress that in turn can induce inflammation. The
pancreas has a weak defense system and repeated inflammation generated by accumulated AGEs can
easily destroy the cells of the pancreas also known as β-cells that secrete insulin.
5.3.9 Potassium
Potassium is not often used to season food because it is bitter and imparts bitterness to food.
However, studies are showing that low level of potassium in the body is a high risk factor for diabetes
development. Low levels of potassium in serum and diets are associated with high risk of diabetes
and high blood pressure [22]. In most developed countries, potassium intake is low and amounts
consumed per day are one-half to one-fourth of the normal intake [23,24]. Studies in humans have
shown that low levels of potassium causes glucose intolerance associated with impaired insulin sen-
sitivity while high intake of potassium reduced the risk of developing T2DM [25]. Animal studies
have shown that potassium can slow the progression of kidney damage [26].
Potassium chloride, the salt that is closely related to sodium chloride has a bitter taste. The rise
in sweet foods associated with the removal of bitter foods from common diets along with the decline
in fruits and vegetable consumption have all contributed to the decline in potassium levels in most
foods. Salt intake has risen while potassium intake has gone down [24]. As a result, insulin sensitiv-
ity decreases and blood pressure increases and so does the risk for CVD and bone demineralization.
5.3.10 Low Birth Weight
Several studies have reported the significant inverse relationship between low birth weight and
T2DM development in adulthood [27–30]. This inverse relationship has so far been explained by the
“fetal origin of adult disease hypothesis” or “thrifty phenotype” hypothesis [30–36].
Maternal undernutrition at critical periods during intrauterine development drives fetal under-
nutrition and the latter leads to organ dysfunction, predisposition to dyslipidemia and arterial
hypertension, reduced development of β-cell mass and pancreatic secretory capacity, and develop-
ment of insulin resistance in peripheral tissues leading to T2DM development later in life [37–39].
While most studies have shown an inverse relationship between low birth weight and T2DM devel-
opment in adulthood, there are cases such as in Pima Indians in Arizona and in children in Taiwan
where children born with high birth weight are at an increased rate of developing T2DM in adult
life [40].
5.4 heALth rISKS ASSOCIAteD WIth DIABeteS
The disease is multifaceted, inflammatory, chronic, degenerating, and creates a serious chal-
lenge to physicians, drug designers, insurance companies, and family relatives. People with diabetes
have an increased risk of developing both macrovascular and microvascular complications.
Macrovascular complications are those that affect large vessels of the body including the arter-
ies leading to CVD including myocardial infarction, stroke, and peripheral vascular disease as a
result of minimal elevation of blood glucose levels. Individuals with diabetes are at higher risk
of metabolic syndrome than individuals without diabetes. The metabolic syndrome encompasses
central obesity, dyslipidemia, hypertension, and insulin resistance, all of which increase the risk of
CVD.
Microvascular complications are those that affect the small vessels of the eye leading to more
blood vessels in the eyes, kidney leading to kidney failure, skin leading to impaired skin smooth-
ness, and peripheral nerves and these complications are closely linked to the severity and duration
of high blood sugar levels. It is suggested that tight control of the glycemic index should help coun-
teract potential damage from microvascular complications. More than 50% of people with diabetes
are obese and more than three-quarter of people with diabetes are overweight. Insulin resistance is
a hallmark of T2DM affecting approximately 80% of people with the disease and is directly cor-
related with weight gain.
5.4.1 hypertension
Hypertension affects more than 70 million Americans and 1 billion individuals worldwide. The
disease is on the rise and will affect close to 1.6 billion people by 2025. Obesity is a major risk factor
for the development of hypertension. Kidney function abnormality is another major factor that leads
to hypertension. High levels of free fatty acids in the circulation, high levels of insulin, and low lev-
els of adiponectin all may contribute to increased hypertension symptoms. The clinical significance
of hypertension is that it is a major risk factor for developing CVD and CVD-associated death. It is
recommended that individuals with diabetes maintain a blood pressure of less than 130/80 mmHg.
High blood pressure can be reduced with
• Improving insulin sensitivity

• Weight loss
• Eating well
• Reducing sodium intake
• Exercise and physical activity
• Drinking one to two glasses of quality red wines a day
5.4.2 hypotension
Hypotension is often observed in T1DM although it can also develop in individuals with T2DM.
The association of hypotension with acute arrhythmia with T1DM has been reported in individuals
who die of nocturnal hypoglycemia also known as “dead in bed” syndrome.
5.4.3 erectile Dysfunction
Individuals with T2DM are up to three times more susceptible to develop erectile dysfunction
compared with nondiabetic individuals. Individuals with erectile dysfunction often experience the
dysfunction of the penis 10–15 years earlier than nondiabetic individuals. The association of diabe-
tes and erectile function is extensively described in Chapter 12 under “Erectile dysfunction.”
5.4.4 Coronary Artery Disease
Coronary artery disease is more frequent in individuals with diabetes than nondiabetic ones.
Since most individuals with diabetes are also carriers of metabolic syndrome, individuals with
T2DM are at high risk of dying from CVD. About 79 million Americans (about 25% of the U.S.
population) have at least one type of CVD. CVD accounts for one-third of the deaths each year
in the United States making CVD responsible for the loss of more lives than cancer, diabetes, car
accidents, or respiratory diseases. The economic significance of CVD is extremely high; in 2007
CVD cost was estimated to be more than $430 billion, in 2010 the cost was about $444 billion, and
by 2030 medical cost for heart disease alone will reach $800 billion.
5.4.5 Atherosclerosis
Diabetes promotes atherosclerosis. As the incidence of diabetes continues to rise worldwide, the
incidence of atherosclerosis is also expected to increase worldwide. Elevated reducing sugar levels
in diabetics induce glycation of extracellular matrix proteins and LDLs that subsequently deposit
in the vessel wall where it stimulates oxidative stress with the formation of ROS, which has been
implicated in driving atherosclerosis. Inflammation fosters diabetes and diabetes induces inflam-
mation that promotes atherosclerosis. ROS activate inflammation and inflammation is the hallmark
of atherosclerosis. The inflammatory mechanisms observed in diabetes-induced atherosclerosis
is similar to the mechanism observed in individuals with non-diabetes-induced atherosclerosis.
Regulating hyperglycemia, insulin resistance, and plasma concentration of “bad” cholesterol may
prevent and slow diabetes-induced atherosclerosis.
5.4.6 Cataract and Diabetes retinopathy
In the industrialized world, diabetes is a major cause of irreversible blindness. Visual loss is
only one of the worst consequences of diabetes. The duration of diabetes is a major risk factor for
the development of long-term eye damage known as diabetes retinopathy. Within 10–15 years of
having diabetes, 25%–50% of patients show signs of the disease, 75%–95% of patients show signs
after 15 years, and close to 95% of people with diabetes show signs of retinopathy after 30 years
of disease development. Diabetic patients are prone to develop cataracts. The removal of cataracts
exacerbates retinopathy. The economic and social significance of diabetes retinopathy is that it
affects a large number of working-age population worldwide.
5.4.7 Kidney Disease
Diabetes accounts for more than 44% of new kidney failure in recent years. AGEs have
been implicated in the development of diabetic nephropathy. T2DM is an important cause of
kidney and end-stage renal disease. As the U.S. population ages, T2DM-associated end-stage
renal disease is increasing and will become a major cause of morbidity and mortality. Diabetic
nephropathy is also associated with an increased risk of vascular disease and patient mortality.
Aggressive management of hypertension is focused on reducing the abnormal subtle increases
in the excretion rate of the protein albumin in the urine, also known as microalbuminuria. The
increase in albumin in urine is an indication of diabetes kidney disease. Control of microalbu-
minuria and tight glycemic control are important therapeutic strategies for renal and vascular
disease prevention in T2DM. Hypertension, AGEs, and increased oxidative stress exacerbate
renal injury.
5.4.8 Nerve Damage
Chronic high blood sugar causes damage to nerves. Nervous system damage is a hallmark of
diabetes and more than half of the people with diabetes often suffer from some sort of nervous
system damage. Nerve damage is associated with blood sugar being elevated for a long period of
time. It affects people who have been with T2DM for a number of years. Complications of nerve
disease lead to lower extremity amputations. The feet and legs are the most affected areas. As
a result, the individual could lose feeling on his or her foot and any injuries that develop on the
foot. Tingling, numbness, burning, and pain are all symptoms associated with diabetes nerve
damage.
5.4.9 Skin Damage
Chronic hyperglycemia reduces blood flow to the skin. The skin of individuals with diabetes
looks older than the individuals’ ages suggesting early breakdown of skin tissue integrity and chem-
istry. Dryness, cracking, thickening, stiffness, yellowing, bacterial infections, carbuncles, irritation,
and itching characterize the skins of more than one-third of diabetic patients. Collagen breakdown
is a major issue in the skin of diabetic individuals.
5.4.10 Periodontal Disease
Periodontal disease is a chronic inflammatory disorder that affects the supporting structures
of teeth leading to soft and hard tissue destruction and eventually loss of teeth [41]. The risk and
cofactors for periodontal disease include genetic factors, periodontal pathogens, host responses, free
radicals, oxidative stress, inflammation, AGEs, the metabolic syndrome, and both T1DM and T2DM.
Gingivitis is the early most common form of periodontal disease. Untreated gingivitis progresses to
a destructive form of periodontal disease. Periodontal disease can also be caused by infections sus-
tained by bacterial pathogens such as Porphyromonas gingivalis, Prevotella intermedia, Tannerella
forsythia, and Aggregatibacter actinomycetemcomitans [42]. Diabetes mellitus, because of its char-
acteristics of high levels of AGEs, leads to a hyperinflammatory response to the periodontal micro-
bial population and impairs resolution of inflammation and repair, which leads to accelerated teeth
loss [41].
5.4.11 Diabetes and Cognitive Brain Function
Diabetes has a negative impact on cognitive function and may contribute to age-related cogni-
tive decline. The brain depends on glucose for its metabolism. Individuals with either T1DM or
T2DM experience hyperglycemia or hypoglycemia on a regular basis. Both of these conditions
decrease mental efficiency in children with T1DM or T2DM [43,44]. There is increasing evidence
that adults with acute T1DM or T2DM show evidence of cognitive disruption with time [45,46].
Elderly diabetic patients without dementia show an accelerated progression to cognitive decline
compared to elderly nondiabetic without dementia.
5.4.12 AGes–Diabetes–Cancer Axis
People with diabetes are at increased risk of developing any type of cancer [47–49]. Diabetes is
characterized by hyperglycemia that induces oxidative stress in various cells thus causing oxidative
DNA damage, a well-established initial step in cancer development. Diabetes as a disease encom-
passes both insufficient and excessive angiogenesis making it one of the worst diseases to handle or
treat. On the one hand, the disease may lead to the formation of excessive blood vessels in the eye
leading to vision loss, and on the other hand, an individual may also have wounds that do not heal.
People with diabetes have high levels of AGEs. Accumulating evidence suggests that AGEs interact
with its receptors, receptors of advanced glycation end products (RAGE), and stimulate oxidative
stress generation, and the latter promotes the formation of AGEs and increases the expression of
RAGE. AGEs are also known to stimulate angiogenesis.
The clinical significance of RAGE is that it is a multiligand receptor that is expressed in a
wide range of cells including endothelial cells, smooth muscle cells, certain neurons, and mesan-
gial cells. As a result, RAGE’s wide range of ligands allow this receptor to be associated with
a wide range of disease conditions including inflammation, diabetes and all its complications,
cancer, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Regular and continuous
consumption of foods rich in AGEs and advanced lipid oxidation products (ALEs) leads to accu-
mulation of these AGEs or ALEs in the body. AGEs or ALEs are known to weaken the immune
system and negatively influence resistance to diseases. AGEs also can induce the secretion of
vascular endothelial growth factor (VEGF), a major stimulator of pathological angiogenesis that
can cause cancer. RAGE has a key role as master switch regulating the development of chronic
degenerative diseases including cancer [50,51].
5.5 DIetArY APPrOACheS tO DIABeteS PreVeNtION
The primary goal of the dietary approach to diabetes is to prevent the development of dia-
betes macro- and microcomplications. To achieve this goal, dietary management of glycemic
level and hypertension is required. Since obesity and insulin resistance are central to the devel-
opment of diabetes, diabetes incidence can also be reduced by preventing obesity or weight
gain and insulin resistance with foods. And since the pancreas possesses a weak antioxidant
system, protecting the pancreas from oxidative stress is also paramount to preventing diabetes
development.
Obesity can best be prevented by avoiding low-nutrient, calorie-dense “junk” foods and AGE-
rich foods and opting for foods that provide enough calories and antioxidants for the day. To prevent
diabetes progression, dietary management of diabetes should take into consideration identifying
any dietary compound, dietary practice, or food processing method that puts diabetic individuals
at risk of developing complications. Caloric restriction involving a balanced diet containing appro-
priate amounts of carbohydrate, protein, and consumption and an increase in unsaturated fats and/
or protein has been reported to enhance body weight loss, improve insulin sensitivity and glucose
tolerance, and decrease cardiovascular risks.
Foods rich in fibers are good candidates for calorie restriction. Foods rich in bioavailable anti-
oxidants are good candidates for pancreas protection against diseases. Unfortunately, these types of
foods are not often commercially available; however, because ingredients are available the best way
to prevent obesity development is for individuals to design their own menus. A balanced diet that
encompasses caloric restriction, antioxidants, and β-cell protecting compounds can do very well to
prevent the development of diabetes. This can also apply to individuals who are genetically prone
to develop diabetes.
5.5.1 Dietary Approach to Prevent t1DM Progression
T1DM has no cure or known way to prevent it. In T1DM, there is an autoimmune destruction
of the insulin-producing β-cells of the pancreas. Oxidative stress is a characteristic of T1DM and is
the result of chronic hypoglycemia that induces an increase in inflammation and a damaging effect
on β-cells. In T1DM, inflammation becomes central to the disease progression. If inflammation
is central or partially central to T1DM, then bioactive dietary metabolites that can reduce inflam-
mation to its physiological level should be investigated for their potentials to prevent further β-cell
destruction.
The gut microbiota may play a role in the pathogenesis of T1DM [52,53], suggesting that
improving the gut microbiota in individuals at risk and T1DM patients should improve the health
of T1DM patients. Consumption of prebiotics and ingestion of probiotics may then help reduce the
risk of T1DM development. The food industry can focus on technologies to deliver prebiotics to the
gut. Dietary fiber, oligosaccharides, dietary pectin from lemon peel, apple skins, plum peel, mango
peel, and others can alter the microbiota and promote the development of healthy gut. While there
has been an emphasis on antioxidants, foods for individuals with diabetes should address the AGEs
load. The reason is that most antioxidants are not AGE breakers.
The foods for individuals with diabetes should be AGE-free, and full of AGE breakers and
antioxidants. Bitter melon or bitter gourd or bitter squash (Figure 5.1), fenugreek (Figure 5.2),
African bitter leaves, amaranth leaves (Figure 5.3), dandelion (Figure 5.4), Chinese Gai Lan
(Figure 5.5), and a combination of bitter melon–pomegranate–lima beans–dandelion (Figure 5.6)
to name a few that have been and continue to be used in complementary medicine are all bitter
and unappealing to our sweet taste. Studying the mechanism by which these ingredients protect
β-cells from oxidizing compounds should lead to developing commercially available food prod-
ucts for individuals with T1DM.
Figure 5.1 Bitter melon is bitter but very good for diabetes management.
Figure 5.2 fenugreek seeds have been used in India for generations to manage diabetes. the seeds can be
boiled for a unique and pleasant tea that contains proteins, peptides, carbohydrates, and saponins
and other bioactive compounds.
T1DM is an autoimmune disease; prevention or treatment of T1DM will require a meticulous

manipulation of immune response and interactions. The amino acid tryptophan, commonly found
in soybean, turkey, chicken, and salmon, is metabolized into the compound nicotinamide adenine
dinucleotide (NAD) that provides dramatic therapeutic benefit for rheumatoid arthritis, T1DM, mul-
tiple sclerosis, colitis, other autoimmune diseases, and schizophrenia in either the clinic or animal
models [54]. There is strong evidence that vitamin D reduces the risk of autoimmune diseases such
as T1DM better than T2DM [55]. Fish rich in omega-3-fatty acids such as wild salmon (Figure 5.7),
sardines (Figure 5.8) or unsalted herring (Figure 5.9), avocado (Figure 5.10), and seaweed are good
foods for individuals suffering from T1DM.
Hypoglycemia is a characteristic of long-standing T1DM and a major risk factor for T1DM
complication and fatality. Recent studies conducted in Florida reported on one patient with T1DM
Figure 5.3 amaranth leaves are rich in anthocyanins and squalene; both are good for diabetes management.
Figure 5.4 Dandelion leaves are good source of anthocyanins and other bioactive compounds that are good
for diabetes.
who successfully added ground grapefruit rinds to his diet and for about 4 years now is in good
health [56]. It was suggested that “evaluating the ability of GRAS agents to enhance glycemic con-
trol, and/or improve anti-inflammatory/antioxidant/immuno-regulatory status, could identify a safe
and cost-effective approach to improving lives and perhaps attenuate disease-associated complica-
tions.” Grapefruit rind is rich in pectin, a carbohydrate that we have suggested for improved insulin
sensitivity. Grapefruit rind is also rich in flavonoids, furanocoumarins, and hydroxycinnamates,
which are good antioxidants. It was suggested that “GRAS therapies (if successful) could provide
a relatively low-cost improvement to this extensive armamentarium, both in the United States and
other developed countries, as well as in third world nations in dire need of cost-effective improve-
ments in diabetes care.”
Figure 5.5 Chinese Gai Lan is a good vegetable for diabetes.
Figure 5.6 Combination of bitter and bioactive compound–rich foods including bitter gourd, lima beans,
pomegranate, and dandelion as a meal for diabetes management.
Pesticide-free apple skins and lemon peel (Figure 5.11) should be added to the list of GRAS for
enhancing glycemic control in T1DM patients. Apple skins would add pectin for glycemic control
and quercetin as a potent antioxidant. Lemon peel would also serve as an excellent source of pectin
for glycemic control, and auraptene for inhibiting hypoxia and the enzyme matrix metalloproteinase
that degrades tissue matrix. Adding grapefruit rinds, apple skins, or lemon peel in small amounts
to foods could provide low glycemic index and resolve hypoglycemia better than glucose tablets,
Mentos dragees, or orange juice used at 0.3 g carbohydrate per kg body weight and reported to
resolve hypoglycemia in children within 15 min [57].
Figure 5.7 Wild salmon is a good source of omega-3-fatty acids.
Figure 5.8 sardines are good source of omega-3-fatty acids.
The steps to prevent episodes of hypoglycemia should include the following:

1. Providing daily protection to β-cell function against oxidizing species and inflammatory agents that
penetrate the islet β-cells
2. Preserving remaining β-cell function in people with new onset of T1DM
3. Restoring β-cell mass and function by altering the autoimmune process directed against β-cells
4. Managing the autoimmune process directed against the pancreatic islet β-cells by preventing further
degradation
5.5.2 Dietary Approach to help Prevent t2DM Progression
Several lines of evidence suggest that chronic inflammation is a mediator of T2DM development
[58–60]. Food plays an important role in diabetes development and complications. It is possible to
directly target the stimulators of inflammation and insulin resistance with the right foods to prevent
Figure 5.9 omega-3-fatty acids can also be obtained from herrings.
Figure 5.10 avocado is rich in bioactive compounds for diabetes health.
the development of insulin resistance and T2DM. The rationale of using foods more and more in
lieu of some drugs is that dietary approaches may carry less toxic side effects and benefit a large
number of people affected by prediabetes or T2DM. The contribution of different players including
the family doctor, food industry, restaurant, consumer, and government in diabetes development
prevention is discussed in the following.
5.5.3 the Family Doctor
Diabetes is most typically diagnosed at the doctor’s office. People listen to their doctors, physi-
cians can really help and are helping people at the prediabetes stage, or people with diabetes adopt
a healthy lifestyle for the rest of their lives. Physicians with knowledge in food science and nutri-
tion can assist prediabetic and diabetic patients in food choices. Nurses and dietitians with training
in food science and nutrition can assist prediabetic and diabetic patients in meal planning.
Figure 5.11 apple skin and lemon peel are rich in phenolic compounds.
5.5.4 Food Industry
T2DM is a global disease that affects rich and poor in every country in the world. Today, people
rely more on the food industry for food ingredients and products. The food industry including the
restaurant industry develops food ingredients, ready-to-eat foods, and meals. To deliver safe, effec-
tive, high-quality, cost-effective foods to individuals with diabetes, an in-depth redesign of the
food ingredients and food products are needed. At present, several food ingredients or products
commonly used for human foods are proinflammatory because of their high levels of AGEs/ALEs
[61–66] or reducing sugars. Regular consumption of foods from these ingredients establishes a
state of chronic inflammation that affects the liver, muscle, and adipose tissue and promotes insulin
resistance.
Physical activity after consuming energy-dense or AGE-loaded meals will not alone solve the
inflammatory conundrum. Therefore, the food industry has to adjust to the new paradigm of human
health and start developing food ingredients and products that are really anti-inflammatory and
protect β-cells for prediabetics, people with diabetes, and the general population. However, the food
industry has been very careful in following the research trends to avoid any backlash. Since pancre-
atic β-cells are very susceptible to oxidative stress, research and product development using cereal,
dairy, fruit and vegetable, meat, or oil products should aim at avoiding technologies that develop
foods known to induce oxidative stress and inflammatory effects on β-cells.
Insulin resistance is the hallmark of T2DM and an important target in the fight against diabetes
development. There is a need for low glycemic foods and beverages. The use of reducing sugars in
foods for human consumption should be significantly reduced or phased out because the increased
incidence of insulin resistance associated with these types of sugars. The use of fructose-rich sugars
including honey and Agave in food product development to generate flavor in cereals, bread, or other
cooked food products should be discouraged and food companies may have to voluntarily phase out
these ingredients. The notion that fructose-rich sugars have low glycemic index does not respond
to the new understanding of the contribution of fructose-rich ingredients to the Maillard reaction.
The industry needs to develop more foods that improve insulin sensitivity. Fenugreek seeds and
leaves, amaranth seeds and leaves, finger millet, grape leaves, apple skins, lemon and grapefruit peels
are good ingredients for developing foods for people with diabetes. Fish oil rich in omega-3-fatty
acids is known for improving the immune system. Atlantic Cod, pike, haddock, pacific salmon,
Figure 5.12 safflower oil has a high smoke point and is good for all people including those with diabetes.
tuna, perch, trout, sardines, mackerel, and unsalted herring are excellent sources of omega-3-fatty
acids that should be in supermarkets for people with diabetes and the general population [67].
Cooking oils including safflower, olive, avocado, coconut, canola, and flaxseed are the best oil
to develop healthy diabetic diets (Figure 5.12). Extra virgin olive oil (Figure 5.13) has several health-
enhancing bioactive compounds including tyrosol and hydroxytyrosol that have anti-inflammatory,
antiangiogenic, antiglycating, and hypoglycemic activities, both of which are essential for diabetes
management [68,69].
Palm oil is the worst cooking oil for individuals with diabetes and should be discontinued and
banned for all diabetic and nondiabetic individuals (Figure 5.14). India has problems with it [70,71]
and so are some people in the rest of the world [72–74]. Others support its use [75,76]. The β-carotene
present in the oil may not match the deleterious effects of palmitic acid. Labeling raw nuts, dark-
green vegetables, and low-sugar fruits as “Good for diabetes management” when cooked with-
out excessive heat and unnecessary oil will help individuals with diabetes adopt healthy cooking
practices.
5.5.5 the restaurant Industry
The restaurant industry largely depends on ingredients from the food industry to develop meals.
It is therefore important that incoming ingredients are not already proinflammatory. It is also very
important that foods prepared in restaurants do not promote oxidative stress. It is becoming impera-
tive for people in the restaurant industry to understand basic food chemistry in order to be able to
Figure 5.13 extra virgin olive oil.
understand and develop healthy recipes and meals for customers. For instance, an understanding
of the levels of AGEs in cheese should help restaurant personnel reduce or avoid adding cheese
on every dish. The same applies to butter, peanut butter, or any nut butter developed using high-
temperature roasted peanut or nut. The same applies to bacon and honey. Consumers should not
always be expected to know better, the food provider should also participate in helping customers
eat healthy. The mere idea that food has to taste sweet, grilled, or crispy when it goes to the table is
not in line with the new concept of healthy eating. It is known that the food we eat goes far beyond
the taste bud; an understanding of the pathway of food components in human body should help
people in the restaurant industry cook and serve their customers better.
5.5.6 the Consumer
Increasingly, consumer education in healthy eating is becoming more and more important
in daily activities. If the consumer is well informed on how to identify unhealthy food ingre-
dients or products versus healthy ones and if there is enough affordable health products, the
consumer may resist or decline to buy the unhealthy foods. Unsold food products will be simi-
lar to unsold magazines and vendors will be forced to remove them and probably be reluctant
to restock them. Better products may then find their ways into the store. Similarly consumers
will learn to order healthy menus in restaurants and refuse to eat foods cooked with unhealthy
ingredients. It is interesting to note that the fetal origins of adult disease are so far more linked
to maternal nutrition than paternal nutrition [7,77–79]. Women of childbearing age need to be
aware of nutritional matters.
Figure 5.14 Palm oil is probably the worst cooking oil for individuals with diabetes.
5.5.7 Governments and Food research Institutions
At the present level of knowledge, government agencies should start stepping up to help more in
the fight for diabetes prevention and management. Putting warning labels on AGE-rich foods will
help consumers be cautious before making purchases. Diabetes is a costly degenerative disease and
all efforts should be made to prevent it from spreading across generations.
The effects of commonly available and consumed foods such as pizza, lasagna, and fried
chicken on insulin secretion need to be known. Although most people would not eat the same
foods every day of the week, the mere knowledge that one can eat different types of processed
foods and still ingest significant amounts of AGEs should serve as an indication that AGEs can
easily and quickly build up in the body. It is therefore important that research looks into how
laboratory animals respond to meals rich in AGEs seven days a week. In vivo, experiments
showed that feeding euglycemic rats and mice AGE albumin led to morphological lesions simi-
lar to lesions observed in diabetes nephropathy [80]. Since the pancreas is critical in food
digestion, the foods that enter the mouth must be of high quality and acceptable for a healthy
pancreas.
Innovation in food technology equipment is needed to replace technologies that develop AGE-
rich food ingredients or cooking techniques that deliver AGE-rich foods to the gut. Similarly,
identifying foods that affect β-cells is better medicine than trying to treat symptoms as it is
often the case. It is more cost-effective to root out the risk factors of the disease than to treat the
symptoms.
5.6 DIetArY MANAGeMeNt OF t2DM tO PreVeNt COMPLICAtIONS
People with diabetes have a two- to fourfold risk of dying from CVD and increased prevalence
of hypertension, obesity, lipid abnormality, and vascular thrombosis [81]. Tight control of blood
glucose is essential to delay/prevent T2DM complications that often lead to substantial morbidity
and mortality. At the time of diagnosis about 50% of β-cell function has already been destroyed;
the ultimate goal of dietary management of T2DM should be to protect the activity of the remain-
ing active β-cells. The goal should also be to protect other body tissues by targeting traditional risk
factors including hyperglycemia, AGEs, inflammation, hypertension, lipid abnormalities, insulin
resistance, and immune system dysfunction.
Pancreatic β-cells can be protected by identifying foods or beverages that impair β-cell mass
and function. Pancreatic β-cells can also be protected by developing foods or beverages that are
β-cell-friendly and improve insulin sensitivity. Foods or beverages that address each one of the risk
factors are discussed in the following.
5.6.1 Controlling hyperglycemia through Caloric restriction
Poor glycemic control (elevated hemoglobin A1c [HA1c]) correlates with increased T2DM com-
plications including macro- and microvascular complications. Caloric restriction without malnutri-
tion including a change in macronutrient composition that emphasizes moderate consumption of
carbohydrates, unsaturated fats, protein, vitamins, and micronutrients should help maintain normal
weight, increase β-cell function, sustain insulin sensitivity, improve glucose control, prevent cardio-
vascular risks, slow aging, and increase lifespan. Tight glycemic control reduces the risk of vascular
and neurological complications of diabetes.
Foods that decrease insulin resistance, insulinotropic foods, and discipline in food selection
are critical in the etiology and management of diabetes. Nutrient-dense minimally processed and
microbiologically safe foods including whole grains, black and red beans, dark-green vegetables,
fish, briskets, AGE-reduced foods, egg whites, and low-fat dairy products can help achieve caloric
restriction and increase insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM)
individuals.
Eleven people with T2DM (49.5 ± 2.5 years; BMI 33.6 ± 1.2 kg/m 2; 9 male and 2 females)
were fed a 600 kcal/day diet for 8 weeks and evaluated for β-cell function and hepatic insulin
sensitivity. Over the course of an 8-week dietary restriction, β-cell function increased toward
normal, hepatic insulin sensitivity fell to normal, liver and pancreatic fat decreased, and HbA1c
remained steady suggesting that β-cell defect in T2DM is reversible by sustained negative
energy balance. The results of the study suggest that a return to normal β-cell function is pos-
sible in individuals with T2DM by restricting dietary energy intake. Participants with a BMI
of 30–40 were fed a very low calorie diet of 400 kcal/day for 7 days and showed significant
improvement in glucose control and β-cell function [82]. Foods that decrease insulin sensitivity
include fast foods and AGE-rich foods, which unfortunately are not good for individuals with
diabetes [83].
Some antidiabetic bioactive compounds reduce hyperglycemia by inhibiting α-glucosidase.
There are several naturally occurring compounds including adzuki beans (Vigna angularis), bean
sprout (Glycine max), blueberry (Vaccinium corymbosum), black currants (Ribes nigrum L), Cassia
alata act by inhibiting α-glucosidase [84].
5.6.2 Controlling AGes in Foods
AGEs/ALEs in the serum are directly linked to inflammation in diabetes. It is well established that
a big portion of exogenous AGEs are absorbed in the body suggesting that diet low in AGEs/ALEs can
be a target for diabetes prevention and management [85–88]. It is also well established that more than
50% of people with diabetes are obese and insulin resistant. Most foods cooked or processed at tem-
perature higher than 310°F including roasting, grilling, broiling, searing, and frying are good sources
of AGEs or ALEs. Because people with diabetes already have abundant AGEs that they do not need,
consuming foods prepared at high temperature regardless of the portion size is not good for diabetes
management. For instance, briskets contain the lowest amounts of AGEs among meat products. The
food industry as well as individuals with diabetes should adhere to foods cooked slowly like briskets.
Diabetes is a very challenging disease because it is the hallmark of both excessive and insufficient
angiogenesis [89–92]. Food scientists have an opportunity to redesign foods that have very low levels
of AGEs or are AGE-free and use other naturally occurring flavoring materials and do not rely on
AGEs or caramel to generate acceptable flavors in foods. Chefs and those involved in the restaurant
industry can still generate revenues through healthy offerings. Avoiding unnecessary high temperature
and unsafe oil cooking in meals can significantly reduce AGE levels in foods. Developing tasty menus
that are not necessarily charred, seared, or broiled can also help reduce AGEs in restaurant meals.
5.6.3 Oxidative Stress and Inflammation
Hyperglycemia induces AGEs, which induce proinflammatory markers. Research has shown
that essential oil rich food ingredients such as lemon grass and lemon oil are good anti-inflamma-
tory compounds. Other studies have shown that foods such as onion, apple skins, or ginger that are
rich in quercetin are good for the health of individuals with diabetes. Green tea epigallocatechin
gallate (EGCG) is effective in protecting against inflammation-mediated pancreatic β-cell destruc-
tion [93,94]. These findings suggest that proper use of green tea or other foods could provide an
effective means of preventing diabetes progression.
The health benefits of ellagic acid, a metabolite of ellagitannin, found in high levels in musca-
dine, pomegranate juice, walnut, and raspberry have been reported and suggest that ellagic acid
inhibits inflammation in pancreatic stellate cells that play a pivotal role in the pathogenesis of pan-
creatic fibrosis and inflammation [95]. Ellagic acid and caffeic acid, a metabolite of chlorogenic
acid found in raw sunflower seeds, inhibit AGE formation and inflammation in the kidney and
provide protection to kidney cells, suggesting that similar protection can be provided to β-cells
[96]. Muscadine (Figure 5.15) is the best source of ellagic acid whose health benefits on diabetes
Figure 5.15 Muscadine is an excellent source of ellagic acid, which has shown health-enhancing properties
for diabetes.
should be mentioned or investigated. T2DM patients were assigned to drink 150 mL of muscadine
wine for 28 days. The diabetic individuals showed better glycemic control as evidenced by lower
levels of blood glucose, insulin, and glycated hemoglobin [97]. Ellagic acid has shown to be a good
antiglycating dietary bioactive compound under ex vivo condition [98]. Since ellagic acid is bio-
available, consumption of ellagic acid–rich foods such as muscadine by diabetic patients should be
encouraged.
Protocatechuic acid, a metabolite of cyanidin-3-glucoside commonly found in berries, hibis-
cus, and black rice, suppressed the production of the proinflammatory and inflammatory mediators
in vitro and in vivo [99]. All these findings address the symptoms that are inflammation and β-cell
death and do not address the roots of diabetes development, which include hyperglycemia.
Various herbs and spices are discussed herein. For example, basil (Ocimum basilicum) is a
good source of ursolic acid that enhances skeletal muscle insulin/IGF-I signaling [100]. Ursolic
also reduced adiposity, fasting blood glucose, and plasma cholesterol and triglycerides. Aqueous
extracts of basil inhibited the formation of AGEs, which are associated with diabetes development
and progression [101]. Basil water extracts, which contained reducing sugars, cardiac glycosides,
tannins, saponins, glycosides, flavonoids, and steroids, may protect against diabetes by inhibiting
the activities of the enzymes α-amylase and α-glucosidase [102].
Ginger (Figure 5.16), the rhizomes of Zingiber officinale Roscoe (Zingiberaceae) including gin-
ger oil, is a good source of several bioactive antioxidant, antimicrobial, anti-inflammatory, immu-
nomodulator, and antineoplastic compounds including gingerols, shogaols, paradols, zingerone,
phenolics, and several terpenes, all of which are beneficial for preventing diabetes progression.
The anti-inflammatory activities of ginger bioactive compounds individually or as a mixture have
been established in vitro and in vivo [103–105]. Gingerols enhance insulin sensitivity; gingerol and
shogaol inhibit α-glucosidase and α-amylase; these two enzymes are very important for T2DM
management [106]. T2DM patients (N = 72) were enrolled in a 12-week double-blind, placebo-
controlled clinical trial and were allocated randomly into the ginger group and control group [104].
Participants consumed 1600 mg ginger versus 1600 mg wheat flour placebo daily. Participants on the
Figure 5.16 Ginger is a good source of several anti-inflammatory bioactive compounds including gingerol.
Figure 5.17 onion is a good source of the bioactives quercetin and kaempferol, both of which are good for
improving diabetes.
ginger group had significantly reduced levels of fasting plasma glucose, HbA1C, insulin, HOMA,
triglyceride, total cholesterol, CRP, and PGE2 compared to the placebo group (p < 0.05). However,
the two groups show similar levels of HDL, LDL, and TNF-α. In another study, 64 T2DM patients
were randomly assigned to ginger or placebo groups and consumed two tablets per day of ginger
or placebo for 2 months [105]. Results showed that participants on ginger showed reduced levels of
TNF-α, IL-6, and hs-CRP compared to the placebo group. However, the levels of IL-6 remained
unchanged in both groups after the ginger or placebo intervention.
Onion (Allium cepa L) (Figure 5.17) is one of the best sources of sulfur containing compounds
such as S-methylcysteine and flavonoids such as quercetin and kaempferol known for their anti-
oxidative activities. Onion improves hypoglycemia in diabetes through its sulfur containing com-
pounds and flavonoids [107]. These bioactive compounds also improve blood glucose, serum lipids,
oxidative stress, and lipid peroxidation, as well as antioxidant enzyme activity and insulin secre-
tion. Extracts of onion normalize the activities of liver hexokinase, glucose 6-phosphatase, and
HMG coenzyme-A reductase, which improve hypoglycemia and hypolipidemia. T1DM and T2DM
patients consumed 100 g of crude onion and 4 h later there was a significant reduction in fasting
blood glucose in both T1DM and T2DM patients [108]. Onion also improved hypoglycemia in both
types of patients.
Saffron (Crocus sativus L) (Figure 5.18) contains the yellow water-soluble diterpenic carotenoid
crocetin (8,8′-diapo-8,8′-carotenoic acid). Crocetin enhances the oxygen diffusivity through liquids,
such as plasma, inhibits inflammation, is neuroprotective, and has been suggested to alleviate cog-
nitive dysfunction in in vitro and animal models [109–111].
Soybean, fenugreek, lima beans, quinoa, barley, and wheat contain the bioactive protein
Bowman–Birk inhibitor (BBI) [112–114] and the peptide lunasin [115–117], which are anti-
inflammatory. Soybean also contains isoflavones. Genistein improves oxidative stress, obesity, dia-
betes, inflammation, osteoporosis, and neuropathy [118]. Soybean is a good source of α-linoleic acid.
Studies have shown that for each 1 g/day increase in dietary ALA, there was a 10% reduction in the
risk of CVD death [119]. Edamame is soybean. The effects of soybean intake on postload plasma
glucose, fasting plasma glucose, and the incidence of T2DM were investigated through the cohort
study that looked at 4318 individuals, aged 30–69 years, who underwent a baseline comprehensive
medical check‐up over 2 days and 1 night between April 2006 and March 2007 at Saku Central
Hospital, also known as the Saku Study [120]. Participants consumed soybean, tofu, freeze-dried
Figure 5.18 saffron is the source of the carotenoid crocetin and has good antidiabetic activities.
tofu, deep-fried tofu, and natto (fermented soybeans) in a portion size of 100 g. Consumption of
milk, egg, fish, meat, fruits, vegetables, and grain intakes at baseline also was assessed. The results
suggest that for men with high body mass index (BMI) of 21.6, intake of soybean various products
was associated with reduction of fasting and postload hyperglycemia. The oligosaccharides of soy-
bean have an antidiabetic effect. Pregnant women (N = 97) with GDM were randomly assigned to
soybean oligosaccharide (N = 51) or placebo (N = 46) [121]. Participants assigned to soybean oli-
gosaccharide consumption also received insulin treatment while the placebo only received insulin
treatment. Soybean oligosaccharide improved insulin resistance in the participants.
Soymilk contains proteins, oligosaccharide, phytic acid, and divalent cations. T2DM patients
with kidney problems (N = 29) were enrolled in a randomized, crossover, and controlled clinical
study whereby they consumed soy milk–rich diet or a cow’s milk–rich diet [122]. There was a
2-week washout period between the soybean and the cow’s milk intervention. Participants on soy
milk improved their blood pressure compared to participants who were on cow’s milk.
Quinoa (Chenopodium quinoa Willd.) (Figure 5.19) is a good source of quercetin, which has
a known antidiabetic effect [123]. Quinoa has been recommended to be incorporated in the diets
of individuals who may be at a high risk of developing T2DM such as Asian Indians living in the
United States, Canada, the United Kingdom, and other parts of Europe [124].
Fenugreek contains BBI, lunasin, hydroxyisoleucine, saponins, and galactomannans. Fenugreek
saponins were given to 46 T2DM patients whose blood glucose levels were not well controlled
by oral sulfonylureas hypoglycemic drug and 23 T2DM that made the control group [125].
Participants took six pills three times a day for 12 weeks. Patients also took original hypoglyce-
mic drugs. The combination of fenugreek saponin and hypoglycemic drug improved blood glucose
and other clinical symptoms associated with T2DM. Fenugreek bread improved insulin sensitivity.
Similarly, fenugreek-enriched cookies should have health-enhancing properties. Restaurants may
develop fenugreek-enriched baked goods for diabetic and prediabetic customers.
The antidiabetic effects of mung bean (Phaseolus aureus, Vigna radiatus) have also been
reported [126]. The beans have the highest tyrosinase inhibitory activity of most legumes [127].
Figure 5.19 royal black quinoa contains the anti-inflammatory protein BBI.
The antidiabetic activity of adzuki beans is in part associated with the bean higher α-glucosidase
inhibition activity compared to other legumes [127] and possibly its high content of procyanidins.
5.6.4 triglyceride Control/Lipid Abnormalities
Triglyceride (TG) control is very critical because triglycerides and LDL are major contributors
to diabetes-related coronary heart disease death. Triglyceride control can be achieved with caloric
restriction [128]. Foods that lower triglycerides in diabetic individuals are beneficial for this group
because triglycerides enhance the risk for myocardial infarction [129,130]. Niacin lowers triglyc-
erides and increases HDL [131]. Foods rich in omega-3-fatty acids such as mackerel, anchovies,
sardines, and seaweed lower triglycerides [132].
It is thought that spices including ginger (Zingiber officinale), fenugreek (Trigonella foenum),
curcumin (Curcuma longa), curry seeds (Murraya koenigii), red pepper (Capsicum frutescens L),
black pepper (Piper nigrum), black seed (Nigella sativa), tamarind (Tamarindus indica), cinnamon
(Cinnamomum verum), cardamom (Elettaria cardamomum), coriander (Coriandrum sativum), gar-
lic (Allium sativum), onion (Allium cepa), and seaweed when used in proper amounts and under the
proper conditions that do not involve high-temperature treatment should lower triglycerides.
Ginger is a spice with several health-enhancing benefits. Bordia et al. [133] administered a
single dose of 10 g of ginger to patients with coronary artery disease and reported a significant
reduction in platelet aggregation and no effect on blood lipids and blood sugar. Ginger administered
in a dose of 2.5 g twice daily for 3 months to coronary artery patients with NIDDM decreased tri-
glycerides and total cholesterol without affecting HDL-v. The same dose administered to NIDDM
patients reduced fasting and postprandial sugar.
Fenugreek seeds and leaves (Figure 5.20) have been used for diabetes management for cen-
turies in India. Twenty-five newly diagnosed patients with T2DM (fasting glucose < 200 mg/dL)
were randomly divided into two groups: those in group I (N = 12) received 1 g/day hydroalcoholic
extract of fenugreek seeds for 2 months and those in group II (N = 13) served as control and received
placebo capsule and usual care. Patients in group I treated with fenugreek extract show a signifi-
cant decrease in triglycerides and a significant increase in HDL cholesterol as compared to control
group (p < 0.05) [134]. Consumption of two slices of fenugreek bread improved insulin sensitivity
in T2DM patients [135]. The literature is also full of animal studies from dogs to rats in which the
Figure 5.20 fenugreek seeds and leaves for diabetes management.
mechanisms of fenugreek management of dyslipidemia and its associated metabolic disorders are
provided. Fenugreek leaves are commonly used in India and can be ordered in Indian restaurants.
The antidiabetic effects of the leaves in animal models of diabetes included improvement of hyper-
glycemia, hypoinsulinemia, hemoglobin glycation, body weight, liver glycogen, and lipid profile,
and carbohydrate metabolic enzymes were similar to the effects of glibenclamide [136,137].
Curcumin is one of the health-enhancing bioactives in turmeric (Figure 5.21). Twenty-four
healthy subjects, 16 males and 8 females with mean age of 29.3 ± 5.4 years and BMI of 22.7 ±
3.3, divided in two groups, consumed 500 mg and 6 g of curcuminoids (a mixture of curcumin,
dimethoxycurcumin, 5′-methoxycurcumin, and dihydrocurcumin) per day for 7 days, respectively
[138]. Supplementation of 500 mg curcuminoids per day was effective in reducing serum choles-
terol or triglyceride. In another study, elderly subjects (N = 36) consumed 4 g/day curcumin, 1 g/
day curcumin, or placebo in a 6-month, randomized, double-blind trial [139]. Curcumin consump-
tion at 4 or 1 g/day had no effect on triacylglycerols, or total, LDL, and HDL cholesterol over 1 or
Figure 5.21 Curcumin is obtained from turmeric, a popular ingredient in Indian cuisine.
6 months, but plasma curcumin positively and significantly correlated with serum cholesterol sug-
gesting that curcumin may increase cholesterol.
It was suggested that high levels of curcumin may not be good for cholesterol. Indians generally
use very small amounts of spices including curcumin in their cooking but often use a combination
of spices. In another small pilot study in which eight individuals consumed 10 mg of curcumin per
day for 30 days, it was reported that curcumin increased HDL cholesterol, decreased LDL choles-
terol, and increased APO A but decreased APO B and APO A/B [140]. Recent literature has been
praising curcumin as the answer to human disease [141,142]. However, in-depth in vivo analysis
of curcumin has shown that tetrahydrocurcumin is curcumin metabolite that is associated with
the health benefits of curcumin and tetrahydrocurcumin is more potent than its parent compound
[143–145].
Red hot pepper (Capsicum) (Figure 5.22) is the major source of capsaicinoids, mixtures of
capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin.
Capsaicin is a ligand for vanilloid receptor 1. Oral administration of 1–24 µg of capsaicin to NOD
mice protected the mice from developing T1DM by attenuating the proliferation and activation
of autoreactive T cells in pancreatic lymph nodes (PLNs) and enhancing a discreet population of
CD11b(+)/F4/80(+) macrophages in PLN, which express anti-inflammatory factors interleukin (IL)-
10 and PD-L1 [146]. The authors observed that oral administration of CP, which impinges on the
gut lymph node, was essential to show an immunosuppressive effect, while other routes such as
intradermal or cutaneous administration were not effective.
Male KKAy mice fed a high-fat diet for 2 weeks which received a 0.015% capsaicin supplement
for a further 3 weeks showed increased expression of adiponectin gene/protein and its receptor
AdipoR2, in adipose tissue and/or plasma, accompanied by increased activation of hepatic AMP-
activated protein kinase, a marker of fatty acid oxidation [147]. Forty women and 40 men aged
42 ± 8 years and BMI of 30.4 ± 2.4 were randomly assigned to oral ingestion of 6 mg/day caps-
inoids (capsiate, dihydrocapsiate, and nordihydrocapsiate) or placebo per day. Capsinoids consump-
tion was associated with fat oxidation and abdominal fat loss [148]. Capsaicin may promote energy
metabolism and suppress fat accumulation.
Black pepper contains the bioactive component piperine, which inhibits lipid oxidation in car-
rageenan-induced rat paw edema [149]. Piperine is good for preventing diabetes progression [150].
Figure 5.22 red hot pepper is anti-inflammatory and good for diabetic condition.
Piperine reduced symptoms of human metabolic syndrome in high-carbohydrate-, high-fat-fed rats

by reducing inflammation and oxidative stress [151].
Coriander seeds fed to rats on high-fat and high-cholesterol diet significantly reduced the lev-
els of “bad” cholesterol and significantly increased the levels of “good” cholesterol, β-hydroxy,
β-methyl glutaryl CoA reductase, and plasma lecithin cholesterol acyl transferase activity compared
to control animals. The hypocholesterolemic effect of coriander seeds was ascribed to enhanced
hepatic bile acid synthesis and the increased degradation of cholesterol to fecal bile acids and neu-
tral sterols [152,153].
Cinnamon (Figure 5.23) is good for diabetes management, although results from cinnamon are
controversial [154]. Thirty men and 30 women with an average age of 52 and all suffering from
T2DM were divided into six groups. Individuals in groups 1, 2, and 3 consumed 1, 3, or 6 g cin-
namon for 40 days and the others were given placebo [155]. The results indicate that cinnamon at
1, 2, or 3 g reduced triglyceride by as much as 30%, LDL cholesterol by as much as 27%, and total
cholesterol by 26%. However, there are several reports that show that cinnamon supplementation
does not improve glycemic control in postmenopausal T2DM patients [156] and has antihypergly-
cemic properties and potential to reduce postprandial blood glucose levels, but more clinical studies
may be needed [157].
Cinnamon improves fasting glucose and has shown improvement in cholesterol levels and sys-
tolic blood pressure, insulin sensitivity but some studies have shown no beneficial effects [154].
The health benefits of cinnamon may not be well realized when cinnamon is delivered in AGE-rich
foods like cinnamon buns or used in very small amounts.
Garlic and onion contain thiosulfinates, volatile sulfur–containing compounds, S-allylcysteine
sulfoxide, S-methylcysteine sulfoxide, diallyl trisulfide, and heat-stable phenolic and steroidal com-
pounds. A 12-week study in which 33 T2DM patients consumed 300 mg garlic tablet containing
1.3% allicin twice a day showed a statistically significant increase in HDL and decrease in LDL
[158]. Welsh onion fibrous root extract (500 mg/kg) or acarbose (50 mg/kg) with a starch solu-
tion (1 g/kg) was administered to streptozotocin-induced diabetic rats after an overnight fast [159].
Welsh onion extract was as effective as acarbose in reducing hyperglycemia and glycated hemoglo-
bin in animal models of diabetes mellitus. Onion is also a good source of quercetin and kaempferol.
Quercetin modulates adipose tissue inflammation in diabetes [160].
Figure 5.23 Cinnamon is a good source of procyanidins and has health benefits for diabetes.
Anise restores liver superoxide dismutase (SOD), catalase, and glutathione and lowers oxidative
stress in diabetic rats [161]. Star anise is a good source of quercetin and gallic acid, both of which are
potent antioxidants and metabolites that can exert their efficacy in vivo [162]. Star anise has insulin
secretagogue activities [163].
Sage (Salvia officinalis) (Figure 5.24) leaves contain terpenes including rosmarinic acid, car-
nosic acid, carnosol, thujone, viridiflorol, oleanolic acid, α-linolenic acid, and 12-O-methyl carnosic
acid. Sage leaves are commonly used as a remedy for diabetes in many countries. The blood glucose
and triglyceride-lowering effects of sage in diabetes may be ascribed to nuclear receptor PPAR-γ
activation by sage terpenes [164,165]. PPAR-γ activators also have anti-inflammatory and antitumor
effects and sage terpenes exhibit all these health benefits. Sage improves lipid profile in T2DM
individuals [166].
Rosemary (Rosmarinus officinalis) (Figure 5.25) is a good source of carnosic acid that stimu-
lates glucose in skeletal muscle [167]. Carnosic acid has antiglycating and antioxidative properties.
Figure 5.24 sage is a good source of anti-inflammatory terpenes.
Figure 5.25 rosemary is good for diabetes and can be made into tea.
Figure 5.26 seaweeds contain health-enhancing bioactives that are not present in terrestrial foods that mod-
ulate metabolic enzymes linked to diabetes.
It inhibits α-amylase and α-glucosidase [101]. Carnosic acid and carnosol are anti-inflammatory and
glucose-lowering effect [164].
Seaweeds (Figure 5.26) are good for individuals with diabetes. Seaweeds contain several
bioactive compounds including fucoidan, carotenoids, polyphenols/phlorotannins, phycobilip-
roteins, peptides, special lipids, and amino acids, all of which can inhibit α-glucosidase and
α-amylase and other metabolic enzymes linked to diabetes [168–170]. Nine men and 11 women
with T2DM controlled by diet and/or oral hypoglycemic agents, body mass index of <35 kg/m 2,
fasting plasma glucose concentrations >150 mg/dL (150–300 mg/dL), not consuming lipid-low-
ering drugs, age 40–70 years old, and in good health were fed a total of 48 g of seaweed contain-
ing equal parts of sea tangle and sea mustard three times a day for 4 weeks [171]. The men and
women performed other daily activities. Seaweed supplementation increased dietary fiber intake
and resulted in lower levels of TG, higher levels of high-density lipoprotein–C (HDL-C), and
decreased levels of fasting blood glucose and 2-h postprandial blood glucose in patients receiv-
ing seaweed supplementation, but there were no significant differences in controls. Alaskan sea-
weed inhibited the activity of the enzymes α-glucosidase and α-amylase, two enzymes associated
with serum glucose [169].
Sweet potato tuber (Figure 5.27) is a source of α-lipoic acid and sweet potato leaves are a source
of lutein. The multipotent liposoluble antioxidant α-lipoic acid improves glycemic control and poly-
neuropathies associated with diabetes mellitus, chelates transition metals, inhibits free radicals,
increases cytosolic glutathione and vitamin C, and reduces oxidative stress, making it one of the
most recommended bioactives for diabetes management [172]. The health benefits of lutein against
macular degeneration have been established. Sweet potato leaves are an excellent source of lutein
[173]. Beef or lamb liver is also a good source of the liposoluble antioxidant α-lipoic acid suggesting
that consumption of beef or lamb liver can provide a significant amount of lipoic acid to the diet.
Other sources of lipoic acid include spinach, yam, broccoli, tomato, Brussels sprout, carrots, red
beets, and rice bran.
Figure 5.27 sweet potato is a good source of lipoic acid and a good food for diabetes.
Ethnopharmacological research on diabetes treatment suggests that bitter, astringent, and tart
foods are good for β-cells and improve insulin sensitivity. It is suggested to put emphasis on incorpo-
rating these compounds in the diets of individuals with diabetes [174–182]. Asparagus, bitter melon,
fenugreek seeds and leaves, African bitter leaves, and dandelion, for instance, may be grown on a
large scale, appropriately processed, and sold in grocery stores to help people with diabetes. The
mechanisms by which these foods improve diabetes include increasing insulin secretion, enhanc-
ing glucose uptake by adipose and skeletal muscle tissues, inhibiting intestinal glucose absorption,
and inhibiting hepatic glucose production [183]. Bitter melon (Momordica charantia) also acts by
inhibiting 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity in adipose tissue [184].
Ethanolic extracts of fenugreek significantly decreased the IL-1α, IL-1β, IL-2, IL-6, and TNF-α
levels in inflamed tissues of albino rats treated with Freund’s adjuvant to induce arthritis [185]. Fenugreek
diosgenin inhibited LPS-induced macrophage-derived inflammatory mediators through the downregu-
lation of IL-1β, CK2, JNK, NF-κB, and AP-1 activation [186]. Fenugreek is a unique legume that
contains the insulinotropic amino acid 4-hydroxy isoleucine (4-OH) whose efficacy has been shown
in vitro and in vivo. The uniqueness of 4-OH isoleucine lies in its ability to stimulate β-cell function and
reduce insulinemia in animal models [187]. There is no confirmation of the effects of 4-OH isoleucine
in humans; however, whole fenugreek is consumed throughout the world to manage diabetes [135].
Spices mentioned earlier are also pancreatic β-cell-friendly. Cranberry is probably the most
underestimated berry when it comes to diabetes prevention or management. Cranberry is not sweet
but has high levels of anti-inflammatory compounds that are pancreas-friendly. Anthocyanins, fla-
vonoids, proanthocyanidins, and the absence of sugar unlike other berries make cranberry one of
the best berries for individuals with diabetes [188–190].
5.6.6 hypertension
Hypertension or high blood pressure is a major risk factor for renal failure, stroke, retinopathy, con-
gestive heart failure, coronary artery disease, and peripheral vascular disease [81]. Controlling blood
pressure slows down the rate of organ and tissue failure. There is strong evidence that sodium chloride
consumption is a major factor for increased blood pressure. Tight control of blood pressure in individuals
Figure 5.28 Coffee.
with both T1DM and T2DM lowers the risk of strokes, heart attacks, and heart failure and slows the pro-
gression of diabetic renal disease. Angiotensin-converting enzyme inhibitors work on both T1DM and
T2DM, but apparently alone these inhibitors do not always work in some individuals [191,192].
Since it is difficult to control blood pressure with drugs alone and since salt that affects blood
pressure is of dietary origin, dietary management of salt intake may be the way to go. A reduction
in salt intake from the current 9–12 g/day, in most countries, to 3–4 g/day as recommended by
the World Health Organization for all adults significantly lowers blood pressure in both hyper-
tensive and normotensive individuals [193]. Lowering phosphorus intake to 500–1000 mg/day is
also good for avoiding diabetic nephropathy [194]. Most breakfast cereals and processed meats are
loaded with phosphates and are not good for individuals with diabetes and those who do not want
to develop diabetes or renal diseases.
Coffee (Figure 5.28) helps improve blood pressure in diabetic patients. Regular intake of
1–3 cups of coffee is inversely associated with risk of diabetes and cardiovascular effects [195]. In
the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe cohort study, cof-
fee consumption was inversely associated with the symptoms of the metabolic syndrome including
waist circumference, hypertension, and triglycerides [196].
5.6.7 Angiogenesis or the Formation or Absence of Blood Vessels
Angiogenesis inhibition in diabetes is complicated by the fact that both types of angiogenesis may
simultaneously exist in one single individual. VEGF, the hallmark of angiogenesis, is insufficient in
diabetic wounds that do not heal, and at the same time VEGF is excess in diabetic macular degenera-
tion. However, stimulators of angiogenesis such as the matrix metalloproteinases can be inhibited to
favor both insufficient angiogenesis and excessive angiogenesis. Ginger oil, lemon oil, orange oil, and
peppermint oil are very active at concentration that is physiologically reachable. The health benefits
of quercetin isorhamnetin and resveratrol against T2DM have been reported [197,198].
5.6.8 Immune Modulation
Studies have shown that imbalance in the gut microbiota may be associated with the
pathogenicity of T2DM. The immune system and diet are some of the main regulators of the
intestinal microbiota. Some interventions have shown that diets rich in prebiotics and probiot-
ics can reduce inflammation, endotoxemia, and cytokine levels and improve insulin resistance
and glucose tolerance leading to improvement of T2DM [199]. Low-grade inflammation can be
induced by obesity and lead to insulin resistance and the development of T2DM. Targeting obe-
sity-associated inflammation with nutraceuticals and functional foods can improve metabolic
syndrome including T2DM [200].
5.7 DeVeLOPING β-CeLL-FrIeNDLY BeVerAGeS FOr PeOPLe WIth DIABeteS
Reducing sugar-based sweetened beverages are not good for individuals with diabetes and for
preventing diabetes development. These include among others beverages sweetened with fructose-
based sweeteners such as Agave. Moringa oleifera, the widely cultivated species in India, is often
cited for its health benefits against diabetes and rheumatism (Figure 5.29). Moringa extracts are rich
in quercetin and kaempferol [201]. Quercetin at 15 mg/kg injected intraperitoneally for 3 days prior
to streptozotocin (STZ) administration preserved the integrity of pancreatic β-cells by decreasing
oxidative stress [202]. Consumption of whole cranberry, cooked Roma tomato, and tea, which are
rich in quercetin, should be encouraged for healthy β-cells.
While several berry types are rich in quercetin, preference should be given to fruits that pro-
vide low glycemic index such as cranberry and apple skins. Quercetin also improves nitric oxide
[203] and unsweetened quercetin-rich fruits or beverages should be good for improving erectile
function in diabetic individuals. Conjugated quercetin metabolites including quercetin glucuronides
Figure 5.29 M. oleifera leaves.

and sulfates accumulate in the plasma after the intake of foods rich in quercetin glycosides and
the conjugates display significant antioxidative properties [204]. Quercetin is also bioavailable as
is or metabolized into isorhamnetin and both are good antioxidants in vivo. An interesting finding
for functional food applications is that quercetin enhances bioavailability, may reduce toxicity and
excretion of toxic drugs such as irinotecan by inhibition P-glycoprotein [205].
Similarly, Choi et al. [206] reported that quercetin at 6–15 mg/kg enhanced doxorubicin
(50 mg/kg) absorption in rat gastrointestinal tract after oral administration via quercetin-induced
inhibition of permeability glycoprotein (P-gp) or multidrug resistance protein and reduced the first-
pass metabolism of doxorubicin due to quercetin-induced inhibition of CYP3A, a protein very criti-
cal for drug metabolism by humans, in the small intestine and/or in the liver rather than reduced
renal and/or hepatic elimination of doxorubicin. Myricetin inhibited CYP3A4 enzyme activity with
50% inhibition concentration of 7.8 μM and enhanced the bioavailability of doxorubicin by the
same mechanism as quercetin [207]. But quercetin bioavailability may be reduced by interaction
with proteins such as ABCG2 that transport various molecules across extra- and intracellular mem-
branes. Kaempferol may enhance quercetin bioavailability by interacting with ABCG2 [208]. This
suggests that if these results can be translated to humans, quercetin or myricetin may enhance the
retention of bioactive compounds in the human body and should be promoted in foods for health
applications.
Cinnamon is a rich source of water-soluble procyanidin A, known to be good for T2DM (Figure
5.23). Cinnamon tea is a very delicious and a simple idea that the food beverage industry can offer
for people with diabetes and those without diabetes. Cinnamon tea is sweet and would be easily
accepted by those who value sweetness more than anything else.
Cardamom (Elettaria cardamomum) tea is delicious (Figure 5.30). Cardamom is a good source
of indole-3-carbinol (I3C), known for its antioxidative and antiproliferative activities. I3C is bio-
available and can metabolize into 2(indol-3-ylmethyl)-3,3′-diindolymethane), which also has anti-
proliferative activities. Cardamom powder, 1.5 g twice a day, effectively reduced blood pressure,
enhanced fibrinolysis, and improved antioxidant status, without significantly altering blood lipids
and fibrinogen levels in stage 1 hypertensive individuals [209].
Hibiscus sabdariffa L. and H. rosa-sinensis L., or vitifolius flowers (Figure 5.31), are very rich
in phenolic acids such as protocatechuic acid, flavonoids, and anthocyanins. Hibiscus tea is dark red
Figure 5.30 Cardamom contains I3C and has antiglycation properties.

Figure 5.31 Hibiscus is a good source of anthocyanins and protocatechuic acid.
Figure 5.32 Green tea.
and has been used in folk medicines for the treatment of hypertension and inflammatory conditions,
atherosclerosis, liver disease, cancer, diabetes, and other metabolic syndromes [210–212].
Green tea (Figure 5.32) is a major source of one of the most bioactive compounds EGCG. Green
tea is also a source of polysaccharides. Epidemiological studies have shown a strong inverse rela-
tionship between green tea consumption and risk of T2DM and its cardiovascular complications and
the beneficial effects of green tea consumption on body weight, body mass index, waist circumfer-
ence, and systolic blood pressure [213,214].
Vegetables and fruits in general (Figure 5.33) are good sources of potassium, fiber, vitamins,
lipoic acid, and other micronutrients that are all important for improving diabetic conditions. Their
usage in ways that do not generate AGEs or ALEs should be encouraged and promoted especially
for diabetic patients. Endives (Figure 5.34) are very good vegetables for diabetes; endives are bitter
and also rich in kaempferol, which has anti-inflammatory properties [215].
Figure 5.33 Vegetables are good sources of potassium needed for improving diabetes.
Figure 5.34 endives are very good for diabetes management.
5.8 treNDS IN DIABeteS
5.8.1 t1DM in Children
The prevalence of T1DM or juvenile-onset diabetes in children is increasing worldwide, partic-

ularly in preschool children [216]. In the United States, the CDC website reports that about 15,000
youths are diagnosed with T1DM each year. In U.S. youth <10 years old, the disease is more preva-
lent in Whites. Between 1990 and 2005, the greatest increase was in the 5–9 year age category
[217]. In the 10–19 age group, the disease is prevalent in Whites followed by African-Americans,
Hispanics, and American Indians. In Europe, there is concern that the number of T1DM in children
younger than 5 years old will double between 2005 and 2020 [218].
Several studies have identified cow’s milk as a major risk factor for the development of T1DM
in children [219–222]. The Finnish Dietary Intervention Trial for the Prevention of Type 1 Diabetes
(FINDIA) recruited 1113 infants with genetic susceptibility to T1DM and randomly assigned
them to receive bovine insulin-free cow’s milk formula (N = 389), whey-based hydrolyzed formula
(N = 350), or whey-based FINDIA formula free of bovine insulin during the first 6 months of life
whenever breast milk was not available [223].
By age 3, children at genetic risk of T1DM on insulin-free cow’s milk formula showed signifi-
cant reduction of incidence of autoantibodies. Cow’s milk stimulates insulin-like growth factor-1
and the latter binds to its receptor that is known to initiate signal transduction associated with sev-
eral noncommunicable diseases. Others have argued that very early exposure to cow’s milk is not a
risk factor for T1DM and may in fact diminish its appearance before age 8 [224].
The best opinions on cow’s milk may come from independent parties not associated with
cow’s milk business rather than those making a living selling cow’s milk. In the meantime, the
international trial launched to determine whether weaning to a highly hydrolyzed formula in
infancy reduces the incidence of T1DM in children at increased genetic disease is ongoing and
will be reporting to the world in 2017 [225]. It would also be good if there was another study that
involves investigating infants who are not genetically at risk consuming insulin-like growth fac-
tor loaded milk.
Unknown environmental factors are changing individuals’ defense mechanisms and it is not
surprising that groups that may have been less susceptible to certain diseases are nowadays becom-
ing susceptible. For instance, until the 1980s food chemistry books regularly discussed lactose
intolerance as being common in Asians and Africans and their descendants. Today, lactose intoler-
ance can affect Caucasians as well as Asians or Africans. People who may not be genetically prone
to T1DM may develop the disease because of maternal error in nutrition as suggested by the fetal
origin of adult disease.
The association of cereal early in life with T1DM has also been reported, and because of the
increased association between T1DM and celiac disease, gluten has been suggested to be the risk
factor [226–229]. Gluten-free meals showed reduced prevalence of T1DM and reduced incidence of
autoimmune antibodies.
5.8.2 t2DM in Children and Adolescents
The prevalence of T2DM in children and adolescents is also increasing worldwide. The CDC
website reports that annually about 3700 youths are diagnosed with T2DM in the United States. The
CDC records show that in U.S. youth aged 10–19 years, the disease is prevalent in American Indians,
African-Americans, Asian/Pacific Islanders, and Hispanics and low in non-Hispanic Whites. Poor
nutrition, physical inactivity, and intrauterine exposure to maternal obesity and T2DM may account
for the increase in childhood T2DM around the world. A cross-sectional school-based study of
4804 U.K. children aged 9–10 years of South Asian, black African-Caribbean, and White European
origin examined the relationships between socioeconomic position and T2DM risk factors [230].
The study concluded that socioeconomic position is associated with T2DM risk factors in chil-
dren, but patterns of association differ by ethnic groups. Children’s very low food security is asso-
ciated with increased intake of energy-dense and nutrient-poor foods and increased incidence of
T2DM among 6–11-year-old Mexican-origin children in Colonias, TX [231]. Research in Canada
has shown that youth with T2DM have up to 23-fold increased risk of renal failure and 39-fold
increased risk of dialysis [232].
5.9 FUtUre DIreCtIONS
The prevalence of both T1DM and T2DM in youth and T2DM in adolescents and adults is
increasing worldwide. A multidisciplinary approach involving the family doctor, food industry,
food science and nutrition research and teaching institutions, culinary schools, consumers, and
governmental and international health-related agencies is needed to stop this epidemic similar to
the way diseases such as polio has been eradicated.
The food industry is full of well-trained scientists who know a lot about the Maillard reaction but
are not doing enough to stop developing AGE-loaded foods. For instance, resistant starch can help
reduce AGE levels in foods. How many pizza manufacturing companies make use of resistant starch
in their pizzas? Some are claiming cost as a limiting factor. Cheese regardless of its animal original
is loaded with AGEs. Knowing that pizza has become the world’s premier food across continents,
it is time for pizza to be healthy. Replacing reducing sugars, developing AGE-free or AGE-reduced
cheese, and phasing out technologies such as spray-drying can significantly reduce AGE levels in
foods (see Chapter 3). The millions of dollars spent on advertising insulin resistance– causing foods
such as pizza and macaroni and cheese could be well spent reformulating food products and creat-
ing minimally processed foods with low levels of AGEs. It is also time for management in the food
industry to be really health-oriented and not only quarterly returns minded. It is not bad to invest
today and reap profits some quarters down the road.
Each consumer needs to understand the Maillard reaction and talk about it regularly at the
kitchen table. This is where fundings are needed for more extension agents to organize community
meetings and spread the importance of understanding the Maillard reaction in healthcare. Not
every family in the world has access to the Internet. It is unproductive to think that the Internet is
available in every home in the West albeit in the developing economies. At the same time, nutrition
extension agents have to have food chemistry training and be knowledgeable in the latest technolo-
gies and science breakthrough in diet-related diabetes research in order to assist the communities
they service.
The family doctor can help people eat well. The family doctor in turn needs to be trained in food
science and nutrition so that during office hours the family doctor can spend time advising patients
on the best foods for the patient’s health. It is this author’s opinion that medical schools introduce
basic food science and nutrition courses in their curriculum.
Political leaders around the world need to know more about AGEs and its side effects, because
with strokes of pens they can legislate for healthier food products on the market. It can be done
because the science and the ingredients are available or can be developed if funds were channeled
to food science and engineering programs to develop needed ingredients and technologies.
Minimally processed, AGE-less, or AGE-free foods can reduce the epidemic of diabetes, save
lives, and reduce healthcare costs. The technologies to develop these types of foods exist and their
use should be promoted. The health risk associated with AGE-rich ingredients or foods extend to
central nervous system diseases such as Alzheimer’s and Parkinson’s.
Recent studies have shifted emphasis on studying the potential of bioactive metabolites on dis-
ease prevention including diabetes. The rationale is that most parent compounds are metabolized
into either a weaker bioactive or a stronger one. Investigation of the efficacy of metabolites at physi-
ological concentrations can assist in designing technologies for improved delivery of parent bioac-
tive to the body. Research activities on the activity of dietary metabolites are in its infancy; the list
is short but will certainly be expanded with time.
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ChAPter 6
hypertension
6.1 DeFINItION OF hYPerteNSION
Hypertension is a pervasive medical condition characterized by high blood pressure (HBP) in the
arteries. Hypertension is the same as HBP. Normal blood pressure can be defined as a combination
of systolic blood pressure (SBP) of less than 120 mmHg and diastolic blood pressure (DBP) of less
than 80 mmHg, both are often reported as 120/80 mmHg. HBP can be divided into three classes:
1. Prehypertension is defined as 120–139/80–89 mmHg.

2. Stage 1 hypertension is considered when an individual’s blood pressure is 140–149/90–99 mmHg.
3. Stage 2 hypertension is a medical condition whereby an individual’s blood pressure is equal or
higher than 160/100 mmHg [1,2].
6.2 rISK FACtOrS FOr hYPerteNSION
Like many chronic degenerative diseases, HBP is a multifactorial disease with several risk fac-
tors including nonmodifiable factors as well as modifiable ones. Age, genetics, gender, race, low
weight at birth, and diabetes are the major nonmodifiable risk factors for hypertension. The preva-
lence of hypertension is highest among persons aged 65 years old or more; about 70% of old people
are affected by hypertension. Age-related HBP has a high incidence of multiple comorbidities. The
U.S. prevalence of hypertension is highest among African-Americans and Hispanic-Americans. As
far as race is concerned, nonchloride sodium salts do not necessarily elevate blood pressure in most
ethnic groups but do so in salt-sensitive black people.
6.2.1 Nonmodifiable risk Factors for hypertension
6.2.1.1 Age
Age is the major nonmodifiable risk factor for hypertension regardless of race. HBP is the most
prevalent chronic degenerative disease among adults regardless of gender or race [3]. HBP affects
about 70% of people 65 years old or more [4]. It has been reported that worldwide roughly a quarter
of those with hypertension are unaware of their condition, and more than half of hypertension cases
are uncontrolled [3]. The high prevalence of hypertension particularly systolic hypertension among
the elderly may be associated with age-related progressive stiffening of the arterial structure in both
sexes [5]. Aging is also associated with the incidence of secondary hypertension mainly owing to
the use of drugs such as NSAIDs that have pressor effects and the presence of chronic kidney dis-
ease, obstructive sleep apnea, and renal artery stenosis [5]. The abrupt fall in circulating estrogen
levels in older women might independently contribute to the rise in blood pressure. In older men
127
and women, although the levels of physical inactivity may be similar for both genders, the higher
prevalence of hypertension, diabetes, and obesity in older women portends a greater risk in women
than in men [6]. Age-related HBP has a high incidence of multiple comorbidities.
6.2.1.2 Genetics or Family History of HBP
Studies have shown that hypertension may be a disease with no known single gene playing a key
role; rather blood pressure is under the control of several genes and each one playing a minor role
and the resulting effect is synergistic.
6.2.1.3 Low Weight at Birth
Individuals born with low weight have low blood pressure at birth; however, as these individu-
als get older, they show an inverse correlation between birth weight and SBP. Individuals with low
birth weight show salt sensitivity of blood pressure in their adult life even when they are healthy.
Studies have shown that individuals born with low weight at birth are at an increased risk of devel-
oping cardiovascular disease (CVD) and non-insulin-dependent diabetes, impaired bone mass and
osteoporosis, impaired glucose homeostasis, and increased risk of early menopause in adult life as
suggested in Barker’s hypothesis [7,8].
6.2.1.4 Gender
Men have higher blood pressure than women through much of life regardless of race and ethnicity.
Women tend to develop hypertension later as they transition into menopause, and during and after
menopause, the development of hypertension in women is independent of age and body mass index
(BMI) but is related to menopause itself. Hypertension occurs in about 8% of U.S. women of repro-
ductive age. Together with the aging process, hypertension is the main risk factor contributing to the
increase in cardiovascular morbidity and mortality in postmenopausal women, with a prevalence of
around 60% in women older than 65 years.
6.2.1.5 Race/Ethnicity
Hypertension affects more African-Americans than any other ethnic groups in the world. The
association of genetics and HBP is strong in African-Americans and starts early in life. African-
Americans have the earliest onset of hypertension with greater severity and more target organ damage,
poorer prognosis, and highest mortality than any other racial/ethnic group. As a result, African-
Americans also have 1.3 times more nonfatal strokes and 1.8 times more fatal strokes than whites.
Environmental and genetic risk factors likely play an important role in the prevalence of hypertension
in African-Americans. The genetic prevalence of hypertension in African-Americans may be associ-
ated with the heritability of the arterial stiffness, which has a 20% chance of transmission to children
[9]. Studies have suggested that in most salt-sensitive blacks, the pressor effect of dietary sodium
chloride involves something more than its capacity to mediate osmotic expansion of plasma volume,
the only capacity of NaCl called for in the traditionally formulated mechanism of sodium chloride’s
pressor effect. Studies including the Bogalusa Heart Study have shown that African-Americans have
higher impaired arterial elasticity than Caucasians or Asian-Americans even after adjusting for all
other risk factors of blood pressure [10,11]. Blacks in general have lower plasma renin activity than
other races and therefore are likely to be more sodium-sensitive than other races.
In the United States, the prevalence of hypertension is also high among Hispanic-Americans.
There are suggestions that genetic differences, socioeconomic, and environmental factors may
in part explain the disparity in hypertension among races/ethnicities. Others have suggested that
HyPertensIon 129
disparities in hypertension risk and outcomes among diverse populations are now believed to be
more a function of personal habits, socioeconomic status, and psychosocial factors rather than race,
ethnicity, or genetics.
6.2.1.6 Diabetes
Hypertension and diabetes frequently occur together and overlap. Diabetes and hypertension
are found in the same individual more often than by chance suggesting some common genetic or
environmental predispositions. About 30% of people with type I diabetes and between 50% and
80% of people with type 2 diabetes in the United States have HBP [12]. Hypertension development
coincides with the development of hyperglycemia. Studies have shown that genetic predisposition
to HBP is associated with an increased risk of CVD in individuals with type 2 diabetes mellitus
[13–15]. The mechanism by which diabetes induced hypertension involves among many other fac-
tors insulin resistance and oxidative stress. Insulin resistance upregulates the enzyme system also
known as the renin–angiotensin–aldosterone system that contributes to the pathogenesis of hyper-
tension and atherosclerosis.
6.2.2 Modifiable risk Factors for hypertension
Nutritional factors including obesity, energy intake, fat intake, sodium intake, potassium intake,
magnesium intake and dietary fiber, smoking, nutrients/gene interactions, and nutrients/medicine
interactions are modifiable risk factors for hypertension. Each risk factor is briefly described in the
following.
6.2.2.1 Obesity and Hypertension
Obese people easily develop hypertension suggesting that the association of obesity and hyper-
tension is very strong. The global epidemic of visceral obesity has and will have a great impact on
global hypertension. About 80% of men with arterial hypertension are obese and about 65% of
women with arterial hypertension are obese [16]. Obesity causes insulin resistance and the latter
causes increased sodium absorption leading to HBP. Obese individuals are predisposed to obstruc-
tive sleep apnea that in turn increases the risk of developing hypertension. Individuals with the
metabolic syndrome are at a high risk of developing hypertension and CVD. Undernourished fetus
during the second and to a lesser extent the third trimester of pregnancy often tends to be born
underweight, but are likely to become overweight in childhood and grow up to become obese, dia-
betics, and hypertensive in adulthood.
6.2.2.2 Dietary Salt and Hypertension
Excessive sodium in foods is a major risk factor for HBP development. The U.S. Department
of Agriculture and U.S. Department of Health and Human Services’ joint 2010 Dietary Guidelines
for Americans U.S. guidelines recommend sodium daily intake of less than 2300 mg/day for all
groups except for African-Americans [17]. For black people, persons aged 51 years old or higher,
or any age with hypertension, diabetes, or chronic kidney disease, the U.S. guidelines recommend
less than 1500 mg/day. The U.S. guidelines recommend 1000 mg/day for children aged 1–3 years
and 1200 mg/day for children aged 4–8 years. The American Heart Association has recommended
that daily sodium intake be less than 1500 mg for adults [17]. However, on average and with-
out taking into consideration salt added at the table, about 3266 mg of sodium is ingested per
day [18]. However, food processors use sodium for many reasons including flavor, taste, texture,
and food preservation at low cost. As a result, manufacturers add lots of salt to most processed
and ready-to-eat foods. The U.S. Institute of Medicine (IOM) has reported that in many foods
the sodium content exceeds the concentration needed for processing and preservation [19]. Most
people have developed a taste for sodium and often do not even recognize highly salted foods, and
will enjoy highly salted foods.
In the United States, the following commonly used food categories contribute about 44% of
sodium intake and include
• Bread and rolls (Figure 6.1)

• Cold cuts/cured meats (Figure 6.2)
• Pizza
• Poultry
• Commercial soups (Figure 6.3)
• Sandwiches
• Cheese
• Pasta mixed dishes
• Meat mixed dishes
• Savory snacks
Studies have shown that salt reduction to an average of 2300 mg/day can prevent 11 million
cases of hypertension and save billions of dollars in healthcare [20]. For black people and even
Caribbean or other people with African ancestry, further reduction of sodium or combination of low
sodium with more potassium and magnesium is needed and advocated because black people appear
to be genetically more prone to hypertension than any other ethnic group [21,22].
Obese individuals tend to have increased sodium intake that may promote HBP. High-salt
diets suppress the function of the renin–angiotensin system, which is the best known regulator of
blood pressure and determinant of target organ damage from hypertension [1]. High salt intake
also increases the risk of bone demineralization [23], stomach cancer [24], and renal disease and
CVD [25,26]. The evidence of the relationship between salt intake and blood pressure is very strong
and overwhelmed and has come from comprehensive epidemiological, interventional, animal, and
genetic studies [27–29]. It has been shown that excessive sodium in diets has a prooxidant effect
and stimulates the production of free radicals [30]. Adoption of high-salt diets, highly sweetened
Figure 6.1 Bread rolls are sources of salt for hypertension.

HyPertensIon 131
Figure 6.2 Cured cuts and cured meats often contain high amounts of salt.
Figure 6.3 Commercial soups often contain high levels of salt.
foods or beverages, smoking, and poor nutrition during pregnancy predispose in postnatal life to
hypertension. Moreover, the prevalence of high sodium in a wide range of commonly consumed
foods is a critical risk factor for the globalization of hypertension. However, there are those who
have suggested that reducing salt intake as recommended by the American Heart Association may
increase the risk of developing cardiometabolic disease and the severity of established cardiometa-
bolic disease and CVD-related mortality [31]. Their rationale is that low salt intake will increase
insulin resistance and dyslipidemia and affect neurohormonal pathways.
Potassium chloride, however, is an antioxidant that counteracts the activities of sodium [32].
Diet high in potassium can prevent or control hypertension, decrease cardiovascular morbidity, and
reduce cardiovascular-related mortality [33]. Potassium chloride is bitter and this limits its applica-
tion in many foods.
6.2.2.3 Dietary Sugar and Hypertension
Chronic intakes of high levels of sugar elevate blood pressure. High-fructose corn syrup, which
accounts for 33% of the sweeteners in U.S. beverages, has been associated with increased blood
pressure [34]. Studies have shown that reduction of one 12 oz serving of sugar-sweetened beverages
per day was associated with an average of 1.8 mmHg reduction in SBP and an average of 1.1 mmHg
reduction in DBP [35,36]. Fructose increases reabsorption of salt and water in the small intestine
and kidney; as a result the combination of salt and fructose has a synergistic effect in the develop-
ment of hypertension [37]. Other studies have suggested that high intakes of fructose-rich beverages
and foods by African-Americans may explain their greater predisposition to develop cardiorenal
disease including hypertension [38]. Individuals with type 1 diabetes who consume high levels of
sugar-sweetened beverage may increase the risk of developing CVD [39].
6.2.2.4 Caffeine and Tyramine-Rich Foods and Hypertension
The effects of caffeine on blood pressure depend on exposure and family history: those who
are infrequently exposed to caffeine, individuals with family history of hypertension, blacks, or
obese individuals can see a blood pressure increase by an average of 4/3–5/3 mmHg and as high as
10 mmHg following consumption of 2–3 cups of coffee [40]; regular coffee drinkers sometimes do
not see the bump in blood pressure [41]. Caffeine in coffee has minimal effect in elevating blood
pressure [42]. However, when used in isolation in the absence of the coffee matrix, caffeine tends
to cause an increase in blood pressure [43,44]. Results of a randomized, double-blind, controlled,
crossover study (N = 20) indicate that healthy nonhypertensive individuals who consumed caffein-
ated 5 h energy increased their SBP and DBP over a 3 h period [45].
Tyramine, a biogenic amine, is found in aged cheese such as Italian-type cheese Parmigiano-
Reggiano, Pecorino and Fossa, and Robiola di Roccaverano [46,47] and in Edam Dutch-type
cheese [48]. Tyramine is also found in beer and mostly draft beer [49,50], Chianti wines [51],
snails [52], chicken liver and sauerkraut [53], aged or cured meat, yeast extract, coffee, soy sauce,
and broad beans [54]. Foods high in tyramine (>6 mg/serving) may interact with monoamine oxi-
dase inhibitors and cause hypertension crisis in individuals taking monoamine oxidase inhibitor
antidepressant drugs.
6.2.2.5 Heavy Alcohol Consumption and Hypertension
There is a strong link between moderate to heavy alcohol consumption (>1 drink/day) and DBP
[55] (Figure 6.4). The association of daily alcohol (vodka, wine, and beer) consumption and the
risk of developing CVD was evaluated by determining CVD risk factors including hypertension
and HDL and triglyceride levels in a 3-year study (2003–2005) that enrolled 6912 Polish men
aged 20–74 years representative of the general Polish population [56]. The participants were classified
into four groups including those who did not drink alcohol, light alcohol drinkers (≤15 g ethanol/
day), moderate alcohol drinkers (15–30 g ethanol/day), and heavy alcohol drinkers (>30 g ethanol/
day). Results were very clear; moderate and heavy alcohol consumption was significantly associated
with both SBP and DBP. Moderate alcohol drinkers had a 37% higher risk of hypertension and
25% higher risk of dyslipidemia compared to nondrinkers. Heavy drinkers had a 52% higher risk
of developing hypertension, 46% higher risk of dyslipidemia, and 95% risk of developing hyper-
homocysteinemia. The study also found that moderate alcohol drinkers decreased the likelihood
of developing diabetes by 35% while the heavy alcohol drinkers decreased their low HDL-C by
44%. It is suggested that heavy alcohol consumption is not the best lifestyle for preventing diabetes
development. However, Jones et al. [57] from the United Kingdom studied light to moderate alcohol
HyPertensIon 133
Figure 6.4 Heavy alcohol consumption is a major risk factor for hypertension development.
consumption in 88 adults (1:1 ratio of males to females) and reported that habitual alcohol consump-
tion may reduce the risk of CVD. Stoutenberg et al. [58] examined the association of alcohol con-
sumption and the development of metabolic syndrome in 7483 Caucasian men in the United States.
All participants had no report cases of metabolic syndrome or CVD at baseline. The study defined
alcohol consumption per week as follows: light (1–3 drinks), moderate (4–7 drinks), moderate–
heavy (8–13 drinks), and heavy (≥14 drinks). Alcohol consumption was inversely associated with
low HDL concentrations. There was a significant association between alcohol (moderate to heavy)
consumption and high fasting glucose concentrations. The association of alcohol consumption and
metabolic syndrome including central obesity, hypertriacylglycerolemia, or hypertension was weak.
There was a significant inverse association between all levels of alcohol consumption and the inci-
dence of metabolic syndrome. Briasoulis et al. [59] analyzed 16 prospective studies that enrolled
a total of 33,904 men and 193,752 women to evaluate the association of alcohol consumption and
hypertension. Men who drank <10 g alcohol/day or 11–20 g alcohol/day had an increased risk of
developing hypertension. The association of alcohol consumption and risk of hypertension was
strong in men who drank between 31 and 40 g alcohol/day. For women, consumption of <10 g of
alcohol/day showed a protective effect, consumption of 11–20 g alcohol/day showed a trend toward
a decreased risk, and heavy alcohol consumption of 21–30 g/day was associated with a significant
risk of developing hypertension. Daily intake of 3 drinks or more by either gender is a risk factor for
hypertension and should be reduced to less than 10 g/day.
6.2.2.6 Cigarette Smoking and Hypertension
On a global level, five million deaths are annually associated with cigarette smoking [60].
Cigarette smoking is associated with about 20% of all deaths in the United States [61]. Smoking is
nephrotoxic and increases blood pressure, and the risk of hypertension is associated with the num-
ber of cigarettes smoked daily and the duration of smoking (Figure 6.5). Cigarette smoking induces
arterial stiffness, increases inflammation in healthy intermittent smokers and increases markers of
inflammation and tissue destruction in atherosclerotic plaques, and has a dyslipidemic effect such as
increasing total cholesterol, low-density lipoprotein cholesterol, triglyceride, and decreasing HDL
cholesterol as well as acceleration of the atherothrombotic process, leading to cardiovascular prob-
lems [62,63].
Figure 6.5 Cigarette smoking is a risk factor for hypertension.

6.2.2.7 Insulin Resistance
Insulin resistance is a risk factor for CVD because insulin resistance may act directly on the
blood vessel walls causing the blood vessel to thicken, which is an early sign of the hardening of
the arteries that can cause heart attacks and strokes. Inflammation is a link between insulin resis-
tance and hypertension because inflammation impairs through inflammatory biomarkers. The co-
occurrence of insulin resistance and hypertension is a heritable condition leading to cardiovascular
complications and type 2 diabetes [64]. The fetal origin of hypertension suggests that changes in the
intrauterine environment including hormonal and nutritional changes alter gene expression in the
kidneys of offspring, which may lead to the development of adult hypertension [65].
6.2.2.8 Physical Inactivity
Physical inactivity is a risk factor for hypertension [66]. Physical activity or physical fitness reduces
the risk of hypertension as a result of positive changes in body weight and increases insulin sensitivity
[67]. Regular fitness activities can delay the development of hypertension. Regular physical activity is
an effective nonpharmacological therapy for the prevention and control of hypertension because it
improves blood flow and reduces tissue dysfunction.
6.3 COMPLICAtIONS OF hYPerteNSION
Hypertension is a risk factor for stroke, arteriosclerosis, atherosclerosis, kidney disease, kidney
failure, aortic aneurysm, dementia, and heart attack. A stroke is marked by a sudden disruption of
blood flow to the brain causing the nerve cells in the affected brain region to become damaged and
die within minutes. Long periods of uncontrolled hypertension are a risk factor for stroke. Essential
hypertension increases the risk of stroke. Several studies including the U.S. National Health and
HyPertensIon 135
Nutrition Examination Survey (NHANES), the Dietary Approaches to Stop Hypertension (DASH),
and the International Study of Salt and Blood Pressure (INTERSALT) have concluded that high salt
intake strongly and significantly contributes to the pathogenicity of stroke mortality independent of
blood pressure. In the United States, studies from the National Institute of Neurological Diseases
and Stroke (NINDS) have designated a stroke belt composed of 11 states including Alabama,
Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina,
Tennessee, and Virginia.
Chronic hypertension can affect blood pressure in the vessels lining the eyes. Hypertension has
profound effects on various parts of the eye. HBP in retinal vessels is associated with end-organ
damage and may be a risk marker of stroke, congestive heart failure, and cardiovascular mortality.
Hypertension is also a risk factor for diabetes retinopathy and age-related macular degeneration.
6.4 DIetArY StrAteGIeS tO reDUCe Or PreVeNt hYPerteNSION
Dietary strategies to reduce or prevent hypertension are part of the well-known DASH diet [68].
DASH is one of the three eating plans that were compared in research studies sponsored by the
National Heart, Lung, and Blood Institute (NHLBI), a division of the NIH whose goal was to study
the effects of diet on HBP. As mentioned early in the book, the best strategy to reduce or prevent
hypertension with diet is to identify dietary factors that promote hypertension and those that protect
against hypertension. There are several players whose roles are critical in the fight against hyperten-
sion. These include the consumer or individual, food industry, research institutions, and the regula-
tory agencies at national and international levels. The role of each player is briefly discussed in the
following.
6.4.1 Individual or Consumer
Most parents know whether the maternal or paternal family has a history of hypertension or
HBP or not. Parents with family history of HBP are responsible for raising their children informing
and constantly reminding them to watch their blood pressure and avoid anything that can raise it up.
Parents and individuals should consult with their family doctors about preventing hypertension. The
following steps can help achieve blood pressure management:
• Reducing sodium levels in diet

• Increasing the consumption of reduced sodium–potassium-rich foods
• Reducing the consumption of advanced glycation end product (AGE)-rich foods
• Avoiding zinc-rich foods
• Adopting the DASH eating plan
• Reducing weight
• Being physical active
• Consuming alcohol in moderation
It is a fact that supermarket shelves contain very few low-sodium processed foods making it
difficult for individuals to find and adhere to the low-sodium diet. In the United States, despite
the good intention of most people to lower their intake of sodium, habituation to high-salt foods
from prenatal throughout life makes it difficult for most individuals to adhere to low-sodium
foods [69]. Consumer education in eating becomes paramount in the fight against hypertension.
Reducing salt is a must especially in ethnic groups where individuals are genetically prone to
hypertension. Individuals who consume processed foods have difficulty finding and adhering
to low-sodium diet because they are asymptomatic and may consider these diet too restrictive and
these foods have reduced palatability [70].
Traditional poor man’s diet is full of potassium-rich foods. Vegetables and fruits are rich sources
of potassium. The USDA on its website advises consumers to select whole fruits or cut up over juices
(http://www.choosemyplate.gov/food-groups/downloads/MyPyramid_education_framework.pdf).
The link between AGEs and hypertension was described early. Reducing the consumption of
AGE-rich foods can significantly help consumer maintain healthy levels of blood pressure. Reducing
fructose levels in foods will curtail hypertension.
6.4.1.1 Reducing the Consumption of Sodium- and Phosphate-Rich Foods
White breads and rolls, pasta, grain mixtures, processed meats including bacon, ham, frankfurt-
ers, sausages, luncheon meats, commercial soups, salty fish including herring and smoked salmon,
dishes developed using poultry, fish or meat including smoked salmon and herring are salty [69]
(Figure 6.6). Some foods also have high phosphate and salt and phosphates and are target for hyper-
tension management [71]. Phosphate salts are preservatives but have side effects. Foods that are rich
sources of AGEs may trigger hypertension.
6.4.1.2 Promoting the Consumption of Food Ingredients and Foods

That Protect against Hypertension
Two scenarios are envisioned here: The first involves the prevention of hypertension development
and the second deals with the intervention for individuals who have already developed HBP. It is
suggested that a diet rich in potassium and low in sodium is a critical low cost but effective strategy
for the primary prevention and treatment of hypertension. Bananas, beans, potatoes, and dark-green
vegetables such as kale and collard greens are excellent sources of potassium. Vegetables more than
fruits contain high levels of different forms of potassium that offer better antihypertensive effects
suggesting that their consumption should be promoted. Studies have shown that potassium supple-
mentation can reduce the need for blood pressure medication, lower blood pressure, and reduce the
incidence of stroke and stroke-related death.
Zinc is a mineral that has several physiological functions. Zinc has been reported to regulate
blood pressure and participate in the development of hypertension. There is a negative correlation
between zinc levels in serum and arterial blood pressure [72]. The association of zinc and hyper-
tension is strong in individuals with type A personality and individuals who suffer from primary
Figure 6.6 salty smoked fish may not be good for hypertension.
HyPertensIon 137
arterial hypertension [73,74]. It is therefore suggested to lower zinc levels in subjects with primary
arterial hypertension. For these individuals, for instance, consumption of foods that contain zinc
binders should be promoted. These foods include soybean, lima bean, black beans, adzuki beans,
amaranth flour, peanut roasted at temperature less than 310°F, and dark chocolate.
These foods contain the protein Bowman–Birk inhibitor and phytic acid, both of which bind
zinc. Adzuki beans are very good sources of procyanidins. Very dark chocolate is an excellent
source of procyanidins. It contains very low amounts of AGEs. Semisweet chocolate chips contain
very high levels of AGEs mentioned in Chapter 1. Peanut skin is also health-enhancing because
of its content of procyanidins and resveratrol. Green tea including green tea ice cream contains
epigallocatechin gallate very well known for its inhibitory activity against enzyme that promotes
hypertension. Cherries and cranberries are rich in procyanidins and good food for hypertension.
Whole cereal grains are rich in phytic acid that binds zinc and help against hypertension. However,
processed cereals rich in AGEs may have a complicated effect on hypertension. Their content of
AGEs may have a negative effect on hypertension. A recent study that examined the association
between zinc and blood pressure in Korean obese women concluded that dietary zinc intake may be
an independent risk factor in SBP development in these women [75].
6.4.1.3 Adopting the DASH Plan
The success of the DASH diet has been demonstrated as this diet plan can reduce blood pres-
sure by 5.5 mmHg for normotensive individuals and 11.4 mmHg for hypertensive people [76]. The
adoption of the DASH diet has been either slow or ignored. Consumers may not have been told
about the DASH diet plan. Consumers may prefer inexpensive processed foods over expensive fresh
vegetables and fruits.
6.4.1.4 Reducing Weight, Being Physically Active, Consuming Alcohol in

Moderation, and Avoiding Smoking
To treat hypertension, weight loss is one of the early and major interventions that are suggested
to hypertensive individuals [77]. Weight loss translates into reducing visceral fat mass [78]. Short-
term nonpharmacological interventions have shown that weight loss of 10 kg can reduce blood pres-
sure by as much as 4.6 mmHg in DBP and 6 mmHg in SBP, respectively [79]. Weight loss yielded
better blood pressure reduction than sodium intake reduction [80].
The association of physical fitness and reduced risk of developing blood pressure is very strong.
Physical activity is inversely associated with HBP suggesting the magnitude of one is inversely
related to the magnitude of the other.
Alcohol is associated with 16% of hypertensive diseases [81]. The association of heavy drinking
and blood pressure is strong, linear, and well established. A 3.31/2.04 mmHg reduction has been
achieved when individuals reduced their alcohol intake by 67%, which also resulted in reduction of
the risk of coronary disease [82].
Avoiding smoking is very beneficial for pregnant mothers to prevent hypertensive
disorders [83]. Avoiding cigarette smoking improves hypertension in chronic kidney disease patients
with diabetes [84]. Smoking triggers endothelial dysfunction, atherogenesis, and hypertension, and
both smoking and hypertension are synergistic risk factors for CVD [85].
6.4.2 the Family Doctor
People listen better to their physicians than others; advice from the family physician will not be
ignored. The combination of diet, weight management, physical activity, and alcohol consumption
is the most effective way in reducing hypertension; therefore, the family physician can help patients
in selecting a diet and lifestyle that is best for helping them manage blood pressure. Family doctors
with knowledge of food science and nutrition will help patients. Sodium and fructose are mostly
ingested through diet and doctors can play a big role in advising patients to reduce their intake of
sodium and fructose. Through their doctor’s advice people can select certain types of foods to avoid
promoting hypertension.
6.4.3 Food Industry
6.4.3.1 Reducing Sodium Levels in Foods
The food industry is a major player in people’s health because people eat food every day and
rely more on processed foods than unprocessed ones. Urbanization and globalization have allowed
the food industry a major role in feeding the world all day long. In foods, sodium improves the
sensory attributes of the food by decreasing bitterness, increasing saltiness and sweetness and other
flavor effects [86]. In brief, the functions of salt in foods are presented in Table 6.1. James et al. [87],
Mattes and Donnelly [88], and The World Health Organization (WHO) [89] reported that about
75% of sodium in human diet is added during food preparation by the food processing and/or food-
service industries. Produce in general contain one-tenth to one-eighth of the sodium we consume;
however, the sodium amount of a single portion is increased during processing and preparation,
and the final product ends up on the dining table with 5–10 times more sodium than the parent
produce [90]. Cereal products in particular bread, soups, preserved meats, and other processed
foods are good sources of sodium in the diet [91].
Despite the benefits, mentioned before, of adding salt to foods, processed foods are the main
source of sodium-associated human diseases. Reducing salt in foods is a must and real challenge for
the food industry. Lowering sodium intake is good for public health [90] and the food industry has
to do it. Several studies including DASH, INTERSALT, and others have shown that
• Perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II con-
tent in adult offspring [92–94]
• Excessively high and low sodium intakes during pregnancy predispose the child to the risk of hyper-
tension later in life [93]
• Salt reduction in the diet to the low level of DASH takes several weeks to lower blood pressure to an
acceptable level in hypertensive individuals [95] and causes 25%–30% reduction in the long-term
(10–15 years) risk of CVD [96]
However, sodium intake reduction to an acceptable level that does not interfere with product
likeability is a challenge to the food industry to adapt to of sodium level of 1200 mg/day.
In the United States, food labeling and consumer education have not succeeded in convincing
and moving people to adapt to recommended sodium intake as reported by the IOM [97]. The IOM
has then recommended a gradual reduction in sodium content of processed and prepared foods
through mandatory national standards. Bolhuis et al. [98] have shown that a salt reduction of up to
52% in bread or even up to 67% in flavor-compensated bread neither affected bread consumption
nor choice of sandwich fillings. Several food companies including Conagra, General Mills, and
Unilever have made the commitment to voluntarily reduce salt levels in their food products. In
France, United Kingdom, Australia, and New Zealand, food companies have developed products
with 10%–30% less sodium including breakfast cereals, fat spreads, soups, sauces, and sweet savory
and snacks [99]. For more information on industrial perspective on salt reduction in food, the reader
is invited to dig into Dötsch et al. [99], Strauss [100], and Liem et al. [101].
Reducing salt in processed foods by 10%–30% will not solve the problem of blood pressure in
salt-sensitive individuals such as black people. It may be time for the food industry to start research-
ing for alternative salts for sodium-sensitive individuals or ethnic groups.
HyPertensIon 139
table 6.1 Functions of Sodium in Food

1. taste and palatability
flavor enhancer and modifier
salt taste sensation activator
Increased palatability and consumer acceptance
appetite enhancer
thirst enhancer
Bitterness blocker
2. Processing aids
Cheese ripening enhancer
Cheese moisture control
Cheese texture enhancer
yeast fermentation control
Dough development in bread
texture (dough, canned foods) enhancer
fat and protein binding enhancer
Water holding
3. Preservation and microbial safety
Preservative
reduced water activity
Inhibition of pathogen growth
Inhibition of spoilage
Catalysis of desirable fermentation
Increased shelf life
4. Micronutrient carrier
Iodine carrier
Glucose and amino acid absorption enhancer
5. economics
Low cost
side effects of current high levels of sodium in foods
Hypertension
obesity
asthma
Diabetes
Cataract
Kidney stones
osteoporosis
stomach cancer
6.4.3.2 Finding Alternatives to Sodium
The most mentioned alternatives to sodium are potassium and spices. Potassium has been
known for years to lower blood pressure [102,103] and protect against stroke [104–106]. Potassium
would be good for sodium-sensitive individuals. However, too much potassium in the body can be
dangerous for the heart’s rhythm. Similarly, too much potassium may be detrimental for individuals
taking potassium-rich prescriptions or those who can’t flush potassium out.
While potassium chloride is bitter, potassium-rich fruits and vegetables are not bitter because in
these foods, potassium exists as organic salts [107]. Potassium-rich vegetables and potassium-rich
fruits are readily available and should be promoted (see the following). Spices, herbs, and other fla-
vorings are also being used and investigated as the healthy alternative to sodium. Ginger and lemon
pepper are currently being investigated. They add antioxidative activities in foods as opposed to the
prooxidative characteristics of too much sodium.
Monosodium glutamate, commonly used in Asian cuisine, has been banned in most restaurants
because of its purported role in inducing headaches among other negative symptoms in susceptible
persons. However, it has resurfaced as a potential sodium substitute.
6.4.3.3 Reducing Sugar Levels in Foods and Beverages
Some breakfast beverages like orange or apple juice can provide more than 30 g of sugar per
serving (Figure 6.7). Along with AGEs that are commonly found in foods, our fight against hyper-
tension may become doomed to failure. Therefore, every effort must be made to significantly reduce
sugar consumption. People consume fruits without adding sugar. Can juice be extracted from fruits
and not be concentrated? Can milk chocolate be made without too much sugar? Can food be cooked
at temperatures that prevent excessive Maillard reaction occurrence? It is suggested that food scien-
tists be also trained in human physiology to help design better and healthier foods.
6.4.3.4 Offering Balanced Potassium- and Sodium-Rich Foods and Beverages
Hypertension is such a bad disease that every effort should be made to prevent it from devel-
oping. Fruits and vegetables rich in potassium that can be useful for use against hypertension can
be produced on a commercial scale to allow more people to consume these products and not their
derivatives that may be stripped of potassium. Banana, plantain, prune, orange, cantaloupe, peach,
and honeydew consumption should be promoted (Figure 6.8).
6.4.3.5 International Agencies
Delegates at the United Nations High-Level Meeting on the Prevention and Control of Non-
Communicable Diseases recommended in 2011 that governments around the world make salt reduction
a top health priority [108]. While in most countries current recommendations are set around 2400 mg
sodium/day or less, the WHO recommends 2000 mg/day. However, recent studies suggest that reducing
the sodium intake to 1200 mg/day might be the global long-term population target that can bring addi-
tional improvement in blood pressure and cardiovascular health [109]. The World Action on Salt and
Figure 6.7 High-sugar containing orange juice may not be good for hypertension.
HyPertensIon 141
Figure 6.8 Banana or banana plantain is a good source of potassium and should improve
hypertension.
Health (WASH), a group of world experts in hypertension established in 2005, recognizes that high salt
intake is the major factor that increases blood pressure and CVD and kidney disease worldwide [110].
WASH encourages multinational food companies to reduce sodium in their products and cooperate
with governments around the world to emphasize the importance of sodium reduction in human health.
6.4.3.6 Government and Government-Funded Research Institutions
The government’s role is to protect people from disaster and disease. In the 1950s, Japan responded
to the high incidence of hypertension and stroke by implementing a salt reduction to 1.5–4 g/day that
resulted in 70% reduction in blood pressure and stroke mortality [111]. Starting in the late 1970s, the
Finish government educated the public and physicians about the benefits of reducing sodium intake
on CVD [99]. In the 1980s, sodium labeling legislation was in place. Sodium labeling became man-
datory: When salt level in a food product is above the set limit, a warning “highly salted” or when
the salt level is below the set limit a warning “low or light salted” is used on the food product. The
collaboration between the Finish government, food companies, healthcare providers, and the media
has led to a 40% reduction in sodium intake [112].
The DASH, an NIH multicenter, randomized, controlled-feeding study of dietary patterns to
lower blood pressure, was the first official U.S. government initiative to use food and diet as a
way to fight hypertension [68]. DASH focuses on dietary pattern rather than single nutrients were
tested and commonly consumed food items were provided to the participants using a standardized
multicenter approach so that if results are positive these food items may be recommended to the
general public. Since then, several studies on DASH have been performed, several have been very
positive [76], and DASH has been endorsed by several groups [77,113–115].
However, because food is not one size fits all, the appropriateness of DASH needs to be
reevaluated in some populations. For instance, Tyson et al. [116] advocated caution before initiat-
ing DASH in individuals with chronic kidney disease, chronic liver disease, and those taking a
renin–angiotensin–aldosterone system antagonist. Similarly, DASH should be modified for indi-
viduals with chronic heart failure, uncontrolled type 2 diabetes mellitus, lactose intolerance, and
celiac disease. Recently, Epstein et al. [117] reported that “greater adherence to the DASH diet was
associated with larger blood pressure reductions independent of weight loss. African-Americans
were less likely to be adherent to the DASH dietary eating plan compared with whites, suggesting
that culturally sensitive dietary strategies might be needed to improve adherence to the DASH
diet.” When 169 Latinos, mostly women (73%), older (66 ± 9 years old), and hypertensive, were
evaluated for accordance/adherence to DASH, the results showed that this group was moderately
DASH accordant and adherent [118]. A recent Korean pilot-study adaptation of DASH concluded
that “A cultural adaptation of DASH using community-based participatory research methodology
produced a culturally relevant and efficacious dietary intervention for the Koreans with high blood
pressure and provided strong preliminary evidence for the efficacy of the Korean-DASH interven-
tion in reducing high blood pressure in hypertensive Koreans” [115].
The International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT)
study was an observational investigation that involved 52 communities with a wide range of sodium
intake [119]. The INTERSALT study showed a positive relationship between 24 h urinary sodium
excretion and blood pressure. The findings from this study have been confirmed by two others
[120,121]. In the United Kingdom, since 2011 the Food Standards Agency worked with the food
industry to set the target of 2400 mg sodium/day by 2010 [99]. Several countries around the world,
the majority of which are in Europe, have targeted sodium reduction ranging from 5 to 8 g/person/
day [122]. In most countries, efforts were led by government, nongovernmental organizations, or
industry. At the same time, governments have been working with industry to reduce the salt levels
in foods. Pharmacists also joined the DASH suggesting that community and ambulatory practice
pharmacists should optimize medication management and incorporate lifestyle interventions that
reduce dietary sodium intake as part of a comprehensive approach to improve hypertension out-
comes [123].
The USDA provides data on sodium levels in U.S. foods. The USDA suggests that achieving
substantial decreases in sodium levels of commonly used foods in the United States is possible.
However, in practice it is difficult to do so. The National Salt Reduction Initiative (NSRI), coordi-
nated by the New York City Health Department, is a partnership of more than 85 organizations and
local and state health authority whose aim is to voluntarily reduce sodium levels in processed foods
by 20% and restaurant foods by 25% by 2015.
The FDA has been invited to look closely at fructose as a risk factor for the rise in hypertension
[124]. Addressing sodium without addressing fructose occupation will not solve the hypertension
epidemic. Consumer education on preventing hypertension is government’s responsibility and is
being done in Western nations. Consumer education of dietary approaches to prevent hypertension
should be encouraged. Consumer education on foods rich in bioactives antihypertensive should
also be encouraged. Cysteine is a very good antihypertensive amino acid. Cysteine can be obtained
from certain foods with soybean being the best of all. The best dietary sources of cysteine include
poultry, soy, grains, and eggs. Similarly arginine is converted by nitric oxide synthase into NO and
the latter is a modulator of vascular homeostasis. Dietary sources of arginine include seeds, soy
proteins, peanut, crustaceans, spinach, and turkey.
Food is not one size fits all. Similarly, salt is not one size fits all. Study after study has linked
AGEs and salt to hypertension and the resulting increase in stroke and heart attacks. To bring blood
pressure down and maintain a healthy level of both SBP and DBP in hypertensive individuals, diet
along with physical fitness is the most cost-effective way of keeping people healthy. Components
in diet that have direct effects on blood pressure are reducing sugar, AGEs, and salt. All the players
including the consumer, the government, the food industry, research institutions, and international
agencies have a big role in the fight against the global epidemic of hypertension. Individuals have
to know more about their genetics and limitations in what they can do and not do instead of eating
anything available. Food is and will become a personalized medicine.
HyPertensIon 143
Governments should protect people by making sure that disease-causing ingredients are not
used in excess in food. If pregnant women, infants, and children can be exposed to less sodium and
reducing sugar, it is possible that these children may not develop a love for highly salty or sweet
foods that are throughout the supermarket. Organic potassium salts and spices need to be investi-
gated as substitutes for sodium. Black people are very sensitive to sodium and top the list of hyper-
tensive communities. Lowering sodium intake to 1200–1500 mg or finding sodium replacement for
black people should be encouraged as research for minority health. Reducing sodium and reducing
sugar consumption in all communities but especially in minority communities is also encouraged.
Hypertension is a silent killer in minority communities. Food scientists wherever they are encour-
aged to pay more attention to these communities and design foods that can reduce the epidemic of
hypertension in these groups. Definitely, food is not one size fits all. The time to act is now.
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ChAPter 7
Atherosclerosis
7.1 DeFINItION
Atherosclerosis is a complex chronic inflammatory disease in the large- and medium-size arter-
ies whereby plaques progressively form and deposit on the surface of the arteries and narrow the
artery wall (Figure 7.1). Atherosclerosis can develop with or without diabetes.
There are two types of atherosclerosis: coronary artery disease and peripheral artery disease.
Coronary artery disease occurs when the plaques build up in the coronary arteries. Coronary artery
disease may result in myocardial infarction. When atherosclerosis develops in the carotid, plaque
formation may lead to a stroke. Peripheral artery disease occurs when plaque formation occurs in
the arteries of the legs, arms, and/or pelvis.
7.2 rISK FACtOrS FOr AtherOSCLerOSIS
Atherosclerosis develops over decades and the prevalence of the disease is increasing in Asian
and other developing economies as a result of lifestyle changes and increased rate of smoking [1].
Atherosclerosis was prevalent in Western nations between the 1960s and 1970s, but the incidence
has been declining since due to drugs that lower hypertension and lipids, changes in lifestyle, and
reduced smoking.
The etiology of atherosclerosis is complex. However, the disease is inflammatory and triggered
by a combination of genetic and environmental factors [2]. Nonmodifiable or genetic factors asso-
ciated with atherosclerosis include age, family history, and gender. The modifiable factors include
diet, lifestyle, and exposure. Diet-induced hyperglycemia, high-fat diet and dyslipidemia, smoking,
chronic inflammation, increased free fatty acids (FFAs), endothelial dysfunction, insulin resistance
(IR), and physical inactivity are risk factors for atherosclerosis development.
7.2.1 Genetic risk Factors
Atherosclerosis develops as a result of the interaction of genetic and environmental factors

including diet, nutritional status, and physiological parameters [3]. The fetal origin of atheroscle-
rosis may result from chronic exposure to oxidative stress and inflammation in utero. The dis-
ease process begins early in life and develops for decades before symptoms appear. Evidence of
impaired vascular growth has been demonstrated in young adults born prematurely [4], discordant
twin growth in utero [5], young adults born in the lowest quartile of birth weight [6], neonates with
intrauterine growth restriction compared to babies with normal birth weight [7], and term infants
[8]. The family history or genetic origin of atherosclerosis seems to predict future impaired vascu-
lar growth in boys more than girls [9]. The fetal origin of atherosclerosis may be associated with
149
Artery
wall
Normal
blood flow
(a) Normal artery
Abnormal
blood flow Plaque
Artery cross section
Narrowed Plaque
artery
(b) Narrowing of artery
Figure 7.1 (a) a normal artery with normal blood flow. (b) an artery with plaque buildup and abnormal blood
flow. (Courtesy of the national Heart Lung and Blood Institute, Bethesda, MD.)
placental mitochondrial dysfunction [10]. Others have suggested that the genetic etiology of athero-
sclerosis is expected to remain unexplained for some years to come [11].
7.2.2 Aging
Aging exerts an impairment of endothelial function because of reactive oxygen species (ROS)
generation and reduced nitric oxide (NO) activity and is a major risk factor for developing athero-
sclerosis. People aged 65 or older are four times more at risk of heart disease than those younger
than 50 years old [12]. Aging is associated with impaired mitochondrial oxidation, which is a major
contributor to endothelial dysfunction. Age-related atherosclerosis affects men sooner than women
of the same age before menopause possibly due to the protective effect of endogenous estrogen.
While premenopausal women are protected, age-related endothelial dysfunction is attenuated in
premenopausal hypertensive women. The protective effect seems to be associated with endogenous
atHerosCLerosIs 151
estrogen because it has been shown that no sex-induced difference is observed after menopause. The
protective effect in women may be associated with endogenous estrogen protection of NO avail-
ability by inhibiting ROS [12].
7.2.3 Gender
Compared to girls of the same age, adolescent men have a less favorable risk of developing ath-
erosclerosis: higher blood pressure, high atherogenic lipid profile, and higher prevalence of cardio-
vascular disease (CVD). Men develop atherosclerosis earlier than women of the same age, probably
for reasons explained in the earlier section [13].
7.2.4 environmental risk Factors for Atherosclerosis
7.2.4.1 Hyperglycemia and Advanced Glycation End Products
Hyperglycemia without diabetes can exert direct effects toward the development of atherosclerosis
through the formation of advanced glycation end products (AGEs) and advanced lipid oxidation end
products (ALEs). For simplicity, both AGEs and ALEs are often referred to as “AGEs.” Energy-dense
high glycemic index diets can induce plasma hyperglycemia. Hyperglycemia induces the formation
of AGEs that bind to its receptor, receptor of advanced glycation end products (RAGE), in endothelial
cells. The AGE–RAGE complex activates the enzyme NADPH oxidase that catalyzes the generation
of oxidative stress by the formation of ROS, and increased oxidative stress promotes inflammation.
There is substantial evidence that the AGEs from Maillard reaction are highly involved in the
progression of atherosclerosis [14]. Accumulation of AGEs in the body often leads to depletion of
good cholesterol and accumulation of bad cholesterol [15]. AGEs also enhance the oxidation of bad
cholesterol and oxidized bad cholesterol easily clogs the arteries [16]. AGEs formed from processed
foods or within the body as is the case with individuals with diabetes inactivate NO in vascular
walls causing defective vascular relaxation and hypertension of diabetes and aging. Individuals
with renal failure whether they are diabetics or not are highly susceptible to atherosclerosis [16–18].
7.2.4.2 Obesity
The association between obesity atherosclerosis development is very strong. Cholesterol crystals
from high-fat diets and obesity deposit in the arteries cause oxidative stress that in turn induces
inflammation [19]. First, arterial plaques contain high levels of inflammatory cytokines such as
IL-1β and IL-1R and the levels of these cytokines are associated with atherosclerosis severity
[19,20]. IL-1β and IL-18 induce more inflammatory cytokines while the level of IL-18 is a biomarker
of atherosclerosis-related death [21,22].
IR is a major risk factor for atherosclerosis development. Actually, IR has to be induced before
it can act as a risk factor for atherosclerosis. IR can be induced by hyperglycemia, increased FFAs,
and hyperhomocysteinemia and is the hallmark of obesity and diabetes.
7.2.4.4 Diabetes
The association of diabetes and atherosclerosis development is strong. Atherosclerosis-induced

mortality and morbidity are elevated in patients with type 2 diabetes mellitus. Diabetic patients expe-
rience higher rates of cardiovascular-related death than their age-matched nondiabetic counterparts.
Because of the increased incidence of diabetes worldwide and the relationship between diabetes
and coronary heart disease, it is imperative to address diabetes in order to prevent atherosclerosis
complications.
Chronic IR and hyperglycemia define diabetes. Chronic hyperglycemia predisposes diabetic
patients to high levels of AGEs. Accumulation of AGEs increases the expression and activity of
NADPH oxidase and the latter is an important source of vasculature oxidative stress in diabetes [23].
7.2.4.5 Abnormal Lipid Levels
Atherosclerosis begins as fatty streaks that underlie the endothelium of large arteries. Bad cho-
lesterol or low-density lipoprotein (LDL)-derived cholesterol form “foam cells” whose accumula-
tion in the arterial cell walls is the hallmark of early atherosclerosis. Macrophage-loaded cholesterol
stimulates the production of inflammatory mediators including cytokines and ROS, which recruit
other cell types and contribute to the development of a complex lesion [24]. High levels of LDL cho-
lesterol and reduced levels of high-density lipoprotein (HDL) favor the progression of cholesterol
within the arterial wall. There are four subtypes of LDL including lipid-enriched, largest, and most
buoyant LDL1 and lipid-depleted, smallest, and most dense LDL4. The smallest lipid-depleted LDL
particles are the most atherogenic because they are more susceptible to biochemical modification
including oxidation, formation of AGEs, and incorporation into immune complex leading to injury
to the endothelium and smooth muscle cells.
7.2.4.6 Hypertension
The association of hypertension and atherosclerosis development is strong [25]. Under normal
physiological conditions, the renin–angiotensin–aldosterone system (RAAS) regulates fluid bal-
ance and sodium levels. However, under pathological condition of hypertension, excessive RAAS
activity initiates and maintains the vascular inflammatory response and catalyzes the development
of atherosclerosis. There is strong evidence of the early involvement of the angiotensin II (AngII),
the hormone that induces vasoconstriction and the development of atherosclerosis. Activation of
oxidative stress by AngII induces inflammation that leads to endothelial dysfunction, an early risk
factor for atherosclerosis.
Hypertension causes damages in several organs including the arteries. Since the RAAS plays a
key role in atherosclerosis, hypertension treatment with angiotensin-converting enzyme inhibitors
and angiotensin II receptor blockers, statins and antioxidants, has shown to slow the inflammatory
process and atherosclerosis progression [26].
7.2.4.7 Smoking
Cigarette smoking and secondhand smoking induce a cumulative risk for atherosclerosis devel-
opment. Smoking induces mitochondrial dysfunction, endothelial injury, platelet activation, oxi-
dation of LDL, and DNA damage, all of which are risk factors for atherosclerosis. In vitro and
animal studies have shown that exposure of animal or human endothelial cells to tobacco smoke or
prooxidant found in tobacco smoke caused loss of mitochondrial potential, impaired mitochondrial
oxidative function, upregulation of mitochondrial DNA transcripts, and cell death [27].
7.2.4.8 Mitochondrial Dysfunction
The mitochondrial dysfunction appears to be a common denominator for all the risk factors for
atherosclerosis. Hyperglycemia, dyslipidemia, oxidized LDL, and FFAs all induce increased ROS
in the mitochondria.
atHerosCLerosIs 153
It is thought that the early stages of atherosclerosis are caused by risk factors including smok-
ing, high levels of bad cholesterol in the blood, hypertension, diabetes, or chronic inflammation.
Individuals with IR, high levels of AGEs and blood fat, and hypertension are at high risk of developing
atherosclerosis suggesting that AGEs should be considered a biomarker of atherosclerosis develop-
ment. The development of atherosclerosis involves the recruitment and deposition of foam cells, made
mostly of oxidized bad cholesterol and inflammatory proteins, on the arterial walls. Atherosclerosis
involves many components of the vascular, metabolic, and immune systems. Oxidized LDL induces
foam cell formation and has been considered for a long time as the most important risk factor for
atherosclerosis. However, in recent years, the contribution of chronic inflammation, the low level of
NO, the burden of high levels of ROS, and the high levels of AGEs derived from the consumption of
fried or grilled foods and consumption of highly sweetened foods accelerate vascular inflammation
leading to increased levels of ROS, elevated plasma C-reactive protein, high levels of the enzyme
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase that also releases high levels of
ROS, and diminished immune system due to increase in enzyme indoleamine 2,3-dioxygenase lead-
ing to increased risk of atherosclerosis. Atherosclerosis is accelerated by diseases such as diabetes
or lupus. The foam cells deposited in the arterial walls create regions where oxygen level is very low
making these regions very hypoxic. There are very few drugs known to be able to treat disease in
hypoxic regions making treatment of advanced atherosclerosis very complicated to modern medi-
cine at current level of knowledge. In recent years, the potential contribution of AGEs to atheroscle-
rosis has gained widespread acceptance. Ingestion of foods containing high levels of AGEs or AGE
precursors leads to increased circulating AGEs, the latter binding to its receptors, RAGEs, leading
to enhanced inflammation, increased generation of ROS, and disease propagation.
7.3 therAPeUtIC APPrOACh tO AtherOSCLerOSIS
Statin drugs were developed to inhibit endogenous synthesis of LDL cholesterol in patients at
high risk for myocardial infarction in whom elevated levels of LDL were difficult to control [28].
Statins are the best options on the market to reduce heart attacks and strokes in people with or at
risk for atherosclerosis. It has been suggested that the best alternative or adjuvants to statins should
be AGE inhibitors or breakers. AGE breakers such as alagebrium (ALT-711) have been designed and
used in clinics. However, there are reports that alagebrium actually does not break preexisting AGE
cross-link in vivo; rather alagebrium like many others reported AGE breakers may inhibit metal-
catalyzed AGEs and protein carbonyl formation [29].
7.4 DIetArY PAtterNS tO PreVeNt AtherOSCLerOSIS DeVeLOPMeNt
The rationale of fighting atherosclerosis at the food industry level is several fold:
• There is no doubt that the food industry feeds people. It is the produce stand in any city that can feed
the major agglomerations around the world. According to predictions, atherosclerosis will become
the leading cause of mortality worldwide by 2020 suggesting that developing technologies or foods
that can prevent the development of atherosclerosis is imperative.
• Food ingredients rich in AGEs or prone to AGE formation often find applications in foods and bev-
erages consumed at breakfast, lunch, dinner, or as snack or desert. The domino effect is so grave
that the best way to treat atherosclerosis is to identify susceptible food ingredients, phase these
ingredients out, and adopt technologies that do not generate oxidized food ingredients. For instance,
oxidized cholesterol that is generated through spray drying of egg yolk and storage can be found
in bakery products [30]. Butter is another example of a food ingredient rich in oxidized cholesterol
[30]. Recent study suggests that diacetyl, a ubiquitous butter-flavoring agent commonly used in pop-
corn, was found to exacerbate amyloid β-peptide involved in Alzheimer’s disease cytotoxicity [31].
• AGE breakers or AGE inhibitors that are effective at high temperature during food ingredient manu-
facturing or cooking need to be identified. Also very few in vivo studies have shown that reduction
of AGE accumulation is effective in repairing injury caused by AGEs on the vasculature [23].
• Most studies targeting atherosclerosis after the oxidized cholesterol has entered the arteries have
shown significant reduction of the risk of CVD but not a complete eradication of the risk.
• Several human trials using dietary bioactives have been disappointing, some have shown inconclu-
sive results, and others have shown no effects on the biomarkers of CVD. Twelve-week intervention
with 500 mg of cyanidin in postmenopausal women showed no effects on platelet reactivity, liver
and kidney function, blood pressure, or pulse [32]. Studies like this are considered disappointing
because the investigators of the study either underestimated or did not factor in the potential contri-
butions of daily use of proinflammatory compounds such as AGE-rich dairy products or processed
meats and most breakfast cereals that are part of our foods along with the cyanidin. This is similar
to trying to solve a problem (platelet reactivity) with a good compound (cyanidin) while the root of
the problem (proinflammatory compounds such as AGEs) is present in all meals consumed along
with the cyanidin.
• Globalization and hurried lifestyle have turned restaurants into people’s choices for regular meals.
But several restaurants are still designing menus based on flavor rather than health. The Maillard
reaction and albeit AGEs is still not well known in these premises and this will always be a problem
until someone keeps talking about this over and over.
As a result, we discuss four dietary patterns for reducing CVD. Pattern 1 briefly describes the
Dietary Approach to Stop Hypertension (DASH). Pattern 2 encompasses improving Western diet.
Pattern 3 covers the Mediterranean diet. Pattern 4 brings to the table the Japanese dietary pattern.
Pattern 5 discusses our Anti-Inflammatory Dietary pattern.
7.4.1 Dietary Approach to Stop hypertension Diet
The DASH was a series of multiyear interventional studies designed at the National Heart,
Lung, and Blood Institute using commonly U.S.-consumed food items [33]. The first study enrolled
459 healthy men and women age 22 and up with untreated systolic blood pressure <160 mmHg and
diastolic blood pressure 80–95 mmHg and comprised 67% minorities. At the start of the study,
participants were fed a control diet for 3 weeks. Then they were randomly assigned to 8 weeks of
(1) control diet, (2) a diet rich in fruits and vegetables, or (3) a combination diet rich in fruits, veg-
etables, low-fat dairy foods, and lean meats reduced in saturated fat, total fat, and cholesterol (the
DASH combination diet) [33,34]. The DASH combination diet, without sodium reduction or weight
loss, significantly reduced hypertension, blood cholesterol, and homocysteine in all groups and
more effectively in African-Americans. Hypertension is one of the major risk factors for atheroscle-
rosis suggesting that the DASH combination diet is one approach to be promoted.
DASH diet also has been shown to reduce blood cholesterol and homocysteine levels and to
enhance the benefits of antihypertensive drug therapy. The first diet was high in fruits, vegetables,
whole cereal products, low-fat dairy products, fish, chicken, and lean meats (low in saturated fat and
cholesterol; moderately high in protein; and high in minerals and fiber). The second experimental
diet was high in potassium, magnesium, and dietary fiber similar to the first diet but its fat, protein,
and calcium dietary fiber tests the effect of fruits and vegetables alone. Its potassium, magnesium,
and dietary fiber content will be at the same high levels as the ideal dietary pattern, while its fat,
protein, and calcium content resembled that of the control dietary pattern.
Our only critique of the DASH is that it does not address the quality of ingredients or make
suggestion on how these ingredients have to be cooked in order to achieve optimal health. For
instance, brisket is healthier than blackened red meat although both may come from the same
animal. Forwarding these recommendations to the restaurant and chefs will really help the restau-
rant industry serve healthier foods.
atHerosCLerosIs 155
7.4.2 Improving Western Dietary Pattern
Western dietary habits can be improved. The following three steps may help reduce dietary-
induced atherosclerosis and its complications in humans:
• Designing technologies that produce AGE-free or AGE-reduced and oxidized-cholesterol-free or

oxidized-cholesterol-reduced food ingredients that imply less heat processed dairy products includ-
ing cheese and ultrahigh-temperature milk, high-temperature processed egg powder, or fructose-
rich cereals. AGE-rich milk ingredients are used in snacks, meals, and almost every food that
can be sold and lead consumers to ingest these AGE-rich ingredients all day long all year around.
Incorporation of AGE-free dairy ingredients should help reduce AGE levels in all the thousands of
foods that contain dairy products.
• Discontinuing foods or food ingredients rich in AGEs [35]. The association of dietary AGEs and
the development and progression of atherosclerosis has been demonstrated in animal models and
humans regardless of the diabetes status [36]. Our understanding of the role of diet in the formation
of AGEs should allow the development of AGE-reduced food ingredients or foods.
• Formulating food ingredients or foods with less reducing sugars or reducing AGE precursors.
High-fructose ingredients including honey and Agave in foods or beverages should be reduced.
These products contain fructose and methylglyoxal, both of which are excellent precursors of AGE
formation.
• Growing, promoting, and making available more dark green or colored vegetables at home and in
restaurants. Promoting better cooking techniques through all media including written and audiovi-
sual media.
• Reducing consumption of sweetened fruits and vegetables including watermelon, table grapes, car-
rots, and sweet corn while promoting reengineering of these products in the laboratory to contain
less sugar.
• Phasing out concentrated fruit juices; making phenolic-rich juices rather than having clear and
good-looking juices with minute amounts of phenolics. Cranberry, one of the best fruits ever, can be
blended and sold as is to allow customers to really benefit from this fruit’s bioactives. Cherry juice
with all its anthocyanins and proanthocyanidins is an excellent beverage.
• Encouraging people to cook food at temperatures of 300°F or less for all meals at home, away from
home, or in all eateries including restaurants and fast-food restaurants. Briskets have fewer AGEs
than the same meat that was barbecued, fried, or grilled.
• Incorporating impactful bioactives currently sold as supplements such as calcium, folic acid, vita-
min D, and vitamin E within appropriate matrices into healthy food formulations or consumption.
Often supplements have failed to deliver because they are consumed in isolation along AGE-rich or
AGE-precursor foods. Children who may also need these bioactives as early as possible do not take
supplements. Recent studies show that the link between calcium supplements and potential CVD is
an indication of improper ways (supplements) of delivering good nutrients to the body.
In the short term, this plan has a low rate of adoption by the food and beverage industry for reasons
that are purely business. However, with time the food industry and all its branches including the
restaurant industry will find itself adapting and adjusting to the trend.
7.4.3 Mediterranean Dietary Pattern
The Mediterranean region includes 21 countries: Southern Italy, Crete, coastal Greece, Morocco,
Tunisia, Algeria, Libya, Egypt, Israel, Lebanon, Syria, Turkey, Montenegro, Spain, Malta, Monaco,
Albania, Slovenia, Croatia, and southern France. The diet in this region is centered on the following:
• Regular and daily consumption of fruits and raw nuts for desserts
• High consumption of whole grains (bread, pasta, rice, polenta, bulgur, potato)
• Regular consumption of vegetables and legumes as part of meals
Figure 7.2 olive oil is the preferred oil in the Mediterranean cuisine and diet.
• Regular use of olive oil for cooking and dressing (Figure 7.2)
• Moderate consumption of wine (a glass or two of wine per day) with meals
• Low consumption of grilled or steamed chicken
• Moderate (few times per week) to high consumption of fish; egg (up to four eggs a week), poultry,
and sweets
• Very low (few times per month) consumption of red meat mostly lamb meat
• Moderate consumption of cheese and yogurt, regular use of fresh fruits for dessert, and customary
daily walks
• The main meal is consumed around noon time while the supper is often light
• Coffee is not consumed in large amounts and all day long
In the traditional Mediterranean society, people walk more than they use individual or public
transit systems. The significance of the traditional Mediterranean diet is that by essence the food is
loaded with all the desired nutrients for good health, no need for supplements, and as a result these
ingredients work synergistically to enhance health resulting in a naturally reduced rate of CVD and
cancer and above all an almost disability-free old age.
Virgin olive oil is rich in oleic acid that may be associated with enhanced cardiovascular health.
Virgin olive oil is also rich in squalene and polyphenolic antioxidants such as hydrotyrosol that
have antioxidative and anti-inflammatory properties to protect against cholesterol and LDL oxida-
tion and at the same time aid in reducing the levels of LDL [37]. The health benefits of virgin olive
oil are in part ascribed to the oil content of bioactive compounds tyrosol, hydroxytyrosol, taxifolin,
oleuropein, and oleic acid.
The Mediterranean diet provides high amount of dietary fiber and monounsaturated fats and
low amounts of saturated fats. High amounts of dietary fiber help the body fight IR making people
healthier and visiting doctors’ offices less often. People in this region remain physically active even
at an age older than 90 years. The Mediterranean Islands Study (MEDIS) study investigated “healthy
aging” of long-lived individuals, who were free of CVD in several regions of the Mediterranean
atHerosCLerosIs 157
including from Cyprus, Mitilini, Samothraki, Cephalonia, Crete, Lemnos, Corfu, and Zakynthos
[38]. The study suggested that adherence to physical activity, Mediterranean diet, midday naps, and
smoking cessation in the elderly was associated with increased longevity in this region compared to
others around the world. People in this region often walk for miles even at old age knowing that it
is a healthy practice. “The island where people forget to die” is a story written by Dan Buettner on
October 24, 2012 and published in The New York Times about centenarians who live an amazing
long life on the island of Ikaria near the Aegean Sea. The story can be read at http://www.nytimes.
com/2012/10/28/magazine/the-island-where-people-forget-to-die.html?src=me&ref=general.
7.4.4 Japanese Dietary Pattern
The Japanese diet is often centered on rice, miso soup, egg or fish, vegetables, fruits, and green
tea. Breakfast is an important meal in Japan and often the largest (Figure 7.3). Rice and noodles con-
tain refined flours and may provide more calories if not consumed properly; the portion size is opti-
mized to avoid excessive consumption of refined flour in one meal (Figures 7.4 and 7.5). The Japanese
diets provide on average a quarter less of calories than the Western style diet. Calorie-dense foods
are often replaced with less energy-dense foods including fruits, vegetables, and broth-based soups.
Since the 1970s, mortality associated with CVD and stroke has declined in Japan compared to
the Western world due in part to decreased smoking although the body mass index has increased
[39]. People reach their mid-1970s mostly disability-free; people live longer than their counterparts
in the rest of the world often reaching life expectancy of 79 years for men and 89 years for women,
respectively.
However, the longer life expectancy compared to the rest of the world is also associated with
the development of dementia and Alzheimer’s disease in the Japanese elderly. The westernization
of Japanese foods such as tempura does not add health. Shrimp is an excellent source of cholesterol.
Frying shrimp creates favorable conditions for oxidized cholesterol formation that is absorbed when
the tempura is ingested. Chronic consumption of tempura can be a good source of inducers of oxi-
dative stress.
Figure 7.3 a sample of Japanese breakfast. from top left to right, Green tea, pickled vegetable (plum and
Japanese radish), natto (fermented soybean) with dry bonito flake and green onions, rice, miso
soup (with Japanese squash, beans, shimeji, mushroom), dried mackerel with Japanese radish
(Japanese daikon), egg, dried seaweed (with soy sauce).
Figure 7.4 a sample of Japanese dinner. from top left, broccoli tossed with dried bonito, okara (roasted
tofu including carrot, shitake mushroom, snow pea, sesame seed, yam cake, seaweed), rice,
soup (with egg, green onions, browned fish sausage, and snow pea), and three different tempura
(shrimp, vegetables mixed with chopped shrimp, sardine rolled with shiso).
Figure 7.5 a sample of Japanese dinner. from top left, tofu (ginger, green onion, dried bonito flake), kimpira
(burdock, carrot, lotus, yam cake, sesame seed), rice mixed with several kinds of cereals (such
as brown rice, millet, pearl barley, red rice, and amaranth), miso soup (seaweed, Japanese rad-
ish, sliced fried tofu, green onions), yellowtail fillet with Japanese radish, at the center yam (with
salmon roe, mentaiko, spicy pollack roe, and seaweed).
7.4.5 Vegetable- and Fruit-rich Diet
The vegetable- and fruit-rich diet is a platform that emphasizes more vegetables, fruits, and a
balanced diet bringing together the best in produce and processed foods from the West, Japan, the
Mediterranean, Africa, Southeast Asia, the Middle East, and Central and South America. Along
with daily light exercise, this type of diet is one that can help individuals at home or in hospital
live healthy to a disability-reduced old age. Vegetables have very little amounts of simple carbo-
hydrates, yet vegetables can provide some of the best and much needed nutrients to counteract
atHerosCLerosIs 159
oxidative stress. Chlorophyll, phenolics, carotenoids, and selenium can all delay oxidative stress in
plants and oxidative stress and markers of CVD in humans who consume vegetables or plants rich
in the bioactive compounds mentioned earlier [40].
The plasma of 39 subjects who consumed 200 mL of fruit and vegetable puree drinks for 6 weeks
showed an increase in endothelial-dependent vasodilation [41]. A Mediterranean vegetable- and fruit-
rich diet is inversely correlated with the risk of CVD [42]. Consumption of green leafy vegetables
and fruits is also associated with reduced risk of high blood pressure, ischemic stroke, and ischemic
heart disease as a result of the high levels of inorganic nitrate that converts into nitrite, and the latter
is converted into NO [43]. However, a recent study using beet juice showed that acute consumption of
nitrate-rich beet juice did not improve muscle oxygenation and blood flow in healthy young men but
did modify arterial pulse wave velocity [44].
7.5 CUrreNt treNDS
The war against atherosclerosis has not yet been won. Small battles may be won here and there
but not the big war.
Cost of food product development has always been one reason behind the food industry’s
unwillingness to reformulate products despite the plethora of information in the literature. Perhaps
if Detroit could move from designing cars that suck gas at 10 miles per gallons to cars that run at
35 miles per gallon, the food industry can develop healthier foods. After all, globalization requires
processed foods to be served at all times and the food industry is paramount to globalization and
will significantly benefit from it. The food industry should not be waiting for issues such as city
mayors to impose limits on food consumption before reacting.
Current trends in atherosclerosis are centered on identifying new lipid lowering drugs or foods
to reduce the risk of atherosclerosis. The potential antiatherogenic activities of several dietary bio-
actives are being tested in in vitro or animal models. The symptoms are the target.
Current trends also focus on developing sophisticated advanced technologies such as nanotech-
nology to enhance the bioavailability of ingested antioxidants. The evaluation of the toxicity of
nanoparticles as food additives deserves more research [45,46]. Because of lung tropism of nanopar-
ticles, the future of nanoparticle foods at the dining table may mire the “Green Revolution.” It came
and disappeared while hunger remained unresolved.
Hyperglycemia can be solved without the sophistication and uncertainty of nanotechnology.
Reduce sugar and remove oxidized cholesterol from ingredients, process foods minimally, store
foods appropriately, invest in prevention rather than treatment. As a result, major issues associated
with AGEs and cholesterol oxidation in the body will be minimized.
Current evidence indicates that functional foods are reducing only a modest fraction of cardiovas-
cular risk burden because these well-intended foods will not do well as long as hyperglycemia, AGEs,
and IR are still the culprit. Major supportive adjustments in the food industry are needed to provide the
consumer with really health-enhancing foods that do not contain unnecessarily reduced sugars, AGEs,
or oxidized cholesterol. Major supportive adjustments are also needed from the restaurant industry
because good and unhealthy ingredients are often combined and cooked to generate flavorful meals
with less consideration to health. This situation will hopefully change when credentialed authorities
require that culinary schools incorporate and teach food chemistry and toxicology to their students.
Dietary intervention against atherosclerosis development and progression should include both
prevention and intervention. Atherosclerosis prevention is a lifelong process that involves adherence
to a dietary regimen low in foods containing oxidized lipids and high in bioactive compounds that
prevent the buildup of foam cells and plaques in the arteries. Foods rich in bioactive compounds that
can inhibit or reduce bad cholesterol synthesis and oxidation, reduce fat in the blood, and inhibit the
inflammatory can prevent the development of atherosclerosis and the resulting CVD.
Vegetables, medium sweet fruits, tart fruits, legumes, low glycemic index carbohydrate foods,
less reducing sugar foods and beverages, and omega-3-fatty acid-rich fish should be consumed regu-
larly and everything else in moderation.
Consumers are encouraged to purchase and use the best oils for cooking while at the same time
regulatory agencies should encourage manufacturers of oils and fats that are not good for the human
body to find alternative nonhuman uses for their products. It is time to consume less of man-made
foods as these may be unhealthy products.
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ChAPter 8
Kidney Inflammation
8.1 INtrODUCtION
The kidney is a filter and the major site for the excretion and sometimes the degradation of
advanced glycation end products (AGEs) and small inflammatory molecules. The cells that make
the kidney are known as podocytes. These cells do not divide or replicate regularly like many other
cells in the human body. Their fate depends entirely on their ability to cope with stress, suggesting
that chronic oxidative stress provided, for instance, by exogenous sources such as regular consump-
tion of foods containing high levels of proinflammatory molecules, is a major risk factor that can
lead to dysfunctional kidney.
8.2 AGeS, Free FAttY ACIDS, AND KIDNeY INFLAMMAtION
Kidney disease is on the rise worldwide as a result of the increase in obesity and diabetes that
have been associated in part with the globalization of the Western diet [1]. Consumption of high-
calorie foods has increased and the price of sugar has increased by 30% since the 1980s, while the
price of fruits and vegetables has increased sharply by 200% [2]. The lifetime risk of developing
diabetes was 1 in 30 in the early part of the century and the lifetime risk of developing diabetes
has changed to 1 in 3 for individuals born in the twenty-first century [3]. In the United States alone,
one-third of the population is overweight and one-third is obese [4].
In most cases, healthy adults have intact or good renal function and some individuals can main-
tain normal renal function with age. However, when excessive inflammatory compounds including
AGEs and free fatty acids such as palmitate from dry heat-treated foods or cooking oils, respec-
tively, are consumed and excreted through or retained in the kidney on a regular basis, the intracel-
lular accumulation of AGEs accelerates and induces oxidative stress. For instance, in the 1950s, the
portion size of a soda drink was 7 oz, the portion size of fries was 2.4 oz, and the portion size of a
hamburger was 3.9 oz; today, the portion size of fries is 6.7 oz, the portion size of a soda is 42 oz,
and the portion size of a hamburger is 12 oz [5]. The increase in portion size has been directly
associated with the increase in protein, sodium, refined carbohydrates, and processed foods. As the
consumption of protein, sodium, and refined carbohydrate increased, so did oxidative stress to the
kidney cells. Oxidative stress causes inflammation and reduced function of the kidney.
Exogenous AGEs from diet are major contributors to the accumulation of AGEs in renal insuf-
ficiency [6]. Regular consumption of foods rich in AGEs, such as omelet sandwich, cheese-loaded
pizza, flamed pizza, and lasagna, can be a risk factor for more inflammatory compounds going
through or depositing in the kidney (Figure 8.1). Methylglyoxal from cola beverages or AGE-rich
foods accumulates in the body (Figure 8.2). Some of the AGEs from these foods are excreted
through the kidney, while some remain in the body and accumulate at different tissues including the
eye, heart, and brain [7,8].
163
Figure 8.1 Cheese-rich pizza is a source of high levels of advanced glycation end products.
Figure 8.2 Cola beverages contain high levels of advanced glycation end products that cause oxidative stress
in the kidney.
AGEs from foods or the body are proinflammatory. When AGE-rich foods are consumed with
little amounts of antioxidants, the kidney allows oxidative stress and inflammation to proceed
unchallenged. AGEs can infiltrate all renal compartments; for instance, in diabetic patients, AGEs
can be found in the kidney vessels, glomeruli, tubules, and interstitium [9,10], suggesting that inges-
tion of AGE-rich foods or AGE-precursor foods can in the long run damage the kidney of individu-
als whose diets are centered around foods containing high levels of AGEs or advanced lipid end
products (ALEs). ALEs from fried foods (Figure 8.3) also induce inflammatory proteins that are
damaging to kidney cells [11,12]. Restriction of AGEs delayed renal fibrosis and dysfunction in the
remnant kidney mode [6].
Chronic kidney inflammation predisposes the kidney to acute kidney injury, kidney dysfunc-
tion, chronic kidney disease, or kidney cancer [13,14]. Glycation can also occur in extracellular
matrix proteins and low-density lipoprotein and AGE-formed deposit in the vessel wall and can
contribute to atherosclerosis development [15]. The clinical, economic, and social significance of
KIDney InfLaMMatIon 165
Figure 8.3 advanced glycation end product–rich fried foods.
kidney inflammation is that chronic kidney disease affects more than 20 million Americans [16],
decreases productivity and severely affects the quality of life when expensive dialysis treatments
are needed, limits life expectancy, and induces several other ailments including bone loss, fractures,
cardiovascular disease, immune suppression, and earlier death. The prevalence of chronic kidney
disease in adults (14.5%) is higher than the prevalence of type 2 diabetes mellitus (8.1%) and higher
than the prevalence of congestive heart failure (2.4%) [16].
Dietary fatty acid intake is associated with renal function. Palmitate from palm oil induces the
production of reactive oxygen species, which can cause inflammation in kidney tissue and kidney
cell death [17–19].
8.3 ASSOCIAtION OF Other DIetArY AND MODIFIABLe

FACtOrS AND KIDNeY INFLAMMAtION
Dietary protein, sodium, inorganic phosphates, indoles, and gut microbiota can also contribute
to the pathogenicity of chronic kidney disease. The association of each dietary factor and kidney
inflammation is described briefly.
8.3.1 Dietary Protein
The levels of proteins in typical U.S. diet are twice the amount recommended by the U.S. dietary
guidelines [20]. Prospective population-based studies have indicated significant decreased in kidney
function among individuals with diabetes and hypertension who consumed high levels of protein of
their diets [21]. Lin et al. [22] examined the associations between Western dietary patterns and kid-
ney function decline also known as microalbuminuria. Participants included female in the Nurses’
Health Study using data from food frequency questionnaires returned in 1984, 1986, 1990, 1994,
and 1998 and urinary albumin–creatinine ratios from 2000 (N = 3121). Comparison was made with
the Dietary Approaches to Stop Hypertension (DASH)–style dietary pattern. The study concluded
that “a Western dietary pattern rich in nondairy animal protein is associated with a significantly
increased odds of microalbuminuria and rapid kidney function decrease, whereas a DASH-style
dietary pattern may be protective against rapid kidney function decline.” The association of high
animal protein intake, high intake of sweets and sweetened desserts, low intake of fresh fruits and
vegetables and low-fat dairy products, and the risk of kidney function decline has also been reported
by other studies [1].
The kidney function declines with aging. However, a recent examination of the association
of high protein intake and kidney function in healthy elderly men and women enrolled in the
Cardiovascular Health Study (N = 3623) and the use of food frequency questionnaire showed no sig-
nificant associations when protein intake was separated by the source (animal and vegetable) [23].
8.3.2 Dietary Sodium
Bread is an excellent source of sodium (Figure 8.4). Fruit pies, regardless of the fruit used, are
sources of high levels of sodium (Figure 8.5). Commercial soups are known for containing high
levels of sodium (Figure 8.6). The sodium content in Figure 8.5 is half of a daily intake of sodium
for an adult. Bacon is salty (Figure 8.7). Luncheon meat is another good example of high sodium
stored in foods (Figure 8.8).
High dietary sodium intakes predispose individuals to salt-sensitive hypertension and promotes
kidney function decline. Ohta et al. studied the influence of long-term salt load on renal function
in 133 hypertensive patients (80 women and 53 men, mean age 60 ± 9 years) for 10 years and con-
cluded that long-term salt load promotes renal damage and function decline in hypertensive patients
[24]. High-salt diets increase the risk of hypertension in normal men [25].
8.3.3 Inorganic Phosphates
The association of inorganic phosphates and kidney function decline and the development of
chronic kidney disease are strong [26]. Inorganic phosphates are used as processing aids in food
product developments but often not reported (Figure 8.9). Inorganic phosphates are bioavailable and
serum levels have been directly associated with the rate of kidney function decline in early chronic
kidney disease [27]. Since levels of inorganic phosphates are not reported, it is difficult to estimate
the real intakes of these salts especially for individuals with kidney diseases. In healthy individu-
als or individuals with moderate kidney dysfunction, the body adapts to counteract the presence of
high levels of inorganic phosphates in serum, but in patients at stages 4–5 of chronic kidney disease,
Figure 8.4 the mighty bread is a source of high levels of sodium and may not be good for the kidney in the
long run.
Figure 8.5 fruit (blueberry, apple, or lemon) pies are rich in sodium and sugar, both of which are not good
for the kidney.
Figure 8.6 Commercial soups are where sodium can be found in very high amount in one serving. this soup
contains 1200 mg of sodium per serving.
hyperphosphatemia occurs [28]. Compared to phosphates bound to proteins, inorganic phosphate

absorption is higher than organic phosphate absorption. About 40%–60% of phosphates bound to
animal proteins are absorbed, while only 10%–30% of proteins bound to vegetable proteins are
absorbed [29].
8.3.4 Indoles
The enzyme tryptophanase found in intestinal bacteria converts tryptophan into indole that
is absorbed into the blood stream and metabolized in the liver into the toxin indoxyl sulfate [30].
In healthy individuals, indoxyl sulfate is excreted into urine. In individuals with kidney function
insufficiency, indoxyl sulfate accumulates in the kidney tissues and induces oxidative stress in kid-
ney cells and reduced kidney function [31].
Figure 8.7 Bacon is salty.
Figure 8.8 Luncheon meat stores high levels of sodium.
8.3.5 Gut Microbiota
There are more than 100 trillion microbial cells in the human gastrointestinal tract. These
microbial cells play a significant role in the nutrition, metabolism, physiology, and immune
function of the host. The association of gut microbiota and kidney function or the kidney–gut
axis has been established mostly in individuals with chronic kidney disease. Gut microbiota
ferment protein and nitrogenous compounds into toxins such as p-cresol and indoxyl sulfate,
which accumulate and translocate into the blood stream, reach the kidney, and since these tox-
ins are not eliminated, the toxins can cause inflammation, kidney failure, and cardiovascular
disease [32,33].
Figure 8.9 typical foods where inorganic phosphates are used as processing aids.
8.3.6 Physical Inactivity
Lack of physical activity can have negative effects on kidney function even in healthy indi-
viduals [34]. Prolonged physical inactivity may reduce kidney function. Physical inactivity is often
observed in patient on dialysis [35].
8.4 DIetArY APPrOACheS tO heALthY KIDNeY
The number of people with impaired renal function is increasing worldwide [36,37]. The evi-
dence that dietary factors are involved in the pathogenesis and progression of kidney inflammation
and chronic disease is mounting. The location of the kidney and its involvement in trafficking food
components or their metabolites suggest that dietary approaches to prevent kidney inflammation
may be the cornerstone to healthy kidneys. Dietary approach to healthy kidney involves
1. The identification of proinflammatory foods that cause or exacerbate inflammation in the kidney
cells and avoidance of these foods
2. Dietary sodium reduction
3. Low-oxalate diet
4. Dietary inorganic phosphate reduction
5. Adoption of low-animal-protein diets
6. Adoption of a diet high in vegetables and fruits
7. Targeting the metabolic syndrome
8.4.1 Identification of Proinflammatory Foods or Food Components that

exacerbate Kidney Inflammation
High-protein diets such as foods with protein content of more than 25% of energy or more
than 2 g/kg body weight per day are often developed with reducing sugars to improve taste and
palatability. These high-protein diets are also promoted for physical endurance and overall general
good health. Protein bars and high-protein smoothies are typical examples of high-protein diets.
Unfortunately, the combination of protein and reducing sugars in these foods creates a favorable
environment for AGEs formation. Studies in mice and humans have shown that high-protein diets
promote inflammation and exacerbate early kidney cell death [29,38]. These types of diets increase
glomerular hyperfiltration, hypertension, and kidney damage and the prevalence of chronic kidney
disease in the general population without preexisting kidney disease [39].
The contribution of AGEs to chronic kidney disease and specifically diabetes-induced kidney
disease and end-organ injury has been identified and demonstrated [40]. Most studies have been in
animal models; however, few clinical studies have shown that inhibiting AGEs ameliorate the disease.
It is suggested that high-protein foods especially animal protein–rich foods be consumed in mod-
eration. Fish, meat, milk, and egg are protein-rich ingredients or foods and should be consumed in
moderation.
8.4.2 Dietary Sodium reduction
The DASH diet has shown that dietary salt reduction can achieve blood pressure reduction. The
DASH diet can also be combined with sodium reduction to achieve better reduction in systolic blood
pressure that can average 12 mmHg among adults with hypertension [41]. Consumption of sodium-
rich foods including hams, bacon, and most commercial soups should be curtailed. In individu-
als with chronic kidney disease, salt reduction improves blood pressure and enhances the effects
of drugs such as the antiproteinuric drugs and angiotensin receptor blockers [42,43]. Significant
salt reduction in foods is a challenge because of the role of salt in foods. Salt, especially sodium
chloride, is used in foods to reduce bitterness and enhance palatability.
The incidence of chronic kidney disease is increasing worldwide due in part to the increase in
the number of diabetes and hypertension. Chronic consumption of salty foods including fast foods
may play a role in the increase of kidney disease incidence. Dietary sodium reduction and restriction
is key to reduce the incidence of chronic kidney damage. Dietary sodium reduction or restriction
improves blood pressure and kidney function [44]. Dietary sodium restriction can be done with
foods prepared at home and foods consumed in restaurants.
8.4.3 Low-Oxalate Diet
Foods containing oxalates are risk factors for the development of kidney stones and include beet
green, rhubarb (stewed, cooked, or canned), spinach, beets, and Swiss chard (Figure 8.10a and b).
Excessive consumption of tea without large amount of water consumed, especially black tea and
coffee, can lead to oxalate formation and accumulation in the kidney.
Diets low in antioxidants such as beta carotene increase the risk of kidney stones [45]. Individuals
with history of kidney stones often have significant low serum levels of carotene antioxidants [45].
8.4.4 Dietary Inorganic Phosphate reduction
Foods that contain added inorganic phosphates may not keep the kidney healthy in the long run
and may be risk factors for hypertension. Inorganic phosphates are easily bioavailable. Uncooked meat
and poultry contain added inorganic phosphates [46]. Most processed foods including cola and soft
drinks, chocolate drinks, cocoa powder, fruit juices, beer, cheese, baked goods, sausages, hams, cold
cuts, canned fish, heat-treated milk products and powders, and dressings contain inorganic phosphates
added as processing aids or ingredients [47]. Since 1990, the daily intake of inorganic phosphates added
to foods has doubled from 500 mg/day to 1000 mg/day [48]. Phosphates are also found in vegetable, but
unlike inorganic phosphates found in processed foods, the bioavailability of phosphates in vegetables is
less than 50%. Since phosphates are not reported on the nutrition facts of foods, individuals with kidney
(a) (b)
Figure 8.10 (a) oxalate-rich beets are not good for the kidney. (b) oxalate-rich swiss chard is not good for
the kidney.
diseases are often unaware of the presence of phosphates in many food products. Excessive phosphates
may lead to hyperphosphatemia, a pathological condition whereby phosphate levels in the blood is
elevated. For persons with normal renal function, excessive phosphates in the blood induce endothelial
cell dysfunction in the vascular system, accelerate renal dysfunction, increase vascular calcification,
promote cardiovascular disease risk factor, and correspond to premature aging and death [47,49–52].
High levels of serum phosphate have been associated with the development and progression of
kidney, bone, and cardiovascular diseases [53]. The abnormal levels of phosphates in diet may disrupt
the regulation of vital bioactive compounds such as calcium and vitamin D and contribute to kidney
disease and bone loss. It is being recognized that too much inorganic phosphates can be damaging
to individuals who are not currently suffering from kidney disease but may be progressively under-
going unnoticed kidney function decline [47,53]. The growing consumption of processed foods rich
in phosphate additives through restaurant meals, fast and convenient foods exacerbate the inability
to estimate phosphate intake in people’s diets [53,54]. While the most attention has been focused
on obesity, salt, sugar, and trans fats, less attention has been given to dietary phosphates. Since the
public is aware of the damage of sodium to the body, educating the public on the potential damage of
too much phosphate in foods should help consumer make healthy choices when purchasing foods or
dining out. For instance, in Finland and the United Kingdom, the amount of sodium added to foods is
indicated on the package as follows: green for low, yellow for medium, and red for high sodium 47].
A similar approach has been proposed for phosphates in foods [47]. Uribarri questioned whether the
2015 Dietary Guidelines for Americans should consider adding phosphorus to the list of nutrients
recommended for reduced intake [53]. The time is right for food scientists and processors to review
the role of phosphates in food formulation in order to address the concern of nephrologists and renal
dietitians about inorganic phosphates in foods and their implication for the general population.
8.4.5 Adaption of Low-Animal-Protein Diets
Diets low in sodium, moderate protein consumption, increased vegetable protein consumption, and
dietary calcium and phosphorus restriction decrease serum phosphorus, uremic toxins, and kidney cell
damage and delay kidney disease progression [55,56]. Low-protein diets are low in phosphorus, sodium,
uric acid precursor, and potassium. Phosphorus is an independent risk factor for kidney-related death in
hemodialysis patients. Low-protein diets improve lipid profile, insulin sensitivity, and blood pressure and
reduce blood glucose [56]. Reducing daily protein intake to about 0.8 g/kg/day, which has been recom-
mended, and increasing the intake of fruit and vegetables may reduce the risk of kidney disease [1].
Figure 8.11 tofu is a vegetable protein and good for healthy kidney.
8.4.6 Adoption of Diet high in Plant Proteins, Vegetables, and Fruits
Plant proteins such as tofu are good for kidney health (Figure 8.11). Vegetables are low in protein
and good food for the kidney especially for individuals with kidney health problems. Vegetables
are also good sources of potassium that unlike sodium is essential for healthy kidney. Diets rich
in vegetables and fruits provide antioxidants for protecting kidney cells from insults or oxidative
stress. Diets rich in vegetables and fruits are also low in AGEs and therefore friendlier to the kidney.
8.4.7 targeting the Metabolic Syndrome
Obesity is a major risk factor for developing kidney disease [57]. Targeting obesity with diet through
weight management improves kidney function. Chronic kidney disease and inflammation deplete the
body of vitamin D. Diets rich in fiber and vitamin D can reduce inflammation in the kidney.
Diabetes is also a major risk factor for kidney damage. Long-term moderate protein diet
improves renal function, oxidative stress, and inflammation in type 2 diabetic with kidney problems
[58]. Diets rich in vegetable proteins are better for individuals with diabetes than diets rich in animal
or bird proteins.
Most cancer proteins are often phosphorylated compared to normal cells. Similarly, tau proteins
in Alzheimer’s disease are highly phosphorylated. The question is, “Once in the body, where do all
the phosphates consumed with foods go?”
8.5 FUtUre DIreCtION
Poor dietary habits rich in sodium, reducing sugars, and inorganic phosphates may be associ-
ated with the high rate of chronic kidney disease among low-income poor. Sodium reduction in
foods is important for healthy kidney. Moderate consumption of oxalate-rich foods is necessary to
keep the kidney healthy. Targeting inorganic phosphate contents of foods available to low-income
poor and those who regularly consume inorganic phosphate-rich foods may help reduce the current
disparities in chronic kidney disease. Adherence to DASH-suggested food types will also curtail the
increasing rate of kidney associated inflammation. Adherence to AGE-less or AGE-free diets will
reduce the incidence of kidney inflammation and associated diseases. Diets rich in vegetables and
fruits are rich in antioxidants and will protect the kidney cells from oxidative stress and subsequent
inflammation and diseases.
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ChAPter 9
Osteoporosis
9.1 INtrODUCtION
The World Health Organization (WHO) defines osteoporosis as a systemic skeletal disease
characterized by low bone mass and microarchitectural deterioration of bone tissue with a conse-
quent increase in bone fragility and susceptibility to fracture [1].
The U.S. National Institutes of Health defines osteoporosis as a disease characterized by insuf-
ficient bone strength that predisposes individuals to a higher risk of bone fracture [2].
Osteoporosis is a systemic disease that develops as a silent symptomless disease. The patient is
unaware while the bone becomes porous and increases its susceptibility to deterioration and break-
down. Osteoporosis-induced fractures occur in adult age and target the hip, spine, leg, shoulder,
forearm, upper arm, distal radius, or wrist.
Osteoporosis is a progressive disease that occurs when the amount of bone tissue and the
material composition of the bone can no longer adapt and respond to the mechanical and physical
demand of the skeleton. The disease affects the whole skeleton. As a result, osteoporosis patients
are at increased risk of falls that play a major role in about 90% of incidence of fractures in these
patients. The average bone mineral density of osteoporotic individuals is lower than the average
mineral density of young adults [3]. Osteoporosis-related fractures especially hip fractures affect
the quality of life, create severe socioeconomic malaise as they are associated with significant
increase in health-care costs, result in loss of independence, and reduce life expectancy because
these fractures induce high rates of morbidity and mortality [4–6].
9.2 COMPOSItION OF hUMAN BONeS
The bone contains organic materials such as collagen and matrix proteins, cells, and inor-
ganic materials such as calcium. Bones and teeth contain about 99% of the calcium in the
human body. The calcium is bound to phosphate in a mixture called hydroxyapatite. Bone mass
density (BMD) and bone quality are used to determine bone strength but is not sufficient enough
to define osteoporosis. The cells that make the bones include the osteocytes, osteoblasts, and
osteoclasts. Bone formation is regulated by osteoblasts, bone remodeling is regulated by osteo-
cytes, and bone resorption is regulated by osteoclasts. During osteoporosis development, an
imbalance in the regulation of bone cells changes the BMD, which in turn leads to a net loss of
bone strength and quality.
177
9.3 PreVALeNCe AND SOCIOeCONOMIC SIGNIFICANCe OF OSteOPOrOSIS
The worldwide prevalence of osteoporosis is very high. There are more than 200 million people
around the world suffering from osteoporosis [7]. About three-quarter of individuals with osteopo-
rosis have not been diagnosed and therefore receive no treatment for their conditions. The disease
is a major worldwide public health concern that encompasses almost all nations [8–12]. According
to Osteoporosis Canada, www.osteoporosis.ca, the prevalence of osteoporosis-induced fractures is
higher than the prevalence of heart attack, stroke, and breast cancer combined.
Osteoporosis affects about 8 million women and more than 2 million men over the age of 50 in
the United States and is associated with about 600,000 fractures yearly [13]. Baby boomers have
a 55% risk of developing osteoporosis, while 44 million Americans are at risk of developing the
disease. More than 1.5 million Canadians aged 40 or older (10% of adult population) have been
diagnosed with osteoporosis. In India, osteoporosis may have already affected more than 25 mil-
lion people [14].
Osteoporosis develops the risk of fractures; patients with osteoporosis are at high risk of
chronic pain, permanent disability, loss of self-esteem, fear, anger, strained relationship with
relatives, and death. Osteoporosis is a major health concern worldwide [15,16]. Osteoporosis-
related hip fractures are associated with increased mortality [17]. In the United States
in 2001, osteoporosis alone accounted for some $17 billion in direct annual health-care
expenditure [18,19]. In 2005, osteoporosis fractures cost the U.S. health-care system an esti-
mated $19 billion [20]. In 2010, Canada spent about $2.3 billion for osteoporosis and osteopo-
rosis-related treatment, which represented 1.3% of the country’s health-care expenditure [21].
It was suggested that osteoporosis-related health-care cost could reach $3.9 billion if individu-
als who developed osteoporosis-induced disabilities had to live in long-term institutional care
facilities due to osteoporosis. The lifetime risk of osteoporosis-induced fractures is 30%–50%
for elderly women and 15%–30% for elderly men [22]. About one-third of individuals who suffer
osteoporosis-induced hip fracture refracture within 1 year, and about 50% of individuals with
refractured bones refracture within 5 years (www.osteoporosis.ca).
9.4 rISK FACtOrS FOr OSteOPOrOSIS
The risk factors for osteoporosis can be classified as nonmodifiable and modifiable.
Nonmodifiable risk factors for osteoporosis include old age, gender, gravida status, age at men-
arche, small thin built, ethnicity, family history of fractures, and diabetes mellitus. Modifiable
risk factors for osteoporosis include low intake or bioavailability of calcium and vitamin D, pro-
tein intake deficiency, sedentary lifestyle, smoking, excessive alcohol consumption, hypertension,
inflammatory bowel disease (IBD), excessive caffeine intake, body weight, and physical activity.
Despite the knowledge of risk factors for osteoporosis, the disease is a silent one that shows no
symptoms until a bone is fractured.
9.4.1 Nonmodifiable risks of Osteoporosis
9.4.1.1 Old Age
Old age is a nonmodifiable risk factor for osteoporosis. The disease can strike at any age but
mostly it affects people aged 40 and older than younger people. It is important to build up strong
bone during childhood and adolescent years because insufficiency in bone strength at young age
will have geriatric consequences. In 2005–2006, an estimated 48% of women older than 85 years
osteoPorosIs 179
old were diagnosed with osteoporosis, and a total of 20% of women had the disease, while only 4%
of old men had osteoporosis [23]. In the elderly women, especially in postmenopausal, the preva-
lence of osteoporosis is the result of an imbalance between bone formation and resorption [14,24].
Life expectancy in the world is increasing. Since osteoporosis is a disease that affects old people,
the burden of disease is emerging as a health concern for all countries.
9.4.1.2 Gender
Osteoporosis affects both men and women but women are the most affected. The size and
structure of men skeleton is different from the size and structure of women skeleton [13]. As
a result, fracture incidence, location, and outcomes differ between men and women. Facts on
osteoporosis in the United States as per the Center of Disease Control website are as follows. In
2005–2006, osteoporosis of the hip affected 8 million women or 10% of women aged 50 or older
and 0.8 million men or 2% of men aged 50 or older. The prevalence of osteoporosis was 9% in
2005–2008. In Canada, 1 in 3 women developed osteoporosis-induced hip fracture, while 1 in
5 men suffered from the same disease. A total of 30%–50% of women and 15%–30% men devel-
oped osteoporosis-induced fracture in old age. The rate of hip fracture is higher in white women
than men; however, the rate of hip fracture in African American or Asian men is almost similar to
the rate of hip fracture in African American or Asian women [25].
9.4.1.3 Gravida Status
Gravida refers to the number of pregnancy a woman is in. In a community-based cross-

sectional study of 158 women aged 35–64 years old that evaluated bone status for osteoporosis
and osteopenia, there was a statistical significant association between osteoporosis and gravida
status [11]. Osteoporosis was prevalent in 13.3% ± 5.29% of the women and osteopenia was preva-
lent in 48.1% ± 7.79% of the women. BMD was inversely related to gravida status. Bone mineral
density may decrease with prolonged breast-feeding [26]. Transient osteoporosis may be precipi-
tated by gravida status but not caused by it [27].
9.4.1.4 Age at Menarche
During menopause and old age bone resorption increases and the inverse association of bone
mineral density and bone resorption rate is even greater. Bone loss is accelerated during the meno-
pausal transition and the loss is greatest during the 3 years that span between the last year of final
menstrual period and the first 2 years that follow the final menstrual period [28].
In a study of 243 Mexican women, aged 31–80 years old, with the use of the WHO criteria, the
results showed 18% of women with osteoporosis and no association between numbers of pregnancy
and osteoporosis; however, the risk of developing osteoporosis was high in postmenopausal women
with a menarche older than 13 years [29]. A cross-sectional study of 6242 Chinese women in Fujan,
aged 21–92 years old, which included 3304 postmenopausal women, has shown that women with
earlier menopause (≤46 years) had a significantly higher risk of developing osteoporosis than oth-
ers [30]. Later age at menarche was associated with strong bone density in adult age and reduced
osteoporosis risk [31]. A study in Japan examined bones of 1611 senior and junior female students
and 1376 mothers with a 5-year follow-up survey [32]. Bone quality was determined by years of
menarche, body mass index, milk consumption by daughter and by age, history of exercise, and
bone fracture. Mothers and daughters with a history of sufficient physical activities had excellent
bone quality. Bone quality increased at 1 year after menarche. For the daughters, peak bone status
was reached 5 years after menarche. Bone quality of mothers and daughters who consumed one or
more servings of milk every day was better than mothers and daughters who consumed very little
milk. The association between the daughter’s bone quality and mother’s bone quality, years after
menarche and physical activity was strong.
9.4.1.5 Small Thin Built
Low body weight is a risk factor for developing osteoporosis in adult age [33]. There is an esti-
mated 25 million of Indians affected by osteoporosis. Indians, in general, have lower BMD than
Western Caucasians. Skeletal size and high prevalence of vitamin D deficiency especially in urban
areas may expose Indians to higher risk of osteoporosis [14].
9.4.1.6 Ethnicity and Race
The association between ethnicity and race and osteoporosis has been established [34]. The inci-
dence of bone fragility varies by ethnic group. The metabolism of calcium and phosphate varies by
ethnicity. In the United States, dietary calcium intake is higher in White Americans than in African
Americans. The number of osteoporotic fractures has increased in Hispanic women. In 2005,
osteoporotic fractures affected 12% of nonwhite women; in 2025, 21% of nonwhite women will be
affected [20]. However, the rate of osteoporosis-induced hip fracture is slightly higher in white men
than it is in African Americans or Asians [35]. The rate of hip fracture is twice higher in Norway
than Singapore and 10 times higher than Chile [34]. American men or women are at higher risk
of hip fracture than Hispanic women or men than Chinese men or women [36]. Among women,
the rate of hip fracture is white > Native American > Hispanic > Asian > African Americans [37].
The Framingham Osteoporosis Study evaluated the bone mineral density of 1946 postmenopausal
women and 1681 men aged 50 years old or older for the period 1987–2001. The study concluded
that nearly 50% of the women participants and 15% of the men participants would be recommended
for osteoporosis treatment. The rate of all fractures is similar among women of different races
and ethnicities. Environmental, lifestyle, body size composition, skeletal size, socioeconomic, and
genetic factors that affect BMD and fracture play a significant role in the association of ethnicity
and osteoporosis [38].
9.4.1.7 Genetics of Family History of Fractures
Osteoporosis is heritable because bone mineral density is heritable and genetic contribution to
bone mineral density has been estimated at 60%–80% [23]. Therefore, family history is a strong
risk factor for osteoporosis. Recently, several genes associated with bone mineral density and frac-
ture have been identified and will assist in developing drugs for osteoporosis [39].
9.4.1.8 Diabetes Mellitus
Individuals with diabetes are at higher risk of developing osteoporosis that the general popula-
tion. Type 1 diabetes increases the risk of bone fracture because type 1 diabetes lowers BMD [40].
Individuals with type 2 diabetes have higher BMD compared to individuals with type 1 diabetes
but may also be susceptible to osteoporosis. Studies have shown that individuals with type 2 diabe-
tes are at higher risk of fracturing their hip, proximal humerus, and foot bone. Analysis of results
from the Women’s Health Initiative Observational Studies have shown that postmenopausal diabetic
women are at higher risk of experiencing hip, foot, or spine fractures [41]. Bone fragility occurs as a
result of sarcopenia [42]. Type 2 diabetic old women tend to fall and fracture bones, thereby increas-
ing the risk of diabetes-induced osteoporosis [43].
osteoPorosIs 181
9.4.2 Modifiable risk Factors for Osteoporosis
9.4.2.1 Low Intake or Bioavailability of Calcium and Vitamin D
Calcium is essential for skeleton growth and maintenance. Calcium bioavailability or absorption
increases in the presence of vitamin D. That is one reason vitamin D rich milk enhances calcium
absorption. Longitudinal studies of Canadian boys and Chinese girls showed that calcium intake and
bioavailability during the peripubertal and pubertal years is a predictor of total body bone mass [44,45].
Metronomic ingestion of dietary calcium has shown to have greater impact on bone development
than ingestion of large amounts of calcium through supplements [46]. While there is no difference
between calcium salts and dietary calcium, it is possible that dietary calcium has strong correlation
with bone development because dietary calcium is ingested regularly at low dose over a long period
of time as opposed to supplements that are swallowed in short period of time to repair for several
years of deficiencies. In 2009, the Australian and New Zealand Bone Society suggested that vitamin
D was essential for calcium bioavailability and bone growth and remodeling. The society suggested a
baseline intake for calcium of 500–900 mg/day [47]. Increasing the intake to 1000 mg/day enhances
bone mineral density. Calcium level beyond 1000 mg/day may not provide additional benefit in bone
development. For the U.S. FDA, calcium at 2000 mg/day does not confer additional benefit to bone
development and 400 mg or more of calcium per day should be enough to sustain bone growth.
9.4.2.2 Cigarette Smoking
Cigarette smoking is a risk factor for osteoporosis (Figure 9.1). Cigarette smoking increases loss
of bone mineral content. Nicotine has a direct toxic effect on osteoblast and osteoclast, vitamin D,
intestinal calcium absorption, oxygenation, vessels, and an indirect effect on sex hormones [48].
Figure 9.1 Cigarette smoking increases the risk of developing osteoporosis.

In a survey of 2050 South African women aged 40 years old or older, the prevalence of osteoporosis
was 17.1% among those who smoked and used snuff in the past or were active users, 5.1% among
those who smoked, and 5% among those who used snuff only [49]. The association of age at the start
of smoking, smoking volume or number of cigarettes per day and year, duration, and age at quitting
and bone quality and fracture risk were evaluated in a cohort study of 1054 25-year-old females
[50]. This population had a smaller tobacco exposure because of shorter duration. The study con-
cluded that only hip BMD was lower in current smokers than in nonsmokers and dose-dependency
decreased with increasing number of cigarettes consumed per day. At this age of peak bone mass
(25–45 years old), there was no association between BMD or fracture and smokers and nonsmok-
ers. The effect of smoking on BMD may have been attenuated by the fact that in this study group,
women who had a long history of smoking had higher BMI than those with short or no history of
smoking. However, the association of smoking and bone health in young men (N = 677) showed
higher risk of osteoporosis compared to young women at similar age of peak bone mass [51].
Secondhand smoking is also a risk factor for developing osteoporosis. The Fourth Korea National
Health and Nutrition Examination Survey enrolled 925 never-smoker postmenopausal women [52].
Bone health was evaluated as the association of self-reported secondhand smoking exposure and
development of lumbar vertebrate and femoral neck fracture. Postmenopausal women who cohab-
ited with smokers had higher rate of lumbar and femoral neck osteoporosis occurrence compared to
women whose household members were not smokers. Participants from households were smokers
who consumed 20 or more cigarettes per day were even at a greater risk of developing lumbar and
femoral neck osteoporosis.
9.4.2.3 High Intake of Caffeine
Several studies around the world have shown that excessive intake of caffeine that may translate
into more than 4 cups of coffee a day is a risk factor for bone density reduction and osteoporosis
development [53–57] (Figure 9.2). Caffeine-rich beverages including tea and coffee were a risk fac-
tor for hip fracture in urban Indian women [58]. Cell culture study has shown that caffeine causes
oxidative stress and kills osteoblasts [59].
Figure 9.2 Caffeine-rich beverage may be a risk for osteoporosis.

osteoPorosIs 183
9.4.2.4 Protein Intake Deficiency
The bone contains protein as one of its major components. The association of protein and bone
health has shown positive effect of high-protein diet among old men and women [60–63] and post-
menopausal women [64,65], negative effect of high protein intake [66,67] or no association [68].
The Western diet is high in animal protein and has been suggested to have a negative correlation
with bone health because the high-protein diet causes high calcium loss in the urine [69]. Protein
and calcium intake must be adequate for protein to be beneficial to bones of young females [70].
9.4.2.5 High Intake of Cola Drinks
Intake of carbonated cola drinks appears to affect bone growth more than other sugar-
sweetened beverages (Figure 9.3). Several studies have shown that cola beverages promote
bone resorption. Kristensen et al. enrolled 11 healthy 22–29-year-old men in a controlled cross-
over study [71]. For 10 days, the participants consumed 2.5 L/day of semi skimmed milk as
low-calcium diet, followed by a 10-day washout period and 10-day consumption of 2.5 L of cola
per day. It was shown that after the cola consumption, bone resorption significantly increased as
compared to milk consumption. Increased bone resorption is a risk factor for cardiovascular dis-
ease development in men [72]. However, in the Framingham Osteoporosis Study of 1413 women
and 1125 men, BMD of older women at each hip site was negatively affected by cola drink con-
sumption and not by other carbonated sugar-sweetened beverages [73]. The trend of decreased
bone mineral density was cola > diet cola > decaffeinated cola. A potential explanation for the
association of cola beverages and low BMD is the presence of caffeine and phosphoric acid in
cola beverages. Decaffeinated cola has phosphoric acid and les caffeine. Other carbonated bever-
ages that do not show negative effect on bone health may do so because some of these beverages
contain citric acid instead of phosphoric acid.
Figure 9.3 Cola-rich beverage containing phosphoric acid.

9.4.2.6 High Intake of Dihydrophylloquinone
Dihydrophylloquinone is a form of vitamin K that is formed during vegetable oil hydrogenation

[74]. This form of vitamin K is found in food products developed with hydrogenated fat including
snack and fast foods. Troy et al. examined the association of dihydrophylloquinone and bone mineral
density of the hip and spine in 2544 men and women who enrolled in the Framingham Offspring
Study [75]. Men and women with high dihydrophylloquinone intakes had lower BMD than those who
has lower intakes. The association was strong and was not affected by other confounding factors.
9.4.2.7 Vitamin K Deficiency
Consumption of the Japanese natto is associated with good bone health because natto is a good
source of vitamin K (Figure 9.4). The positive association of vitamin K and osteoporosis has been
demonstrated in Japanese elderly (N = 1662) who regularly consumed natto and have higher BMD
and lower risk of hip and neck fracture [76]. In the Framingham Heart Study (1996–200), the asso-
ciation of vitamin K and BMD was shown in women (N = 1479), but not in men (N = 1112) [77].
9.4.2.8 B-Vitamin Deficiency
Deficiency in B-vitamins may be associated with unhealthy bone. A follow-up study of the
Framingham Osteoporosis Study examined the association of vitamins B6 and B12, folate, and
homocysteine with bone health and hip fracture in 1002 men and women with a mean average of
75 years old. There was a strong inverse association of B-vitamins and bone and hip fracture. Hip
fracture risk was as high as 70% in elderly with high plasma homocysteine (>14 µmol). Bone fragility
increases and bone mineral density is reduced in individuals with high levels of homocysteine [78].
9.4.2.9 Alcohol Consumption
Alcohol is toxic to bone formation and growth. Heavy chronic high intake of alcohol causes
alcoholic liver disease and 5%–40% of individuals with alcoholic liver disease suffer from osteopo-
rosis [79,80]. Chronic alcohol intake is associated with low bone mass and increases the incidence
of bone fracture and complication.
Figure 9.4 Japanese natto.

osteoPorosIs 185
9.4.2.10 Sedentary Lifestyle
Physical inactivity is a risk factor for osteoporosis. Regular exercise improves blood pressure,
coronary artery disease, diabetes, lipid profile, osteoporosis, mood, cognitive function, and overall
quality of life and morbidity and mortality.
9.4.2.11 Use of Glucocorticoids
Glucocorticoids are good anti-inflammatory drugs that are often prescribed by physicians to
children and adults for the management of conditions such as allergies or asthma. Glucocorticoids
are also used by clinicians to help patients with autoimmune diseases. However, the side effects of
glucocorticoids include the development of osteoporosis, diabetes, or obesity [81,82]. Even when
glucocorticoids are used continuously or intermittently at substandard or moderate levels, the side
effects cannot be avoided. Physiological concentration of glucocorticoids helps in bone develop-
ment, but supraphysiological concentrations have lasting negative effects. It has been shown that
30%–50% of patients of long-term systemic glucocorticoid develop fragility fracture that does not
abate to baseline even discontinuing the use of glucocorticoid [83]. Glucocorticoids cause an imbal-
ance in bone cell dynamic. Glucocorticoids cause the death of bone cell osteoblasts and osteocytes.
Glucocorticoids decrease bone formation [83].
9.4.2.12 Medical Conditions That Inhibit Nutrient Absorption
Calcium absorption is very low in patients on hemodialysis. Armas et al. [84] showed that for
patients at stage 5 of kidney dialysis, calcium supplementation does not improve calcium absorp-
tion, suggesting that these patients are at increased risk of developing osteoporosis. The following
section on inflammatory describes a medical condition that reduces calcium and vitamin D absorp-
tion and has negative effect on bone health.
9.4.2.13 Inflammatory Bowel Disease
Osteoporosis has been reported in as many as 42% of IBD patients, while reduced BMD affects
up to 72% of IBD patients [85]. A potential explanation for the strong association between IBD and
osteoporosis is a combination of change in diet, weight loss, malabsorption of nutrients and micro-
nutrients (calcium, vitamin D), and the use of anti-inflammatory drugs that are as toxic and detri-
mental to bone growth such as glucocorticoids. Vitamin D deficiency is prevalent in IBD patients
[86]. Intake of high levels of calcium (1000–1200 mg/day) and vitamin D (600–8000 IU/day) is
recommended to help IBD patients offset calcium and vitamin D malabsorption [85].
9.5 therAPeUtIC APPrOACheS tO OSteOPOrOSIS
Commercially available drugs for osteoporosis act as inhibitors of bone resorption or stimulators
of bone formation. Bisphosphonates, estrogen receptor modulators, and hormone therapy replace-
ment inhibit bone resorption. Parathyroid hormone stimulates bone formation. Commercially avail-
able drugs are costly and cannot be found worldwide. Also these drugs do not simultaneously
prevent bone resorption and promote bone formation.
Osteoporotic fractures affect women twice more than men but the severity of the fractures
tends to be more severe in men than women [87]. There are similarities in the pathophysiology
of osteoporosis between men and women. Commercially available drugs for osteoporosis act as
inhibitors of bone resorption or stimulators of bone formation. Bisphosphonates, estrogen receptor

modulators, and hormone therapy replacement inhibit bone resorption. Other drugs include alen-
dronate, risedronate, and zoledronic acid and the antiresorptive monoclonal antibody denosumab
[87]. The monoclonal antibody romosozumab increased bone mineral density and bone formation
and decreased bone resorption in postmenopausal women with low bone mass [88]. Parathyroid
hormone stimulates bone formation. Teriparatide is also a bone-forming agent. Commercially avail-
able drugs are costly and cannot be found worldwide. Also most of these drugs do not simultane-
ously prevent bone resorption and promote bone formation.
9.6 DIetArY APPrOACheS tO OSteOPOrOSIS
Diet is a modifiable risk factor for osteoporosis suggesting that diet is a natural approach
to prevent bone resorption and promote bone formation. While emphasis has been placed on
calcium and vitamin D, other nutrients including vitamin K, potassium, protein, and bioactives
in fruits, nuts, legumes, and vegetables have not been investigated much for their potentials on
bone health. For instance, although the Western diet is rich in calcium and protein, when this
type of diet is compared to Western diet, the Mediterranean diet is associated with low to moder-
ate intake of dairy products. The incidence of osteoporosis is lower in the Mediterranean region
and people consuming a typical Mediterranean diet have healthier bones than those consuming
a typical Western diet [89]. There must be a compensatory mechanism that is probably associated
with the Mediterranean diet.
9.6.1 Calcium and Vitamin D and Bone health
Calcium supplements are good for bone health; but excessive supplementation has been
associated with increased risk of cardiovascular disease development [90]. Vitamin D is highly
needed and effective for improved calcium absorption. The form of vitamin D that improves
calcium absorption is 1α,25-dihydroxyvitamin D, which is the form of vitamin D after it has
passed through the liver. It has been shown that in the presence of vitamin D metabolite, the
absorption of calcium can increase by as much as 30%–40% [91]. The role of vitamin D in bone
health and several other physiological and preventive functions has been confirmed by small
interventional, retrospective observational and case–control, and experimental and ecological
studies [91]. Supplementation of vitamin at the level not less than 30 ng/mL is often recom-
mended. A daily dose of 3000 IU of vitamin D is adequate to maintain serum level of vitamin D
in the 40–60 ng/mL [91]. Absorption of vitamin D does not require fat in the meal and vitamin
D can be absorbed on an empty stomach.
The best dietary sources of calcium include tofu, canned sardines, and canned salmon with
bones because these foods contain high levels of chewable bones that can be easily absorbed. Filets
of salmon, sardine, trout, or perch are not good sources of calcium because calcium is not in the
flesh but in the bones. Other sources of calcium include okra, kale, white beans, collards, edamame,
broccoli, fig, orange, and spinach. Vitamin D is abundant in fatty fish such as salmon, Atlantic
mackerel, egg yolk, cheese, beef liver, and foods that have been fortified with vitamin D such as
orange juice, soybean milk, and cereals. Both calcium and vitamin D3 are good for reducing the
risk of hip fracture.
The Asian diet is associated with consumption of dried fish (Figure 9.5), which is an excellent
source of bioavailable calcium that is better than many traditional sources of calcium. The reduced
rate of osteoporosis in many Southeast Asia may also be associated with the high consumption of
dried fish in Asian cuisine.
osteoPorosIs 187
Figure 9.5 Dried fish.
9.6.2 Mediterranean Diet
The low incidence rate of osteoporosis and associated fractures in the Mediterranean region
is associated with its balance of dietary bioactives rather than its rich composition in calcium.
Traditional Mediterranean foods are good sources of several naturally occurring bioactive com-
pounds, some of which are antioxidants, anti-inflammatory, and have alkalinizing properties, and
in combination these foods can spare bones from deterioration [92,93].
The Mediterranean diet is rich in unprocessed olive oil, vegetables, fruits, nuts, and legumes,
all of which are rich in phytonutrients such as carotenoids, minerals, polyphenols, and essential
fatty acids that protect against damaging effects of aging. Bioactive compounds in extra virgin
olive oil can modulate calcium deposition in bone and the maturation of bone cells [94]. The extra
virgin oil is a good source of polyphenols and squalenes, which are good antioxidants. Vegetables
and fruits contain significant amounts of alkaline ions such as potassium, magnesium, and cal-
cium, which promote calcium balance by lowering dietary acid load. The Mediterranean diet is
low in red meat unlike the Western diet where red meat consumption is very high. However, stud-
ies have also shown the lack of association between adherence to the Mediterranean diet and bone
mineral density [93].
9.6.3 Vegetable Protein and Bone health
Vegetable proteins such as tofu have positive effect on bone health (Figure 9.6). Vegetable proteins
do not cause as much calcium excretion through the urine as animal proteins [66]. For instance, the
Mediterranean diet is higher in vegetable protein than animal protein including hummus, and this
may explain the bone health benefits that have been ascribed to the Mediterranean diet (Figure 9.7).
Soybean milk is a good source of vegetable protein and this explains why soymilk ranks well as a
good food for osteoporosis prevention (Figure 9.8). It has been suggested that protein increases gut
calcium absorption.
The human bone is 50% protein by volume and 25% protein by mass. Adequate protein intake
can overcome protein turnover in older people because this group has a high-protein turnover
whereby a large proportion of amino acids are not reutilized [95]. Protein supplementation provides
needed amino acids for matrix building and this is very significant in older people.
Figure 9.6 tofu as a good source of vegetable proteins.
Figure 9.7 Hummus is a vegetable protein.
9.6.4 Dairy Foods
Parmigiano-Reggiano cheese has been reported as a good source of peptides, calcium, and vita-
mins (Figure 9.9). This type of cheese has been recommended as good for osteoporosis because the
peptides are easily digested and the contents of calcium and vitamin D are good [96]. Significant
bone fracture reduction, as much as 24%, and bone mass reduction can be obtained following cal-
cium and vitamin D3 supplementation [97].
9.6.5 Prebiotics
Prebiotics are foods for probiotics growth and sustainability. It has been shown that oligofruc-
tose stimulates calcium absorption. About 15 g of oligofructose was fed to 12 healthy adolescents
aged 14–16 years old for 9 days [98]. When calcium was given orally to the adolescent, absorption
was significantly high. Other prebiotics that may stimulate calcium absorption include inulin, poly-
dextrose, and galactomannan. Artichoke is a good source of inulin (Figure 9.10). Fenugreek seed is
a good source of galactomannan.
osteoPorosIs 189
Figure 9.8 soy milk.
Figure 9.9 Parmigiano-reggiano cheese.
9.6.6 reducing Inorganic Phosphate Load in Foods
Several processed foods such as processed meat (Figure 9.11) and cereals (Figure 9.12) are
developed with inorganic phosphates [99–101]. It is known that inorganic phosphates are detrimen-
tal to bone growth yet inorganic phosphates are not listed as risk factors for osteoporosis. Reducing
inorganic phosphates in foods that are consumed regularly such as processed meats (Figure 9.11)
and cereals (Figure 9.12) should assist in delaying the development of osteoporosis. Calcium reten-
tion is improved by increasing consumption of inorganic phosphate. Together, calcium, inorganic
phosphate, protein, and vitamin D increase bone formation and reduce bone resorption [102].
9.6.7 Diet of the Blue Zones
The diets of the Blue Zones (see Chapter 18) are not one size fits all. However, like the Mediter-
ranean diet these diets must be associated with less calcium excretion in urine making them good for
Figure 9.10 artichoke is a good source of inulin.
Figure 9.11 fried chicken batter is a good source of inorganic phosphate.
osteoporosis prevention. Traditional diets in these regions are rich in vegetables and fruits and moderate
in meat [103]. The reason diets in the Blue Zones are mentioned is that centenarians are less prone to
bone diseases that cause osteoporosis or bone fracture.
Osteoporosis prevention is a lifelong activity. It should not start after menopause for women and
after age 60 for men. Consumption of foods that excrete less calcium is important, suggesting that
foods rich in advanced glycation end products should be avoided as much as possible. Tofu, canned
sardines, and salmon consumption is good for osteoporosis prevention. In addition to milk, these
foods are really rich in calcium and can offset the effect of steroid drugs. Dark green vegetables
osteoPorosIs 191
Figure 9.12 Cereals are a good source of inorganic phosphates.
Figure 9.13 edamame.
such as collar green, broccoli, kale, and legumes such as Edamame are good sources of calcium for
healthy aging (Figure 9.13). Adopting the Mediterranean or the Blue Zone diet can also reduce the
incidence of bone loss and promote healthy aging.
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ChAPter 10
eye health
10.1 INtrODUCtION
The eye is exposed to oxygen for more than 12 h every day and is thus very susceptible to oxygen
and age-related damage. The eye is also a rich niche of unsaturated lipids and lipid-bound proteins
aka lipoproteins that are very susceptible to oxidation. In absence of protective endogenous and/or
exogenous antioxidants, oxidized lipoproteins and free radicals accumulate in the retina and serve
as local trigger for retinal low-grade inflammation.
10.2 DIetArY rISK FACtOrS FOr retINA CeLL INFLAMMAtION
Oxidative stress is the main determinant for various age-related retinal damages. High levels
of advanced glycation end products (AGEs), free fatty acids and high dietary intake of saturated
fats, low-dietary intake of antioxidants, low-dietary intake of zinc, and high levels of sugar also
known as hyperglycemia in the blood originating from poor nutrition are risk factors for retinal cell
inflammation and subsequent age-related macular degeneration (AMD). The accumulation of the
aforementioned risk factors even in the absence of diabetes leads to the development of preinflam-
matory condition, which, if not treated, becomes chronic low-grade inflammation. Chronic low-
grade inflammation can lead to insulin resistance in various tissues. Insulin resistance promotes
the expression of various growth factors, some of which are involved in the development and pro-
gression of age-related macular diseases. Therefore, poor nutrition can also contribute to oxidative
damage of eye tissues through the contribution of endogenously generated AGEs.
10.3 INFLAMMAtOrY retINAL DISeASeS OF PUBLIC heALth SIGNIFICANCe
Retinopathy of prematurity, diabetic retinopathy, and AMD are three major inflammatory
diseases of public significance. Retinopathy of prematurity is a retinal blood vessel development
disorder that affects premature infants. It will not be discussed here. Diabetes retinopathy is a com-
plication of diabetes whereby the retina experiences the combination of high levels of sugar, elevated
oxidative stress, elevated levels of AGEs, and high levels of proinflammatory proteins, all of which
contribute to the development of more blood vessels in the eye and blindness in diabetic individuals.
AMD is a progressive disease of the macula that makes it difficult to see object as clearly and finely
as possible. It is a major risk factor for vision loss among Americans. There are two types of AMD:
the dry and wet macular degeneration. The dry form is associated with the formation of small yellow
deposits under the macula when the blood vessels become thin and brittle. As the yellow deposits,
also known as drusen, grow in size, the central vision of the eye becomes blurred. Most individuals
197
affected by macular degeneration start with the dry form of the disease. The wet form of the disease
is a condition whereby brittle blood vessels break down and new but leaky and fragile blood vessels
grow under and damage the macula. Wet macular degeneration affects about 10% of individuals with
macular degeneration; however, most people with wet macular degeneration progress to vision loss.
10.4 AGe–ALe AND retINAL INFLAMMAtOrY DISeASeS
The association of advanced glycation end production and loss associated with macular degen-
eration, cataract formation, diabetic retinopathy, and glaucoma is strong [1]. AGEs accumulate in
ocular tissues where they cause inflammation, disrupt adenosine triphosphate production, enhance
oxidative stress, and modulate the genes associated with the inhibition of new blood vessel forma-
tion (angiogenesis) and inflammation. There are several risk factors or sources that can contribute
to the production and accumulation of AGEs in the retina including aging, genetic factors, lipid
disorders, kidney diseases, ascorbic acid, smoking, and diabetes [2]. Exogenous sources of AGEs
include the consumption of foods cooked using dry heat at very high temperature above 300°F [3].
Since AGEs are not completely eliminated from the body, it is the accumulation of these AGEs that
is life threatening because it leads to undesirable pathological conditions. AGEs have been reported
to increase the permeability of the retinal blood–brain barrier, cross the blood–brain barrier, and
be associated with the occurrence of eye and brain diseases. The receptors of AGEs are found in
various tissues of the body including retinal tissues. As mentioned early, interactions of AGEs and
RAGE can stimulate the formation of new blood vessels or angiogenesis and neovascularization
in the eye leading to undesirable reduced vision capability. In diabetic individuals the interactions
exacerbate the progression of retinopathy. The presence of low-grade inflammation in the retinal
tissues has been established and low-grade inflammation can lead to chronic inflammation if oxida-
tive stress in retinal persists or is sustained for a long period of time. Retinal inflammation is a seri-
ous issue for people with diabetes. About half of people with diabetes develop retinopathy within
15 years of the onset of the disease. AGEs induce the production of tyrosine kinase, enzyme known
to initiate the activation of inflammatory cells. The retina contains high levels of polyunsaturated
fatty acids and is also regularly exposed to potentially damaging oxidants. As a result, the retina
accumulates various ALE species. ALEs in the retina can significantly contribute to the generation
of AGEs in the retina inside the human body. The combination of AGEs and FFA in the retina tis-
sues can be devastating to the eye tissues and affect vision.
10.5 DIetArY INterVeNtION FOr heALthY eYe
Chronic eye inflammation and associated diseases such as AMD are progressive diseases that
can rob an individual of his or her vision. Chronic ocular diseases such as AMD are public major
health issue whose incidence is increasing around the world. The best dietary approach for prevent-
ing retinal inflammation and the subsequent consequences that may involve vision impairment is
the combination of (1) Foods or beverages to avoid or consume in moderation, (2) Protective foods,
and (3) Adopting a healthy lifestyle.
10.5.1 Foods or Beverages to Avoid or Consume in Moderation
Any food whose regular consumption leads to accumulation of risk factors of retinal inflam-
mation including high levels of oxidative stress, AGEs, free fatty acids, reduction of insulin sen-
sitivity, and weakened immune system should be avoided. Typical foods have been mentioned in
eye HeaLtH 199
Chapter 1 and under the topic on inflammation. Several of these foods that include pizza, lasagna,
oven-baked macaroni, and cheese, among others, have been reported by studies that showed that
these foods are proinflammatory [3]. Excessive and chronic consumption of the standard Western
diet has been identified as a major cause of inflammation associated with oxidative stress, obesity,
diabetes, pancreatic cell injury, cardiovascular disease, and even cognitive function [4]. High-AGE
diet is one where the estimated dietary AGE intake is greater than 15,000 AGE kU/day. Low-
AGE diet is one that provides less than 15,000 AGE kU/day. Chicken back or thigh with skin on,
roasted and then barbecued, provides 16,668 AGE kU/serving [3]. Although most foods in the list
provided by Uribarri et al. [3] do not provide more than 15,000 AGE kU/day, a combination of
high- and low-AGE foods can easily exceed the level of 15,000 AGE kU/serving or per day. Such
foods include cream cheese (3265 AGE kU/serving), peanut butter (2255 AGE kU/serving), broiled
beef frankfurter (10,143 AGE kU/serving), fried beef steak (9052 AGE kU/serving), breaded and
oven fried chicken breast (8965 AGE kU/serving), skinless breaded chicken breast (4102 AGE kU/
serving), skinless chicken breast roasted with barbecue sauce (4291 AGE kU/serving), skinless
pan fried chicken breast kebab (5510 AGE kU/serving), fried bacon (11,905 AGE kU/serving),
Italian sausage barbecued (4355 AGE kU/serving), Big Mac (7801 AGE kU/serving), pizza (6825
AGE kU/serving), Double Quarter Pounder with cheese (6283 AGE kU/serving), Filet-O-Fish
(6027 AGE kU/serving), open-faced cheese melt sandwich (5679 AGE kU/serving), macaroni and
cheese (2728 AGE kU/serving), and baked ziti (2795 AGE kU/serving) [3]. Figure 10.1 presents
some of the foods that contain significantly high levels of AGEs per serving size and whose con-
sumption may exacerbate the levels of serum AGEs.
Foods that contain high levels of the prooxidant methylglyoxal include steak pan fried in olive
oil (18,150 nmol/100 g), cheese (16,790 nmol/100 g), salmon broiled in olive oil (14,950 nmol/100 g),
fried egg (13,670 nmol/100 g), and French fries (13,130 nmol/100 g) [3].
Goldberg et al. [5] showed that beef boiled for 1 h contains 11 AGE kU/g and the same type
of beef meat broiled for 15 min contains 60 AGE kU/g, chicken breast broiled for 15 min contains
58 AGE kU/g and chicken breast fried contains 61 AGE kU/g, fried egg contains 27 AGE kU/g and
boiled egg yolk contains 12 AGE kU/g, raw tofu contains 8 AGE kU/g and broiled tofu contains
41 AGE kU/g. These data show that food preparation method can have a significant effect on the
formation of AGEs in foods. It was also shown that food composition has a significant effect on
the formation of AGEs in the foods. Protein-rich foods along less known sugars such as ribose
Figure 10.1 a prototype of advanced glycation end product–rich foods.

Figure 10.2 sugar-coated snacks. these products are composed of 80% sugar.
can generate high levels of AGEs during meat cooking. Foods containing high levels of lipids and
protein are also very susceptible to lipoxidation and the formation of AGEs. Raw foods have very
low or negligible levels of AGEs. Apple, banana, carrots, and green beans have 0.13, 0.01, 0.1, and
0.18 AGE kU/g, respectively [5].
Whole cow’s milk contains 0.05 AGE kU/mL, the infant formula Enfamil contains 4.86 AGE
kU/mL, defatted cow’s milk contains 0 AGE kU/100 mL, defatted cow’s milk microwaved for
1 min contains 2 AGE kU/100 mL, defatted cow’s milk microwaved for 2 min contains 8 AGE
kU/100 mL, and defatted cow’s milk microwaved for 3 min contains 34 AGE kU/100 mL [5]. These
numbers although very small and insignificant illustrate the effect of processing on AGE forma-
tion. Whole milk contains water, sugar, fat, and protein that are essential for glycoxidation reaction.
Defatted milk contains sugar and protein that are also essential for AGE formation.
Zinc is essential for eye health. However, too much zinc promotes the activity of enzymes that
carve the tissues and lead to disease propagation. Consumers are advised to avoid foods that contain
too much zinc. Zinc is not an aphrodisiac.
Sugar-coated snacks such as dried fruits contain more unhealthy reducing sugars than the bio-
active compounds such as carotenoids or anthocyanins that can protect the eye. It is suggested that
these types of foods be avoided or consumed at the minimum. These foods may be tasty and calorie
rich but they do not contribute to health. They may contribute to hyperglycemia, which is a risk
factor for inflammation in the eye. Figure 10.2 shows some of the sugar-coated snacks that have
less health-enhancing bioactive compounds and more calorie-enriching sugar. Most of these snacks
have 80% sugar of their total weight.
10.5.2 Foods that Protect against retinal Inflammation
When considering protective foods for retinal tissues, the major and foremost criterion for any
food and active molecule in food to be considered for retinal tissue health is the ability for the mol-
ecule to cross the blood–brain barrier. Most compounds that easily cross the blood–brain barrier are
water or lipid soluble and very small in size.
Foods rich in lipid-soluble antioxidants that can prevent the absorption of free fatty acids in
the central nervous system and certain water-soluble compounds including minerals such as zinc
have been shown to significantly reduce the progression of retinal diseases. Dark-green vegetables
eye HeaLtH 201
Figure 10.3 Kale is a good source of lutein.
rich in lutein and zeaxanthin lead the way among foods that are good for retinal diseases. Kale
(Figure 10.3) and sweet potato leaves are the best sources of lutein and zeaxanthin [6]. Spinach,
broccoli, collard green, and turnip green leaves are also very good sources of lutein and other carot-
enoids. Sixty grams of spinach a day can provide significant daily intake of lutein [7,8]. Fenugreek
(Trigonella foenum-graecum L) and Moringa oleifera Lam leaves are good sources of lutein and
β-carotene [9]. Although there are several lipid-soluble antioxidants including several carotenoids
such as lutein, astaxanthin in salmon, and cryptoxanthin in oyster, lutein has been the only carot-
enoid that has been quantitatively measured in the eye tissues [10]. Raman spectroscopy was used to
show for the first time that lutein level in the normal eye decreases with aging [11].
Chronic exposure to AGE-rich diet can cause retinal inflammation. In the Western countries,
AMD has been identified as the leading cause of vision impairment and loss in the elderly. Foods with
high levels of lutein may help protect against diet-induced and age-induced retinal inflammation.
More research is needed to determine whether other carotenoids also deposit in the eye tissues
and protect the tissue from oxidative damage. Foods that inhibit polyunsaturated oil oxidation are
needed to protect the eye from oxidative stress. Lipid-soluble vitamins including vitamins A, D, E,
and K are very protective of the retinal tissues. Rich sources of these vitamins include fatty fish and
avocado (vitamins D and E and carotenoids), marine foods including algal oils, oysters, and clams,
and green vegetables (vitamin K).
Foods rich in the mineral zinc are also good candidates for healthy vision and include crab, oys-
ter, lean beef, and poultry. Green vegetables including kale, spinach, mustard green, Swiss chard,
collard green, and turnip green are good sources of vitamin K1. Vitamin K2, also known as mena-
quinone-4 or K-4, maintains cornea health and visual acuity [12]. Vitamin K2 can be found in organ
meat including liver and in chicken, beef, and egg yolk. Natto is a good source of vitamin K2 that
is biosynthesized by microorganisms used to ferment the soybeans.
Regular consumption of high levels of fish oil–rich DHA and EPA protects against and reduces
the risk of developing AMD and inflammation [13,14]. The amino acid glycine, which is found in
high levels of sugar beet, is a very good candidate for eye health. Food sources of glycine include
gelatin, pork skin and ears, chicken breast, lamb meat, shrimp, lobster, and crab meat. Glycine is
good for osmoregulation.
The amino acid taurine is also protective to the eye. Taurine has antioxidative and antistress
properties in the eyes [15]. Fish such as capelin is a good source of taurine. Cooked crab is also rich
in taurine. Chicken liver is an excellent source of taurine. Lamb liver and beef liver are also excel-
lent sources of taurine. Lamb, beef, specially the heart, and fish are good sources of taurine.
Carrot (Figure 10.4), mango (Figure 10.5), tomato (Figure 10.6), papaya (Figure 10.7), and
cassava leaves are dietary sources of β-carotene and lycopene. The bioavailability of carotenoids
including lycopene, β-cryptoxanthin, and β-carotene from papaya is at least 2.3 times higher than
the bioavailability of the same carotenoids from carrot or tomato [16]. Butternut squash is a good
source of β-carotene, lutein, and violaxanthin [17]. Figure 10.3 presents some carotenoid-rich foods
that are good for healthy eyes.
Blueberry (Figure 10.8) anthocyanins were detected in the eyes of pigs whose diet was supple-
mented with 4% blueberries for 4 weeks [18]. The health benefits have blueberries are known. The
physiology of a pig is similar to the physiology of a human. It is suggested that the potential health
benefits that blueberries can provide to pigs can also be provided to humans.
Figure 10.4 Carrots are a good source of β-carotene.
Figure 10.5 Mango is a good source of carotenoids.

eye HeaLtH 203
Figure 10.6 tomato is a good source of lycopene.
Figure 10.7 Papaya is a good source of readily bioavailable carotenoid.
Coenzyme Q-10 protects the eye tissue against ultraviolet radiation and reduces corneal damage
that causes inflammation in the eye [19,20]. Foods rich in coenzyme Q10 such as organ meat are
good for healthy eyes.
Insulin sensitivity is related to almost every chronic disease. Foods that improve insulin sen-
sitivity including fenugreek soluble fiber, apple skins, and lemon peel are also good candidates for
healthy vision. Foods that enhance the immune system include foods that protect against trypto-
phan degradation and those that inhibit oxidative stress. Proanthocyanidin-rich berries, cinnamon,
adzuki beans, almond, and peanut skins are good foods for eye health.
Figure 10.8 Blueberries contain anthocyanins that have been detected in pig’s eyes.
10.5.3 Adopting a healthy Lifestyle
Cigarette smoking, heavy alcohol drinking, hypertension, obesity, high dietary intake of fats,
low zinc diet, chronic consumption of foods containing high levels of reducing sugars, and physical
inactivity may play a significant role in the development of retinal inflammation and eye diseases
such as AMD. AMD is a neurodegenerative diseases that no cure at the current level of knowledge.
While age is a risk factor for the development of macular degeneration, lifestyle can accelerate the
aging process and the disease such as AMD that are associated with aging.
Cigarette smoking is a well-known risk factor for retinal inflammation and AMD. Cigarette
smoking is a good source of oxidative compounds, reactive oxygen species, and AGEs, which
are detrimental to eye health. The strength of association between cigarette smoking and AMD
increases with the intensity of smoking [21–24]. The advent of e-cigarette may not change the asso-
ciation of cigarette smoking and eye inflammation, but only time will tell.
Chronic heavy alcohol drinking is associated with vision impairment [25]. It has been shown,
through a prospective population-based study, that there is a weak association between heavy alco-
hol consumption and risk of vision impairment [26]. Cross-sectional data have shown an association
between alcohol consumption and diabetic retinopathy [26].
Hypertension is a risk factor for diabetic retinopathy and AMD. The renin angiotensin II is a
hormone that raises blood pressure and is present in the eye. Dietary sodium is a risk factor for rais-
ing blood pressure. It is suggested that chronic high dietary intake of sodium is a risk factor for the
development of eye inflammation and AMD.
Obesity is inversely associated with decreased macular pigment. Obese people with higher body
mass index (BMI) had lower levels of retinal lutein and zeaxanthin than obese individuals with
lower BMI [27]. Carotenoids concentrate in adipose tissues and in obese individuals adipose tissues
retain most of the carotenoids making these molecules unavailable for binding to the retinal tissues.
Reducing the daily intake of sodium, saturated fat, sugars, and refined grains and increasing
the daily intake of dark-green vegetables and fruits, legumes, whole grains, raw unsalted nuts and
seeds, soy products, seafood, and low-fat milk products can help delay the onset and development
of eye inflammation and the subsequent diseases such as AMD.
Consumption of foods rich in zinc is essential for healthy eyes. Adopting a physically active
lifestyle developed by the USDA and outlined in the Dietary Guidelines for Americans, 2010,
eye HeaLtH 205
which encompasses the consumption of nutrient-dense foods and the maintenance of caloric
balance over time, will help delay the onset and possibly the development of diet-induced eye
inflammation.
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ChAPter 11
Multiple Sclerosis
11.1 DeFINItION
Multiple sclerosis (MS) is an immune-mediated disease in the central nervous system (CNS,
i.e., the brain and spinal cord), which damages the myelin sheath that protects the nerve fibers cells
in certain parts of the CNS and affects the brain and spinal cord functions. For example, because of
the damage to the spinal cord, the brain cannot properly communicate with the rest of body. During
disease development and relapse (attack), the myelin becomes inflamed, damaged, and lost, sug-
gesting that inflammation (immune cell attack) drives the disease process and relapse. As a result,
individuals affected by MS develop signs and symptoms that include visual disturbances, muscle
weakness, numbness, difficulty with balance and coordination, thinking and memory deficits, paral-
ysis, and death. There are four distinct clinical disease patterns in MS: relapsing–remitting MS
(RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive
relapsing MS [1,2].
RRMS is associated with the early stage of the disease in about 80%–90% of people presenting
with MS. RRMS is characterized by a disease attack (the relapsing phase) clinically with the devel-
opment of inflammatory lesions in the CNS histologically and symptom-free periods during which
the disease turns to a complete or incomplete remission (the remitting phase). Relapses can occur
within weeks or decades. RRMS and SPMS can be actually two successive stages of the disease,
in order. In SPMS, the disease continually progressed without remission in a more chronic course
with nerve loss. About half of the MS patients presenting RRMS develop SPMS within 10 years,
and 90% within 30 years, respectively. PPMS, affecting about 10%–20% of MS patients, is charac-
terized by steady progressive neurological damages from the beginning with no clear relapses and
remissions leading to a gradual decline in the individual’s physical abilities.
MS pathogenesis has been suggested to be neuroinflammatory and autoimmune diseases,
induced by the attack of autoreactive T cells, B lymphocytes, macrophages, and microglial cells
against the brain’s white matter.
11.2 SYMPtOMS OF MS
There are various symptoms or complaints that lead to MS diagnosis:
• Most people first experience blurred or double vision, red–green color distortion, or even blindness
in one eye between the ages of 20 and 40.
• Most people with early onset of MS experience muscle weakness in their extremities and difficulty
with coordination and balance that may impair walking or standing.
• In the worst-case scenario, some MS patients experience partial or complete paralysis.
207
• Most people with MS also experience paresthesias, numbness, prickling, or “pins and needles”
sensations, or pain.
• Other frequent complaints include speech impediments, tremors, and dizziness.
• MS patients may occasionally have hearing loss.
• Mild cognitive impairment such as difficulties with concentration, attention, memory, and poor
judgment affects almost half of all people with MS.
• Most people with MS experience depression.
11.3 rISK FACtOrS FOr MS
The etiology of MS remains unknown. However, it is hypothesized that MS is a complex auto-

immune disease with a genetic predisposition that is triggered by a combination of epigenetic and
environmental factors such as poor diet, smoking, vitamin D deficiency, and viral infections.
11.3.1 Age, Gender, and race
MS affects primarily young people through what is called “shift work at younger age.” Two inde-
pendent studies one, from a Swedish study, found that teens at age before 20 who worked overnight
for 3 h or more were twice more likely to develop MS compared to those who never worked the same
shifts [3,4]. A potential explanation from these investigators is very that sleep deprivation interrupts
the circadian rhythm, interferes with melatonin secretion, and may therefore increase the inflamma-
tory response. Similar associations of sleep deprivation with increased chronic inflammatory diseases
including heart disease [5] and breast, colorectal, and prostate cancers [6] have been reported.
MS affects mostly young adult Caucasian of central and northern Europe and the United States.
The disease generally begins between age 20 and 40 and often peaks around age 30; however, the
CDC web page reports that between 2% and 5% of the cases begin before age 16. MS occurs at least
twice as frequently in women as in men [7]. Lower age at puberty is associated with an increased risk
of MS in females but not in males [8]. The disease has a later onset in men than women, and male
gender is associated with more progressive onset and with accelerated clinical progression. MS affects
mostly Caucasian populations; however, in other races or ethnicities, MS patients are reported to
experience a more aggressive disease course [9]. The disease affects more than 400,000 Americans.
11.3.2 environmental Factors and Lifestyle
Genes that are associated with MS have recently been identified. In genetically susceptible
individuals, it is thought that MS may be triggered by environment factors that affect T-cell auto-
immune response in the CNS. The three major environmental factors associated with the risk of
developing MS include latitude, sunshine exposure and its effect on vitamin D, and smoking. Diet
may not be a risk factor for MS but diet may exacerbate the disease.
Less sunny latitude is a risk factor for developing MS. People moving from sunny latitude to less
sunny latitude such as Tasmania in the southern part of Australia and northern Canada or area such
as Wisconsin may suffer from vitamin D3 deficiency due to less exposure to the sun.
Serum vitamin D3 level inversely related to MS relapses and progression [10,11]. Individuals
with serum vitamin D < 25 ng/mL are considered deficient; those with serum vitamin D3 between
21 and 29 ng/mL have insufficient levels.
Smoking and low level of education are risk factors for developing MS [12,13]. The increase in
smoking among women compared to the decline among men tends to show a higher incidence rate
in women than men. Smokers are three times more susceptible to progress from relapsing–remitting
to progressive MS (RRMS).
MuLtIPLe sCLerosIs 209
The Epstein–Barr virus (EBV) infection is prevalent in 95% of adults and affects 100% of adult-
onset cases of MS [10,14]. It has been hypothesized that following primary infection with EBV,
the virus may remain latent in the memory B-cell population for life and may thereby disrupt the
epigenetic status of the host such as repression of the tumor suppressor gene Bim, predisposing the
host to MS development [15].
Cesarean delivery may also be a risk factor for developing MS by individuals delivered by
Cesarian section. Offspring of MS mothers are more likely to develop MS than offspring of MS
father [10]. MS may have a fetal origin suggesting that in utero exposure to MS may have an effect
on MS development in adult life.
11.3.3 Advanced Glycation end Products from Foods
Demyelination is an inflammatory process that is a characteristic of MS and leads to oxidative

stress in the CNS, and the response of oligodendrocytes to oxidative stress involves the receptor for
advanced glycation end products (RAGEs). This receptor binds with its ligand advanced glycation
end products (AGEs) and the complex-induced inflammation that exacerbate MS. Under normal
physiological conditions and in healthy individuals, the serum is rich in soluble RAGE (sRAGE),
which serves as a decoy to prevent the interactions of RAGE and its ligand AGE. Several studies have
reported that the levels of sRAGE are low in MS patients and are even lower in female MS patients.
Several studies have also shown that dietary proinflammatory AGEs present in some processed foods
are found in high levels in the sera of MS patients. The proinflammatory AGEs Nε-(carboxymethyl)
lysine (CML) and Nε-(carboxyethyl)lysine (CEL) have been identified and quantified in several food
ingredients and products. High levels of CML and CEL have been measured in the plasma of MS
patients. CML and its receptor RAGE have been measured in higher levels in the hippocampus in
the brain of MS patients and Alzheimer’s disease (AD) patients compared to age-matched control
subjects. CML and CEL have been measured in 250 common foods and beverages by Goldberg et al.
[16], in more than 550 foods and beverages by Uribarri et al. [17], and in 26 food products by Assar
et al. [18]. Other studies such as those of Vlassara et al. [19,20], Uribarri et al. [17], Bengmark [21],
Van Nguyen [22], and Henle [23] have either covered CML or CEL implications in human health
and/or suggested ways to reduce it.
Because these molecules are proinflammatory and MS patients often consume the same foods as
other people, it is possible that MS patients who consume these types of foods add proinflammatory com-
pounds to an environment that is already inflamed, thereby exacerbating the inflammatory continuum.
Accumulated AGEs sustain local oxidative stress and subsequent inflammatory response, all leading to
the deteriorating inflammatory conundrum in MS patients whose diets revolve around foods rich in AGEs.
11.3.4 Oxidative and Nitrosative Stress
Oxidative stress is the result of imbalance between prooxidants such as AGEs and antioxidants
such as vitamin C in favor of prooxidants. Oxidative stress can also be the result of the body’s
inability to neutralize or eliminate reactive oxygen species (ROS). The CNS is sensitive to oxida-
tive stress and oxidative stress is present in the establishment and development of MS. There is
evidence of oxidative stress in MS because numerous AGEs and advanced lipoxidation end prod-
ucts (ALEs) have been found in MS lesions compared to normal subjects. In MS, ROS, generated
in excess primarily by macrophages, have been implicated as mediators of demyelination and
axonal damage [24]. In MS, oxidative stress is observed prior to RRMS as evidenced by the levels
of oxidative stress products in blood samples of patients with RRMS that showed higher values for
carbonylated proteins, 8-hydroxy-2′-deoxyguanosine (8OHdG), total glutathione (GSH), reduced
GSH, GSH/GSSG ratio, SOD, GSH reductase, and global oxidative stress, and low oxidized GSH
(GSSG) compared to healthy matched controls [25].
Nitrosative stress is a result of proinflammatory nitric oxide–induced protein damage in the white
matter from MS brains [26,27]. Nitrosative products, such as 3-nitrotyrosine, are confined to large
plaques in the white matter region. Nitrosative products including peroxynitrite and 3-nitrotyrosine
are associated with axonal damage in MS.
11.3.5 Inflammation
Inflammation is a characteristic of MS. Recent experiences with aggressive anti-inflamma-

tory treatment suggest that inflammation drives neuronal damage in patients with RRMS [28].
Tryptophan is an essential amino acid. Under inflammatory conditions such as MS, there are high
levels of the enzyme indolamine-2,3-dioxygenase 1 (IDO1) that depletes tryptophan for the genera-
tion of the immune suppressive kynurenines. IDO1 is a major immunosuppressive effector whose
activity contributes to the immunosuppressive phenotype of MS. It is suggested that IDO1 may
be instrumental for the therapy of MS [29]. Opitz et al. have recently shown that toll-like receptor
(TLR) ligands activate immunosuppressive tryptophan catabolism via IDO1 in MS [30] and
augment the immunosuppressive properties of MS in absence of IFN-γ. It was also shown that
inhibition of IDO1 reverses MS-mediated T-cell paralysis.
11.4 eCONOMIC SIGNIFICANCe OF MS
There are more than 400,000 MS patients in the United States [31], more than 380,000 MS
patients in Europe [32], and more than 2.1 million MS patients worldwide [33]. Because MS onset
occurs in young people and MS patients can live for decades, the economic burden is significant for
individuals who carry lifelong disability and for relatives who care for MS patients. In Europe alone,
the total annual cost in 2005 was estimated at €12.5 billion [32]. In the United States, in 2011, the
total all-cause care costs for MS including direct and indirect costs range from $8,528 to $54,244 [34].
11.5 therAPeUtIC APPrOACheS tO MS
Therapeutic options for MS aim to achieve fewer relapse, less disability, fewer neurological
deficits, fewer T2 lesions, less axonal loss and brain trophy, and more safety [35,37,38]. INF-β,
which has been the baseline therapy for MS, is only effective when the disease depends on the
NLRP3 inflammasome pathway [36,39]. The U.S. FDA has so far approved the following drugs
for MS management: two immunomodulating drugs including INF-β and five immunosuppressive
drugs including fingolimod, teriflunomide, dimethyl fumarate, natalizumab, and mitoxantrone.
Corticosteroids are used for MS patients with acute and significant symptoms [40]. Corticosteroids
induce the enzyme indoleamine 2,3 dioxygenase (IDO) that may be associated with fatigue that
characterizes MS patients. For details on drugs for MS, the reader is welcome to read the studies by
Wipfler et al. [35], Minagar [37], and Saguil et al. [40].
11.6 POteNtIAL CONtrIBUtION OF the FOOD INDUStrY

tO PreVeNtING MS DeVeLOPMeNt
The functional food industry including the dietary supplement industry is spending billions of
dollars to help alleviate the pains from chronic diseases. In 2003, Bowling and Stewart wrote, “No
diet or dietary supplement has been definitively proven to modify the course of the disease.” Yadav
et al. [41] wrote,
Clinicians might offer oral cannabis extract for spasticity symptoms and pain (excluding central neuro-
pathic pain) (Level A). Clinicians might offer tetrahydrocannabinol for spasticity symptoms and pain
(excluding central neuropathic pain) (Level B). Clinicians should counsel patients that these agents
are probably ineffective for objective spasticity (short-term)/tremor (Level B) and possibly effective
for spasticity and pain (long-term) (Level C). …fish oil is probably ineffective for relapses, disability,
fatigue, MRI lesions, and quality of life (QOL) (Level B); ginkgo biloba is ineffective for cognition
(Level A) and possibly effective for fatigue (Level C); …bee sting therapy is possibly ineffective for
relapses, disability, fatigue, lesion burden/volume, and health-related QOL (Level C). Cannabinoids
may cause adverse effects. Clinicians should exercise caution regarding standardized vs nonstandard-
ized cannabis extracts and overall CAM quality control/nonregulation. Safety/efficacy of other CAM/
CAM interaction with MS disease-modifying therapies is unknown.
In 2008, Schwarz et al. [42] reported MS patients who adopt complementary and alternative
medicine do so because rare unwanted side effects associated with this type of medicine compared
to conventional Western medicine. Recently, Riccio [43] summarized the potentials of foods for MS
management.
A review of Uribarri et al.’s work [17] shows clearly that most of the foods that are available to
the general population as well as MS patients are either rich in AGE precursors or rich in AGEs.
The impact of AGEs on CNS diseases including MS, AD, and Parkinson’s disease (PD) has been
recognized by many studies [44–47]. Therefore, ingredients or foods low in AGE precursors such as
methylglyoxal or low in AGEs such as CML or CEL are needed to prevent oxidative and nitrosative
stress and slow down the exacerbation of MS, AD, or PD.
Since AGE precursors or AGEs in foods affect overall health in healthy as well as MS individu-
als, it is suggested that all involved in food production including food scientists, food engineers,
nutritionists, culinologists, and dietary supplement experts reevaluate the ingredients or foods
entering into commerce. Foods for preventing or managing the development of MS should address
the following:
• Proinflammation in ingredients and foods

• Oxidative stress
• Neuroprotection
• Inflammation
The following paragraphs will cover several dietary bioactive compounds that should help
the food industry, restaurant, and households in the fight against MS. Rather than treating symp-
toms that are reflected by biomarkers of inflammation, dealing with the roots of inflammation
can provide long-lasting prevention and inhibition of inflammation along with avoiding MS
degeneration.
11.6.1 Proinflammatory Ingredients, Foods, or Catalysts for MS
The potential contribution of foods to the inflammatory process that defines MS has never been
imagined because (1) few would believe it; (2) foods generally induce low-grade inflammation that
requires several additional steps before becoming high-grade inflammatory process, and by the
time symptoms occur, very few can trace it back to the food consumed; and (3) as far as the steps
of MS are described, nobody wants to identify foods (deficiency in vitamins C, E, and D and lipoic
acid) as risk factors for MS although these bioactives are regularly mentioned as contributing risk
factor for MS [48]. However, we have identified food technologies that are associated with the
production of proinflammatory ingredients or foods that enter the food processing lines and end up
in the foods or beverages that consumers purchase and use. Foods from such technologies may not
be appropriate to fight MS and may worsen the disease.
11.6.1.1 Spray-Dried Milk or Milk By-Products
These by-products are an excellent source of AGEs. Spray-dried milk powder (Figure 11.1) finds
applications in several food formulations including soups and infant formulas [17,49] (Figure 1.4).
Despite warnings, AGE-rich ingredients are widespread in food formulations [50,51], large amounts
of AGEs are ingested, and 10% of it accumulate in the body [44] and surely will contribute to the
inflammatory process that characterizes MS.
11.6.1.2 Sweetened Condensed Milk
This is also an excellent source of AGEs [52]. Sweetened condensed milk (Figures 11.2 and 1.4.)
finds applications in fudge, pudding, caramel, ice cream, pie, Colada, truffles, toffee, streusel, and
many other foods. Again consumption of these products spreads and expands the use and absorption
of AGEs into the human body. When MS patients consume such foods, chances are that they will
ingest enough AGEs to advance disease progression.
11.6.1.3 Evaporated Milk
This by-product contains large amounts of AGEs [18,50,53] (Figures 11.3 and 1.4). Recipes that
contain or use evaporated milk are countless. Fudges, pies, soups, cereals, French toast, mashed
potatoes, creamed vegetables, white sauces, gravies, meat cutlets, coffees, and teas can use the
popular evaporated milk. Like the general population of non–MS patients, these tasty foods are also
consumed by MS patients.
11.6.1.4 Spray-Dried Egg Yolk
Spray-dried egg yolk is also a common ingredient in food preparations at home, in restaurants,
and in food processing operations. Oxidized phosphatidylcholine can be found in spray-dried egg yolk
(Figure 11.4) as a result of high temperature encountered during spray-drying of egg yolk [54–56]. Oxidized
phosphatidylcholine in spray-dried egg yolk can enter the human body through foods such as mayonnaise,
cakes, cake mixes, doughnut mixes, sweet doughs, pastries, pies, delicacies, ice cream, salad dressings,
egg noodles, pasta and bakery products, canned foods, and cooked dishes and even through cosmetics.
Figure 11.1 spray-dried milk.

Figure 11.2 sweetened condensed milk.
Figure 11.3 evaporated milk.
Figure 11.4 spray-dried egg yolk.

Figure 11.5 fried foods.
11.6.1.5 High-Temperature Processing
This kind of processing of foods including broiling, grilling, frying, and searing generates pro-
inflammatory AGEs, which are detrimental for MS patients (Figure 11.5). Bread toast, pizza, and
all its variations are all typical of foods consumed by all including MS patients. Uribarri et al. [17]
extensively expanded on these products and others.
11.6.1.6 Methionine-Rich Foods
Elevated plasma methionine has been identified in MS and is unrelated to deficiency in B vita-
mins and folate, oxidative stress, or immune activation [57–59]. Higher plasma homocysteine levels
were associated with male patients than females [59]. Elevated plasma homocysteine is associated
with dietary intake. Food sources of homocysteine include chicken as methionine is supplemented
to broilers to mitigate the effects of stress [60]. It appears that chicken and turkey meat (Figures 11.6
and 11.7) consumption by MS patients should be reduced.
Figure 11.6 Chicken meat is a good source of methionine.

Figure 11.7 turkey drumstick.
11.6.1.7 Butter, Cheese, Margarine, and Other Fat-Rich Foods
When Napoleon ruled France, butter was the food for rich French people, and margarine was
butter substitute for poor French people. Unfortunately, both make no exception and are extremely
rich sources of AGEs. Butter or margarine is frequently used in restaurant cooking for flavor gen-
eration. Both are major sources of saturated fats. It has been shown that from 1750 to 1930, daily
saturated fat food consumption in industrialized countries increased from 60 to 140 g, and the link
between saturated fat consumption and MS began to surface [61]. For 50 years, Swank studied
saturated fats and MS and along with colleagues reported that absorbed chylomicra from meals
rich in saturated fatty acids have the tendency to aggregate and be more adhesive and blockade
circulation in capillaries in the CNS leading to lesions seen in MS patients [62,63]. Butter, cheese,
and margarine are excellent sources of AGEs and through the RAGE may contribute to the com-
plications of MS.
11.6.1.8 Palmitate-Rich and Other Cooking Oils
Palmitic acid is a proinflammatory at concentrations between 50 and 500 µM found in human

plasma also known as physiological concentration. Unfortunately, palmitic acid is present in several
cooking oils including palm oil, cottonseed oil, rice bran oil, avocado oil, corn oil, olive oil, peanut
oil, sesame oil, soybean oil, almond oil, and canola oil. It is suggested that oils that are very rich in
palmitate should not be part of the diet of MS patients because of the inflammation generated by
palmitic acid. Oils rich in n-6 fatty acids including soybean, corn, sunflower, and sesame should
also be removed from MS diets. Sesame oil is constantly used in Chinese restaurants throughout the
United States, suggesting that individuals with MS should be careful when consuming foods from
Chinese restaurants.
11.6.2 Gut Microbiota
Studies that show potential links between human gut microflora and MS development are emerg-
ing [64–66]. The gut microflora modulates local immune functions; it also may affect local compo-
sition of the microflora. Comparative studies of populations across the world show that populations
consuming Western style diets that are rich in refined carbohydrates and fats can develop a gut
microflora that is conducive to promote inflammation. Healthy gut, healthy life, inflamed gut, and
inflamed CNS are bad news for MS.
11.6.3 Identifying Antioxidative Foods for Preventing MS Development
Oxidative stress precedes RRMS and the latter is dominated by inflammation. The ultimate goal
of all day dietary intervention for MS individuals and those who are genetically at risk should be to
avoid adding more proinflammatory compounds in foods and instead focusing on anti-inflammatory
foods as long as possible. Once proinflammatory foods have been removed from the diet, antioxida-
tive foods can be selected among the following well-known food ingredients or foods. Oxidative
stress can also be reduced by consumption of antioxidant-rich foods including both liposoluble
and water-soluble antioxidants. Most foods or ingredients that reduce oxidative stress are also anti-
inflammatory, and the foods or ingredients that are good for individuals with MS are discussed below.
Due to the fact that MS events occur in the spinal cord and CNS, it is important to select low-
molecular-weight antioxidative stress compounds or compounds whose metabolites can cross the
blood–brain barrier and be effective against MS.
11.6.4 Developing Seasonal and Year-Around Foods

for Preventing MS Development
Vitamin D deficiency is a known risk factor for MS. Reports show that vitamin D deficiency
and insufficiency is common in children and the Institute of Medicine recommends that children
0–1 year and 1–18 years take 400 and 600 IU/day, respectively, of vitamin D for maximal skeletal
health [67]. In the very northern and very southern regions of the world, during winter people are
exposed to less sunshine. Given that serum levels of 25-hydroxy vitamin D are known to be low
in winter time (vitamin D deficiency is <25 ng/mL of serum 25-hydroxyvitamin D and vitamin D
insufficiency is 21–29 ng/mL of serum 25-hydroxyvitamin D), while viral infection is the highest
at this period, the food industry should boost vitamin D levels in seasonal foods from late October
to mid-April or early May to help reduce individuals with MS and those at risk of developing MS.
Vitamin D strengthens the innate immune system through production of antimicrobial and antien-
dotoxin cathelicidin and defensins [68,69].
Consumption of dietary supplements may be enhanced if ingested with appropriate food matrix.
For instance, because vitamin D is liposoluble, it may be better consumed with fish that are good
sources of omega-3-fatty acids including mackerel, salmon, sardine, herring, or anchovies to
improve vitamin D absorption.
Seasonal foods are commonly developed by the food industry for use at specific times of year.
At Christmas, special foods such as eggnog appear on the market and disappear from the market
after the season. The industry can release vitamin D–rich products during winter periods in regions
of the world where MS strikes hard.
11.6.5 Identifying Neuroprotective and Myelin Protective

Foods for Preventing MS Development
Chronic inflammation as observed in MS induces axonal damage and the latter induces neu-
ronal death. Deficiency in fatty acids can seriously impair myelin synthesis and fatty acids such as
oleic acid can protect neurons [70]. The presence of fish oil may help in the remyelination process
although it has been reported that fish oil alone does not help very much with MS [41]. Other dietary
bioactives with potential protective effects against inflammation in MS include phenolic acids and
triterpenoids with potentials to regulate antioxidative process in the CNS. Sage (Salvia officinalis)
contains terpenes and polysaccharides that possess immunomodulatory and antioxidative properties
[71,72]. Studies have shown that green tea EGCG inhibits inflammation in hippocampal neurons
and can protect neurons against different models of oxidative damages including MS [73–75].
11.6.6 Developing Good Mood Food for MS Patients
The lifetime disability created by MS can significantly affect an individual’s mood and perfor-
mance. Mood food can help people with MS stay calm. The components of mood foods are basically
anti-inflammatory, soothing, and calming. Most of the bioactive compounds that are neuroprotec-
tive including limonene, rosmarinic, and oleanolic acids are ingredients of mood foods [76–78].
11.7 COOKING tO PrOVIDe heALth-eNhANCING FOODS tO MS PAtIeNtS
Cooking is often one way to convert ingredients or some raw foods before it is delivered to the
body. Appropriate cooking is often what is missing when ingredients from excellent agriculture
are used to deliver bioactives inside the body. Very-high-temperature cooking or any temperature
above 300°F is very detrimental to food quality except for flavor. The high cooking temperature is
a source of inflammatory or proinflammatory compounds such as AGEs; therefore, cooking for MS
patients whether at home or away from home should bear this critical factor in mind. The best cook-
ing methods that deliver less proinflammatory compounds and more health to the body are boiling,
stewing, steaming, or cooking at temperature of 300°F or below.
Adding fish oil to foods that is baked at 450°F is counterproductive. This is where culinologists
and chefs with an understanding of the Maillard reaction and AGEs have to draw the line and start
designing flavorful foods without the use of high temperature. Frying cheese for MS patients is
not health enhancing. Grilled, seared, and broiled foods are not health enhancing for MS patients
because despite their rich flavors, these foods are big reservoirs of AGEs that are not good for MS.
The ultimate cooking for MS patients should involve
• Recipes without proinflammatory ingredients including cheese and peanut butter

• Recipes that use antioxidative ingredients as much as possible
• Recipes that use ingredients that help manage the inflammatory and immunosuppressive aspects of
disease as much as possible
11.8 CUrreNt treNDS
Most MS patients rely on dietary supplements that are mostly pills to improve their conditions.
The efficacy of certain dietary supplements is questionable. Isolated molecules such as the ones
found in most pills often work well in vitro, but become questionable in vivo. MS strikes mostly
young people and most young people do not swallow pills; managing MS with pills may not be help-
ful for fighting MS. Current trends in MS have neglected the significant contribution to AGEs/ALEs
and other proinflammatory dietary compounds to the disease, and this is not helpful.
MS often carries a lifetime disability. The QOL and economic burden associated with MS are
painful and enormous, respectively, because those who are affected often carry the burden from
their young age until the time of their death. With the increase in health-care costs and nations’
reduced ability to care for the aging populations, it is suggested that disease prevention through bet-
ter lifestyle prevails over the culture of medication for every disease.
Studies have shown that epigenetics plays a significant role in MS development and progres-
sion; therefore, the following recommendations are suggested. First, because the maternal parent-
of-origin effect in MS is critical, women should be given the best nutrition ever throughout their
lives. Second, the inflammatory nature of MS suggests that adequate food processing techniques to
be adopted must provide less proinflammatory ingredients to the consumer whether these consum-
ers are MS patients or not. The multinational nature of several food companies and globalization
of the food system suggests that food companies invest in better technologies that provide reduced
proinflammatory foods. Third, health-care officials around the world need to ensure that foods
are not the vehicle of inflammation to the people. It is suggested that nations invest in food safety
research the same way huge fundings are being provided for biomedical research. After all, food is
a biomedical need for people because food is medicine. Food safety is not synonymous of E. coli or
Salmonella outbreak; it encompasses microbial and chemical safety. Fourth, fundings are needed
to identify the levels of dietary bioactive metabolites that provide protection against disease pro-
gression. This in turn will allow the adoption of foods whose absorption can help deliver those
needed metabolites at desirable concentrations in the CNS so that MS can be cost-effectively
managed using foods. Designing mood foods for MS patients should also be a prospective for
MS patients.
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ChAPter 12
erectile Dysfunction
12.1 DeFINItION AND INtrODUCtION
Erectile dysfunction (ER) is the inability to attain or maintain a sufficient penile erection for a
satisfactory sexual intercourse [1]. ER affects nearly 2% men under the age of 40 and 50%–86% of
men aged 45 or older [2,3]. The disease affects about 18.4% of Americans aged 18 years or older
[4] and 152 million men worldwide [5]. The term ER has also replaced the term “impotence” that
is not often used any more.
12.2 rISK FACtOrS
There are several risk factors associated with the development of ER. Aging is one of the major
nonmodifiable risk factors and diabetes being the other nonmodifiable risk factor. Modifiable risk
factors associated with ER include smoking, sedentary lifestyle, obesity, insulin resistance, lack of
exercise, hypertension, hypercholesterolemia, alcohol consumption, and cardiovascular disease [6].
Risk factors can also be classified as vascular, endocrinal, traumatic, psychological, and neurologi-
cal. Psychology accounts for 20% of the ER causes. Nonmodifiable and modifiable risk factors for
ED are briefly described in the following sections.
12.2.1 Age
Age is a major risk factor for ER [6,7]. In a study of 108,477 Australian males aged 45 years
old or older between 2006 and 2010, it was shown that after adjusting for socioeconomic factors,
the rate of ED increased by an average of 11.03% each year from the age of 45 years old and up.
Men 18–29 years old have a 10% risk of developing ED and the incidence increases to 3.5 times
higher for men aged 50–59 years [8]. Between the age of 40 years old and 70 years old, the preva-
lence of ER is 52% and increases for men older than 70 years old [9,10]. Aging is sometimes not
associated with ER [11]. Increasing age is associated with increased storage of cholesterol and risk
of metabolic syndrome suggesting that metabolic syndrome can be an independent risk factor for
ED development. An evaluation of data collected from the Fangchenggang Area Male Healthy and
Examination Survey from September 2009 to December 2009 in which 3197 men aged 17–88 years
old in Guangxi were enrolled concluded that after adjusting for age, physical activity, smoking,
body mass index, and alcohol consumption, the metabolic syndrome was an independent risk factor
for ED development specially in Chinese men of middle age [12]. Low-grade inflammation may
also be a risk factor for ED [13]. Statins reduce cholesterol but have often shown no effect on ED
improvement [14,15]. However, it has also been shown that ED was not associated with age in 54%
of healthy or 41% of sick old men between 65 and 70 years of age [16].
223
12.2.2 Diabetes
ED affects 50%–75% of diabetic men who accumulate advanced glycation end products
(AGEs) in penile tissue and AGEs can quench endothelial and neuronal derived nitric oxide
(NO) and decrease cavernosal smooth muscle relaxation [17–20]. Hyperglycemia is a char-
acteristic of individuals with type 2 diabetes especially those who do not control their sugar
levels. Increased AGEs may inhibit the interaction of NO and the enzyme guanylate cyclase
resulting in decreased cyclic guanosine monophosphate (cGMP) level and dysfunctional penis
[21]. The association of diabetes and poor quality of life in men with ER is strong [22]. The
occurrence and prevalence of ED in diabetic patients is also a combination of both physical
and psychological factors [19]. AGE cross-link breakers have shown to prevent ED in diabetic
animals because these breakers can cleave AGEs and reverse ED and reduce serum and penile
tissue AGEs levels [21].
12.2.3 Cyclic Guanosine Monophosphate
cGMP mediates vasodilation. The lack of or insufficient level of cGMP decreases the level of
NO and leads to ER [3,20,23]. Interest in drugs that raise the level of cGMP is associated with the
ability to increase the level of NO and in some instance when the level of NO is very low, patients
under those conditions cannot respond to drugs such as sildenafil [3].
12.2.4 Smoking
A meta-analysis of a combination of cohort and case-control studies involving more than 28,000
participants concluded that there is a strong association between smoking and, in particular, current
smokers followed by former smokers and the risk of ER [24]. Smoking is considered as a threat
to world’s health. It is also suggested that smoking cessation improve erectile function. Smoking
induces oxidative stress and oxidative stress disrupts NO production directly or by inducing insulin
resistance [25].
12.2.5 Dietary Advanced Glycation end Products
Diet can have a significant effect on erectile function. Accumulation of AGEs in the penile tissue
is a major risk factor for ER in individuals with type 2 diabetes. This chapter will limit itself to the
contribution of exogenous AGEs to ER. Increasing evidence shows that the presence and severity
of ED correlate with the presence of metabolic syndrome including hypertension, diabetes mellitus,
dyslipidemia, and the number of cardiovascular risk factors such as atherosclerosis [26]. Exogenous
AGEs are hallmark of metabolic syndrome. Exogenous AGEs are bioavailable and accumulate in
long-lived proteins such as collagen, leans proteins, and penile proteins suggesting that the dietary
AGEs can easily accumulate in penile tissues to lead into inflammation, oxidative stress, inhibition
of NO production, and weakening of the penile tissue function.
12.2.6 Obesity
The association of obesity and ER is very strong [7,27]. Up to 80% of overweight or obese
men suffer from ER. The odds of ED appear to increase with increase in body mass index; it is
higher for individuals with body mass index between 25 and 30 kg/m2 and becomes even higher
in men with body mass index greater than 30 kg/m2 [28]. Obese men (N = 33) were enrolled in a
study that evaluated the relationship between obesity and ER with respect to five specific areas
of sexual functioning including erectile function, sexual desire, orgasm, overall satisfaction, and
ereCtILe DysfunCtIon 225
intercourse satisfaction [29]. Statistically significant dysfunction was observed in erectile func-
tion, sexual desire, orgasm, and overall satisfaction. The results suggest that in obese males obesity
reduces the quality of sexual life. A study enrolled 47 obese men with ER and 45 healthy men
to evaluate the relationship between neck circumference and metabolic syndrome and ER [30].
A cut-off of 34.75 cm was set for ED and metabolic syndrome, a cut-off value of waist circumfer-
ence was 105.5 cm for ED and 102.5 cm for metabolic syndrome. Individuals with ED had higher
neck circumference and higher waist circumference than the volunteers. The study suggested using
neck circumference as a potential indicator of ED in patients with metabolic syndrome. The asso-
ciation of obesity to ER has been supported by findings that showed that one-third of obese men
who lost weight, exercised regularly, and consumed healthy foods for 2 years recovered their normal
sexual activity [31].
12.2.7 hypertension
High blood pressure has a negative impact on erectile function and both hypertension and erec-
tile function are strongly inversely related. About 30% of individuals who suffer from high blood
pressure develop ER [32]. Two potential mechanisms have been identified for the strong inverse
association between blood pressure and erectile function. Endothelial dysfunction is the common
denominator between blood pressure and erectile function. Hypertension disrupts endothelial func-
tion which in turn leads to increased vascular muscle contraction. Drugs such as diuretics and
β-blockers that treat high blood pressure cause and worsen ER [33,34]. However, there is evidence
that hypertension precedes endothelial dysfunction. There is also evidence that some of the drugs
that treat ER such as the phosphodiesterase-5 inhibitors, calcium antagonists, and angiotensin-
converting enzyme inhibitors can improve hypertension in older people [35] and can have neutral or
enhancing effects on erectile function.
12.2.8 Depression
The association of depression and erectile function is strong but it is not known whether depres-
sion is a risk factor for ER or vice versa [36]. Antidepression drugs currently in use tend to worsen
ER and delay ejaculation [28]. The most identified drugs are the serotonin-reuptake inhibitors.
12.2.9 Atherosclerosis
Vascular disease and ER share the same risk factors [37]. Atherosclerosis has a strong asso-
ciation with ER because most of the risk factors for atherosclerosis including diabetes, lipid
abnormalities or dyslipidemia, smoking, and obesity are also risk factors for ER [38]. Endothelial
dysfunction is the hallmark of atherosclerosis. Endothelial dysfunction causes ER and predicts
the future onset of ER [39]. ER is also a major risk factor for and predictor of cardiovascular
disease [10,40,41].
12.3 DIetArY APPrOACh tO IMPrOVe ereCtILe DYSFUNCtION
The association of diet and ER is supported by several epidemiological studies and an under-
standing of the link between diet and the mechanism by which ER may occur. Micronutrient-dense
foods such as soybean, fruits and vegetables, and micronutrient-dense beverages such as green
tea have shown to positively impact sexual health [42]. Long-term regular consumption of the
Mediterranean diet, for instance, has shown reduced prevalence of ER in men with type 2 diabetes
mellitus [43]. The potential contribution of other diets such Caloric restriction, the Okinawan, the
Ikarian, Cretan, Nicoyan, and Seventh Adventists diet on erectile function improvement has never
been discussed. The following sections discuss all the diets mentioned earlier in the context of their
potential contribution to healthy penile tissue.
12.3.1 Caloric restriction
Caloric restriction involving reduction of visceral fat and sugar intake without a reduction in
essential nutrient intake is associated with weight loss, decreased endothelial dysfunction, and
improved vascular function. Caloric restriction with a weight loss of 5%–10% showed improved
erectile function [44,45]. Bariatric surgery is a classic example of weight loss and short- and long-
term data from bariatric surgery have all shown significant improvement in erectile function or
testosterone levels [44,45]. In men with type 2 diabetes, the association between visceral fat and ER
is strong [46].
Meal replacement is also a good calorie reduction and weight loss alternative. Asian men (mean
age of 40.8 years with a range of 30–61 years old) enrolled in a meal replacement program or con-
ventional reduced-fat diet whereby they reduced their daily caloric intake by 400 kcal for 12 weeks
showed significant erectile function improvement with meal replacement compared to conventional
reduced-fat diet [47]. When the participants switched to or continued conventional reduced-fat diet,
improvement in sexual health including erectile function and testosterone levels was maintained
at 40 weeks. The improvement in sexual health was greater with meal replacement than conven-
tional reduced-fat diet. Caloric intake reduction is associated with reduced metabolic abnormalities
including inflammation and insulin resistance. As a result, caloric reduction has a positive impact
on erectile function.
12.3.2 Mediterranean Diet
The metabolic syndrome is a risk factor for ER as it induces endothelial dysfunction, insulin
resistance, and the prevalence of ER. A study enrolled and assigned the Mediterranean-style diet
for 2 years to 35 men and a control diet to 30 other men [48]. The Mediterranean-style diet con-
sisted of lots of fruits, vegetables, nuts, whole grains, and olive oil. After the intervention period,
the results showed that men on the Mediterranean-style diet had improved score of inflammatory
biomarkers including C-reactive proteins. Erectile function was improved in 37% of the men on the
Mediterranean diet. In men with type 2 diabetes, obese men and men with metabolic syndrome,
adherence to the Mediterranean-style diet is associated with greater value of the International Index
of Erectile Function and erectile function than those who did not do so [11,49]. The Mediterranean-
style diet is micronutrient dense. Several bioactive compounds found in the components of the
Mediterranean diet improve endothelial function, oxidative stress, and inflammation, all of which
are early risk factors associated with ER.
12.3.3 Okinawan Diet
The Okinawan diet is a combination of low-calorie, nutrient-dense foods, antioxidant-rich, and

low-fat foods that makes the traditional meals consumed by the people of Okinawa. The Okinawan
diet is a calorie-reduced diet in principle [50]. The diet of Okinawans has always been associated
with longevity, reduced age-related chronic disease, disability-free old age, and extended health
span but the association of Okinawan diet and erectile function has never been investigated or
discussed. This section suggests that the components and characteristics of the Okinawan diet are
similar in functionality to the components and characteristics of the modern Dietary Approaches to
Stop Hypertension (DASH) diet or the Mediterranean diet. The Okinawan diet brings to the dining
table more unrefined carbohydrates including root vegetables such as sweet potatoes, dark-green and
yellow vegetables, variety of legumes of which soybean products predominate, medicinal plants,
marine foods, and foods rich in monosaturated and polyunsaturated fats [51]. Consumption of lean
meats, fruits, medicinal garnishes, spices, tea, and alcohol is moderate. These three diets includ-
ing the DASH, Okinawan, and Mediterranean-style diets are rich in nutrients that improve erectile
function. For that reason, it is suggested that the Okinawan diet be considered when evaluating diet
as a lifestyle component for better erectile function.
12.3.4 Ikarian and Cretan Diets
Long before the word “nutraceutical” was coined, the long-lived and Centenarians of Ikaria
Island and Crete enjoyed longevity, extended lifespan, and health span. An analysis of the com-
ponents of the Ikarian and Cretan diet shows that the diet of the centenarians of Ikaria is a classic
example of nutraceuticals at work and properly used. Their diet is rich in virgin olive oil, herbs,
vegetables, raw nuts, and less meat. The long-lived Ikarians also avoid smoking, nap at mid-day,
engage in daily physical activity, and have low rate of cardiovascular disease and depression [52], all
of which have shown to enhance sexual life and ER in other studies. The diet of Ikarians, Cretans,
and Sicanians is similar in chemical characteristics to the Mediterranean diet. It is therefore sug-
gested that the diet and lifestyle of the Ikarians be considered and investigated as modifier of and
treatment of ER.
12.3.5 Nicoyan’s Diet
The inhabitants of Nicoya are known for exceptional longevity and are part of the “Blue
Zones.” The diet is mostly centered on high-calcium and magnesium water, fiber-rich grains and
vegetables, antioxidant- and anti-inflammatory-rich fruits, and less processed foods. The diet is
supported by a lifestyle that includes community living and lots of rest in the form of long sleep-
ing hours. Again this diet which resembles the DASH diet in some aspect is composed of nutra-
ceuticals but has never been linked to erectile function. It is also suggested that the diet of the
inhabitants of the Nicoya Peninsula be investigated for its potential and association with healthy
sexual life.
12.3.6 Seventh Day Adventists’ Diet
The Seventh Day Adventists experience longevity with less threat of chronic degenerative
diseases than their aged-matched who adhere to the Western diet-style characterized by regular
consumption of proinflammatory foods and beverages. The diet of the Seventh Day Adventists is
similar to the Mediterranean-style diet although it does not have olive oil and humus on the menus.
The diet is rich in plant-based and fiber-rich foods, less meat, and avoids consumption of spices,
coffee, and hot condiments. Nuts are consumed and most members avoid proinflammatory foods.
Smoking is avoided. The elements of such a diet and the lifestyle of the members of this community
protect endothelial cells from becoming dysfunctional, protect against oxidative stress and inflam-
mation, and reduce the risk factors of ER. It is suggested that the diet of the Seventh Days Adventists
be investigated for its health benefits on erectile function.
12.3.7 Advanced Glycation end Products-Less Diet
Throughout this book, it has been shown that dietary AGEs that characterized the Western diet
and the diet in many parts of the world are proinflammatory. Such diet is a risk factor for endothe-
lial cell dysfunction, oxidative stress, and inflammation because AGEs accumulate in the serum
and tissues that make the penis. The ingredients that make AGEs-rich foods are also developed to
become reactants for the AGEs formation. Studies in diabetic animal models of ER have shown that
drugs that break down AGEs rather than drugs that inhibit AGEs formation reversed ER [21]. The
drug ALT-711 breaks down preformed AGEs and the drug aminoguanidine inhibits AGEs forma-
tion [21]. The effects of these drugs show that once the AGEs have been formed, dietary inhibitors
of AGEs formation are ineffective in helping restore erectile function. Dietary AGEs-breakers need
to be identified for cases where ER has already developed. Otherwise, for prevention of ER, dietary
approaches to anti-AGEs formation are needed.
The diets described earlier including the Mediterranean-style, Okinawan, Ikarian and Cretan,
Nicoyan, and Seventh-Day Adventists have in common the use of minimally processed ingredients
and minimal cooking temperature to prepare meals. The Western-style diet which is the world-style
diet is the opposite of the diets mentioned earlier. Adopting minimally processed ingredients and
cooking techniques that protect against the formation of AGEs can bring to the world better foods
that can help fight the development of ER.
12.3.8 Food extracts with Potential for Improving Sexual Dysfunction
Fenugreek seeds (Figure 12.1) contain the bitter saponin called protodioscin [53,54] which has
shown through clinical trials to improve sexual desire and enhance erection via the conversion of
protodioscine to De-Hydro-Epi-Androsterone (DHEA) [54]. Fenudioscin is a protodioscin-enriched
fenugreek extract available from Cepham Inc., Piscataway, NJ, that maintains sexual function,
although the company insists that the statement have not been evaluated by the FDA. Fenudioscin
is enriched with 22.5% protodioscin and contains other fenugreek saponins.
Moringa oleifera (Figure 12.2) parts including extracts from leaves, seeds, bark, flowers, sap, or
roots are used in traditional medicine. Health benefits associated with Moringa consumption include
improvement of diabetes hyperglycemia and dyslipidemia, tissue (liver, kidneys, heart, testes, and lungs)
Figure 12.1 fenugreek seeds contain several bioactive compounds with health-enhancing activities against
erectile dysfunction.
Figure 12.2 Moringa oleifera is a good source of bioactives for improving erectile dysfunction.
protection, analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions [56].

Moringa leaves extracts have been reported to improve sexual dysfunction in animals [57] and humans
[58,59].
12.4 LIFeStYLeS thAt IMPrOVe ereCtILe FUNCtION
Physical inactivity, sedentary lifestyle, and smoking are risk factors for ER. Physical activity
ameliorates endothelial function and erectile function [60]. Studies have shown that exercise and
physical fitness can prevent chronic Western-style diet-induced ER [61]. Reducing physical inactiv-
ity by adopting physical fitness and avoiding smoking should reduce the risk of endothelial dysfunc-
tion, oxidative stress, chronic inflammation, and potentially ER. Moderate alcohol consumption can
help men aged 45–54 years old but not those older than 54 years of age [6].
The globalization of the world’s economy has also led to the globalization of the world’s diet.
The diet of high-income economies of the West has been adopted by most developing economies
of the world for several reasons including convenience and availability. This Western-style diet
is often loaded with proinflammatory AGEs which deposit in the penile tissues and promote the
development of ER. Chronic consumption of such diet which is what most people around the world
are doing can be associated with rise of ER as a chronic disease and risk factor for cardiovascular
disease. Drugs are being developed with some success and risks associated with their use. Foods are
consumed throughout lifetime. Foods would be the best medicine against the development of ER.
Developing technologies that reduce the development of AGEs in foods, improving the Western-
style diet which has become the world’s diet will be the best medicine that can curb the rising
number of men who are developing ER around the world. The scenario of men with ER will be
worst in the years to come as most popular and tasty foods are being with pro-AGEs and proinflam-
matory ingredients.
reFereNCeS
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dysfunction. Presse Med 2012;41:593–597.
3. Kemp-Harper B, Schmidt HH. cGMP in the vasculature. Handbook of Experimental Pharmacology
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ChAPter 13
Insomnia and Sleep Disorders
13.1 DeFINItIONS
Insomnia is the inability to initiate or maintain sleep or early-morning awakening followed by

the inability to go back to sleep or feeling unrested during the day.
Sleep apnea is a chronic sleep disorder in which breathing stops for few seconds to minutes
or becomes shallow while the individual is sleeping and the breathing starts again. Sleep apnea is
characterized by a loud snoring, choking sound or fatigue even after a full night’s sleep. People with
sleep apnea move out of deep sleep into light sleep, have poor quality sleep, are often tired during
the day, and may experience excessive daytime sleepiness at work or while driving. Obstructive
sleep apnea (OSA) and central sleep apnea are the two major types of sleep apnea.
OSA is most common. In this condition, during sleep, the individual experience shallow breath-
ing or breathing pauses as a result of airway collapse or blockage. Snoring is a result of the airway
collapse or blockage. Overweight people tend to experience sleep apnea but anyone including chil-
dren can have sleep apnea.
Central sleep apnea is a condition in which the individual can go without breathing for brief
periods of time because the breathing muscles do not receive the right signal from the brain. Central
sleep apnea affects mostly people with medical conditions or under certain medical prescriptions
but it can also affect anyone. People with central sleep apnea do not necessarily snore.
Hypersomnolence is characterized by long hours of nighttime sleep and recurrent episodes
or daytime sleepiness. Hypersomnolence is associated with impaired intellectual acuity and job
performance and the risk of getting involved into serious accidents. The condition also has grave
physical and medical consequences.
Restless legs syndrome (RLS), also known as Willis–Ekbom disease, is a neurologic disor-
der that affects sensorimotor function. The disease affects about 4%–10% of the U.S. population.
During episodes of RLS, which often occur in the evening, the individual is irresistibly urged to
move his/her legs with unpleasant pulling, tugging, or creeping. As a result, RLS disrupts sleep and
negatively affects the quality of life. Iron deficiency, diabetes, end-stage renal disease, pregnancy,
and rheumatoid arthritis have been identified as risk factors.
13.2 rISK FACtOrS FOr INSOMNIA
13.2.1 Age and Gender
Sleep is very important for growth, development, and quality life. Poor quality sleep affects
mental, physical, and emotional function [1]. Poor quality sleep has been associated with increased
adolescent morbidity, mortality, and poor overall quality of life. Insomnia affects about 30% of the
233
general population [2]. A 13–15 years follow-up study of 6236 Norwegian participants aged 40–45
who provided information on self-reported insomnia concluded that insomnia was associated with
a threefold risk of mortality over 13–15 years follow-up [3]. Mortality rate was particularly high
in participants with insomnia and short sleep duration of less than 6.5 h. Insomnia with normal
or high sleep duration was not associated with high mortality. The National Health and Nutrition
Examination Survey, 2005–2010 found that the use of prescription sleep aids among Americans
increases with age and education, adult women use prescription sleep aids more than adult men,
and non-Hispanic white adults who use prescription sleep were more likely to use sleep aids (4.7%)
than non-Hispanic black (2.5%) and Mexican-American (2.0%) adults [4]. Sleep disturbances sig-
nificantly affect women during mid-life or menopause. A study of females from a cross multiethnic
group found that 38% of women in mid-life had sleep difficulties [5].
13.2.2 Socioeconomic Status
An examination of data from a longitudinal Mobile Youth Survey (MYS; N = 11,838, 49% female,
93% African-American) that looked into trajectories of sleep problems by age (10–18 years) among
impoverished adolescents as a function of gender, feelings of hopelessness, and exposure to violence
concluded the followings [6]. Hopelessness increases the symptoms of apnea, insomnia, nightmares,
RLS, or periodic limb movement disorder (RLS/PLMD), and daytime sleepiness. Exposure to vio-
lence increases the symptoms of insomnia, RLS, and nightmares, as well as daytime sleepiness. The
combination of hopelessness and exposure to violence exacerbates insomnia and RLS/PLMD more
than hopelessness or violence alone. Women who have experienced hopelessness and been exposed
to violence experience the worst symptoms of RLS/PLMD than men. Poor sleep quality leads to
worst outcomes among impoverished adolescents as compared to other matched groups.
The National Health and Nutrition Examination Survey, 2005–2010 found that the probabil-
ity of using sleeping aid is higher among non-Hispanic white adults than non-Hispanic black and
Mexican-American (2.0%) adults.
13.2.3 Work time Control
People who cannot influence the duration and positioning of their work time are at increased
risk of sleep disturbance compared to employees who have a say on their work time. Sleep dis-
turbances are also high in people working long hours and having very high levels of control over
working times.
13.2.4 ethnic Origin
The prevalence of sleep-disordered breathing is high in the U.S. Hispanic/Latino populations

and is a risk factor for the high prevalence of diabetes and hypertension in this population group.
The Boston Area Community Health (BACH) Survey randomly evaluated sleep restriction (< or =
5 h/night) and restless sleep at baseline and approximately 5 years later in 5502 participants aged
30–79 at baseline and 4145 participants who completed the study [7]. White, Blacks, and Hispanics
were surveyed. The minority populations investigated had higher rates of obesity, type 2 diabetes
mellitus (T2DM), hypertension, coronary heart disease, stroke, and mortality. The study found
significant differences in sleep and its associated problems at baseline by race and socioeconomic
status. The social disparities in sleep duration and restless sleep and the incidence of obesity, dia-
betes, hypertension, and cardiovascular disease were also significant by race and socioeconomic
status at follow up. The National Health and Nutrition Examination Survey, 2005–2010 found that
non-Hispanic white adults use prescription sleep were more likely to use sleep aids (4.7%) than non-
Hispanic black (2.5%), and Mexican-American (2.0%) adults [4].
InsoMnIa anD sLeeP DIsorDers 235
13.2.5 Pathological Conditions
Poor sleep quality frequently occurs among hemodialysis patients [8]. In this group of patients,
insomnia occurs four times more than daytime sleepiness. Hemodialysis patients also suffer from
sleep disturbance such as RLS/PLM and a high risk for sleep apnea. The prevalence and risk factors
for OSA are high in patients with schizophrenia because these patients have high rates of obesity
and cardiovascular morbidity [9].
Sleep–wake disturbance and insomnia affects cancer patients at diagnosis and during treatment
survivorship, and negatively impacts the quality of life compared to the general population [10,11].
Although common in most cancer patients, these patients are seldom treated for insomnia and/or
sleep disturbances [12].
The association between sleep disturbances including OSA, sleep-disordered breathing, exces-
sive sleepiness, insomnia, RLS, and metabolic syndrome including obesity and T2DM is strong
[13,14]. OSA can be a risk factor for insulin resistance, glucose intolerance, and type 2 diabetes
development [15].
Sleep deprivation has been identified as a risk factor for neurologic diseases including stroke,
multiple sclerosis, Alzheimer’s disease, headache, epilepsy, pain, and somnambulism but sleep loss
appears to be a potential protective factor against Parkinson’s disease [16]. Fatigue and sleep distur-
bances are among the most common and disabling symptom of MS [17].
13.2.6 Psychiatric Disorders
People with psychiatric disorders including anxiety tend to have difficulty sleeping normally.
Insomnia can precede and predispose to psychiatric disorders [18], can be comorbid with and exac-
erbate psychiatric disorders, and can occur as part of psychiatric disorders. RLS is associated with
considerable sleep disruption and reduced work productivity.
13.2.7 Inflammation and Sleep Disorders
The association of poor sleep and inflammation has been established and is mediated by mark-
ers such as cytokines. For instance, obesity is correlated with inflammation and while obesity is
associated with poor sleep the effect of interaction between insomnia and obesity on inflammation
is not well known. Chronic poor sleep quality is associated with increased inflammation. Eleven
insomnia patients (8 women and 3 men) had greater values of inflammation markers across the day
than 11 gender matched [19]. A small sample of 10 young healthy men and women who were sleep
deprived from 8.2 to 4.2 h for ten consecutive nights showed a fivefold increase in inflammatory
markers such as C-reactive protein when the non-sleep-deprived group maintained the same low
levels of C-reactive protein [20]. Chronic inflammation may deregulate sickness behaviors that lead
to long-lasting symptoms such as appetite changes, poor sleep, and behavioral inactivity and cul-
minate into depression. There is a positive association between poor sleep and major depression as
90% of depressed people report frequent insomnia episodes [21]. It has been suggested that factors
including adiposity, smoking, alcohol use, physical inactivity, and poor sleep may contribute to high
levels of inflammatory markers in depressed individuals [19].
13.2.8 health, economic, and Social Significance of Insomnia and Sleep Disorders
Good sleep promotes good health and sleep is a critical factor for good health. Sleep distur-
bances including insomnia are a risk factor for infectious diseases and the development and man-
agement of chronic inflammatory degenerative diseases and conditions including type 2 diabetes,
cardiovascular disease, obesity, anxiety, hypertension, stroke, osteoporosis, asthma, angina, and
depression and contribute to all-cause mortality [22]. In the United States, about 25% of the popula-
tion complain about insomnia and about 10% are diagnosed with insomnia and the disease persists
in 50% of patients [23–25].
Chronic or persistent insomnia affects approximately 10% of the world population [26].
Japanese average 6 h 22 min of sleep, which is about 30–40 min less on workdays than work-
ers in the other developed countries [27]. Japanese also sleep less year by year. There are many
reports that insomnia has been suggested to cause depression and other mental disorders. And
epidemiological evidence supports a link between sleep loss and obesity. Obesity is one of the
risk factors of OSA syndrome, which causes cognitive dysfunction, mood disorders, and so on.
Sleep loss and sleep insufficiency can cause mental disorders and be impaired cognitive function
and performance.
The symptoms of insomnia are more prevalent among women, older adults, and in individu-
als with less education [28]. The association of insomnia and primary care patients, the elderly
and individuals with health or mental conditions is strong [28–30]. Insomnia increases the risk of
depression, suicidal thoughts, and behaviors and reduces the quality of life [31–33].
13.2.8.1 Sleep Disturbance and Infectious Disease
A prospective and observational cohort study of 56,953 female nurses (ages 37–57 years old)
participating in the Nurses’ Health Study II concluded that poor sleep efficiency of less than 5 h
and prolonged habitual sleep of more than 9 h were associated with increased risk of pneumo-
nia [34]. Sleep disturbance including insomnia is associated with chronic infectious disease
such as HIV; insomnia or sleep disturbance may have a significant impact on cognitive performance
in HIV-positive individuals [35]. Sleep disturbance has also been associated with susceptibility to
the common cold [36].
13.2.8.2 Insomnia and Diabetes
Insomnia negatively affects blood sugar control and the quality and duration of sleep and has
been identified as predictors of levels of hemoglobin A1c. Diabetes complications can precipitate
insomnia symptoms. Insomnia and diabetes can be exacerbated with inappropriate lifestyle. The
high comorbidity between insomnia and diabetes is associated with the mutual interaction between
the two diseases that leads one to develop the other and vice versa [37]. Lack of sleep and metabolic
dysregulation-induced circadian disruption may impair timing and amount of food intake, affect
energy balance and inflammation, alter glucose tolerance and insulin sensitivity, and contribute
to weight gain, obesity, and type 2 diabetes. It is important to investigate the association of sleep
disturbance and metabolic disorders such as diabetes especially nowadays when the diabetes is on
the rise.
13.2.8.3 Insomnia and Cardiovascular Disease
Sleep apnea is a risk factor for the development of cardiovascular disease including hyper-
tension, stroke, coronary heart disease, and irregular heartbeats [38]. Inflammation mediates
all stages of atherosclerosis from disease initiation to the development of complications includ-
ing cardiovascular disease [39]. Sleep disturbance including insomnia mediates the association
between depression and hypertension development. The association of sleep disturbance and
reduced sleep duration and cardiovascular disease especially hypertension have been shown to
be strong in some cases, moderate in some cases, or nonexistent in others [40–43]. Insomnia is
a major risk factor for the development of cardiovascular disease in men and women with low
socioeconomic status [44].
13.2.8.4 Insomnia and Obesity
Short sleep duration and sometime longer sleep may be associated with the development of exces-
sive body weight or obesity and eating patterns in all age groups and the association is particularly
strong with children [45–48]. Children need to sleep more because sleep aids in brain development.
Sleep disturbance including insomnia affects the region of the brain associated with appetite and energy
expenditure [49]. Obesity is a risk factor for OSA syndrome and the latter is in turn a risk factor for
cognitive dysfunction and mood disturbances. We should recommend more sleep to prevent obesity.
13.2.8.5 Insomnia and Depression
The relationship between sleep and depression is complex. Sleep disturbance including insom-
nia can predispose to depression or can occur as part of depression [18]. Treatment of insomnia or
sleep apnea reduces depressive symptoms [50,51]. Insomnia was highly frequent among patients
during admission in Palliative care [52]. Adults (N = 11,329, ≥18 years) who participated in the
National Health and Nutrition Examination Survey (NHANES) during the years 2005–2008 were
examined for the association of insomnia and depression [53]. Depression rates were 33.6%, 22.2%,
27.1%, for those who reported insomnia, OSA, or comorbid insomnia-obstructive sleep symptoms,
respectively. Analysis of cross-sectional data from the National Longitudinal Study of Adolescent
Health [n ≈ 287 MZ (monozygotic) twin pairs; 50% male; 22% Black; mean age = 15.75] showed
statistically significant association between sleep duration and depression [54].
13.2.8.6 Insomnia and Suicidal Thoughts
There is a need to investigate the relationships between sleep disorders and suicidal thoughts
or ideation. Suicidal ideation is a predictor of suicide and its association with sleep disturbance has
been established [55]. In a study of 98 non-selected patients classified as “suicidal ideators” or “non-
ideators,” who responded to a specific question on the Beck Depression Inventory, it was revealed that
poor sleep quality is directly associated with suicidal ideation, depression, and anxiety and is a good
predictor of suicide in subjects with epilepsy [56]. A sample (N = 404) of members and veterans of
Canadian Forces seeking treatment at a hospital-based Operational Stress Injury Clinic was examined
for the association of sleep disturbances and suicidal ideation [57]. The examination was carried out
after controlling for probable posttraumatic stress disorder (PTSD), major depressive disorder (MDD),
generalized anxiety disorder (GAD), and alcohol use disorder (AUD). The study reported that 86.9%
of the patients had insomnia but sleep disturbances did not predict suicidal ideation.
13.2.8.7 Insomnia and Obstructive Sleep Apnea
Insomnia and OSA often co-occur and each is an independent risk factor for cardiovascular
disease. An evaluation of participants (N = 795) from the Heart Strategies Concentrating On Risk
Evaluation (Heart SCORE) showed a strong association (22.5%) of insomnia and sleep apnea [58].
13.3 DIetArY AND ArOMAtherAPhY MANAGeMeNt OF INSOMNIA
Dietary interventions for the management of both sleep onset insomnia (difficulty falling asleep)
and sleep maintenance insomnia (difficulty staying asleep) is a safer option than most of the pre-
scription drugs currently available on the market [59,60]. This chapter will discuss dietary habits
to avoid any potential foods and beverages that may help in overcoming sleeps of short durations
at night.
13.3.1 Dietary habits and Lifestyle that Are Counterproductive

for Managing Insomnia
Red Bull was introduced in Austria in 1987 as a beverage with significant amount of caffeine
as stimulant. Since then caffeine addition in foods and beverages has soared. In addition, foods or
beverages containing caffeine are not required to report caffeine level on the label. Caffeine depen-
dency has been recognized as a clinical disorder [61]. Excessive caffeine consumption stimulates
sleep disturbance development, and habitual and prolonged use over lifespan especially up to 6 h
before going to bed reduces the quality and duration of sleep [62–64]. As a result, regular consump-
tion of stimulant beverage containing large amounts of caffeine tends to increase daytime sleepiness
[65,66]. Daytime yawning is a characteristic of heavy coffee drinkers [67]. Most coffee drinkers
combat yawning with more coffee during daytimes but ignore the detrimental effect of caffeine
when the daylight is over.
Caffeine is found in coffee (Figure 13.1), decaffeinated coffee, tea, and many herbal teas.
Caffeine has a protective role in plants and therefore is almost ubiquitous in several plants that
humans have selected as beverages for one reason or another.
Sleepiness including insomnia cannot be fought with coffee consumption regardless of the time
of the day. The taste and flavor of coffee has created addiction in millions of people while the dam-
aging effect of excessive caffeine seems to be ignored during the day or at meal time in the evening
but takes center stage at night when the need to sleep becomes important. Coffee overuse may
exacerbate the sleep disturbances in the young and elderly [68,69].
Tea leaves, in general, contain approximately 5% caffeine suggesting that tea contains more
caffeine than decaffeinated coffee, which has less than 3% caffeine. Tea (Figure 13.2) cannot be a
substitute for coffee for people trying to overcome insomnia although tea has a calming effect that
coffee does not have. Green tea, like most teas, is a very good source of caffeine. Some green tea
powders are highly concentrated in caffeine and contain more caffeine than regular coffee. Green
tea cannot be a substitute for coffee for people who have problem falling asleep or staying asleep
throughout the night.
Figure 13.1 excessive consumption of coffee can cause sleep disturbances.

Figure 13.2 tea has caffeine but also has calming effect.
Heavy alcohol consumption, for example, ≥5 standard alcohol ingestions in a day decreases the
quality and duration of sleep [70]. Alcohol is a potent somnogen; some people use it as a sleep aid.
However, in non-alcoholics, binge drinking may help only during the first half of the night but disrupts
sleep during the second half [71]. For alcoholics, binge drinking disrupts sleep both during drinking
periods and during abstinences, and causes profound insomnia and excessive daytime sleepiness [71].
A self-administered diet history questionnaire was given to 3129 female Japanese workers aged
34–65 years to investigate the association of diet and sleep quality [72]. Low intake of vegetables
and fish was associated with poor sleep quality. Similarly high intake of sweets including confec-
tionaries was associated with poor quality of sleep. Cross-sectional and epidemiologic studies have
demonstrated individuals who consume less vegetables and consume more energy-dense foods such
as refined carbohydrates and fats sleep less [73].
13.3.2 Beverages that May help Improve Sleep time and Quality
Herbal teas that do not contain caffeine are frequently used for chronic primary insomnia.
The safety of some herbal teas is uncertain. Chamomile, valerian, and kava are commonly used.
However, randomized control trials have shown no statistically significant difference between any
of the three herbal medicines and placebo [74]. In a randomized, double-blind, placebo-controlled
pilot trial that lasted 28 days, chamomile consumption had no significant effect on sleep time, sleep
efficiency, sleep latency, wake after sleep onset, sleep quality, and number of awakenings [75].
Cherry (Prunus cerasus) juice (Figure 13.3) has been reported to improve sleep. Pigeon et al.
[76] performed a randomized, double-blind, crossover where 15 older adults suffering from chronic
insomnia but otherwise healthy received a tart cherry juice blend and a placebo for 2 weeks with a
2-week washout period. The results of the study indicate that tart cherry juice modestly improved
the quality of sleep in these adults. The outcome was faster and better than sleep quality reported
using valerian. The participants fell asleep 17 min earlier than usual. When the results were com-
pared to melatonin, which is the standard natural product for insomnia, the results equaled some of
the reports obtained with melatonin.
Howatson et al. worked with 20 volunteers who consumed either a placebo or tartcherryjuice
concentrate for 7 days using a randomized, double-blind, placebo-controlled, crossover design [77].
Figure 13.3 Cherry juice.
Cherry juice increased plasma melatonin and the participants on melatonin significantly improved
their sleep time and efficiency. Montmorency tart cherry juice was also used in a randomized dou-
ble-blind, crossover pilot trial where 7 participants (age 68 ± 9 years) with insomnia consumed the
juice and the placebo in 2 weeks separated by a 2-week washout period [78]. Tart cherry increased
the sleep time by 85 ± 17 min. The juice had no vitamin C.
Cow’s milk (Figure 13.4) can have tranquilizing properties. Cow’s milk is a good source of
melatonin and contains 10–40 ng/L melatonin when the cow is milked in the darkness at nighttime
[79]. In 1934, Laird and Drexel reported that corn consumption of flakes and milk helped adults
Figure 13.4 Cow’s milk from cows milked at night has a sleep-promoting effect.
sleep without interruption [80]. Nighttime milk (0.5 L) was fed to 81 healthy elderly through a cross-
over study and comparison was made to a group consuming daytime milk as control [79]. The end
point was sleep quality and circadian activity. The group that consumed nighttime milk showed
improvement in morning and daytime activity later during the study suggesting that even low level
of melatonin can help the elderly improve their daytime activity.
13.3.3 Aromatherapy
Aromatherapy involves inhaling pure essential oils from plants to improve mood, relaxation,
insomnia and the quality of sleep, and the quality of life in general. It is used by the patients in
care units as well as by individuals at home. Hwang and Shin reviewed randomized controlled and
quasi experimental trials on aromatherapy and sleep and analyzed 12 studies that met the inclu-
sion and exclusion criteria [81]. It was concluded that aromatherapy appeared to be effective in
improving sleep. Lillehei and Halcon also reviewed studies that investigated the effect of aroma-
therapy on sleep [82]. Aromatherapy, mostly with lavender essential oil, improved sleep in people
with mild sleep disorder.
13.3.4 Foods that May help Improve Sleep time and Quality
High-glycemic index foods tend to improve sleep time and quality [83]. Recent studies show
that rice consumption can improve the quality of sleep [84]. Rice (Figure 13.5) has a high-glycemic
index, which may explain increased tryptophan absorption during or following rice consumption.
In a study that included 1848 Japanese men and women between 20 and 60 years of age it was
shown that rice promotes sleep better than bread and noodle. The association of noodle and sleep
was poor and there was no association between bread and sleep. The investigators suggested that
the difference in glycemic index among the foods studied may explain their strong or weak asso-
ciations with sleep.
The dietary glycemic index (GI) of the general Japanese population is higher than the dietary
glycemic index of Western populations (approximately 70 vs 48–60, respectively) [85–88]. Seventy
percent of cereals consumed in Japan are rice based, which accounts for 59% of the dietary GI of
Figure 13.5 rice has a high glycemic index and promotes sleeping.
the Japanese population. The potential mechanism associated with the improvement in sleep time
by high-glycemic foods is due to the postprandial rise in tryptophan by the carbohydrate.
Tart cherry fruits (Figure 13.6) should also be good somnogens. The bioactive compounds
including melatonin and proanthocyanidins found in tart cherry juice are also present in cherries
and can be found in higher concentration in the fruit that includes the juice and the pomace.
Kiwi fruits (Figure 13.7) have been reported to improve sleep time and quality. A clinical trial in
which 24 healthy participants consumed two kiwi fruits an hour before bedtime for 4 weeks showed
that total sleep time and sleep efficiency increased by 13.4% and 5.41%, respectively [89]. Kiwi
contains serotonin. Kiwi also contains more vitamin C per serving than orange. Vitamin C delays
sleep; the effect of kiwi on sleep is not well understood.
Figure 13.6 Cherries contain melatonin and proanthocyanidins that may help improve sleep time and quality.
Figure 13.7 Kiwi fruits have been reported to improve sleep.

Melatonin promotes sleepiness. Melatonin-rich foods have been identified and include Shiya
tea-leaf > mulberry leaves > wolfberry > aloe vera > radish seed > raspberry > red sage root >
Chines licorice > white and black mustard seeds > fenugreek seeds > almond seeds > sunflower
seeds > sour cherries [90]. Melatonin has also been found in onion, garlic, banana, asparagus, oat,
corn rice, ginger, and wheat [91]. Since only very low level of melatonin may be needed to promote
sleepiness, it appears that there may be a way to manipulate these foods to promote sleepiness.
Chrononutrition is a field between nutrition and circadian clock that addresses food com-
ponents that regulate circadian clocks and meal times that affect metabolic homeostasis [92].
Chrononutrition involves the consumption of foods at times of the day when they are more useful
for health in order to improve biorhythms and physical performance. Tryptophan-enriched cere-
als were fed to 35 middle-aged/elderly (aged 55–75 years old) at breakfast and dinner for 3 weeks
in a simple blind assay. Tryptophan in 22.5–30 mg level was added to 30 g cereals [93]. Cereals
containing 60 mg tryptophan decreased sleep fragmentation and improved actual sleep time and
efficiency.
13.3.5 Future Direction
Treatment of insomnia is crucial because insomnia induces several problems including cog-
nitive inefficiency, sleepiness, mood disturbances, impaired attention and performances, memory
deficits, and fatigue [94]. Treatment of insomnia becomes difficult as more and more individuals
rely on stimulants to solve their fatigue and inefficiency issues. Change in dietary habits, adopting a
healthy lifestyle combined with chrononutrition, may help those individuals who are prone to daily
insomnia.
Societal contribution to the fight against insomnia is not necessarily a moral issue; it is very
much an economic issue. Insomnia generates fatigue and fatigue induces low performance, which
translates into economic loss. The food industry cannot stay insensitive to the phenomenon of
insomnia that affects about 30% of the world population because foods can help fight insomnia.
The time is now to put knowledge to work to develop foods that do not disturb people’s moods.
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ChAPter 14
Parkinson’s Disease
14.1 DeFINItION, SYMPtOMS, AND hIStOrY OF PArKINSON’S DISeASe
Parkinson’s disease (PD) is a movement disorder pathology caused by a progressive loss of brain
cells, known as the dopaminergic neurons in the region of the brain known as the substantia nigra,
which produce the chemical dopamine that is involved in the control of voluntary movements [1]
and the degeneration of monoaminergic neurons in the brain stem [2].
As dopamine level in the brain decreases, PD develops gradually through symptoms that include
trembling of hands, arms, legs, jaw, and face; stiffness of the arms, legs, and trunk; slower and rigid
movements; postural instability; impaired reflexes and coordination; and difficulty walking and
talking [3] (http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html, last accessed: March 3,
2015). As the disease progresses, other problems including depression, sleep disturbances, fatigue,
anxiety, emotional changes, cognitive function decline, urinary problems, frequent and recurrent
falls and trouble chewing, swallowing, speaking, or dementia develop [4–6].
The symptoms of the shaking palsy were described for the first time in 1817 by James Parkinson
[7]. Later, in 1872 Jean-Martin Charcot described the disease in greater detail and named it after
Dr. Parkinson [8]. In 1912, protein aggregates were identified in brain cells outside the substantia
nigra by Fritz Heinrich Lewy. Similar protein aggregates were found in the substantia nigra in 1919 by
Konstantin Nikolaevich Tretiakoff. This time, Tretiakoff named the aggregates Lewy bodies (LB) after
Fritz Heinrich Lewy. Analysis of the LB led to the identification of α-synuclein (α-syn) as the main pro-
tein of the bodies. In 2003, the potential mechanism of PD progression involving α-syn from the dorsal
motor nucleus of the vagal nerve to the substantia nigra and other regions of the brain was proposed [7].
Although the mechanism of dopaminergic neurons death is complex and not completely under-
stood, the misfolding and aggregation of the α-syn protein has been identified as central to the
neuropathology of PD. The contribution of the other synuclein proteins including β and γ-syn has
never been demonstrated [9].
Laboratory tests to detect PD do not exist. Instead, doctors rely on medical history and neuro-
logical examination of the patient. It may take up to 2 years from symptoms to diagnosis [5].
14.2 PreVALeNCe, INCIDeNCe, AND eCONOMIC AND

SOCIAL IMPACt OF PArKINSON’S DISeASe
PD is the second most common progressive neurodegenerative disease, following AD, that
affects about 1.5% of the population aged 60 years old and above [1], 1%–2% of the elderly aged
above 65 years old, and 4% of people who are above 85 years old [10]. Worldwide, the statistics are
expected to increase with the increasing lifespan around the world.
PD has no cure, is progressive, and worsens over time. The disease can be managed. The social
and economic significance of AD is worrisome. After diagnosis, most people with PD can live for
249
decades. AD is the sixth leading cause of all death in the United States and it is the fifth leading cause
of death in the elderly [11]. However, as the disease progresses, PD patients feel embarrassed, left
out, uncomfortable, and need more assistance as these patients can easily and frequently fall causing
injuries. The disease affects social interactions. PD patients need assistance such as housework, home
maintenance and outdoor work, emotional support, transportation to medical facilities, and for errants
and meal preparation. The assistance from caregivers is provided on a daily basis. The disease also
draws more out of pocket expenses [5]. The combination of movement disorder, cognitive function
decline, and depression becomes a burden for the caregivers [12]. The financial strain is on the sick,
relatives, and neighbors. The emotional strain is mostly on the spouse especially women as the disease
affects more men than women at any age, and healthcare systems. The worldwide increasing elderly
population adds a rising economic burden on patients and healthcare payers.
In 2010, approximately 630,000 people in the United States were diagnosed with PD [13]. The
diagnosis will likely double by 2040. In 2010, PD cost the United States more than $14.4 billion
(approximately $22,800 per patient), $8.1 billion higher ($12,800 per capita) than expected for
individuals without PD [13]. Indirect costs associated with PD were conservatively estimated at
$6.3 billion (or close to $10,000 per person with PD) [13].
14.3 rISK FACtOrS FOr PArKINSON’S DISeASe
The risk factors for PD include nonmodifiable and modifiable ones, and cross-talk between non-
modifiable and modifiable components. The contribution of genetic or environment alone to PD is
very small but the synergistic effects of both the genetics and the environment seems to play a much
bigger role than the individual component [14]. Aging, genetics, and gender are nonmodifiable risks
for the disease. Modifiable risk factors for PD include overweight and obesity [15], diabetes, diet,
and dairy products including milk and cheese [16]. Yet, the etiology of the disease remains unclear.
14.3.1 Nonmodifiable risk Factors for PD
14.3.1.1 Age and Parkinson’s Disease
The association of aging and PD has been established. Aging is a major risk factor [17,18].
For individuals over the age of 60 years old, the incidence of PD increases exponentially at about
400 times with aging, PD-related mortality is 0.02% for PD patients less than 60 years old and 8.7%
for PD patients aged 85 years old or more [19]. Treatment worsens with aging making aging the
most critical variable in PD development.
14.3.1.2 Genetics, Gender, and Parkinson’s Disease
Genetics appears to be associated with very few cases of PD [14]. However, some of genes that
play an important role in PD have been identified and include α-syn, Parkin, DJ-1, Pink1, and SNCA
[10,20]. PD affects more men than women at any age [5,21]. The association of gender and PD is
stronger for men than women [22].
14.3.2 Modifiable risk Factors for PD
14.3.2.1 Metabolic Syndrome and Parkinson’s Disease
Oxidative stress, insulin resistance, adiposity and central obesity, glucose intolerance, dyslip-
idemia with elevated triglycerides, hypertension, hyperhomocysteinemia, endothelial dysfunction,
and inflammation are components of metabolic syndrome. Oxidative stress is an early modulator
ParKInson’s DIsease 251
of metabolic syndrome. The brain is a highly oxygenated tissue that is also high in lipids making it
very susceptible to oxidative stress. The presence of oxidized lipids, DNA, and proteins and reactive
oxygen species (ROS) has been reported in the brains of PD patients [23].
Midlife adiposity predates and predisposes to PD. Increased triceps skinfold thickness mea-
sured in 7990 men in the Honolulu Heart Program (aged 45–68 years and without PD) between
1965 and 1968 was associated with an elevated risk of future PD [24]. Adiposity increases the risk
of neurodegenerative disease [25]. Obesity is a major risk factor for PD. The body mass index (BMI)
is a risk factor of PD independent of other risk factors [26]. The growing incidence of obesity will
lead to more PD cases as the world population of elderly increases. Obesity induces the production
of pro inflammatory cytokines and the onset of insulin resistance and insulin-like growth factor
(IGF-1) resistance. Excessive plasma pro inflammatory biomarkers lead to the disruption of the
blood–brain barrier, the traffic of the inflammatory stimulators to the brain, the development of
neuroinflammation and potentially the onset of neurodegeneration associated diseases [27].
Chronic hyperglycemia induces oxidative and nitrosative stress, and damages the central ner-
vous system, and diabetes is a risk factor for PD development [28,29].
The association of hypertension and PD has been hard to demonstrate through either prospec-
tive or theoretical studies [30]. Hypertension has shown to be less frequent in PD patients [31].
Elevated levels of homocysteine or hyperhomocysteinemia are a risk factor for endothelial dys-
function and have been shown to contribute to oxidative damage of neurons and may contribute to
the pathogenesis of PD [32].
Exposure to toxicants such as pesticides, herbicides, heavy metals, or infectious agents can
cause neuroinflammation, which in turn can lead to PD development [14,33]. The involvement of
cytokines including interleukin-1 beta (IL-1β) and IL-6, tumor necrosis factor (TNF-α), and ROS in
the etiology of PD has been investigated and demonstrated [34].
14.3.2.2 Dietary Advanced Glycation End Products (AGEs) and PD
Pentosidine, pyralline, and Nε-carboxymethyllysine (CML) are some of the most important
AGEs that occur in vivo and have been identified in aged brains, pigments of Alzheimer’s disease,
and cataracts, and have been extensively implicated in neurodegenerative diseases [35–37].
Diet, especially the Western diet, is an excellent source of exogenous AGEs and its precursors
[38–40]. Dietary methylglyoxal is a very reactive precursor of AGEs and is abundant in carbonated
beverages [41]. Pyralline, pentosidine, CML, and carboxyethyllysine (CEL) are abundant in several
commonly consumed food products including bacon, pizza, lasagna, macaroni and cheese, bread,
and sweetened condensed milk [40,42]. These AGEs and their precursors are also found in foods
sold in ethnic food stores that include carbonated beverages, pizza, dairy products, and meats. It has
been shown that 10% of ingested AGEs are absorbed [43,44]. Once absorbed, dietary AGEs behave
the same way as endogenous AGEs, are pro-oxidants, induce oxidative and carbonyl stress, and
accelerate the formation of ROS-free radicals.
α-syn contains 15 lysine residue that are very reactive during glycation or Maillard reaction.
In vitro studies have shown the potential glycation ability of α-syn in the presence of D-ribose or
carbonyl compounds such as methylglyoxal leading to the formation of aggregates that induce cell
oxidative stress and toxicity [45–47]. The glycation of α-syn leads to its aggregation and the forma-
tion of LB and the development of PD [48]. AGEs such as CML and N3-(carboxyethyl)lysine (CEL)
and their receptors RAGE have been shown to co-localize with α-syn and accelerate α-syn aggrega-
tion [46]. Histochemical analyses of frontal cortex, amygdala, and substantia nigra of PD patients
have shown higher levels of AGEs and RAGE compared to frontal cortex of healthy match controls
[49]. Glycated proteins including α-syn have altered function. Glycated proteins including α-syn
generate ROS, which increase cell oxidative stress and lead to neuronal cell death. Glycated α-syn
can oligomerize and it has been shown that oligomeric α-syn is more toxic than α-syn aggregate.
Figure 14.1 soursop or guanabana contains neurotoxin that may be a risk factor for Parkinson’s disease.
Oligomeric α-syn can cause neuronal cell apoptosis through generation of ROS, which increase
oxidative stress and cell death; proteasome dysfunction that leads to neuronal cell death; or altera-
tion of cell membrane permeability and loss of membrane homeostasis leading to neuronal cell
dysfunction [50].
14.3.2.3 Soursop and Parkinson’s Disease
An atypical type of PD has been identified in Guadeloupe and suspected to be associated with
the consumption of soursop (Annona muricata) [51] also known in Spanish as guanabana or graviola
(Figure 14.1). The cognitive profiles and neuroimaging features of the atypical Guadeloupean par-
kinsonism are similar to classical cases of PD; however, the disease also has neuropsychological and
neuroradiological features that are different from standard clinical symptoms [52]. The atypical PD in
this country may be associated with a dietary neurotoxin present in the soursop. Annonacin, a natural
environmental neurotoxin present in soursop, may be implicated in the development of PD in this
population. Whereas soursop is discredited for being a risk factor for PD, recent studies have shown
that guanabana or graviola can inhibit pancreatic cancer cell metastasis in vitro and in vivo [53,54].
14.4 DIetArY APPrOACheS tO PArKINSON’S DISeASe
14.4.1 Introduction
PD is an age-related neuropathology. Such an association may involve the contribution of foods

consumed over the years by the PD patient. Also, the association of dietary patterns and PD devel-
opment has been hypothesized and demonstrated in humans and in animal models in vitro and
in vivo. This section attempts to identify dietary patterns that may expose individuals to increased
risk of developing PD and dietary approaches that should reduce the potential of developing PD.
14.4.2 Dietary Patterns and risk of Parkinson’s Disease
The incidence of PD is high in Kiribati, Cook Islands, Malta, Luxemburg, Armenia, Iceland,
Finland, the United Kingdom, the United States, Austria, Haiti, the Netherlands, Trinidad and
Tobago, Belize, and Switzerland (www.worldlifexpectancy.com).
Dietary approach measures the overall diet, the interactions among components in the food, and
the effects of metabolites on potential diseases. The use of single nutrients or single foods, regard-
less of their potency, to determine the risks/benefits associated with diseases may be very simplistic.
The association of dietary pattern and PD was evaluated in two studies including the Health
Professional Follow-Up Study (1986–2002) and the Nurse’s Health Study (1984–2000). Men
(N = 49,692) and women (N = 81,676) were included in the study [55]. After 16 years of follow-up,
508 participants developed PD. The study concluded that diet with high intakes of vegetables, fruits
and fish was inversely associated with PD risk and the Western diet was not.
A case-control study in which 249 PD patients and 368 healthy controls were enrolled was con-
ducted in a multicenter hospital-based setting in Japan to determine the association of dietary pat-
tern and PD [56]. There was an inverse relation between diets characterized by high intakes of green
and yellow vegetables, seaweeds, pulses, mushrooms, potatoes, fish, fruits, seafoods, miso soup,
Japanese and Chinese tea, and low level of alcohol. The investigators found no association between
the Western diet and PD risk. In this case, the Western diet pattern was made of high intakes of beef,
pork, chicken, vegetable oil, shellfish, processed meat, salt-rich seasonings, and eggs. Similarly
there was no association between a diet made of high intake of bread, confectionaries, dairy prod-
ucts, sugar, black tea, fruit and vegetable juices, coffee, cocoa, butter, noodles, and soft drinks.
AGEs-rich in diets may have an association with PD. The glycation of α-syn may have exog-
enous triggers. The combination of genetics and environmental factors may trigger the development
of PD. Diets rich in calorie and fats have shown to increase the risk of PD [57]. Diets rich in refined
sugars are associated with the generation of AGEs when the refined sugar is heated at very high
temperature as is the case in many Western cuisine. AGEs are bioavailable and toxic.
14.4.3 Dietary Approached to reduce the risk of Parkinson’s Disease
The inverse association of caffeine-rich coffee and PD developed has been demonstrated and
shown that moderate intake of one to three cups of coffee per day reduces the risk of PD and the
effect is independent and strong [57–59] (Figure 14.2). Tanaka et al. [60] investigated the potential
association of Japanese and Chinese tea and the risk of PD. PD patients (N = 249) and control sub-
jects (N = 368) provided information through a self-administered diet history questionnaire. The
study confirmed that high intake of Japanese and Chinese tea was inversely related to the risk of PD.
Higher adherence to the traditional Mediterranean-type diet has shown to reduce the odds of
developing PD [61,62] (Figure 14.3). Similarly diets rich in vegetables and fruits containing anti-
oxidants show inverse relationship with PD development. The traditional Mediterranean diet may
be a good diet for dopaminergic neurons.
Figure 14.2 Coffee has been identified as beneficial against Parkinson’s disease development.
Figure 14.3 traditional Mediterranean diet.
PD is a fatal disease. PD creates dependency on relatives and communities. PD is costly. The role
of AGEs in PD has been proposed and demonstrated. The AGE-RAGE axis for PD has been identi-
fied as a potential target for PD prevention and possible treatment. Potential options for preventing
the development and progression of the disease involve inhibiting AGEs, breaking the AGE-RAGE
axis, protecting neuronal cell from glycation, and oxidative and carbonyl stress. The identification
and application of dietary bioactive compounds or food systems that can delay α-syn glycation and
oligomerization will contribute to the management of PD development.
Efforts to identify dietary risk factors should help in restricting the consumption of such foods
and allowing research to focus on other environmental and lifestyle factors to reduce the occurrence
and mortality associated with PD.
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ChAPter 15
Cancer
15.1 INtrODUCtION
Cancer is a complex disease that uses the body’s own blood vessels, organs, nutrients, growth
factors, and immune system to fit in, seed, weaken the body immune system to evade surveillance
and survive in the lymph node, grow at its own pace, and travel from one organ to another without
fear of being killed, until it depletes the body of any strength or ability to fight back leading to pre-
mature death. Cancer is the second leading cause of death in the United States and the world after
cardiovascular disease.
Despite decades of and billions of dollars invested in research to find magic bullets for cancer,
durable disease-free states remain rare in patients with advanced disease, and survival benefits from
new drugs are often negligible. Prevention, early diagnosis, and treatment, rather than expensive
therapeutic intervention late in advanced disease, have been associated with the decreased mortality
observed in some types of cancer.
15.2 rISK FACtOrS FOr CANCer
There are several risk factors associated with the development of cancer. The most common
ones include age, smoking, the ultraviolet radiation coming from the sun or tanning booths, expo-
sure to ionizing irradiation, inflammation, exposure to certain chemicals (asbestos, vinyl chloride,
paint, construction materials, pesticides, acrylamide, fuel burning appliances, pressed-wood prod-
ucts, engine oil, solvents, chemicals in meats, and food cooked at temperature higher than 300°F),
viral or bacterial infection, hormone prescriptions, family history of cancer, having more than two
alcoholic drinks a day for several years, poor diet, high-fat diets, lack of physical activity, and being
overweight. Except for age, most risk factors can be prevented.
There are two types of inflammation: acute and chronic inflammation. Acute inflammation is
of short duration and is often the response of the body immune system to harmful stimuli. As sug-
gested in Chapter 2 under inflammation, chronic inflammation is mediated by some of the same
inflammatory proteins that promote cancer development. As a result, the link between inflammation
and cancer is no longer a matter of if but a matter of what we can do to prevent inflammation from
leading to cancer.
Until we really know better, cancer is thought to originate from normal cells that undergo
genetic and environmental alterations that endow the cancer cells with sets of weapons required
for its growth, survival, evasion of toxic agents and immune surveillance, moving around the body,
invasion of other organs, and ability to deliver death to the host. While genetic alteration may seed
cancer cells in the body, it is thought that the environment in which cancer cells are seeded exerts
powerful effects in determining whether the newly seeded cancer cells or cancer initiating cells will
259
die, remain dormant, or progress into full blown cancer that leads to challenging the host, doctors,
and drugs. As a general underlying process, cancer cells develop an environment that allows them
to (1) develop their own set of proteins that help them to grow without much help from the body’s
supply of growth factors, (2) become insensitive to antigrowth signals (compounds that prevent
them to grow), (3) evade normal or provoked death, (4) replicate indefinitely, (5) develop new blood
vessels to connect the tumor cells to the nearby blood vessel from which the tumor extract oxygen
and nutrients and through which the tumor cells discharge their waste to the circulation and travel
to other tissues in the body, (6) evade immune surveillance, (7) invade other organs and metastasize,
and (8) ungratefully kill the host.
15.3 ChArACterIStICS OF CANCer CeLLS
In 2000, Hanahan and Weinberg [1] published a seminal paper entitled “The Hallmarks of
Cancer” that has become not only one of the most cited papers in Cancer Research but also the
guideline to a cure for almost every cancer researcher on this planet. Hanahan and Weinberg identi-
fied six hallmarks of cancer including self-sufficiency in growth signals, insensitivity to anti-growth
signals, evasion of death, unlimited replicative potentials, ability to induce the formation of new
blood vessels or angiogenesis, and tissue invasion and metastasis.
In 2011, Hanahan and Weinberg published another seminal paper in which two emerging hall-
marks of potential generality including reprogramming of energy metabolism and evading immune
destruction were added [2]. In addition to cancer cells, tumors exhibit another dimension of com-
plexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisi-
tion of hallmark traits by creating the “tumor microenvironment.”
Recognition of the widespread applicability of these concepts will increasingly affect the devel-
opment of new means to treat human cancer. These characteristics are discussed later in the context
of the potentials of dietary compounds against the “tumor microenvironment” created by these
eight characteristics.
15.3.1 Self-Sufficiency in Growth Signals
When the body needs to repair a damaged tissue or heal a wound, normal human somatic cells
require exogenous stimulatory signals that help them respond to a need from the body. By respond-
ing to the body’s need, the normal cells move from a quiescent to a short-term proliferative state.
In order to become proliferative, the body needs stimulators. These stimulators can be hormones,
nutrients, growth factors, small cell-signaling proteins in the nervous system known as cytokines,
or neurotransmitters.
Each stimulator has its own receptor. Exogenous signal is received by the receptor. The receptor
is a transmembrane protein that has a protein protruded outside the cell and an enzyme at the end
of the protein docked inside the cell and terminated by an enzyme generally known as a receptor
kinase. The exogenous signal also known as a ligand binds to its receptor and creates favorable con-
ditions for the enzyme on the inside of the receptor to be activated by adding some phosphate groups
on some specific amino acids such as serine, tyrosine, or threonine. The activated enzyme or recep-
tor then serves as docking site for a cascade of intracellular reactions that transduce signals to the
cytoplasm and nucleus resulting in particular gene expression patterns and protein synthesis. These
signal transduction processes can induce various biological activities, such as muscle contraction,
gene expression, cell growth, wound repair, or nerve transmission. The signal is turned off when the
body no longer needs the process to continue. The body does so by turning on the “inhibitors of the
stimulators” to balance the system and stop the process.
CanCer 261
In cancer cells, the process is dysregulated, the growth factors as well as their receptors are
overexpressed and exist at levels that are way above what normal cells need, and as a result the
overexpression stimulates more cell proliferation, loss of cell differentiation, cell cycle arrest, for-
mation of new blood vessels (or angiogenesis), invasion, metastasis, evasion of death (apoptosis), and
unlimited replication, all of which are characteristics of cancer cells.
Cancer cells use the same growth signaling as normal cells, but in these cells, the process is
dysregulated and cancer cells show a greatly reduced dependence on exogenous signals because by
some unknown mechanisms cancer cells acquire the ability to generate most of the growth and pro-
liferation signals they need. As a result, cancer cells obviate dependence and rely less on exogenous
growth stimulatory from other cells or the environment within the normal tissue microenvironment.
By synthesizing these growth factors to which they become responsive, cancer cells create a positive
feedback signaling also known as autocrine stimulation.
For instance, most cancers of the brain (also known as glioblastomas) and cancer of the bones
(also known as sarcomas) manufacture their own platelet-derived growth factor (PDGF) and tumor
growth factor-α (TGF-α). Most cancer cells generate their own osteopontin, a growth stimulatory
protein that is ubiquitous to most cancer cells for survival and proliferation. Because these factors
are overexpressed they can easily trigger excessive cell proliferation leading to a rapid increase in
the number of cancer cells in the tissue environment, an attribute that normal cells would not be
able to do.
Cancer cells do not follow instructions from the body to stop their proliferation, rather these cells
create evading mechanism that allow them to elude the check points and growth arrest by endog-
enous inhibitors by secreting stimulators that overpower the inhibitors. Also, by some unknown
mechanism, cancer cells may also acquire growth stimulatory autonomy and release a flux of pro-
teins that allow them to connect to many receptors and promote their growth without the need for a
stimulatory signal from their normal upstream stimulators. As an analogy, the number of pathways
connecting stimulators and their receptors inside the cell is greater than adding together the number
of all the runways at major airports including JFK, LAX, O’Hare, and Houston. This analogy is
based on the number of pathways that we know and the ones that we do not know and have yet to
be discovered. Since cancer cells use the same pathways used by normal cells, cancer cells make
it difficult to develop drugs that inhibit their viability and growth without damaging normal cell
growth and development.
15.3.2 Insensitivity to Anti-growth Signals
The ability of normal tissues in the body to maintain a normal and dynamic internal stability is
provided by a wide range of endogenous soluble growth inhibitors and insoluble inhibitors embed-
ded and immobilized in the extracellular matrix and on the surface of nearby cells. Under normal
(disease-free) condition, the levels of antigrowth outweigh the levels of progrowth signal factors.
In adult tissues, there is a balance between programmed cell death (apoptosis) and cell division
(proliferation).
Cell duplication is regulated by the cell cycle process. The cell cycle is a highly and tightly regu-
lated process consisting of two main phases, the synthesis phase (or S phase, or “doubling” phase
in which the DNA is copied and replicated) and the mitosis phase (or M phase), culminating in cell
growth and division into two daughter cells containing an equal number of chromosomes. The cell
goes through several checkpoints or gaps to ensure that DNA is replicated as accurately as possible
without error, once during S phase and identical chromosomes are equally delivered to daughter
cells at the M phase. Each checkpoint has the responsibility to ensure that the previous state has
been turned off before the next state of cell cycle takes place. In the cell cycle, the anti-growth
signals are mostly funneled through the retinoblastoma protein (pRb) or the protein transforming
growth factor-β (TGF-β) to stop normal cells from going beyond the G1 phase. In cancer cells,
functional pRb may be mutated or eliminated and therefore loses its proliferation blocking power.
There are several endogenous growth and antigrowth factors available to the human body.
Cancer cells, however, turn off the expression of antigrowth factors and create an environment
wherein cell cycle regulation is gone awry and normal cell growth is lost. Cancer cells disrupt the
pRb pathway and render antigrowth signals dysfunctional.
15.3.3 evasion of Death
There are approximately 1014 cells in the human body and each day billions of cells including dam-
aged, superfluous, infected, transformed cells as well as self-reactive clones from the immune system,
and ectopic cells must be eliminated by an intrinsic suicide program to regulate development and main-
tain internal cell and organ stability. Over time, older cells become damaged and must be eliminated.
There are two major categories of cell death: controlled (physiological) and uncontrolled
(necrotic). Physiological death occurs by apoptosis, necrosis, or autophagy. Apoptosis (from Greek
to mean “falling off”) is a precisely and sequentially regulated intrinsic physiologically programmed
cell death required to maintain tissue internal stability and normal body development and health.
Apoptosis is a self-destruction of an isolated cell, affects only the isolated single cell, and operates
in a way that minimizes the leakage of cellular constituents such as enzymes (catalysts) that could
damage adjacent cells or stimulate an inflammatory process from dying cells. Apoptosis is also
characterized by cell shrinkage without losing integrity, increased mitochondria membrane perme-
ability, and activation of caspase enzymes.
Cell death can also occur by necrosis or autophagy. Necrosis is an uncontrolled process that
affects a group of neighboring cells and results from trauma that causes loss of energy (ATP),
osmotic swelling, and lysis of injured cells followed by lysosomal leakage and release of cytoplas-
mic materials that stimulate an inflammatory response and random degradation of DNA (very late
if at all) and ingestion of lysed cells by macrophages.
Autophagy is another mechanism of programmed cell death whereby cells undergo par-
tial autodigestion associated with the appearance of double-membrane cytoplasmic vesicles aka
autophagosomes designed to engulf various cellular constituents including cytoplasmic organelles.
Autophagic cell death has been recognized as a different cell death mode because some cells die in
a nonapoptotic and noninflammatory manner when exposed to certain cytotoxic compounds such
as etoposide, ceramides, or staurosporine. Autophagy may lead to cell survival and does not neces-
sarily lead to cell death. However, when a cell is under extreme conditions such as lack of growth
factors, exposure to toxic compounds, it will take any available route to die.
Apoptosis can vary with tissue and cell type and is a major regulator of homeostasis. Apoptosis
deregulation plays an essential role in several pathological conditions. Insufficient apoptosis is asso-
ciated with autoimmune disorders while a slow progression to apoptosis may contribute to certain
neurodegenerative diseases; increased apoptosis may contribute to cerebral ischemia, Hepatitis B
and C virus infection, and other liver diseases such as alcoholic liver disease.
First, the mitochondria are essential for cell death by apoptosis since they provide energy in
the form of ATP for cells to die by apoptosis pathway. The mitochondria also contain proapoptotic
proteins, antiapoptotic proteins, and catalysts of apoptosis, all of which are sequestered in the inter-
membrane space. The balance between the two subfamilies dictates whether a cell will undergo
programmed suicide or not. The apoptotic machinery includes the sensors, effectors, and catalysts
of apoptosis. The sensors monitor the extracellular and intracellular environment for conditions of
normality or abnormality (irreversible DNA damage or an overexpressed oncogene, hypoxia, imbal-
ance provoked by oncogenes) that influence whether a cell should live or self-destroy. Tumor suppres-
sor p53, sometime called the guardian of the genome, is one of the best known molecular effective
triggers of apoptosis. p53 is a DNA binding protein and transcriptional activator that regulates cell
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cycle, blocks cell proliferation, and may function as a sensor of DNA damage. Mutations in p53 have
been observed in about 50% of human cancers and mutated p53 favors hypoxia and overexpression
of oncogenic proteins that inhibit apoptosis.
Cancer cells develop mechanisms to escape apoptosis by activating antiapoptotic genes and pro-
teins such as NF-κB that upregulate antiapoptotic proteins thereby repressing apoptosis. Defective
apoptosis allows cancer cells to become resistant to therapies such as chemotherapy. Most cancer
cells have a redundant number of regulators and effectors of apoptosis, have lost some but have
also retained some others. Since apoptosis plays a role in development and pathological conditions,
naturally occurring compounds that catalyze the apoptosis of abnormal cells are good candidates
for stimulating cancer cell apoptosis.
15.3.4 Unlimited replicative Potential/Sustained Immortalization
Normal cells divide, get old, and must be eliminated by apoptosis. Cancer cells can proliferate
indefinitely. The unlimited replicative potential of cancer cells has been so far associated with the
existence of an enzyme at the chromosome end termed “telomerase” and cancer initiation cells or
cancer stem cells (CSCs).
During each round of cell division, the chromosome ends shorten and limit normal cells replica-
tive potential to about 50–70 population doublings. Telomeres are noncoding DNA sequences at the
end of linear chromosomes that maintain chromosomal integrity and prevent duplication of defec-
tive genes. When normal cells reach the end of their replicative potential and a critical telomere
length, the cells have no choice but to exit the cell cycle and die. Cell biologists have suggested that
human lifespan is determined by the replicative potential of telomeres. Therefore, telomeres define
and protect the ends of all linear chromosomes and shorten with cellular aging. There are several
risk factors associated with telomere shortening.
Oxidative stress and reduced levels of antioxidants to name a few have been reported as major
contributors to telomere shortenings. However, cancer cells activate the enzyme termed telomerase
and telomerase provides cancer cells with the ability to indefinitely avoid the progressive loss of
telomeric DNA at the ends of the cell’s chromosomes that occurs during each round of cell division.
Tumor cells may also ensure unlimited replicative potential through mutation or by losing senes-
cence-inducing proteins such as p53. In normal cells, except proliferating progenitor/stem cells and
activated lymphocytes, telomerase activity is undetectable. However, in 85%–90% of cancer cells
whether primary or established cell lines, telomerase level is very high and its inhibition is always
associated with rapid inhibition of cancer cell proliferation. It is important to mention that in solid
tumors such as prostate and breast cancer telomere length is tumor-specific being reduced or elongated.
Telomerase also known as the survival enzyme allows long-term unlimited growth, maintains
the integrity of chromosomes during cell division, and improves cellular resistance against a variety
of stressors and cytotoxic agents including oxidative stress and lack of antioxidants favoring the
prolonged life of cancer cells. Sustained telomerase activity is a hallmark of refractory and relapsed
solid malignancies and target for therapy.
Telomere length has been inversely associated with the prevalence of a wide range of chronic
nonneoplastic degenerative diseases including myocardial infarction, atherosclerosis, Alzheimer’s
dementia, dementia after stroke, and cardiovascular comorbidity. All these diseases mentioned are
associated with short telomeres.
Emerging evidence suggests that the bulk of cancer cells is a mixed population containing a sub-
set of cells identified as cancer initiation cells or CSCs. Reports from clinics indicate that these CSCs
represent a small percentage (typically 0.1%–5% of total tumor cells) of the total cancer cell popula-
tion but possess the stem cell–like property of unlimited self-renewal and subsequent proliferation.
There are reports that these cells resist and evade chemotherapy and immune surveillance and
after the therapy has ceased these cells reemerge stronger than before and regenerate the original or
worst tumors. The existence of tumors enriched with CSCs following radiation or chemotherapy has
been demonstrated in acute myelogenous leukemia and breast, brain, bone, colon, head and neck,
liver, lung, skin, pancreas, and prostate cancer.
The clinical relevance of CSCs has been confirmed by the detection of higher levels of CSC
populations following chemotherapy in patients with locally advanced cancer. These CSCs are not
one size fit all for all types of cancers. In fact, they appear to be different with different types of
cancer but in some cases so far research data are showing some common markers in some cancer
types. For a complete remission from cancer, there is a need to eradicate the population of CSCs
that establish the phenotype.
15.3.5 Angiogenesis or Ability to Induce the Formation of New Blood Vessels
In 1971, Dr. Judah Folkman (1933–2008) from the Children Hospital and Harvard Medical
School in Boston, MA, published a groundbreaking paper in the New England Journal of
Medicine volume 285, issue 21, pages 1182–1186, in which he wrote “In the absence of vascu-
larization, most solid tumors stop growing when they are 2 – 3 mm in size and enter a dormant
though viable state.” Almost half a century later, his statement has become an area of intensive
research for cancer treatment. Folkman’s hypothesis has been confirmed clinically as reported by
Drs. Folkman and Kalluri in 2004 when they wrote in the scientific journal Nature vol. 427, issue
6977, page 787, that “Many of us may have tiny tumours without knowing it. In fact, autopsies of
individuals who died of trauma often reveal microscopic colonies of cancer cells, also known as
in situ tumours. It has been estimated that more than one-third of women aged 40–50, who did not
have cancer-related disease in their life-time, were found at autopsy with in situ tumours in their
breast. But breast cancer is diagnosed in only 1% of women in this age range. Similar observa-
tions are also reported for prostate cancer in men. Virtually all autopsied individuals aged 50–70
have in situ carcinomas in their thyroid gland, whereas only 0.1% of individuals in this age group
are diagnosed with thyroid cancer during this period of their life. Therefore, it has long puzzled
physicians and scientists why cancer develops and progresses to be lethal only in a very small
percentage of people. The realization that a lot of us carry in situ tumours, but do not develop the
disease, suggests that these microscopic tumours are mostly dormant and need additional signals
to grow and become lethal tumours. So, what are these additional signals, and why are most of us
protected from them?” Drs. Folkman and Kalluri went on to write “The most likely answer is our
body’s inherent capacity to prevent the majority of these in situ tumours from recruiting their own
new blood supply, thus preventing further growth owing to a lack of oxygen and nutrients. In the
absence of a new supply of blood vessels by a process known as angiogenesis, an in situ tumour
can remain dormant indefinitely.”
Angiogenesis is the formation of new blood vessels from preexisting ones. The process of angio-
genesis is a critical factor for normal development and tissue repair. The formation of new blood
vessels associated with baby’s development in the womb is “angiogenesis.” A wound is healed by
the process of angiogenesis.
Professor Peter Carmeliet, from Leuven University in Belgium, compared blood vessels to
hosepipes on a farm: “Hosepipes deliver water to every field while blood vessels deliver oxygen
and nutrients to every organ and tissue” [3]. Under physiological conditions, the cells are under
a balance between the stimulators and the inhibitors of angiogenesis. However, under pathologi-
cal conditions, the stimulators of angiogenesis prevail and stimulate the progression of disease.
Pathological angiogenesis is critical to human health because more than 70 chronic degenerative
diseases including diabetes blindness and cancer are angiogenesis dependent. There are two types
of pathological angiogenesis: the insufficient and excessive angiogenesis. Insufficient angiogenesis
can lead to diseases such as impaired wound healing, stroke, infertility, and scleroderma. Excessive
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angiogenesis can lead to the development of macular degeneration, AIDS, Lou Gehrig disease, and
cancer (Figure 15.1).
Cancer cells use blood vessels to obtain oxygen and nutrients from the bloodstream. Tumor
angiogenesis is also an attractive target for cancer treatment because up to 90% of solid tumors con-
tain and express high levels of angiogenic proteins such as the vascular endothelial growth factor
(VEGF) and some of its receptors leading to poor prognosis.
Oxygen is a major resource for life. Cancer cells that grow near the vicinity of blood vessels
obtain oxygen and nutrients needed for growth from the blood vessels. However, as the tumor
mass increases, cancer cells that develop far from the blood vessels have limited access to oxy-
gen (Figure 15.2). Tumors that develop away from oxygen adapt to a low oxygen environment
Parkinson’s disease Retenosis Cancer Alzheimer’s

disease
Scleroderam
Rheumatoid
arthritis
Ulcers Osteoporosis
Lou Gehrig’s
disease
Stroke Insufficient Pathological
Excessive Diabetes
angiogenesis
blindness
AIDS
complications
Infertility
Crohn’s disease
Heart disease Age-related
macular degeneration
Multiple sclerosis Psoriasis Glaucoma
Figure 15.1 Diseases associated with pathological angiogenesis.
Hypoxic cancer cells
Blood vessel
Figure 15.2 Cancer cells growing in a low oxygen environment away from major blood vessels become hypoxic.
by expressing a protein known as hypoxia-inducible factor-1α (HIF-1α) that allows tumor cells
to adapt to the low oxygen environment. Cancer cells adapted to hypoxic environments are very
difficult to treat with conventional therapies because these tumor cells have chaotic and disor-
ganized structures [4–6]. Drugs that rely on oxygen have difficulty penetrating these chaotic,
disorganized, and lowly oxygenated tumor cells leaving behind tumor cells that are not eradicated
by the treatment [6,7].
Tumor cells rely on blood vessels to survive, migrate, and invade at distant locations from
the original spot of the tumor suggesting that cutting off the blood vessels that connect to
tumor cells should prevent tumor cells from spreading throughout the body. During solid tumor
growth, a tumor cell in close vicinity to a blood vessel has easy access to oxygen and nutrients
from the bloodstream, which are important for the tumor survival and growth. However, as
a tumor mass expands, cancer cells that develop distant from the blood vessels have limited
access to the blood vessel and oxygen and nutrients. The cells that grow far away, a mere distant
of approximately 70 μm, are almost deprived of oxygen (<1% oxygen available) and nutrients
and become hypoxic; the farther away from the blood vessel, the more hypoxic the tumor
cells become.
Pictures of tumor cells often show a highly disorganized and chaotic structure; as a result, the
lack of coherent structure diminishes the oxygen availability within the tumor cell. These hypoxic
tumor cells will not die because cancer cells just do not die easily. Rather, these cells adapt to the
low oxygen environment by changing their phenotype and secreting protein such as the HIF-1α that
allows the tumor cells to survive the low oxygen environment.
Hypoxia enhances the expression of VEGF and aggressiveness of cancer cells and their resis-
tance to conventional cancer chemo- and radiotherapies for the following reasons: First, radio-
therapy requires oxygen to generate cytotoxic free radicals that ultimately kill cancer cells. The
poorly oxygenated and organized tumor cells contain pockets of cells that do not communi-
cate among themselves suggesting that the lack of oxygen prevents radiotherapies to effectively
eradicate these hypoxic tumor cells. Second, tumor cells survive the low oxygen environment by
expressing and secreting proteins including the HIF-1α that allow these cells to survive the low
oxygen conditions, and because of change in their phenotypes, these cells are more aggressive
and resistant to apoptosis.
Clinical trials using single antiangiogenic drugs have in most cases shown a response rate of less
than 10% regardless of the tumor origin [8,9]. However, combination of conventional therapies and
drugs that work well under hypoxic conditions appears promising [10]. This is an area of intense
research because hypoxia is critical not only to cancer but also to diseases such as atherosclerosis,
sickle cell anemia, asthma, and obesity.
15.3.6 Addiction to Sugar
Most of our foods except for water contain refined carbohydrate. Breakfasts, lunches, dinners,
juices, malt beverages, desserts, and you name it, all are very rich sources of sugar, specifically
fructose (Figure 15.3a–15.3d). When the food or beverage is ingested or consumed, the sugar is
absorbed, broken down in the mitochondria into energy and as source of compounds that are used
as building blocks for the synthesis of big molecules that are needed for the cell to grow. Normal
cells have a normal demand for energy because they regenerate slowly and every once in a while.
Under normal conditions, one simple sugar molecule such as glucose is converted into two mol-
ecules of ATP.
When cells are deregulated like in cancer, glucose is converted into lactic acid. Cancer cells
to the contrary grow fast, multiply fast, need energy and nutrients to fulfill all these require-
ments and therefore have high requirements for glucose consumption and at the same time these
cells also render their environment very acidic compared to surrounding normal tissues. Several
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studies have shown that cancer cells create a persistent acidic condition in its surrounding, and
such environment allows only cancer cells to survive and continue to proliferate at the expense
of normal cells, invade other tissues, and even suppress the body’s immune surveillance (see the
following) [11,12].
The suppression of the immune system surveillance mechanism creates conditions that facili-
tate cancer cell migration, invasion, and metastasis. By producing excessive lactic acid, the tumor
environment becomes very acidic, in absence or presence of oxygen, and the acidic environment
favors the survival of cancer cells more than normal cells. The abnormal love for glucose plays a
significant role in cancer progression, aggressiveness, and poor survival rate. Several studies have
consistently identified genes associated with glucose trafficking in cancer cells as a common cancer
gene signature that was found in high levels regardless of the type of cancer that was studied sug-
gesting that glucose or to put it very simple “Sugar is the Love of cancer cells.”
(a)
(b)
Figure 15.3 (a) refined carbohydrate-rich breakfast. (b) refined carbohydrate-rich dinner meal. (Continued )
(c)
(d)
Figure 15.3 (Continued ) (c) refined carbohydrate-rich beverage. (d) refined carbohydrate-rich pie.
15.3.7 Mitochondria
The mitochondria are the power house inside the cell because it generates the majority of
energy as ATP to meet the energy requirements for cell growth, metabolism, and other functions
such as generation of reactive oxygen species (ROS), and regulation of cell death. In normal cells,
the levels of water- and lipid-soluble antioxidants are good enough to control the ROS produced
by the mitochondria. However, under disease condition such as cancer, the production of ROS
may cause cell damage if produced excessively. Because of their high growth rate, cancer cells
often become hypoxic because of the inability of cells to access oxygen in the nearby blood
vessels. The mitochondria are unable to provide enough ATP for cell survival under hypoxic
conditions; as a result cells under hypoxic conditions induce HIF, a protein that stimulates key
steps of glycolysis; controls angiogenesis, cell survival, and invasion; and stimulates the produc-
tion of lactic acid. Compared to normal cells, the mitochondria of cancer cells are structurally,
molecularly, and functionally altered and compromised, producing elevated and sustained lev-
els of ROS that increase mitochondrial DNA damage and mutation. In the mitochondria, the
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tumor suppressor protein known as p53 regulates mitochondria function; in most cancer cells
p53 is mutated and its function is lost. As a result, DNA repair mechanism is destroyed, there is
increased mutations, and increased cancer cell production. It has been suggested that compounds
that can further elevate ROS production in cancer cells can selectively push these cells to death
also known as apoptosis. Mitocans (acronym for mitochondria and cancer) are such compounds.
Dietary mitocans known to date include resveratrol, coenzyme Q10, and phenethylisothiocyanate
(from watercress), which can specifically target the mitochondria of cancer cells without impact-
ing the mitochondria of normal cells because normal cells are endowed with greater antioxidant
defense and contain high levels of the enzyme esterase that inactivates prooxidant molecules such
as ROS.
15.3.8 Immune escape
Cancer cells create an environment that allows them to avoid, evade, and defeat immune
surveillance by (1) increasing the acidity of its environment that leads to the destruction of the cells of
the immune system such as the cytotoxic T lymphocytes and natural killer cells resulting in the attrac-
tion of inflammatory cells to cancer cells to assist them to grow and invade other organs in the body,
(2) producing high levels of an enzyme catalyst termed indoleamine 2,3-dioxygenase (IDO) whose
role is to degrade the amino acid tryptophan and cause cachexia and create a tolerogenic milieu in the
tumor mass and lymph nodes, and (3) using the immune-suppressive properties of thymus-derived
naturally occurring regulatory T-cells to remain viable and proliferate without any fear of being inhib-
ited. Evading immune surveillance has been touted as a critical gateway to cancer metastasis because
the immune system is a multiarmed and essential mode for cancer suppression that may have an
impact on the early stage of cancer. In order to completely eradicate cancer cells, the acquired state of
immune tolerance of cancer cells must be overcome. Inhibition of IDO and some regulatory T-cells
may enhance the eradication of cancer cells. Tumor cells secrete lactic acid that in turn destroys T-cells
and promote inflammatory proteins to be released. Reducing lactic acid in and around tumor cells may
be part of the arsenal against cancer.
15.3.9 Loss of Cell-to-Cell Communication
Adjacent cells communicate with each other through special internal channels known as gap
junctions. These gap junctions regulate cell growth by exchanging growth-regulatory signals includ-
ing small molecules between adjacent cells. The internal channels are made of special proteins
known as connexins. There is considerable evidence that most cancer cells have defective gap junc-
tions compared to normal cells. Most tumor promoters inhibit gap junctions and induce connexin
degradation. There is evidence that upregulation of gap junctions in cancer cells suppress cancer
cell tumorigenicity. Cancer cells are known to be tortuous, irregular, disconnected from each other
making drug penetration and activity on these cells very difficult and incomplete. Dietary com-
pounds including carotenoids such as lutein and stilbenes such as resveratrol protect against loss of
cell-to-cell communication [13] suggesting that consumption of foods containing these compounds
before and during cancer treatment may help speed up the curing process.
15.3.10 tissue Invasion and Metastasis
Activation of the protein HIF-1α causes the loss of proteins needed for maintenance of intracel-
lular contact within the epithelial cells and induces the expression of proteins that are crucial for
the cancer cells to spread to other organs by a process known as metastasis. Cancer cells create an
environment that is very acidic and this supports the activation of enzymes known as cathepsins
and matrix metalloproteinases (MMPs) that carve the tissues to allow cancer cells to migrate and
spread throughout the body. Foods that can inhibit the enzymes associated with tissue degradation
including the cathepsins and MMPs and enzymes that cause increase in lactate production would
have antimetastatic and antitumor effect. Avoiding foods rich in lactic acid may also help cancer
patients decrease the rate of lactic acid levels in the body.
15.4 SYMPtOMS COMMON tO CANCer PAtIeNtS
Most cancer patients experience a variety of symptoms including inflammation, fatigue, anorexia,
pain, general malaise, shortness of breath, dry mouth, nausea and vomiting, cough/sputum, diffi-
culty remembering, sadness, loss of appetite, lack of enjoyment of life, insomnia, psychological
distress, constipation, delirium, and difficulty walking. Cancer treatments such as chemotherapy
and radiotherapy are also known to cause most of the symptoms mentioned earlier. The symptoms
are observed individually or they occur in combination. A high prevalence of symptoms occurs in
cancer patients in tertiary care, hospice, and community environments. The following is a brief
description of some of the symptoms common to most cancer patients.
15.4.1 Chronic Inflammation
Chronic inflammation is a risk factor for cancer and associated with poor prognosis. Chronic
inflammation is also a common symptom associated with several types of cancers. Chronic inflam-
mation suppresses the immune system. The protein NF-κB has been identified as one of the medi-
ators of cancer development. Other inflammatory mediators are the cytokines and chemokines.
There are several other inflammatory markers associated with cancer progression including tumor-
associated macrophages (TAMs), MMPs, sphingosine 1-phosphate (S1P), C-reactive protein (CRP),
tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Some markers are commonly
found in some types of cancer like TAM and MMPs are highly concentrated in breast cancer [14];
TNF-α and IL-1β are in pancreatic cancer [15]; CRP is an important biomarker in urological can-
cers [16]; and TNF-α, IL-1, and IL-6 are in lung cancer [17].
15.4.2 Cachexia and Fatigue
Most cancer patients have problem with nutrition. Most of them do not eat well yet they either
feel full and often are constipated or feel hungry but cannot eat. Cachexia is a combination of
metabolic syndrome associated with most chronic degenerative diseases including cancer, AIDS,
rheumatoid arthritis, and cardiac chronic and renal failure. Cachexia is associated with weight loss,
muscle wasting with or without loss of fat, loss of appetite, weakness and fatigue, and general debil-
ity that most patients experience. Cachexia is not a voluntary fast or starvation or sarcopenia, rather
a disease-led inability to consume food. Most cancer patients lose their taste receptors on their buds
as a result of drastic therapies. Between 70% and 100% of cancer patients experience cachexia and
children and the elderly experience it commonly while the severity of the syndrome increases with
disease progression. As high as 80% of individuals with advanced disease including breast, colon,
gastrointestinal tract, lung, prostate, pancreas, and sarcoma experience it the most. More than three-
quarter of individuals with gastrointestinal or pancreatic cancer experience it early in the disease
progression, while 60% of individuals with lung cancer experience it upon diagnosis. As a result,
close to 30% of cancer-related death is caused by cachexia as a result of cardiac and respiratory
failure. The clinical manifestation of cachexia includes progressive weight loss (weight loss of at
least 5% in 12 months or less), anorexia, increased inflammation biomarkers (CRP > 5.0 mg/L, IL-6
>4.0 pg/mL; TNF-α, IFN-γ, IL-1β, IL-2, IL-15), low serum albumin (<3.2 g/dL), anemia (<12 g/dL),
asthenia, insulin resistance, weakness and fatigue, oxidative stress, overexpression of myostatin,
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enhanced enzymatic degradation of muscle resulting in muscle breakdown, increased risk of com-
plication in surgery, and impaired tolerance to cancer therapy including chemo- and radiotherapy.
The progressive loss of muscle mass and function is a predominant phenotypic feature of cancer
cachexia as a result of elevated enzymatic activity in muscle leading to muscle degradation and has
been only minimally reversed with currently used nutrition and drugs for cancer patients. It has
been suggested that cachexia also adds to psychological distress and leads to reduced quality of life.
Dietary compounds that inhibit myostatin would have anticachexic and antitumor effects.
Soybean, lima beans, fenugreek seeds, and most legumes contain the Bowman–Birk inhibitor, a
protein known for its ability to inhibit myostatin, and are good candidates for the diets of cancer
patients. It has also been suggested that aerobic exercise which indirectly implies should be included
in the treatment package for cancer patients. Decreased insulin sensitivity accelerates myostatin deg-
radation. Foods containing high levels of soluble dietary fiber including Quaker oats, apple skins,
citrus peels, lima beans, lentils, and fenugreek tea are also good candidates for cancer treatment.
15.4.3 Anorexia
Anorexia, a lack of appetite for food and eating disorder in most patients, is one of the major
pathogenesis associated with cachexia. The lack of appetite or the feeling of fullness has been iden-
tified as a result of pain, depression, constipation, mechanical obstruction in the gastrointestinal,
malabsorption, mucositis, and vomiting that may arise from cancer itself or the drugs. The loss of
appetite is in part associated with the production of systemic proinflammatory cytokines by the
tumor cells; the cytokines cross the blood–brain barrier and activate nerve cells that inhibit food
intake. Foods that can inhibit inflammation can help overcome cachexia.
15.4.4 Muscle Wasting
Muscle wasting is one of the most visible manifestations of cancer cachexia. The skeletal muscle,
the largest organ in the human body and important in body movement and metabolism, is lost dur-
ing muscle wasting. Muscle degradation and loss are the result of overexpression of myostatin and
activation of calpains, a family of calcium-dependent cysteine proteases (calpains) that may initiate
the breakdown of myofibrillar proteins to release proteins known as actin and myosin that are suit-
able for further degradation by other enzymes. Myostatin expression is associated with muscle loss.
Calpains have been associated with muscle protein depletion in muscle dystrophies. An increase in
intracellular calcium levels creates favorable conditions for muscle dystrophies suggesting that indi-
viduals with muscle dystrophy may have to avoid calcium-rich food products. The lysosomal system
includes mainly the cathepsin family of cathepsin B, L, and D. In normal tissues, the cathepsins
are sequestered in the lysosome where their activities are controlled by cysteine protease inhibitors
known as stefin A and cystatin C. In normal tissues, the levels of stefin A and cystatin C are higher
than the levels of cathepsins. Cystatin C is a very strong inhibitor of cathepsins (B). In cancer cells,
the lysosome is broken and cathepsins are released. Cathepsins are matrix enzymes that cancer cells
utilize to invade and metastasize by degrading collagen, laminin, and proteoglycan, activating pro-
collagenase and urokinase type of plasminogen activator. Cathepsin B degrades laminin, fibronectin,
and all types of collagen. Cathepsin L degrades type I and IV collagen, elastin, and fibronectin.
Cathepsin B has also been identified on the surface of cancer cells. Cathepsin B and L catalyze the
dissolution of extracellular matrix in contact with the tumor cells. In cancer cells, the levels of inhibi-
tors of cathepsin B and L are low and favor the continuous action of cathepsin B and L until suitable
inhibitors can be found. For instance, the level of cathepsin B in stomach cancer tissue is 30 times
more than in normal tissues. Also, in stomach cancer, the level of cathepsin L is as much as 70 times
higher than it is in normal tissues. Brain tumor cells contain very high levels of cathepsins, MMP,
and plasminogen activators, all of which are associated with the invasiveness and short survival rate
associated with these kinds of tumor. Cathepsin B has been implicated in enhancing tumor invasive-
ness and metastasis suggesting that inhibitors of cathepsin B could be good anticancer and antimeta-
static agents. One way to remember the ability of cathepsins to degrade normal tissue and invade is
to remember the meat tenderizer, which is nothing else than a cathepsin-like enzyme from papaya.
Cathepsins degrade tissue in the body similar to the effect of meat tenderizer on softening meat tissue
and making meat suitable for easy cooking. Cathepsins generated by tumor cells degrade the sur-
rounding tissues to allow cancer cells to migrate, invade other tissues in the body, metastasize, and
cause death. Also, remember that cancer cells have the ability to generate their own growth factors
whenever needed and cathepsins may also be among those growth factors generated by cancer cells.
Increased levels of cystatin are needed to protect cells from cathepsin degradation.
Insulin resistance contributes to cachexia and is also present in cachexia. Tissue sensitivity
to insulin is significantly reduced in cachexic individuals. Food that enhances insulin sensitivity
including soluble dietary fiber in fenugreek, citrus peel, and apple skin would therefore be good for
cancer patients.
15.4.6 Weakness and Fatigue
Weakness and fatigue due to cachexia is the result of muscle wasting, excessive inflammation,
and increased energy expenditure. Asparagus, ginseng, rosemary, and sage are good candidates for
reducing weakness and fatigue. Soybean has compounds that can help the body fight fatigue. Cocoa
has been used throughout history to help with fatigue.
15.4.7 Significance of Advanced Glycation end Products and Cancer
Consumption of food high in advanced glycation end products leads to the induction of high lev-
els of receptor for AGEs (RAGE). In the majority of healthy human tissues, RAGE is expressed at a
very low level in many cells of the body including endothelial cells, smooth muscle cells, mesangial
cells, mononuclear phagocytes, and certain neurons. The interactions of RAGE and its ligands such
as AGEs in fried foods trigger reactions that lead to the generation of ROS and inflammation. It is
well established that increased systemic inflammation is associated with several chronic degenera-
tive diseases, suggesting that RAGE is de facto associated with the pathology of several chronic
diseases including chronic inflammation, atherothrombosis, aging, diabetes, renal and heart failure,
arthritis, stroke, Alzheimer’s disease, and cancer. The expression of RAGE has been demonstrated
in a variety of human tumors, including brain, breast, colon, colorectal, lung, prostate, oral squa-
mous cell, and ovarian cancer, lymphoma and melanoma. Since AGEs induce overexpression of
RAGE and RAGE leads to ROS and inflammation, one can say that food high in AGEs can activate
inflammation in cancer cells. It is therefore suggested that restricting the intake of proinflammatory
compounds such as AGEs and lipoperoxidation products (ALEs) can reduce RAGE levels.
15.5 DIetArY APPrOACheS tO CANCer
15.5.1 Dietary Patterns Associated with high risk of Cancer
Observational studies are basically one way to look at the association of dietary patterns
and cancer. Therefore, information provided in the following sections is based on observa-
tional investigations. The incidence of esophageal and gastric cancer is very high in China and
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Japan [18]. Esophageal cancer has 84% mortality rate in the United States [19,20]. The survival
rate is 20% at 5 years [21]. The incidence of this disease is increasing in the developed world
[22]. Alcohol consumption (36.4% among Japanese men and 6.9% among Japanese women) and
smoking (38.2% among Japanese men and 10.9% among Japanese women) are major risk factors
in Japan.
Gastroesophageal reflux disease (GERD), obesity, and smoking are major risk factors. Cohort
studies have shown that consumption of hot tea is associated with 1.6-fold increase of esophageal
cancer risk in Japan. In China, the evidence is not strong to support the association of hot green tea
consumption and esophageal cancer. Other risk factors include consumption of opium, hot bever-
ages, pickled vegetables, and carbonated beverages; poor oral health; exposure to human papilloma-
virus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and mycotoxins such
as fumonisins; and low intake of fresh fruits and vegetables.
In the United States and Canada, dietary patterns associated with esophageal and gastric cancer
include higher intakes of high-fat dairy and meats including red meat and poultry and lower intake
of vegetables. The incidence of esophageal and gastric cancer is increasing in both the United States
and Canada.
The association of red meat consumption and esophageal cancer is strong. It has been suggested
that the high content of AGEs in red meat induces insulin resistance, which may be a common
denominator for degenerative diseases such as esophageal cancer [23].
The association of high dietary glycemic load and total carbohydrate intake and colon cancer devel-
opment and progression is very strong [24,25]. Stage III colon cancer patients who consumed high
levels of sugar-sweetened beverages were associated with a very high rate of recurrence and mortality
[26]. Foods with very high glycemic index include baked russet potato, fruit roll-up, white baguette,
cornflakes, white rice, instant mashed potato, oven-baked pretzel, and pizza. Diets high in processed or
red meat cooked at high temperatures is associated with increased risk of colorectal cancer [27].
Chronic high alcohol consumption and smoking are major risk factors for pancreatic cancer
initiation and development [28]. Dietary patterns high in animal fats are associated with increased
risk of pancreatic cancer [29]. AGEs are found in uncooked and cooked foods. Higher levels of
AGEs Nϵ-(carboxymethyl)lysine (CML) are found in red meat and red meat cooked at high tem-
perature is an excellent source of AGEs and mutagens. The association of higher intake of red
meat rich in AGEs such as CML and pancreatic cancer in men is very strong [30]. Other foods
that characterize the Western dietary pattern include higher intake of red and processed meats,
potato chips, sugary beverages, sweets, high-fat dairy, eggs, and refined grains, and potato. High
intakes of these foods were associated with a 2.4-fold increased risk of pancreatic cancer in men
but not in women [31]. Other studies that are mostly observational have found non-association of
red meat intake and pancreatic cancer in postmenopausal women [32] or in large cohort studies
of men and women [33].
Abdominal obesity, dyslipidemia, elevated blood pressure, and impaired glucose tolerance
are characteristics of metabolic syndrome. Meta-analysis of observational studies suggests that
the association of metabolic syndrome and breast cancer [34–36], liver cancer [37,38], lung, blad-
der, breast postmenopausal, renal cell and liver cancer in men, pancreatic cancer and endometrial
and pancreatic cancer in women [39,40] is positive. Adherence to alcoholic beverages may be
associated with increased risk of breast cancer [41]. Diets rich in mycotoxins such as aflatoxins
are major risk factors for hepatocellular carcinomas, with some of the highest incidence rates
found in China [42].
Two large Swedish cohort studies enrolled 61,433 women (aged 39–74 years at baseline) in one
study and 45,339 men (aged 45–79 years at baseline) in another study, respectively [43]. Participants
were provided with food frequency questionnaires and followed up for an average of 20.1 years. It
was found out that in both cohort studies participants with higher intake of milk were associated
with a higher rate of mortality than those who had normal intakes.
15.5.2 Dietary Patterns Associated with Low Incidence of Cancer
It is important to focus on the impact of a holistic dietary approach to cancer rather than looking
at the effects of single compounds because people eat foods. The traditional Mediterranean diet is the
most written about among dietary patterns that are associated with low incidence of cancer of almost
all types. High adherence to the traditional Mediterranean diet lowers insulin resistance, which is the
characteristic of metabolic syndrome and the common denominator to many chronic diseases includ-
ing cancer. The traditional Mediterranean diet is an intermediate level of carbohydrate diet. Higher
adherence to the traditional Mediterranean diet, that is, olive oil, vegetables and fruits, nuts, legumes,
nonrefined cereals, fish, and moderate consumption of red wine with meals, has been shown to be
associated with significant risk reduction for overall cancer mortality/incidence [44,45]. The tra-
ditional Mediterranean diet has low or very low levels of AGEs because of the cooking methods
employed to develop these diets (Figure 15.4). Parsley is rich in apigenin, which has shown through
human studies to be systematically absorbed and to increase the levels of the antioxidant enzymes
erythrocyte glutathione reductase and superoxide dismutase [46]. The potential of apigenin as che-
mopreventive has been raised by several studies [47–49]. Animal studies have shown that apigenin
orally fed to diabetic mice improved hepatic antioxidants, hyperglycemia, and serum cholesterol and
increased serum insulin [50]. Parsley contains 1.6% lipid and is the best source of sulfoquinovosyl-
diacylglycerol, which inhibits DNA polymerase, telomerase, angiogenesis, and inflammation [51].
High adherence to beverages rich in angiopreventive compounds including epigallocatechin
(green tea), triterpenoids (citrus juices), resveratrol (red wine), xanthohumol, procyanidin (choco-
late), and caffeine (coffee) may reduce the rate of a wide range of cancer. In the Nurses’ Health
Study, an ongoing prospective cohort study of 121,700 nurses enrolled in 1976; it was shown that
greater adherence to the Mediterranean diet was associated with long telomeres that translated into
healthy life and longevity [52]. These beverages have zero levels of AGEs.
Caloric restriction diet such as the Okinawan diet centered around sweet potatoes, marine-based
carotenoid-rich foods, and turmeric is associated with healthy living, less cancer, and longer lifes-
pan [53,54]. Adherence to high vegetable intake, but not fruit, was associated with lower risk for
hepatocellular carcinoma. For every 100 g/day increase in vegetable, there was an 8% decrease in
the risk of hepatocellular carcinoma [55]. The Okinawan diets are also very low in AGEs because
the cooking methods employed to develop these diet limit the development of AGEs.
Vegetarians represent 5% of the U.S. population. Vegans represent 2% of the U.S. popula-
tion. Analysis of three prospective cohorts of Adventists in North America, Adventist Mortality
Figure 15.4 olive oil, tabouleh, falafel, and moussaka make the traditional Mediterranean diet.
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Study, Adventist Health Study, and Adventist Health Study-2, showed that vegetarian diets confer
protection against some cancers, cardiovascular disease, and total mortality [56]. The associations
of health benefits in black Adventists were better and more significant than there were in black
non-Adventists on a national level [57]. Vegan diets appeared to offer more protection against obe-
sity, hypertension, type 2 diabetes, and cardiovascular mortality than lacto-ovo-vegetarian diets.
The associations of vegetarian or vegan diet and the disease were more significant in men than
in women. The cancer rate of vegetarians appear to be moderately lower than the cancer rate of
nonvegetarians living in the same communities and their life expectancy also appears to be greater
than the life expectancy of nonvegetarians living in the same communities [58]. The cooking
methods employed to make these diets are not conducive to developing high levels of AGEs.
The ketogenic diet is rich in fats, moderate to low in protein, and low in carbohydrates including
glucose (Figure 15.5a and 15.5b). The ketogenic diet forces the body to burn fat as source of energy
(a)
(b)
Figure 15.5 (a) the ketogenic diet focuses more on fat, protein, and green and less carbohydrate. (b) the
ketogenic diet is developed around more fat followed by protein and green and carbohydrate is
not taken into consideration.
Figure 15.6 the paleo diet relies on unrefined food for the best of health benefits.
instead of glucose or other refined carbohydrates as is usual with refined carbohydrate-rich diets.
About 90% of energy in the ketogenic diet comes from fat, 8% from protein, and 2% from carbo-
hydrate. In comparison, average American diet provides 50% calories from refined carbohydrates,
35% energy from fats, and 15% energy from proteins. The Atkins diet, for instance, provides 64%
energy from fats, 32% energy from proteins, and 4% energy from carbohydrate. Clinical studies
have a case report of two female pediatric patients who were on ketogenic diet and had a 21.8%
decrease in tumor standardized uptake value [59]. A 65-year-old woman who presented with glio-
blastoma was fed a ketogenic diet concomitantly with the standard treatment period [60]. Vitamins
and minerals were supplemented to her diet. After 2 months of treatment, the cancer had disap-
peared and the patient had lost 20% of her body weight. It has been suggested that the ketogenic
diet sensitize cancer cells to chemotherapy and radiation. The ketogenic diet was shown to improve
emotional functioning and insomnia in cancer patients [61]. Potential acute side effects associated
with the ketogenic diet include gastrointestinal discomfort, nausea and vomiting, elevated blood
ketones, hypoglycemia, and deficiency in trace minerals [62]. Potential chronic side effects associ-
ated with the ketogenic diet include increased low density lipoprotein cholesterol, bone mineral
loss, kidney stones, and renal damage [62].
The ketogenic diet can only be good if the cooking method employed to develop ketogenic foods
does not lead to the formation of AGEs. The ketogenic can only be good when unrefined fats and
low cooking temperature are used. Otherwise, cooking at high temperature will turn the ketogenic
foods into sources of AGEs. Bacon cannot make good ketogenic diet because of the prevalence of
AGEs in it.
Adherence to the Paleolithic diet pattern (Figure 15.6) and greater adherence to the Mediterranean
diet pattern may reduce the risk of sporadic colorectal adenomas [63]. The paleo diet relies on unre-
fined ingredients for meal preparation. As a result, AGE formation is low when low-temperature
cooking methods are used.
15.5.3 Dietary Approach to Cachexia and Anorexia
Most cancer patients experience malnutrition, and when the disease is progressing, muscle wast-
ing adds up to malnutrition. Approximately 700,000 cancer patients die in North America each year
as a result of malnutrition and muscle wasting [64]. Cachexia is a pathological weight loss that is
associated with skeletal muscle and adipose tissue wasting.
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Cancer is an inflammatory disease. Muscle catabolism exacerbates the inflammatory process

because the very same inflammatory stimulators that promote tumor growth are also stimulators
of cachexia/anorexia, pain, debilitation, and reduced quality of life and survival. A multimodal
approach that addresses muscle catabolism and the inflammatory process may be better than
addressing muscle wasting or inflammation alone. It is also suggested that early start of oral therapy
has more chance to delay muscle wasting and cachexia than waiting until the patient shows sign of
body catabolism.
There are no standard therapies for stopping muscle atrophy due to cachexia. Effective therapeutic
intervention that prevents, reverts, or delays the progressive loss of muscle mass and function has not
emerged. However, recent efforts have shown that targeting inflammation and the immune system can
improve cachexia and increase survival in cancer patients. Nutrition technology aimed at delivering
therapies rich in anti-inflammatory and immune modulating dietary bioactive compounds should be
an important adjuvant strategy in the approach to cancer treatment as soon as after diagnosis.
Anorexia or loss of appetite may be the result of decreased taste and smell of food that may
be associated with a dysfunctional hypothalamus region of the brain and increased production of
inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) and CRP by the cancer or the host’s
immune system in response to cancer [65]. Cytokines may stimulate the inhibition of orexigenic
neuropeptide Y pathway. An imbalance between appetite-suppressing anorexigenic and appetite-
inducing orexigenic peptides is created in favor of the appetite-suppressing peptides. As a result,
satiety increases and the patient develops early satiety, feeling full after ingestion of small amount
of food, odor threshold, and taste change, and chemotherapy or radiation may worsen the anorexia.
Over a short period of time, the patient undergoes weight loss and decline in physical performance.
Therapeutically, it has been shown that corticosteroids reduce anorexia but for a short period of time
because within 4 weeks anorexia resurfaces in the patient.
Muscle degradation is the result of the combinatorial activity of the five classes of enzymes
and the cytokines. The use of dietary anti-inflammatory and cocktails of protease inhibitors may
help slow down cachexia. During cancer progression, tumor cells produce inflammatory cytokines
including IL-6, TNF-α, and IL-1β that stimulate fat depletion in adipose tissue of the host [66].
Dietary compounds with inhibitory activity against the aforementioned cytokines may help fight
inflammation and fat depletion in cancer patients. Intervention strategies that include the provision
of orexigenic agents to promote voluntary food intake and the supplementation of specific nutrients
such as amino acids and n-3 polyunsaturated fatty acids have been used [64].
Dietary compounds that inhibit myostatin would have anticachexic and antitumor effect.
Soybean, lima beans, fenugreek seeds, and most legumes contain the Bowman–Birk inhibitor, a
protein known for its ability to inhibit myostatin, and are good candidates for the diets of cancer
patients. Decreased insulin sensitivity accelerates myostatin degradation. Foods that improve insu-
lin sensitivity such as fenugreek seeds should be considered in the regimen of cancer patients as
early as possible before the symptoms of cachexia appear.
Several clinical studies have shown that L-carnitine at 15 mg/kg body weight to 4 g/day
improves inflammation, protein synthesis, and muscle wasting [67]. Fenugreek seeds improve
insulin sensitivity [68]. Amla or Indian gooseberry improves insulin sensitivity in animals [69,70].
Seaweed improves insulin sensitivity [71,72]. Average daily consumption of seaweed in Japan is
4–6 g and it has been suggested that at this level seaweed consumption may be associated with
low metabolic syndrome prevalence [73]. Foods containing high levels of soluble dietary fiber
including Quaker oats, apple skins, citrus peels, lima beans, lentils, and fenugreek tea are also
good candidates for cancer prevention and treatment. Inulin has been reported to protect against
AGE-related pathology in people at risk of developing type 2 diabetes [74]. Creatine as a supple-
ment may improve insulin sensitivity [75]. Foods in the form of concentrates may be the way to
provide large amounts of bioactives in small volume to cancer patients who may not want to eat
large quantities of foods.
The National Comprehensive Cancer Network provides recommendations and guidelines for
nutritional recommendations for the treatment of cancer-related fatigue [76]. Foods or dietary sup-
plements that can address fatigue are needed for cancer patients. The quality of diet following the
diagnosis of breast cancer patients was inversely and independently associated with fatigue [77].
Again fatigue is associated with inflammation. Anti-inflammatory foods can address fatigue in
cancer patients. Asparagus can reduce fatigue [78]. Creatine may reduce fatigue [75]. Diets rich
in green leafy vegetables, tomatoes, whole grains, and foods with anti-inflammatory compounds
cooked at low temperature improve persistent cancer-related fatigue [76]. In breast cancer patients,
fatigue was lower for participants who consumed >25 g dietary fiber per day than those who con-
sumed <25 g dietary fiber per day [79]. It was suggested that diet low in fat and high in fiber
improves fatigue in breast cancer survivors. Such a diet should be adopted by breast cancer patients
during treatment and survivorship.
The gut microbiota composition is essential for healthy life. Prebiotics and probiotics are needed
for healthy gut. Inulin, polydextrose soluble fiber such as DuPont Litesse, fenugreek, artichoke,
asparagus, cocoa, and adzuki beans are good sources of prebiotics. Probiotics including Howaru
from DuPont and the Nutrish Cultures from Chris Hansen can be used to formulate healthy foods
and beverages that can help improve the gut microflora composition. It has been suggested that
aerobic exercise should be included in the treatment package for cancer patients.
15.6 FUtUre PrOSPeCtS
Advances in technologies and the increased lifespan around the world are driving the cost of
healthcare to new high all the time. Reducing the risk factors of cancer can help the incidence
of the disease and the costs associated with treatment. Prevention should be part of reducing the
risk factors.
Dietary patterns that increase the risk of cancer development are known and efforts should be
made to discourage chronic adherence to such diets. In a global society where farmers represent less
than 5% of the population, the responsibility of providing safe and healthy ingredients and foods lie
in the hands of governments, food producers, and food processors. The consumer is responsible for
making healthy eating choices.
Food science including its components such as food chemistry, biochemistry, and toxicology
is more complex than it is being considered in recent years. It is the opinion of this author that
given the major contribution of foods to human survival, a more rigorous training is needed in food
science and nutrition. Brighter students are needed to fill the classrooms and research laboratories.
At the same time, a more accountable food industry is needed in lieu of an industry that develops
food based on flavor and taste. Food science programs should develop marketing courses as part of
the curriculum so that food scientists can handle the marketing of foods based on science and stock-
holders on priorities. It is suggested that children be taught early the chemistry, biochemistry, and
toxicology of foods to help them understand the risks and benefits associated with certain foods
and at the same time develop healthy eating habits.
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ChAPter 16
Alzheimer’s Disease
16.1 INtrODUCtION
Alzheimer’s disease (AD) is a complex age-related inflammatory neurodegenerative disease of

the brain. The disease is multifactorial, slow, but progressive and irreversible. There are two forms
of AD: the rare familial early onset caused by gene mutations and the sporadic AD that is correlated
with aging.
There are basically two pathological hallmarks for AD including the extracellular deposition of
senile plaques and the intraneuronal deposits of neurofibrillary protein tangles in the brain regions
of the hippocampus and cortex of patients with AD. The symptoms of AD include a decline in
cognitive function that interferes with daily life and activities or dementia, disorientation, daily and
sustained loss of memory, judgment as well as abstract thinking, mood, and behavioral and com-
municative skills. AD is the main cause of dementia in the United States.
The disease was first observed when a 51-year-old woman Auguste Dieter from Frankfurt
presented a peculiar dementia during a visit in 1906 at the office of neurologist and psychiatrist
Dr. Alois Alzheimer. Auguste Dieter died at age 56 of the unusual mental illness [1]. Autopsy of
her brain showed protein plaques and tangles. The disease is named after Dr. Alzheimer. It is the
creation of the American Alzheimer Association in 1979 that provided scientific and public boost
to recognize the severity of AD.
16.2 PreVALeNCe, INCIDeNCe, AND SOCIAL AND

eCONOMIC IMPACt OF ALZheIMer’S DISeASe
The prevalence of AD in the United States and other regions of the world is shown in Figures
16.1 and 16.2. AD affects 5.2 million Americans and is projected to reach 7.1 million people in 2022
(www.alz.org) [2,3]. About 33.9 million people have AD worldwide [4]. According to the Alzheimer
Society of Canada, there are more than 500,000 Canadians affected with the disease of which 72%
are women, and the number is expected to reach 1,300,000 by 2034. In South Korea, 7.2% of its
over-65-year-old population had AD in 2000, and the number is expected to reach 14% of its over-
65-year-old population afflicted with dementia by 2020 and 30% of AD individuals among the over-
65-year-old population by 2040 [5]. In the developed nations, AD doubles every 5 years in persons
aged more than 65 years and one in ten people is affected by some degree of dementia [6]. The
prevalence of AD is low (about 1%–3%) in sub-Saharan Africa and India and high (≥5%) in certain
Asian (China) and Latin American (Brazil, Argentina, Chile) countries [7]. In Taiwan, dementia
is a hidden issue and therefore underestimated [8]. In China, Cuba, and Brazil, the prevalence of
dementia is high in urban areas and comparable to the prevalence in developed nations [6]. The
incidence of AD is 19.4/1000 person-years for people older than 65 years in Europe and about 15.0
283
Return USA health menu Alzheimer’s Alzheimer’s

Death rate per 100,000
Select cause
DC
High Low

age adjusted
Figure 16.1 Prevalence of alzheimer in the united states. (Courtesy of www.worldlifeexpectancy.com)
Return world health menu Alzheimer’s/dementia Alzheimer’s/dementia

Select cause
age standardized
High Low

Next
Figure 16.2 Prevalence of alzheimer in the world. (Courtesy of www.worldlifeexpectancy.com)
(male, 13.0; female, 16.9) in the United States. The incidence increases exponentially after 75 years
of age until 85 years of age [6]. In Japan, there are about 1.16 million Alzheimer adults aged older
than 65 years, and by 2025 the number is expected to rise to 2.2 million [9].
The social and economic significance of AD is worrisome. After diagnosis, most people with
AD over the age of 85 can live an average of 3–4 years, and people at age less than 85 years can
live 7–10 years and require around the clock care. AD is the sixth leading cause of death in the
United States, and it is the fifth leading cause of death in the elderly [10]. The demand imposed by
the disease to society is very high and costly: individuals with AD can live as long as two or three
decades, care for patients with AD is around the clock, and the needs increase with the severity of
the disease and the latter increases with age. The majority of AD care givers develop psychological
illnesses [3,11]. As a result, the financial strain on the sick, the relatives, and healthcare provid-
ers is very significant and may become worse as the number of people developing AD increases
aLzHeIMer’s DIsease 285
with time. In 2010, AD cost the United States about $172 billion [12,13]. In Germany, the financial
burden associated with AD was about 6 billion Euros [14]. In Europe, 27% of the overall popula-
tion was affected by a combination of Alzheimer’s dementia, Parkinson’s disease (PD), stroke, or
depression with annual costs of care exceeding those of cancer, cardiovascular conditions, and dia-
betes [15]. According to New York Times report of November 25, 2010, South Korean children are
being taught as early as kindergarten to stop drinking too much sugar to protect their brains. The
government has launched a campaign to train students as old as 11 years old to recognize symptoms
of dementia and care for old people with dementia including their own relatives. Sometime, family
members are giving up work to care for relatives.
16.3 rISK FACtOrS FOr ALZheIMer’S DISeASe
There are several nonmodifiable and modifiable risk factors for AD. Nonmodifiable risk factors
for AD include age, genetics, gender, Down syndrome, and traumatic brain/head injury. Modifiable
risk factors for AD include diabete, midlife hypertension, midlife obesity, depression, low educa-
tional attainment, physical inactivity, poor nutrition, metabolic syndrome, hyperglycemia, mito-
chondria dysfunction, low insulin levels and insulin resistance within the central nervous system,
and environmental and lifestyle factors that include smoking, heavy alcohol drinking, education,
social activity, physical activity, and occupational exposure to chemicals and excessive minerals,
side effects of certain drugs, depression, and gene/environment interactions.
16.3.1 Nonmodifiable risk Factors for Alzheimer’s Disease
16.3.1.1 Age
Older age is a major nonmodifiable risk factor for sporadic AD and there is no obvious inheri-
tance pattern for sporadic AD [16]. There is a significant worldwide variation in AD incidence rate
[17]. AD affects 1% of individuals aged 60 years, 10% of individuals of 65 years of age, and nearly
45% of individuals aged 85 or higher [18–21]. Age also increases the level of the molecule homocys-
teine in the plasma and elevated homocysteine is a risk factor for AD [22–26].
Oxidative stress and damage cause an increase in reactive oxygen species, which have been
associated with aging-induced AD [27–30]. However, like the first known victim of AD, the German
woman Auguste Dieter who died at age 56, in recent years, symptoms of AD have apparently been
showing in persons less than 65 years old. Dementia is characteristic of old age and is a major risk
factor for and predisposes to AD [18]. People with dementia have twice the risk of developing AD.
AD accounts for more than 50% of the dementia in the elderly.
16.3.1.2 Genetics
AD is highly heritable [31,32]. The ε4 allele variant of apolipoprotein E (APOE) is the best
validated AD risk factor in both sporadic and familial AD [33,34]. Familial form of AD accounts
for less than 1% of all AD cases, strikes early in life between the ages of 30 and 60 [35,36], and
is known as the early-onset AD (EOAD); 50% of EOAD may have genetic factors that are differ-
ent from amyloid precursor protein (APP) mutations. The familial AD that strikes after 65 years
old is known as late-onset AD (LOAD). This form of familial AD appears to have less aggressive
phenotypes. LOAD is associated with 99% of the AD population after the age of 60 and a mixture
of genetic and nongenetic (sociodemographic such as education, lifestyle such as diet and fitness,
environment, and medical history such as smoking and vascular disease) risk factors. The Swedish
and Finnish twin studies on AD confirmed and suggested that AD has a strong genetic influence for
both men and women and high (≥74%) heritability [31,36]. However, genetic factor does not explain
or predict the majority of the cases that are sporadic [24]. Few cases of AD are either early-onset or
inherited [24]. Clinical and epidemiological studies have shown that maternally inherited AD may
account for over 20% of all LOAD cases, and children of AD mothers are at higher risk of develop-
ing AD than children of AD fathers [36]. AD transmission from mothers to adult offsprings may be
via mitochondrial DNA, which is exclusively maternally inherited in humans [36]. A recent study
of the neuropathological examination of Auguste Dieter brain showed that (1) she had numerous
neurofibrillary tangles and amyloid plaques, (2) she was not genetically predisposed to AD, (3) she
may have descended from the Volga German, and (4) the cause of AD is different in Auguste Dieter
than in Volga Germans [37,38].
16.3.1.3 Gender
The prevalence of AD for persons over 80 years old is higher in women than men, but it is not
well established whether women are more susceptible to AD than men or not [40]. In all groups
studied, the proportion of women suffering from AD was higher than men [41]. Studies in develop-
ing countries of Asia, Africa, and Latin America have also confirmed that women are marginally
more likely to develop AD or dementia in old age than men [42]. Besides women living longer than
men, other plausible explanation for the higher incidence of AD in women than men in the Western
world includes the increased rate of women who smoke, suffer from obesity, and have diabetes and
depression. In South Korea, the prevalence is higher in women than men but rapidly increases with
age in both sexes [43].
16.3.1.4 Down Syndrome
Down syndrome is a risk factor for AD. Plaque deposits are found in the brains of individuals
with Down syndrome at a very young age, around 8 years of age, and by the time these individuals
are adults, they all carry excessive plaque deposits in their brains [44,45]. However, a case study of
a 70-year-old man with Down syndrome (“Mr. C.”) and well-documented triplication of chromo-
some 21 showed that the man who was followed for 16 years showed no sign of decline in cognitive
function or development of dementia [46].
16.3.1.5 Traumatic Brain/Head Injury
Individuals with traumatic brain injury (TBI) are at high risk of developing AD because brain
injuries tend to form amyloid plaques similar to the plaques observed in individuals with Down syn-
drome [44,47]. TBI is often associated with toxic amyloid plaque formation that can occur within
hours after injury, regardless of the patient’s age [48]. Surgically resected temporal cortex tissues
from patients with severe TBI showed higher levels of toxic amyloid plaque (Aβ[1–42]) but not the
nontoxic form (Aβ[1–40]) peptide; half of them were at increased risk of developing AD later in life
[48]. Stroke and cerebral infarction increase the risk of AD.
16.3.2 Modifiable risk Factors for Alzheimer’s Disease
The majority (90%–95%) of AD is sporadic and only a small fraction of AD is caused by auto-
somal dominant mutations. So what is causing the prevalence of sporadic AD? Increasing evidence
suggests that AD is probably a result of complex interactions involving genetic, epigenetic, and
environmental factors. The interactions of AD and modifiable risk factors are discussed in the fol-
lowing sections.
16.3.2.1 Chronic Oxidative Stress
The brain has the highest levels of polyunsaturated fatty acids. Oxidative stress is involved
in the pathogenesis of AD as a causative and contributing agent. As a causative agent, oxidative
stress is involved in transition metal, such as copper, zinc, and mainly iron, catalyzed free radicals,
enhanced polyunsaturated lipid oxidation in the brain, increased tau protein increased in phosphate
groups or phosphorylation, protein oxidation, and increased deoxyribonucleic acid (DNA) damage.
The human body has a wide range of endogenous antioxidants that prevent the onset of oxidative
stress. However, with aging, oxidative stress can contribute to the formation of Aβ plaques [49–53].
The endogenous antioxidants available for defense include catalase, superoxide dismutase, gluta-
thione reductase, glutathione, uric acid, α-lipoic acid, acetyl L-carnitine, melatonin, dehydroepian-
drosterone, and bilirubin. The high levels of ROS generated by Aβ makes the brain very vulnerable
to ROS toxicity.
16.3.2.2 Advanced Glycation End Products
Advanced glycation end products (AGEs) play a significant role in aging and the progression
of chronic degenerative diseases. Smoked foods and food cooked at high temperature under dry
conditions are excellent and major sources of AGEs. Analyses of the brains of patients with
AD have shown that AGEs contribute to amyloidosis in AD. Evidence showed that plaque frac-
tions of AD brains contained threefold more AGE adducts per milligram of protein than age-
matched healthy control brains [54]. The presence of AGEs in tau protein and senile plaques
was also demonstrated in paired helical filament tau in neurofibrillar tangles in homogenates
of temporal lobe from patients with sporadic AD [55]. AGEs are neurotoxic. Senile plaques
showed enhanced formation of chronic myeloid leukemia (CML), the most prominent species
of AGEs in tissues, and showed higher levels of CML in the hippocampus, while AD patients
with diabetes mellitus showed even higher levels of CML [56]. AGEs have a well-established
role in AD, playing a role in disease progression by rendering glycated tau protein and Aβ
deposits insoluble and undigestible and enhancing the inflammatory process characteristic of
AD [57,58]. Glycated tau protein may contribute to tangle formation in AD [59]. AGE levels in
neurons and astroglia increase with age and in AD patients with the progression of the disease
causing inflammation and neuronal dysfunction [58]. Most proteins linked to AD including Aβ
and tau found in patients with AD are glycated giving these proteins increased stability through
the formation of cross-links that stabilize the protein aggregates. Most AGE-positive neurons
are also hyperphosphorylated tau-positive suggesting a link between AGEs accumulation and
the formation of early neurofibrillary tangles [60]. The formation of AGEs may occur in the
early stage of plaque formation, and AGEs may represent a driving force in the acceleration of
Aβ deposition and plaque formation [61].
16.3.2.3 Chronic Inflammation
A higher level of serum inflammatory biomarker C-reactive protein in midlife and older age has
been associated with increased risk of AD and vascular dementia development. Chronic inflam-
mation of the central nervous system associated with hyperactive states of glial cells is a risk fac-
tor for AD [62]. There is increasing evidence that inflammation is the primary instigator of AD.
A multicenter European study and U.S. longitudinal study investigated the plasma of patients with
AD, subjects with mild cognitive impairment, and healthy controls to identify plasma proteins asso-
ciated with AD pathology using a combination of advanced protein analysis and neuroimaging
approach [63]. The results were impressive: high plasma levels of acute-phase proteins including
C-reactive protein, α1-antichymotrypsin, and clusterin in the serum and cerebrospinal fluid (CSF)
before any indication of fibrillar Aβ or tau deposition [63,64]. Upregulation of secretase (BACE1)
by the AGE/RAGE complex via the NF-κB pathway provides strong evidence of the link between
chronic inflammation and AD [65].
16.3.2.4 Midlife Visceral Obesity
Insulin resistance, bad cholesterol, diabetes, hypertension, and atherosclerosis are individually
associated with cognitive decline and AD [44,66,67]. Each one of these factors is associated with
oxidative stress and inflammation making both the oxidative stress and inflammation the precursors
of and risk factors for metabolic syndrome. Metabolic syndrome factors are frequent among patients
with AD [68].
A large study (N = 10,136 participants) that investigated the association between obesity in
midlife and the risk of AD and vascular dementia in an average of 36 years later in life showed that
obesity in midlife is associated with a threefold increase in the risk of AD and a fivefold increase
in the risk of vascular dementia, independent of stroke, cardiovascular, and diabetes comorbidities
[69]. Visceral obesity in midlife around 50 years of age may be a risk factor for AD 20–25 years
later in life, whereas visceral obesity after 65 years of age appears to be inversely related to AD
risk [70]. BMI decline with age was associated with a higher risk of AD 5 or 6 years down the road
[70]. Adipose tissue from central obesity also secretes inflammatory markers such as interleukin-6
(IL-6) and tumor necrosis factor-α (TNF-α), both of which alter synaptic function in the brain [64].
TNF-α, which is elevated in the brain and CSF of patients with AD, also inhibits Aβ transport from
the brain to the periphery, thereby increasing its concentration in the brain.
Insulin resistance, the hallmark of metabolic syndrome, is a characteristic of AD brains.

It links diabetes and metabolic syndrome with AD [71]. Insulin crosses the blood–brain barrier
and is transported to the brain by insulin receptors. The localization of insulin in the hippocampus
and temporal cortex regions of the brain is consistent with evidence that insulin plays a role in
memory. Insulin-resistant conditions, such as diabetes, hypertension, obesity, dyslipidemia, and
vascular dysfunction, reduce insulin transport across the blood–brain barrier and disrupt insulin
functions in the brain including memory [72–74]. Insulin resistance may also be associated with
reduced cerebral glucose metabolic rate and subtle cognitive impairments at the earliest stage of
disease, even before the onset of mild cognitive impairment [75]. Therefore, insulin resistance
exacerbates AD.
16.3.2.6 Type 2 Diabetes
Diabetes is associated with two- to threefold increased risk for AD development [13]. People with
diabetes are also at 2–3 times higher risk of developing AD than nondiabetic individuals [76–81].
Diabetes encompasses a wide range of abnormalities including hyperglycemia, insulin resistance,
microvascular disease, glucose toxicity, oxidative stress, inflammation, and atherosclerosis through
which the disease affects brain function [67]. Hyperglycemia participates in the formation of AGEs
that are known as risk factors for AD. Insulin is critical for memory function and insulin impairment
affects memory [82]. Cumulative effects of long-term hypertension, even in pre-DM stages worsen
cognitive functioning in patients with type 2 diabetes [83]. Mild cognitive decline is observed in
early stage of type 2 diabetes [84]. Worldwide prevalence of diabetes is projected to increase from
285 million adults in 2010 to 439 million adults in 2030 suggesting that AD prevalence is also pro-
jected to increase significantly [4].
16.3.2.7 Midlife Chronic Hypertension
Chronic hyperglycemia in midlife is a risk factor for AD because hypertension-related patholo-

gies, including stroke, atherosclerosis, and arteriosclerosis, diabetes mellitus, obesity, and hyper-
cholesterolemia, are all risk factors for AD. Chronic hypertension especially at midlife but not late
in life predisposes to cognitive decline, vascular dementia, and AD in old age. Several longitudinal
studies have linked hypertension to AD development and progression [4,85]. A study of 546 patients
(150 had subjective complaints, 140 had mild cognitive impairment, and 256 had AD) showed that
hypertension was directly related to protein tangles in AD patients’ brains [86]. Hypotension in old
age is a risk factor for AD and dementia development [4].
16.3.2.8 Hyperlipidemia or “Bad” Cholesterol
“Bad” cholesterol is a strong risk factor for decline cognitive function. High-density lipoprotein
(HDL) is the key carrier of cholesterol to the brain where elevated level of cholesterol improves
synapse growth and regeneration, prevents inflammation and the aggregation and polymerization
of Aβ, and decreases the risk of AD independent of APOE status [87]. APOE-4 transports choles-
terol and fats to the brain for protection against oxidative stress. However, conflicting results on
the effects of HDL on dementia, vascular dementia, or AD using subjects older than 75 years old
have been reported, but the effects of HDL on cognitive decline in midlife have not been reported
[88]. Midlife serum total cholesterol and even moderately elevated cholesterol has been shown to be
associated with an increased risk of AD and vascular dementia [89].
However, the development of metabolic syndrome late in life, after age 65 and more than
65 years, does not appear to be associated with dementia [90]. A study was conducted to determine
whether the metabolic syndrome late in life was associated with dementia, incident dementia, AD,
or vascular dementia. Italian elderly (N = 749) aged 65 and older, free of cognitive impairment, were
followed for 5 years for incident dementia. The study concluded that metabolic syndrome or any
of its components was a risk factor for dementia, vascular dementia, or AD in participants younger
than 75 years old. For participants aged 75 and older, the metabolic syndrome was a low risk factor
for AD, and visceral obesity was a low risk factor for dementia, while the metabolic syndrome in
general was not a risk factor for vascular dementia [60].
16.3.2.9 Elevated Plasma Level of Homocysteine
Homocysteine, a plasma metabolite of methionine, has been identified as a strong independent

risk factor for AD development. Epidemiological investigations, including observational studies
and randomized controlled clinical trials, indicate that of 12 of such prospective studies, 83% of the
studies (10 of 12) detected a correlation between hyperhomocysteinemia and AD development or
cognitive decline [91]. Homocysteine is a neurotoxic molecule. Elevated levels of homocysteine in
the plasma are a marker of vitamin B (folate, B6, B12) deficiency. Epidemiological studies support
a positive, dose-dependent association between elevated levels of plasma homocysteine and the risk
of AD, vascular dementia, cognitive impairment, or stroke [24].
16.3.2.10 Estrogens
The role of sex hormones, such as estrogens, in mild cognitive impairment and AD is still controver-
sial, and the role of endogenous estradiol on early or undiagnosed AD is awaiting ongoing clinical trials
[62]. However, several early studies have proposed and supported that estrogens play the role of anti-
inflammatory, neuritogenic, and neuromodulator during brain development and anti-inflammatory and
neuroprotective during brain pathologies such as ischemia and neurodegeneration [92–98]. Estradiol
protects the mitochondria from fragmentation and the role of mitochondrial dysfunction in AD pathol-
ogy has been established and is discussed in the following paragraph.
16.3.2.11 Mitochondrial Dysfunction
The mitochondria are the “powerhouses of cells” where ROS are produced and at the same time
mitochondrial DNA, lipids, membranes, and proteins are targets of ROS toxicity [99]. The pathology
of AD is considered to be associated with mitochondrial dysfunction at the early stage of AD before
the onset of clinical symptoms [100,101]. Neurons contain a high number of mitochondria and depend
heavily on the mitochondria for energy production [102]. Neurons in postmortem brain specimens from
patients with AD, cells expressing human AD mutation, and animal models of AD have revealed the
presence of APP, APOE4, and Aβ peptide in the mitochondrial membranes and in the matrix of neu-
rons of patients with AD. Aβ peptide is very toxic. Presumably, early in the AD process, APP and
Aβ accumulate in the mitochondria in the brain of patients with AD; the toxic Aβ peptide enters the
mitochondria where it interacts with mitochondrial proteins leading to mitochondrial dysfunction char-
acterized by an increased production of reactive oxygen species (ROS), lipid peroxidation, oxidative
DNA damage, oxidative protein damage, and decreased activities of cytochrome c oxidase. Deficiency
in cytochrome c oxidase favors ROS production and alter energy metabolism. The elevated levels of
mitochondrially generated ROS disrupt the mitochondria respiratory chain leading to decreased cellu-
lar ATP production and cell viability [102,103]. As a result, mitochondrial dysfunction leads to synaptic
stress, disruption of synaptic transmission, apoptosis, and neuronal metabolic dysfunction [99,104,105].
Mitochondria in postmortem brain specimens show increased levels of mitochondria DNA defects
compared to DNA changes in postmortem brain tissue from young and healthy subjects [106,107].
16.3.2.12 Poor Nutrition or Harmful Dietary Habits
Poor nutrition for AD susceptibility includes diets low in B vitamins and folate, vitamin B12, and
vitamin B6, high in meat and dairy products, high in saturated fatty acids, and high in refined sugar;
foods rich in AGEs; foods that lead to metabolic syndrome, type 2 diabetes development, low insulin lev-
els, and insulin resistance within the CNS; and diets low in tryptophan or low tryptophan absorption, low
in plant (legumes, greens, fruits, and vegetable) food consumption, and low in protective antioxidants.
16.3.2.13 Vitamin Deficiencies
Deficiency in B vitamins including folic acid and vitamin B12 is common in the elderly and is
closely associated with a high incidence of AD [108,109]. Folate deficiency predisposes to AD and
potentiates senile plaque toxicity. Risk factors for vitamin B deficiency include low dietary intake,
malabsorption in the gastrointestinal tract, vegetarian diet, and interactions with medication such as
metformin or omeprazole, or the presence of tumors. Low levels of vitamin B, including folate and
vitamin B 12, are inversely associated with homocysteine levels in the plasma [110,111]. Since vitamin
B deficiencies are common in the elderly, homocysteine level is often high in this group. Homocysteine
is neurotoxic and damages the brain by a mechanism not well known [112]. The potential harmful
effect of elevated plasma homocysteine can be reduced by folate and vitamin B12 supplementation
[91]. These vitamins also improve the response of patients with AD to cholinesterase inhibitors.
16.3.2.14 Deficiency in Polyunsaturated Fatty Acid
Docosahexaenoic acid (DHA, C22:6 n-3), the most abundant n-3 polyunsaturated fatty acid
in the brain, is essential for brain growth and development and neuroprotection and appears to be
deficient in AD brains [113]. A substantial number of recent epidemiological studies have demon-
strated that deficiency in omega-3 fatty acids, such as DHA, in AD may be associated with cognitive
decline [109,113–115]. DHA is anti-inflammatory and good for vision and must be obtained from
dietary sources to maintain homeostasis. A word of caution is that recent data do not show that a
diet rich in omega-3 fatty acids or consumption of fish oil supplements containing DHA and EPA
protect against AD [116]. However, fish oil may contain other nutrients that may protect against
AD progression. Most reports on the beneficial effects of fish oil on AD are generated using animal
models of AD. Also, most studies with fish oil are generated on individuals who used it late in life
when it may have been too little too late. Because of the susceptibility of polyunsaturated fatty acids
to oxidation, adding fish oil to an inflamed AD brain can only exacerbate the inflammation.
16.3.2.15 Dairy Products
Dairy products include milk, butter, cheese, ice cream, and whey. Milk has very low or no
AGEs. Butter is very rich in saturated fat. There are reports that show that saturated fats induce
aggregation of tau protein and Aβ, and higher intake of saturated fats may be a risk factor for AD
[117–120]. Cheese is precipitated casein and casein is a major source of AGEs [121–125]. AGEs are
also found in whey and whey-derived products [125–129]. The countries that top the list of preva-
lence of AD have the highest butter and cheese consumption in the world (Table 16.1). In recent
years, butter and cheese have become the omnipresent ingredients in almost every food because
these ingredients make the food taste good. We may be sacrificing health for taste and flavor. It is
suggested that butter finds nonfood applications.
16.3.2.16 Meat Products
When past and present meat consumption are factored in, there is three times the risk of develop-
ing Alzheimer’s in meat eaters as opposed to vegetarians [130]. Except for Cuba, the top 25 countries
with the highest incidence of AD-related death are countries with the highest red meat consumption
in the world (Table 16.1). Red meat cooking methods in those countries may also be a contributing
factor to the development of this deadly disease. European countries that top the list are countries
where red meat cooked at very high temperatures is a traditional way of eating. Smoked and salted
meat or fish has been a tradition in those countries. Curing food is always a common practice in these
countries. If cigarette smoke is a major contributor to AGEs formation, smoked meat or fish or foods
in general are reservoirs of polycyclic aromatic compounds whose contribution to AD may have been
overlooked or underestimated.
16.3.2.17 Energy-Dense Foods
Foods high in saturated fats and trans fats have been reported to be associated with a higher
risk of cognitive decline [13,109,118,131]. One serving of butter (14 g or 1 tablespoon) provides 7 g
of saturated fat and 35% of the daily value of saturated fatty acids. One serving of margarine stick
provides 2 g of saturated fat and 10% of the daily value of saturated fat. One serving of margarine
tub provides 1 g of saturated fats or 5% of daily value of saturated fat. While butter contains no
trans fat, one serving of margarine stick delivers 3 g of trans fat and one serving of margarine tube
provides 0.5 g of trans fat. Palmitic acid is present in large amounts in palm oil, which happens to
be the cooking oil on a large worldwide scale. Recent studies have shown that palm oil is a major
risk factor for ischemic heart disease in many developing countries [132]. It is time to investigate
the potential of palm oil in human health especially on inflammation, cardiovascular disease, and
neurological disease. It may also be wise to ban this oil for use in cooking and divert its use to
entirely nonfood uses.
table 16.1 top 40 and Last Countries with the highest rate of A/Dementia Death in
the World
rate per rate per
rank Country 100,000 People rank Country 100,000 People
1 finland 34.9 26 Iran 11.4
2 Iceland 25.1 27 Laos 11.0
3 united states 24.8 28 Bangladesh 11.0
4 sweden 21.5 29 st. Kitts 10.8
5 the 21.4 30 Malawi 10.3
netherlands
6 switzerland 20.0 31 Luxemburg 10.3
7 Cuba 19.6 32 Israel 10.1
8 Chile 19.6 33 Guinea-Bissau 9.9
9 andorra 19.4 34 Democratic 9.8
republic of
Congo
10 spain 18.7 35 Italy 9.7
11 norway 18.6 36 ethiopia 9.7
12 uruguay 17.5 37 Cyprus 9.6
13 Denmark 17.4 38 Burundi 9.6
14 united 17.1 39 zambia 9.5
Kingdom
15 france 16.6 40 Costa rica 9.5
16 Canada 16.0 176 Qatar 0.5
17 australia 15.3 177 Peru 0.5
18 new zealand 15.2 181 Kuwait 0.3
19 Belgium 14.6 182 saudi arabia 0.2
20 Pakistan 14.3 185 Malaysia 0.2
21 Bhutan 13.4 188 arab emirates 0.2
22 Malta 13.0 189 singapore 0.0
23 south Korea 12.0 190 fiji 0.0
24 Ireland 11.8 191 Georgia 0.0
25 Hungary 11.5 192 Monaco 0.0
Source: http://www.worldlifeexpectancy.com/ (accessed March 5, 2015).
16.3.2.18 Refined and Reducing Sugars
Reducing sugar is more reactive than sucrose and has been implicated in the pathogenicity of
AD [13]. There is increasing evidence that refined sugars added to food or beverages may be a risk
factor for the development of AD. Fructose may be considered a risk factor for AD development
because fructose is more reactive than glucose and leads to the formation of AGEs. Foods or bev-
erages rich in refined sugar including fructose and high fructose corn syrup become a risk factor
because excessive consumption of such foods may increase the risk of AD. Reducing sugars bind
to amine groups of basic amino acids to form AGEs, the latter binds to RAGE at elevated tempera-
ture. Amyloid binds to RAGE and is transported to the brain by RAGE. In the brain, high levels of
RAGE have been identified in the hippocampus. Since RAGE is known to stimulate inflammation,
it is hypothesized that the upregulation of RAGE in cells of the hippocampus exacerbates inflam-
mation and may lead to neuronal cell death. Reactive oxygen species generated by exogenous or
endogenous oxidative stress are among the risk factors that initiate and promote brain cell death in
AD as well as PD. It has been suggested that in healthy individuals and with optimal flow of insulin,
the latter binds to its receptors at a synapse leading to memory formation. In the presence of amyloid
plaques, neurotoxic amyloid-derived diffusible ligands compete with insulin for the binding site on
the synapse and alter the binding site, and as a result insulin can no longer bind to the synapse and
there is insulin resistance and no memory formation. While it is well known how caloric intake
can induce AD, it is being established that caloric restriction delay impaired cognitive impairment.
People with metabolic syndrome are diagnosed with AD at a younger age than AD patients with-
out metabolic syndrome. Insulin activates pathways required for learning and long-term memory.
Most of the insulin receptors in the brain are located in the region of the brain associated with cog-
nition including the cerebral cortex, olfactory bulb, hippocampus, cerebellum, and hypothalamus.
16.3.2.19 Lactic Acid and Lactic Acid–Rich Foods
Lactic acid–rich foods have never been considered as a risk factor for AD because it appears that
there is no reason to incriminate lactic acid. However, it has been reported that high lactate levels
are characteristics of diseases caused by mitochondrial dysfunction, including vascular disease,
stroke, and cerebral ischemia [37,133,134]. Also, there are reports of fourfold increase in brain lac-
tate in early AD patients [135], a 5.5% increase in brain lactate level production in dementia [136],
and a 15% increase in CSF lactate in moderate AD patients compared to control [137]. Following
exercise lactate levels in muscle can increase nearly 10-fold [138]. The increase in brain lactate
could be caused by the observed inhibition of (1) ketoglutarate dehydrogenase and (2) oxidative
phosphorylation along with the observed stimulation of lactate dehydrogenase (LDH) [138]. This
author reported that lactic acid at 0.5 and 1 mg/mL (pH 7.1 and 6.9, respectively) caused a dose-
dependent alteration of neuronal processing into potentially amyloidogenic forms. Recently, lac-
tic acid at physiological concentration of 6 or 12 mM was shown to increase the levels of Aβ40
and Aβ42 in culture medium of neuroblastoma (SH-SY5Y) cells and decreased the levels of APP
metabolites such as sAPPα [37]. These authors also reported that incubation with 6 mM lactic acid
lowered the pH from pH 7.2 in control medium to pH 7.0; incubation with 12 mM lactic acid low-
ered the pH to 6.7 without loss of cell viability. High lactate levels have been reported in the CSF
of patients with AD [139].
Is there a correlation with lifelong consumption of fermented food products high in lactic acid
and the occurrence of dementia? How can we understand the high prevalence of dementia in popu-
lations that consume large amounts of lactic acid–rich foods? Can lactic acid accumulation in the
brain be a risk factor for AD development? Sauerkraut, sourdough bread, and lactic acid–rich sau-
sages deserve attention. What about individuals who consume kimchi on a daily basis, which is also
rich in lactic acid? Shouldn’t it be time and appropriate to investigate the potential role of lactic acid
accumulation in AD development? If brain injury may lead to excessive lactic acid accumulation,
then lifelong consumption of lactic acid–rich foods may also be a risk factor for AD.
16.3.2.20 Alkaloids in Foods
Beta-carbolines are neurotoxic, inhibit monoamine oxidase, and interact with 5-hydroxysero-
tonine uptake although a correlation with AD has not been established yet. Beta-carboline alkaloids
occur in marine organisms, mammalian and human tissues and fluids, and processed foods and are
unavoidable components of the Western diet [140]. Beta-carbolines are also formed in foods during
cooking, fermentation, heating, smoking, and storage [140]. Beta-carbolines, such as harman and
norharman, are found in high levels in meat grilled on an open flame, in meat extracts and bouil-
lon cubes, vegetable-derived flavors, soy sauce, cooked fish, soups, breakfast cereals, cooked meat,
bread, citrus juices, jams, and brewed coffee. Brewed coffee is one of the major dietary contribu-
tors of beta-carbolines harman and norharman, and one serving of brewed coffee may contain up
to 24 μg of beta-carboline [140]. Beta-carboline concentration in brewed coffee is higher than in
ground coffee. Brewed coffee alone contributes more carbolines than the maximum daily intake
of harman and norharman [140]. Exogenous intake of beta-carbolines is higher than endogenous
beta-carbolines. Is there any correlation with lifelong consumption of marine foods rich in beta-
carboline and AD? Safe exposure levels of these compounds are not known and the time has come
for this to be known.
16.3.2.21 Capsaicin
Capsaicin from hot pepper is an intriguing molecule that may be a double sword. It is a very
good anti-inflammatory and anticancer molecule [141–143]. However, recent studies show that cap-
saicin is also carcinogenic [144] and neurotoxic [145] and influences APP processing in the direc-
tion of Aβ production in vivo [146].
16.3.2.22 Environmental Lifestyle and Exposure
16.3.2.22.1 Heavy Smoking
Heavy smoking lowers the onset age of AD. Tobacco use was associated with increased risk
of developing AD [147]. Early age of smoking onset was related to poor working memory and
smokers perform worse than nonsmokers in all measures of sustained attention and information
processing speed [148]. Toxic compounds in cigarettes including carbon monoxide, free radical
precursors, and polynuclear aromatic compounds may be directly cytotoxic to neurons, glia, and
mitochondrial respiration chain and induce insulin resistance, which is known to affect neurocog-
nition [148].
16.3.2.22.2 Heavy Alcohol Consumption
Heavy alcohol consumption lowers the onset age of AD. Individuals carrying the APOE ε4
allele who consume alcohol heavily in midlife are at increased risk of dementia later in life com-
pared to individuals without APOE. For those who are not APOE ε4 allele carriers, the risk exists
although it is not as high as for the APOE ε4 allele carriers. Heavy alcohol consumption can over
time cause brain injury. Heavy alcohol consumption such as six or more drinks per day over a long
period of time can cause progressive cognitive impairment, and heavy drinkers often demonstrate
gradual multidomain cognitive impairment [149,150]. There are reports showing that alcohol-related
dementia can represent up to 10% of all cases of dementia while heavy alcohol consumption may
contribute more than 10% of all cases of dementia [151,152]. However, mild-to-moderate drink-
ing of one-half to two drinks per day has shown, through numerous studies, to be neuroprotectant
because it raises the blood level of good cholesterol, lowers the level of bad cholesterol, increases
insulin sensitivity, and reduces inflammation [153].
16.3.2.22.3 Occupational Exposure to Heavy Metals
Aluminum and mercury have been suggested as risk factor for AD but has not been substanti-
ated [70]. Exposure to heavy metals such as lead and others, such as aluminum, iron, and copper,
early in life may lead to early onset of AD later in life. Higher levels of free copper have been mea-
sured in the serum of individuals affected with mild cognitive impairment. However, occupational
exposure to extremely low-frequency electromagnetic fields has been investigated and confirmed as
a risk factor for AD [70,154,155]. Side effects of certain drugs have also being mentioned as poten-
tial stimulator of early onset of AD.
16.3.2.22.4 Lower Level of Education
High illiteracy and low level of education have also been reported by investigators as a robust
risk factor for the development of AD across the world and the major one in most developing coun-
tries [42]. Lower education was associated with a greater risk of dementia in many but not all studies
and more years of education do not uniformly attenuate the risk of dementia [156].
16.3.2.22.5 Physical Inactivity
Physical activity throughout life was evaluated in 9344 women including teenagers, age 30,
age 50, and late life [157]. Logistic regression was used to determine the association between
physical activity status at each age and likelihood of cognitive impairment. The study con-
cluded that women who were physically active as teenagers or at some points in their life
course had lower risk of developing cognitive impairment in adult life [157]. Others have used
meta-analytical techniques to quantify the association between physical activity and risk of
neurodegenerative diseases using only studies that involved physical activity and cognitive
with diagnosis of a neurodegenerative disease and reported that physical activity is inversely
associated with risk of dementia [158].
16.3.3 Medical risk Factors
Chronic depression is a risk factor for AD development. People with depressive episodes early
in life are at increased risk of developing AD compared to individuals without a history of depres-
sion [159,160]. Depression is a neuropsychiatric symptom found in 90% of people with AD [161].
Antidepressant drugs particularly those with anticholinergic compounds can impair or worsen cog-
nitive function [4]. Trauma brain injury as explained earlier is also a risk factor.
16.4 UNMODIFIABLe AND MODIFIABLe rISK FACtOr INterACtIONS
While genes and environmental risk factors associated with AD have been and continue to
be identified separately, little has been said about the potentials of genes and environmental
factors including diets on the development of AD especially EOAD. Therefore, gene/environ-
ment interactions as a risk factor for AD need to be addressed. Recent studies have shown
that gene/lifestyle may lead to LOAD. However, we notice here in the Volga Germans that
the EOAD is common. The first ever recorded patient with AD, Auguste Dieter, was a Volga
German, had EOAD, and died at age 56. It is common for Volga German to have EOAD by the
age of 48 and die from AD by the age of 53. Auguste’s father died at age 45. Some people in
the Volga region must have shared common ancestral heritage and mutation in the gene that
encodes presenillin-2 (PSEN2). We also notice here that the diet of the Volga Germans includes
cabbage, meat (including ham, weiner), sauerkraut, sour cream, cheese, butter, roasted water-
melon, and roasted sunflower seeds. All of these foods are very rich in AGEs and lactic acid.
Korean kimchi is a fermented food very rich in lactic acid and the neurotoxin capsaicin heavily
consumed throughout lives. The question we are asking is “Can the diet of the Volga Germans
trigger EOAD in individuals with genetic predisposition?” Also, can lactic acid- and capsaicin-
rich meals be investigated as a long-term risk factor for AD? Recent studies have shown that
consumption of tofu from midlife may increase the risk of AD [162,163].
16.5 DIetArY APPrOACh tO ALZheIMer’S DISeASe
16.5.1 Introduction
AD is a health and social problem. The Alzheimer’s Association has predicted that by the year
2050, there will be nearly one new case of AD every 33 s and a million new cases per year, and there
will be about 13.8 million individuals in the United States with AD [164]. The disease could cost
the United States alone $1 trillion (in today’s dollars) by the year 2050 [164]. Advances in neuroscience
and biomedical research have not unraveled the real cause(s) of AD. Yet the incidence of the disease is
growing worldwide and there are very few regions where the incidence is almost zero.
The development of AD in most cases encompasses a combination of the risk factors associated
with major chronic diseases, including obesity, metabolic syndrome, chronic inflammation, and
cancer. The disease develops over years or decades during which amyloid deposition and subse-
quent cascades of events occur before diagnosis. Therefore, an emphasis should be placed on pre-
venting or delaying the onset of the disease rather than waiting until it is too late to fix it.
AD has no cure and is characterized by a progressive loss of cognitive function; the best medi-
cine for AD, at the current level of knowledge, is a progressive and sustained prevention of the onset
and development of cognitive dysfunction. For individuals who have developed dementia or are
patients with AD, identifying foods or dietary patterns that slow the progression of the disease is
probably the best approach to follow.
If the onset of AD can be reduced by as little as 1 year, the prevalence of AD could be reduced
by 10% [119]. George Bray said of obesity that the genetic background loads the gun, but the envi-
ronment pulls the trigger [165]. Making a similar analogy to AD, if food is part of the trigger, then
it is imperative to identify compounds in foods and foods that may be associated with cognitive
decline in old age and start a campaign of advising people to reduce their consumption of these
foods. Several studies have shown that in the United States alone the incidence of AD is prevent-
able in the 50%–70% range using a combination of better nutrition; dietary supplements; lifestyle;
avoidance of certain types of foods, beverages, and environmental toxins; and better medication
[13,166–168]. We suggest that early AD development may also be preventable in those with a family
history of AD by adopting appropriate lifestyle thereby avoiding the early trigger.
16.5.2 Dietary Patterns, Lifestyle, and risk of Cognitive Dysfunction and AD
Diet is a modifiable risk factor and potentially an effective preventive strategy for healthy old
age cognitive function. The study of the association of dietary patterns and AD has advantage over
the investigation of the association of individual compounds and AD because foods are often con-
sumed in combination. This allows studying the potential interactions among components in the
foods investigated.
The Western dietary pattern is characterized by high intakes of red meat, refined grains and car-
bohydrates, and sugar and has been shown to be associated with the high incidence of certain types
of obesity, metabolic syndrome, insulin resistance, cancer, coronary heart disease, diabetes, and AD.
The Western dietary pattern is characterized by ingredients or foods with high contents of AGEs.
There is increasing evidence that dietary pattern rich in AGEs is a major risk factor for AD devel-
opment. Patients with AD have higher levels of AGEs compared to age-matched healthy controls
[169–171]. Dietary AGEs are also known as glycotoxins, promote brain injury, have been implicated
in stroke, and increase the toxicity of amyloid plaques [172]. Higher levels of plasma AGEs acceler-
ate memory decline in young people with normal cognition and mild cognitive impairment [173].
Red meat and cheese are the foods with the largest amount of AGEs [174]. Dietary patterns
with high intakes of red meat and cheese are associated with a high risk of AD development [175].
Dietary pattern high in refined carbohydrates and low in fat is also a risk factor for AD development
because of the formation of AGEs.
Serum methylglyoxal (MGO) was measured in 378 participants (mean age 72.1 years, SD 7.1,
male: 55%) in the Tasmanian Study of Cognition and Gait [176]. It was found that participants
with higher levels of MGO had poorer memory than those with lower levels of MGO. Fructose
mediates the accumulation of MGO in adipose tissue [177]. MGO is a precursor of AGEs and
is found in fructose-rich beverages [178]. Individuals with higher levels of dietary AGEs such as
Nε-(carboxymethyl)-lysine (CML) and cardiovascular disease have severe cognitive impairment
[179]. Higher than normal levels of serum concentration of the glycotoxin MGO in 267 nondemented
elderly was associated with a faster rate of cognitive decline after about 36 months of follow-up
[180]. Higher levels of pentosidine in urine was also associated with greater cognitive decline [181].
Young nondemented people with higher levels of AGEs were found to be associated with faster rate
of decline in memory [182].
The integrity of the blood–brain barrier is significantly associated with hippocampal stability,
cognitive function, and dementia status. Several studies have shown that high intakes of Western
diets that are high in saturated fat and simple sugars can increase the levels of circulating plasma
amyloid-β. High levels of amyloid-β have shown to disrupt the blood–brain barriers of rats, enter
the brain, and increase neuroinflammation particularly in the hippocampus region of the brain. As a
result of high adherence to Western diet chronic neuroinflammation may contribute to impaired
learning and memory function [183].
The Three-City study that enrolled 8085 nondemented participants aged 65 and over in
Bordeaux, Dijon, and Montpellier (France) in 1999–2000 and followed them for years concluded
that diets rich in vegetables, fruits, nuts, fish, and antioxidant-rich foods may protect against demen-
tia and AD development, especially among ApoE ε 4 noncarriers [184].
A group of 71 Polish people (42 females and 29 males) with AD and 72 healthy, age- and
gender-matched control were enrolled to study the potential association of dietary pattern and AD
development [185]. Food frequency questionnaire based on 12 major food groups was presented to
the participants. The reports from AD participants showed a pattern of high intake of meat, but-
ter, high-fat dairy products, eggs, and refined sugar, the reports from the healthy matched controls
showed a high intake of grains and vegetables.
A study that followed 2148 community-based elderly subjects (aged ≥ 65 years) without demen-
tia in New York for years showed that 253 subjects developed AD during a follow-up of 3.9 years.
The study concluded that higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous
vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products,
red meat, organ meat, and butter may be associated with a decreased risk of developing AD [175].
The Swedish Twin Registry study that followed 3779 members of the registry suggested that greater
fruit and vegetable consumption may lower the risk of dementia and AD, especially among women
and those with angina pectoris [186].
Several longitudinal and prospective studies have shown that higher adherence to the traditional
polyphenol-rich Mediterranean dietary pattern was protective against cognitive decline, demen-
tia and AD development [187–192]. High consumption of olive oil, vegetables, fruits, nuts, seeds,
beans, fish, moderate consumption of wine and dairy products including cheese or yogurt, and
low consumption of red meat are characteristics of the traditional Mediterranean diet. A study of
dietary habits in older people suggested that low meat intake may help support healthy cognitive
aging [188]. For individuals with AD, higher adherence to the Mediterranean diet has shown to be
with lower mortality [193].
An ongoing population-based prospective cohort study of 1,081 elderly Japanese in the town of
Hisayama also known as the Hisayama Study began in 1961 to determine the risk factors of cere-
bro- and cardiovascular diseases in Japan [194]. Subjects were followed up for 17 years between
1988 and 2005 during which 303 individuals developed dementia, 25 developed AD, and 18 had
vascular dementia. The study found a significant inverse relationship between milk and dairy intake
and the risk of dementia including AD and vascular dementia.
However, Crichton et al. [195] reported that low fat dairy may have beneficial effects on mem-
ory, while whole fat dairy may be associated with poorer psychological well-being. Garcia et al.
used a cross-sectional design to examine dairy consumption, cognitive dysfunction, and cerebral
blood flow in a sample of older adults with heart failure and reported that greater dairy intake was
associated with poorer memory performance in this group [196].
Singh et al. (1997) reviewed 664 prospective cohort studies with longitudinal follow-up on the
association of the Mediterranean diet with mild cognitive impairment and AD and selected the five
best studies that met the eligibility criteria. These reviewers found that participants with higher
adherence to the Mediterranean diet had 33% less risk of developing cognitive impairment.
The Women’s Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vita-
mins for cardiovascular disease secondary prevention, included 2475 women older than 65 years
who were followed up for years using a validated 116-item food frequency questionnaire [198]. The
study observed significantly slower rates of cognitive decline with increasing consumption of caf-
feinated coffee. Moderate coffee intake may also reduce the risk of stroke, the overall risk of cancer,
and AD [199,200]. However, another study has shown that coffee was not effective in women as far
as cognitive function was concerned.
A cross-sectional study using data from the Korean Multi-Rural Communities Cohort Study
used a quantitative food frequency questionnaire with 106 food items to study the association of
dietary patterns and cognitive health in 806 (340 men and 466 women) subjects aged ≥60 years
[201]. The study suggests that dietary pattern centered on white rice without well-balanced meals
may increase the risk of cognitive decline. Consumption of a high glycemic diet such as white
rice was also associated with poorer cognitive performance as assessed by the Mini-Mental State
Examination (MMSE) that examined cognitive impairment in 208 subjects of which 94 were males
and 114 females; aged 64–93 years [202]. AD has been identified as type 3 diabetes and uncon-
trolled diabetes increases neurodegeneration [203,204].
The DASH (Dietary Approach to Stop Hypertension) and Mediterranean diets share several
common food components. A prospective Chicago cohort study of 826 memory and aging partici-
pants (aged 81.5 ± 7.1 years) showed that higher adherence to the DASH and Mediterranean dietary
patterns is associated with slower cognitive decline [205].
A prospective study that enrolled 923 participants, ages 58–98 years, followed on average
4.5 years to investigate the relation of DASH, Mediterranean diet, or a hybrid of both DASH and
Mediterranean diet also known as MIND diet [206]. Higher adherence to DASH, the Mediterranean
or MIND diet was shown to slow cognitive decline. A moderate to MIND was also effective in
slowing cognitive decline. After all, the DASH diet addresses hypertension, which is a risk factor
for AD.
Cherbuin and Anstey assessed 1528 individuals, aged 60–64 years, in a large longitudinal
investigation of generally healthy individuals [207]. Participants were tested for mild cognitive
impairment using either the International Consensus Criteria or the Clinical Dementia Rating
scale at two time points, 4 years apart. They found no association between the consumption of the
Mediterranean diet and cognitive dysfunction.
There are clusters of countries with very low AD incidence. Bolivia, Peru, Colombia, Venezuela,
Guyana, Suriname, French Guiana, Nicaragua, and Honduras are countries to mention in Central
and South America. Sudan, Egypt, and Libya have the lowest incidence in Africa. In the Middle
East, Syria is the only country with high incidence. Afghanistan, Kazakhstan, Turkmenistan,
Mongolia, Ukraine, Russia, Belarus, and Japan have low incidence in Asia. What are the dietary
patterns in these countries?
Despite being the spice capital of the world, the incidence of AD in India is not low [208–211].
Similarly, despite low meat and dairy consumption, the incidence of AD in China is not low [212–214].
In South Korea, dementia affects 10% of the elderly population and the incidence is as high as in most
Western nations [5,215].
The ketogenic diet (KD) may be effective against AD. The KD is a low-carbohydrate and high-
fat diet that is often used for medically intractable epilepsy. There is increasing evidence that the KD
diet has broad neuroprotective properties against diverse neurological disorders. The KD increases
ketone bodies and reduces oxidative stress.
The paleolithic diet focuses on African Paleolithic foods that included lean meat, tubers, fish,
and vegetables and fruits. There is little evidence to support that such diet can be effective in the
development of AD. There is also little evidence to suggest that the Paleolithic diet can be a risk
factor for AD. However, it is important to invite the readers to revisit the semi high incidence of AD
in most African countries except for South Africa, Egypt, and Libya. Is there any correlation with
starchy foods that populate African cuisine? Is there any correlation with the way Africans cook
their foods? Frying and smoking foods are very popular in African cuisine.
16.5.3 Dietary Approach to Alzheimer’s Disease
To use a dietary approach to prevent AD development, two strategies must be employed:
1. Identify dietary habits including toxins generated through diets that promote the development
of AD. These risk factors for AD development include risk factors for AGE formation, insulin
resistance, oxidative stress in the brain, chronic inflammation, mitochondrial dysfunction, blood–
brain barrier disruption, Aβ production, and tau protein hyperphosphorylation. The rationale for
identifying dietary compounds as well as dietary habits that are risk factors for AD development
is twofold:
a. These dietary risk factors converge to AD onset and/or progression and removing these factors
should significantly reduce the risk for AD development.
b. Before AD development, most of these risk factors induce the development of other chronic
degenerative diseases such as insulin resistance, diabetes, hypertension, and stroke that are
life-threatening. Therefore, preventing the development of insulin resistance, obesity, diabetes,
hypertension, and stroke can also delay the onset of AD.
2. Identify dietary compounds, foods, or dietary patterns that show reduced risk factors for AD devel-
opment and good cognitive function in old age.
The rationale for investigating bioactive compound–rich foods or dietary habits for AD preven-
tion or delay is severalfold:
a. The cure for AD is not currently available. Recent estimates suggest that a 10–25% reduction in all
AD risk factors could potentially prevent between 184,000 and 492,000 cases of AD in the United
States and as many as 1.1–3.0 million cases around the world [4]. Food is the best medicine for
prevention.
b. AD does not develop overnight, and when AD symptoms are evident, it is late to reverse the course
of the disease even with the most powerful drugs known to people. Foods rich in bioactive com-
pounds that have shown inhibitory activities against risk factors of AD can be consumed over a
long period of time to modulate the activities of these risk factors throughout life and help delay the
development of the disease.
c. Most drugs being designed for AD treatment are irreversible inhibitors of enzymes such as the
aspartic protease BACE1, which initiates the formation of the neurotoxic amyloid beta (Aβ) that is
a major constituent of the amyloid plaque and one of the hallmarks of AD [216]. However, these
enzymes such as the BACE1 have other important physiological functions and their irreversible
inhibition can have serious physiological consequences [217]. Most dietary bioactive compounds are
reversible inhibitors of enzymes involved in AD development and can be used on and off throughout
life to prevent AD development.
d. Populations with lower rate of AD prevalence including individuals in the Middle East or those
consuming traditional Mediterranean diet may consume low levels of AD dietary risk factors.
Also, these populations do not consume molecules, for example, curcumin, epigallocatechin gallate
(EGCG), or lipoic acid. Clinical studies carried out in China and the United States have not shown
any beneficial effects of curcumin as magic bullet on improving cognitive function [218] suggesting
that AD is more complicated than diseases that are easily cured using one compound.
e. Since only small fractions of dietary bioactive metabolites ingested reach the circulation, and not
all parent molecules that are active in vitro lead to active metabolite(s) in vivo, selection for and sus-
tained consumption of foods susceptible to generate active metabolites that can be used metronomi-
cally would be an effective way of chronically inhibiting vascular recruitment by AD stimulators
instead of waiting when it becomes too little too late.
f. The brain tissues are rich in polyunsaturated fatty acids and polyunsaturated fatty acids are suscep-
tible to reactive oxygen species-induced degradation. It may be wise to nurture the brain throughout
life with oil-soluble antioxidants and avoid feeding the brain foods or compounds that promote brain
lipid oxidation or brain protein phosphorylation and plaque formation.
16.5.4 Dietary Bioactives or Supplements with Potentials

to Slow Alzheimer’s Disease Progression
Identifying dietary compounds or diets that can delay the progression of AD in individuals
already carrying the disease is very challenging. Several enzymes are associated with the develop-
ment and progression of AD. The best known and characterized are acetylcholinesterase (AChE),
α-secretase associated with the non-amyloidogenic pathway, β- and γ-secretases associated with
the amyloidogenic pathway, and others associated with Aβ-induced neurotoxicity or Aβ-induced
neuroinflammation.
AChE inhibition is currently the major target for AD treatment. AChE inhibitors can alleviate
the symptoms of AD, do not halt the progression of the disease, have modest benefits and the out-
come has not been consistent [219]. It may be too little too late. The inhibition of this enzyme can
reduce the aggregation of β-amyloid and the formation of neurotoxic fibrils in AD patient brains.
Dietary and medicinal plant inhibitors of AChE are being considered as a strategy for AD progres-
sion delay. Galantamine is among the leading compounds that have shown efficacy alone or in
combination with other AChE inhibitors [220]. Natural products rich in monoterpenes may have
the potential to inhibit the activity of AChE [221,222]. Essential oils appear to be more effective
than single components [223]. Lemon peel essential oils comprising sabinene, limonene, α-pinene,
β-pinene, neral, geranial, 1,8-cineole, linalool, borneol, α-terpineol, terpinen-4-ol, linalyl acetate,
and β-caryophyllene inhibited AChE activity in vitro [224]. However, in some cases, individual
components such as limonene and 1,8-cineole in essential oils have often shown no activity against
the enzyme [221], but in others, the enzymatic activities were decreased by individual compounds
[225]. The AChE inhibitory activities of bioactive compounds in essential oils showed the following
trend: thymohydroquinone > carvacrol > thymoquinone > essential oil > thymol > linalool [226].
Alkaloids in general have inhibitory activities against AChE. Dietary alkaloids including triter-
penoid alkaloids, steroidal alkaloids, indole alkaloids, isoquinoline alkaloid, and lycopodane-type
alkaloid are the major types of alkaloids having significant anticholinesterase activity making them
promising candidates to be used as cholinesterase inhibitors in clinical practice.
A mixture of naturally occurring dietary bioactive compounds including curcumin, piperine,
EGCG, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate in a dietary supplement
improved cognitive functioning and decreased Aβ and oligomerization in a mouse model of the dis-
ease [168]. It was suggested that the dietary supplement may represent a safe and natural treatment
for AD. A diet of a single bioactive component such as omega-3 fatty did not protect mice against
cognitive decline [227].
Compounds that inhibit γ-secretase may cause intestinal goblet cell hyperplasia, thymus atro-
phy, decrease in lymphocytes, and alterations in hair color, effects associated with the inhibition of
the cleavage of Notch, a protein involved in cell development and differentiation [228]. However,
recent data support the use of secretase inhibition to slow AD progression [229].
Souvenaid® (Nutricia N.V., Zoetermeer, the Netherlands) is a combination formula for cognition
improvement in individuals with mild AD [230,231]. It is a 125 mL beverage that delivers 300 mg
of EPA, 1,200 mg of DHA, 106 mg of phospholipids, 400 mg of choline, 625 mg of uridine mono-
phosphate, 40 mg of vitamin E, 80 mg of vitamin C, 60 µg of selenium, 3 µg of vitamin B12, 1 mg
of vitamin B6, and 400 µg of folic acid. Souvenaid may also help individuals with behavioral distur-
bance and social cognition skill. However, Souvenaid used for 24 weeks showed no efficacy on cog-
nitive decline in patients with mild to moderate or advanced memory impairment [232]. Souvenaid
is tolerable and has shown high intake adherence, good tolerability in a study that investigated the
safety of the supplement for 48 weeks [233].
While studies show that most patients with AD are deficient in specific micronutrients such as
selenium, vitamin K, omega-3 fatty acids, B vitamins, or folic acid, intake of these micronutrients
alone does not always confer reduction in disease progression [234]. For instance, vitamin E isomers
together may be protective, while consumption of α-tocopherol alone provides no benefits [235].
Combination foods or supplements appear to have some effects [234]. Patients with AD (N = 36) had
lower levels of macular pigments including lutein and zeaxanthin than healthy matched controls.
The low levels of macular pigments correlated with poor vision and higher occurrence of cognitive
decline [236]. However, can consumption of lutein and zeaxanthin alone improve cognition func-
tion in patients with AD? Nobiletin (10–50 mg/kg), a bioactive compound in citrus peel, was given
daily to various mice models of dementia for 1 month and improved several pathological features of
AD including oxidative stress, amyloid-β, tau phosphorylation, cholinergic neurodegeneration, and
dysfunction of synaptic-plasticity-related signaling [237].
16.5.5 Future Prospects: Designing Foods with Potentials in

Alzheimer’s Disease Development Prevention
Dietary prevention of AD should begin during childhood and continue throughout adolescent
and adult life. The efficacy of foods against the risk factors (oxidative stress, inflammation, meta-
bolic syndrome, and others) for AD is known. It is suggested that the food industry plays a big role
in designing the following type of healthy foods and beverages to prevent the development of AD:
1. Foods for good maternal nutrition

2. Foods for good infant nutrition
3. Foods for good or improving mood
4. Foods for healthy gut (AGE-reduced or AGE-free)
5. Foods that enhance insulin sensitivity in the brain
6. Foods that modulate or prevent the buildup of the activity of AChE
7. Foods that prevent plasma and brain Aβ buildup
8. Foods that prevent tau protein hyperphosphorylation
9. Foods that prevent inflammation in the central nervous system
10. Foods that prevent mitochondrial dysfunction
11. Foods that enhance the immune system
12. Anti-inflammatory foods for the body
13. Insulin sensitivity–enhancing
14. AGE-reduced foods
Ingredients and technologies to develop the foods for AD as mentioned earlier are available.
It is suggested that consumer advocates and researchers take time to reevaluate dietary patterns
and take bravery stands to canvass/fund research for the avoidance of foods/ingredients/processing
techniques with the high incidence of AD risk. There are several dietary bioactive compounds that
have shown efficacy against AD biomarkers. Developing dietary pattern rich in these compounds
may help curb the progression of AD provided that people consume these foods and stir away from
the dietary patterns that are AD-prone.
It is prudent and good to project the high cost that will be associated with AD in 2031 or 2050.
It will be better to stand up to the risk factors that are still on the market. It will take individual dis-
cipline, a village and collective efforts to fight AD because the disease knows no social boundaries.
We are what we eat and AD may be just what we eat.
It is critical to recognize and implement the combination of healthy eating, exercise, and criti-
cal thinking for a healthy brain throughout life. It is also important that we recognize the dire
consequences of our lifestyle that is more and more focusing on instant gratification while ignoring
that we all want to live long and it costs more to live long. The marches to political capital cities
or for cure and the funds generated may not compete with the rate at which the disease destroys
the human body.
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PArt III
Part III entitled “Champagne, Caviar, Good Cuisine, and Ice Wine” invites the reader to enjoy
life and embrace food as a lifelong weapon against some disease development. You are what you eat.
The gut is the epicenter of healthy life, suggesting that healthy gut is healthy life. The most coveted
diets including the Western, traditional Mediterranean, and Okinawan diets are discussed. The diets
of the centenarians who live in the “Blue Zones” and remain active members of their communities
at very advanced ages are also described. The differences between the Western and Mediterranean
diets are revealed.
A healthy pantry at home or away from home is the starting point for healthy eating. The reader
is invited to think out of the traditional box and develop a healthy pantry. Food preparation tech-
niques including their advantages and disadvantages are presented. Responsible entities and adults
should know how to address healthy eating to the children and youth because they represent the
future and can develop better eating habits. Laisser le bon temps rouler with champagne, caviar,
good cuisine, and ice wine because after all life should be good.
ChAPter 17
healthy Gut, healthy Life
17.1 INtrODUCtION
Dr. Minora Shirota, the founder of the great Japanese Yakult Honsha, once said “Prevent dis-
ease rather than treat disease, a healthy intestine leads to a long life; and deliver health benefits to
as many as possible at an affordable price.”
The human gut is the gateway of nutrient intake that fuels the entire body. The gut is also the
habitat for a plethora of nearly 100 trillion bacteria (microbial population) and the largest site of the
immune cells in the body, all of which play a key role in shaping health and disease. The gut micro-
bial population, also known as gut microbiota, is distributed throughout the gut and has a need for
nutrients for their sustainability and performance. The gut microbiota performs essential metabolic,
protective, and structural and histological functions.
The immune system is the first line of defense that neutralizes and eliminates infectious and
invading agents inside the human body. The gastrointestinal tract harbors about 70% of the body’s
immune system and produces over 90% of immunoglobulins in the body. Secretory immunoglobu-
lins are located in the proximal small intestine where they can unselectively trigger bacterial agglu-
tination in the mucus and limit microbial penetration into the mucosa. The gut’s arsenal of immune
defensive tools also includes constitutively expressed proteins such as defensins and inducible pro-
teins such as lectins that bind with the lining of the small intestine. The gut immune system requires
certain key nutrients such as glutamine that help optimize immune function. Both the microbiota
and the immune system cells extract their nutrients from the food ingested by the host, suggesting
that the food ought to be appropriate for each group present in the gut; otherwise the microbial
group population declines or disappears and the immune system collapses.
17.2 heALthY GUt MICrOBIOtA AND IMMUNe

CeLLS FrOM BIrth tO ADULthOOD
The human gut is segmented into four/five major sections through which ingested food and
its breakdown products travel. These sections are: the oral cavity, the stomach, small intestine,
and large intestine. Until recently it was generally accepted that at birth, the baby’s gut is sterile.
However, recent studies have shown that before birth the fetus ingests amniotic fluid containing the
mother’s gut microbiota [1]. It has also been suggested that a vaginally delivered infant receives
several strains of Bifidobacteria from the mother compared to an infant delivered by C-section
who may not receive any Bifidobacteria at all [2,3]. Subsequently, in addition to the mother’s gut
microflora, the child’s gut is rapidly and successively colonized by a complex microbial community
representing the major bacterial phyla whose composition evolves throughout life from childhood
to old age.
315
Several bacterial divisions make up the gut microbiota: the Bacteroidetes and Firmicutes make
up the majority, about 97%, of the human gut microbiota; the Actinobacteria, Proteobacteria,
Fusobacteria, Verrucomicrobia, and Cyanobacteria make up the remaining minority of the gut
bacterial population. These bacteria thrive in a largely anaerobic luminal environment. Biology has
carefully divided the human gut into two sections, the proximal region where nutrients obtained
from food digestion are absorbed into the body and the large intestine, which is the habitat for the
majority of the gut microbial population. This allows less conflict between the host and the majority
of the gut microbial population. Some have argued that the biochemical milieu of the gut includ-
ing pH, bile acids, digestive enzymes, and mucus is responsible for the qualitative and quantitative
distribution of the microbiota along the length of the gut.
Ingested food is first degraded in the mouth by enzymes from the saliva. These enzymes
mostly degrade carbohydrates and fats/oils. Then the partially degraded food travels down the
esophagus and enters the stomach where additional enzymes are thrown on the food to digest
proteins in a very acidic environment. The mixture of degraded and nondegraded food mate-
rials travels through the gut and additional enzymes are added from the pancreas to further
degrade the fat/oils and carbohydrates. Further down after the pancreas, the gut is less acidic
and enzymes that degrade proteins and protein fragments that were not degraded in the stomach
are applied to the food mixture. This environment is neutral and becomes alkaline further the
line of digestion.
At this point, food components that are degradable by any of the enzymes added so far have
been broken down into simple sugars, amino acids, and fatty acids. These are nutrients needed to
fuel the immune cells and body and these nutrients are absorbed in the body when they reach the
small intestine. The remaining undigested food components comprising undigestible carbohydrates,
fiber, resistant starch, some large protein fragments, waxes, and other large lipids cross the ileocecal
valve into the large intestine.
The beneficial bacterial population in the large intestine is mostly represented by the
Bacteroidetes that provide the body (host)-enhanced metabolic capabilities and aid in the digestion
of indigestible compounds that enter the large intestine through the ileocecal valve. The metabolites
or products of this digestion are essential nutrients necessary to promote enteric nerve function,
defend against opportunistic pathogens, modulate gastrointestinal development, and contribute to
the development and regulation of the immune system.
In the large intestine, good bacteria ferment undigested carbohydrates including carbohydrates
from shed mucus, fiber, resistant starch, and polymers of phenolic compounds into short-chain fatty
acids and other acids. Similarly, good bacteria ferment undigested nitrogenous compounds includ-
ing large proteins, peptides, (and proteins from host cells) into ammonia. Many of the B vitamins
are synthesized by good bacteria. The short-chain fatty acids generated by the Bacteroidetes are
absorbed and provide energy for the gut epithelial cells.
Maternal microbiota is inheritable. The mother’s diet is the starting point for future healthy
gut microbiota. Breastfeeding prepares and adapts the baby to tolerate oral ingestion of microflora
and food antigens. Breast milk is also rich in complex carbohydrates that are either deficient or of
different composition in baby formulas. A two and a half year examination of fecal samples from a
healthy infant revealed that early on the gut microbiome was enriched in microbes that facilitated
milk sugar (lactose) degradation into its component galactose and glucose. Before the introduction
of solid foods, the gut microbiome was enriched in microbes capable of metabolizing plant polysac-
charides. By the time solid adult foods were introduced, a more stable gut microbiome community
enriched in Bacteroidetes started filling in as shown by the production of short-chain fatty acids,
vitamin biosynthesis, and xenobiotic degradation.
Conversely, an infant or a child with a gut enriched in Firmicutes and other unwanted bacteria
develop a gut with impaired homeostatic and physiological signals. The Firmicutes and other Gram
negative bacteria in the gut continuously release a major component from their outer layer called
HeaLtHy Gut, HeaLtHy LIfe 317
“lipopolysaccharide” (LPS). This complex of lipid and sugar is known to stimulate inflammation.
Studies have shown that LPS is absorbed from the gut and absorption occurs in all humans whether
healthy or not, low levels of LPS are detected in the blood. Individuals with type 2 diabetes have
high levels of LPS in their blood and this LPS correlates with insulin levels. In brief, the levels of
Firmicutes and other unwanted bacteria in the gut can set up the tone for a low-level inflammation
that can persist in the body.
The Western-style diet centered on energy-dense and advanced glycatin end product (AGE)-rich
foods and beverages appears to be a good promoter for a gut full of Firmicutes. Northern Europe
infants had higher populations of Bifidobacteria in their gut microbiota and Southern Europe
infants had more Bacteroides and Lactobacilli [4]. It was shown that Italians had higher popula-
tions of Bifidobacteria than French, Swedes, or Germans [5].
The 1908 Nobel laureate Elie Metchnikoff is credited for his pioneering work on the interplay
between nutrition and microbial flora as critical factors for human well-being. Metchnikoff rec-
ognized that the human colon is full of intoxicating microorganisms that can cause disease and
premature death. So he proposed a diet of milk and milk products that would mildly acidify the
gut and promote the growth of beneficial lactic acid–producing bacteria at the expense of bad bac-
teria. He championed both a probiotic and prebiotic diet as the basis for well-being. Metchnikoff
can also be viewed as the champion of human microbiome. Increasing evidence through epide-
miological and clinical studies shows that diet plays a major role in shaping the gut microbial
population, the immune cells and system, and can promote a healthy or unhealthy gut [6–8].
Healthy gut, healthy life.
17.3 eNVIrONMeNtAL AND LIFeStYLe FACtOrS thAt

CAN PrOMOte UNheALthY GUt MICrOFLOrA
The incidence of unhealthy guts has increased dramatically around the world since World
War II suggesting that genetics has little to do with unhealthy guts. Among the environmental fac-
tors that might affect the development of unhealthy gut condition are (1) improved sanitary condi-
tions including decrease in infection from helminthic parasites in the developed nations leaving
the gut without natural immunity defense; (2) fetal, infant, and adult nutrition; (3) decrease in the
number of anaerobic bacteria and Lactobacillus; (4) cigarette smoking; (5) antibiotic use; (6) the
use of contraceptives; (7) high intakes of processed but nonfermented foods; and (8) the imbalance
between proinflammatory and anti-inflammatory proteins.
The lack of parasitic microbial burden and decreased burden of infection in the gut of Western
children as a result of contemporary lifestyle may predispose these individuals to the development
of allergic or autoimmune diseases. In a fascinating and moving story, a group of Italian scientists
led by Paolo Lionetti investigated the association of gut microbiota with different diets in human
populations by comparing the fecal microbiota of 15 healthy Italian children (nine males and six
females) from Florence, Italy consuming typical Western diets and 15 healthy Burkinabe children
(nine males and six females) living in a rural village in Burkina Faso, West Africa and eating a
typical rural African diet [9]. Children were 1–6 years old and had not taken antibiotics or probi-
otics in the 6 months before the time of fecal sample collection. Using advanced analytical tech-
niques, Lionetti and his collaborators suggest thought-provoking results. There was a dominance of
Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria in the gut microbiota of all of the
Burkinabe and Italian children.
However, there was a dramatically different bacterial colonization of the gut in the two groups.
The dominant bacteria found in the gut microbiota of the Burkina Faso children were the good bac-
teria Bacteroidetes and Actinobacteria with more than 70% of the bacteria belonging to the genus
Prevotella and Xylanibacter known for their ability to digest and degrade resistant polysaccharides
(sugars) including xylan, xylose, pectin, and carboxymethylcellulose and produce health-enhancing
short-chain fatty acids such as acetate, propionate, and succinate with a small amount of malate.
The Burkinabe children also showed relative absence of inflammatory bacteria in their fecal sam-
ples. The gut microbiota of the Italian children contained more than 70% of Firmicutes. Lionetti
and collaborators surmised that the dominance of Firmicutes over Bacteroidetes possibly driven by
the calorie-dense diet of the Italian children might predispose these kids to obesity in the future.
Studies have shown that obese individuals harbor more Firmicutes than Bacteroidetes but the ratio
tilts in favor of Bacteroidetes when obese individuals lose weight.
The typical Western diet that is characterized by the consumption of high-fat and low-fiber
foods is nowadays considered as a trigger for the development of chronic diseases on the rise in the
West including obesity, diabetes, and cancer. Increasing evidence shows that diet shapes the gut
microbiota and controlling the gut microbiota composition by appropriate diet may help control or
prevent the development of chronic diseases. For instance, a high-fat diet is capable of altering the
gut microbiota balance in favor of Firmicutes at the expense of Bacteroidetes. The prevalence of
Firmicutes leads to increased energy harvest from the diet, changes in energy expenditure and stor-
age, and alteration in gut permeability often leading to increased levels of LPSs in serum resulting
in metabolic endotoxemia, inflammation, and insulin resistance. High fat also leads to increased
inflammation and insulin resistance.
The positive correlation between diet and gut health has been reported by several studies.
A Japanese retrospective study showed that greater consumption of sugars/sweeteners, sweets, fats
and oils, and total fat increases the risk of Crohn’s disease (CD) by as much as twofold, whereas
vitamin C consumption showed an inverse relationship [10]. In other studies, consumption of high
amounts of vegetables, fish, and dietary fiber protected against CD; consumption of long-chain
omega-3 fatty acids was negatively associated with CD, and a higher ratio of fish oil versus veg-
etable oil significantly reduced the risks for CD. Despite genetic susceptibility difference between
Japanese and Westerners, the positive correlation between over consumption of certain diets such
as sweets and fats has been shown in both societies.
Smoking has a paradoxical association with an unhealthy gut. Smokers have a lower risk of
developing ulcerative colitis (UC) [11,12]; quitting smoking is a risk factor for UC, whereas continu-
ing smoking is a risk factor for CD [13]. Nicotine inhibits helper protein functions. A paradox exists
in that the highest incidence of smoking is found in countries with the lowest incidence of inflam-
matory bowel disease.
Antibiotic use has been positively correlated with increased incidence of unhealthy guts, especially
CD. Early disruption of bowel colonization with antibiotics has shown to increase the risk of inflam-
matory bowel disease suggesting that antibiotics may negatively affect the gut microflora. Recent stud-
ies have shown a positive correlation between contraceptive use and the development of inflammatory
bowel disease, in particular CD and the risk is reversed when contraceptive use is discontinued [14,15].
17.4 GUt MICrOBIOtA AND ChrONIC DISeASeS
Studies have shown that the human gut microbiome, also known as the collection of genes
encoded by the gut microbiota, is shared among family members; the maternal gut microbiota is
shared with the children and monozygotic or dizygotic twins living at different locations conserve
similar gut microbiota [16].
Bacterial infection disrupts the commensal microbiota. Individuals with CD are depleted
with Bacteroidetes and Firmicutes [17,18]. Elderly individuals with Clostridium difficile-causing
diarrhea have reduced numbers of health-promoting Bifidobacteria. Good bacteria in the gut
microbiota produce short-chain fatty acids that are anti-inflammatory and promote the growth
of Bifidobacteria and Lactobacilli. The feces of colorectal cancer patients often show reduced
quantities of anti-inflammatory producing bacteria Eubacterium rectale and Faecalibacterium

prausnitzii and increased levels of superoxide radical producers Enterococcus faecalis compared
to healthy individuals.
Clinical observations of individuals with inflammatory bowel disease have shown that some of
these individuals have reduced proportions of short-chain fatty acids, due to reduced levels of pro-
tective bacteria such as Bifidobacteria and Lactobacilli and elevated proportions of C. difficile that
increase intestinal inflammation. Chronic inflammation and immune suppression in the gut are risk
factors for developing colorectal cancer [19–21].
Obese individuals have reduced numbers of good bacteria Bacteroidetes in their gut microbiota
[16]. Obese individuals have shown to have significantly higher concentrations of Lactobacillus,
Enterococcus, Prevotella, Clostridium, E. coli, Staphylococcus, Eubacterium, and Roseburia [22].
Lean individuals had higher concentrations of Bifidobacterium, Bacteroides, Methanobrevibacter,
and Treponema [22]. Studies have shown that the gut microbiota of individuals with type 2 diabetes
have lower levels of beneficial Bifidobacteria than healthy individuals [23].
Some individuals with type 2 diabetes have reduced numbers of bacteria that alleviate insulin
resistance including Bifidobacterium and Lactobacillus [24] and an increased ratio of Bacteroidetes
to Firmicutes and Bacteroides–Prevotella to Clostridium [25]. Analysis of the gut microbiota of
patients with type 1 diabetes has identified microbial alteration associated with disease progression
[26]. An increase in the ratio of Bacteroidetes to Firmicutes has been observed [27,28]. The glyce-
mic level between type 1 diabetes children and healthy children may be associated with the altered
ratio of Bifidobacterium, Lactobacillus to Clostridium, and Firmicutes to Bacteroidetes [29]. The
study also showed that children with type 1 diabetes had significantly lower concentration of bacte-
ria needed to maintain gut integrity than their healthy counterparts. Infants regularly on antibiotics
are likely to develop asthma than those not on frequent antibiotics.
Adequate intake of fish oil, from fish that consumed phytoplankton rich in omega-3 fatty acids,
reduces the risk of inflammatory bowel disease. The microbiota of individuals with allergies
show decreased intestinal counts of Bifidobacteria and higher counts of Staphylococcus aureus
and E. coli compared to nonallergic individuals [30]. Nonallergic individuals had higher levels of
Bifidobacterium and Lactobacilli in their fecal samples compared to allergic ones.
17.5 StrAteGIeS FOr A heALthY GUt
Unlike the human genome, the composition of the intestinal microbiota can be modified with
food or other ingestible compounds. The diversity of the human gut microbiota is closely related
to dietary habits. For example, the gut microflora of Italian children was devoid of Prevotella,
Xylanibacter, and Treponema, while children from Burkina Faso had all these bacteria as a result of
unrefined carbohydrates used in their diets [9]. Both Italian and African children had Bacteroides
and Faecalibacterium and it was hypothesized that their presence in the gut of both children popu-
lations was associated with their potential anti-inflammatory activities.
Strategies to optimize and sustain healthy gut or reverse pathological changes in gut microflora
and local immunity include (1) avoiding proinflammatory foods and beverages, (2) caloric restric-
tion, and (3) enhancing consumption of probiotics, prebiotics, synbiotics, and antioxidant-, anti-
inflammatory-, and immune system modulating–rich foods.
17.5.1 Avoiding Proinflammatory Foods and Beverages
Avoiding regular consumption of foods that promote inflammation should lead to a healthy gut.
Some of these types of foods were described in Chapter 3. Proinflammatory foods can significantly
affect the gut microflora composition. Chronic exposure to high-fat diet impairs gastrointestinal
signals, induces inflammatory markers IL-1, TNF-α, and IL-6 and has shown to change the gut
microflora in favor of Gram negative bacteria and reduce the number of Bifidobacteria and the ratio
of E. rectale to Clostridium coccoides [23]. The Western diet includes high-fat, high red meat, high
levels of sweeteners, and high levels of AGEs that are proinflammatory and high caloric, induces
obesity, heightens the local and systemic inflammatory state with increased inflammatory biomark-
ers, and changes the gut microflora composition [31].
A high-fat diet is often associated with LPS that promotes the release of inflammatory cytokines
and alters the microbiota composition. Forty morbidly obese patients who consumed a fat overload
diet showed a significant increase in LPS in serum and decrease in superoxide dismutase, which
may be associated with an increased inflammatory state [32]. The diet of the African children from
Burkina Faso versus their Italian counterparts shows that diet has a significant effect on gut micro-
biota population.
A gluten-free diet has been suggested to individuals with inflammatory bowel diseases. These
diseases include UC, CD, and celiac disease. While a gluten-free diet is recommended to inflam-
matory bowel disease (IBD) patients especially those with celiac disease, it may not be a good
option for healthy individuals. Gluten-free products are more expensive than gluten-rich products
and poorly available and create an economic burden to those who are adopting this type of diet [33].
Gluten-free diets reduced the number of healthy Bifidobacterium/Lactobacilli bacteria and
increased the number of unhealthy Enterobacteriaceae [34]. As a result, a gluten-free diet reduces
the levels of anti-inflammatory proteins such as interleukin-10 (IL-10) or anti-inflammatory short-
chain fatty and organic acids. Results of removal and safe replacement of dental work such as mer-
cury in fillings, nickel in crown material, and the high anaerobic bacteria of root canals make such
cases nonexistent [35].
17.5.2 Caloric restriction and Gut Microflora
Data from humans and lab animals have consistently shown that caloric restriction prolongs
lifespan and helps the gut maintain a healthier immune system. Thirty-nine overweight and obese
adolescents (body mass index [BMI] mean 33.1, range 23.7–50.4; age mean 14.8, range 13.0–16.0)
consumed a calorie-restricted diet (calorie reduction = 10%–40%) and increased their physical
activity (calorie expenditure = 15–23 kcal/kg body weight per week) for 10 weeks [36]. The adoles-
cent lost more than 10 lbs each. The proportion of the Bacteroides–Prevotella group increased; the
proportion of Clostridium histolyticum, C. lituseburense, and E. rectale–C. coccoides decreased
significantly; and the proportion of E. rectale–C. coccoides significantly correlated with weight
and BMI z-score reductions in the whole adolescent population. Eight-day fasting, however, was not
associated with change in gut microflora [37].
17.5.3 enhanced Consumption of Probiotics, Prebiotics,

Synbiotics, and high-Fiber Foods
Probiotics are good commensal bacteria that include Enterococcus faecium, Lactobacilli sp.,
Bifidobacteria, and some Saccharomyces such as Saccharomyces boulardii. Probiotics help keep
the colon healthy by fighting bad bacteria such as E. coli. In vitro and in vivo experiments have
shown that probiotics can (1) prevent and/or reduce rotavirus-induced diarrhea; (2) alleviate lactose
intolerance; (3) reduce and prevent cancer-promoting enzyme and putrefactive bacterial metabolites
in the gut; (4) alleviate inflammation; (5) normalize passing stool and stool consistency in individu-
als with irritable colon or having constipation; (6) prevent or alleviate allergies and atopic diseases
in infants; (7) prevent infections, such as respiratory tract infections including flu and influenza and
urogenital infections; (8) improve mouth flora and prevent dental caries; and (9) ameliorate autoim-
mune diseases such as arthritis.
Ten CD patients with diarrhea and pain as main symptoms were enrolled in a symbiotic therapy that
included daily ingestion of 75 billion colony-forming units of Bifidobacterium and Lactobacillus and
9.9 g of psyllium as prebiotics for 13.0 ± 4.5 months [38]. The results of the Crohn’s Disease Activity
Index (CDAI) analyzed before and after the trial showed that six patients showed a complete response,
one patient had a partial response, and three did not respond as determined by the CDAI score.
Probiotics are often used in dairy products such as conventional yogurt, drinkable yogurt,
cheese, fermented vegetables or meats, and pharmaceuticals. The proliferation of probiotic-rich
foods or pharmaceuticals is on the rise. These probiotics claim to improve colonic transit time
[39,40]. Others were claimed to reduce Candida colonization of HIV women oral and vaginal
mucosa [31]. Orthodontic patients were fed probiotic curd (N = 20), probiotic toothpaste (N = 20), or
served as control (N = 20). Probiotic cheese was supplemented to a hypocaloric diet and fed to 25
obese hypertensive patients for 3 weeks versus 15 control who consumed control cheese [41]. BMI
and arterial blood pressure were significantly reduced in the probiotic cheese group compared to the
control cheese group. However, Tulk et al. [42] showed recently that in a short-term study, probiotic
did not improve gastrointestinal time.
S. boulardii is a probiotic that has been used around the world for a long time. It is delivered in
capsules. The health benefits of S. boulardii include its ability to help against diarrhea and infec-
tious diarrhea [43,44], prevention of enterocolitis [45], as an adjunct for the treatment of recur-
rent C. difficile [46], improving intestinal epithelial following inflammatory disease [47,48], and
reduction of serum cholesterol [49]. Other health benefits associated with S. boulardii include toxin
inhibition, resistance to bacterial growth, antisecretory effects, and trophic effects [50]. However,
the S. boulardii have to be viable to show efficacy in stimulating the human immune system [51].
The probiotics can only sustain doing this good job if the probiotics are well nourished and not
eliminated by drugs such as antibiotics. Antibiotic therapy has shown to reduce the population of
good bacteria in the gut often leading to the recolonization with harmful bacteria. Probiotics need
prebiotics, which are nutrients that help maintain healthy commensal bacteria such as Bifidobacteria
at the expense of harmful bacteria such as C. difficile. A prebiotic is a nondigestible food ingredient
(carbohydrate) that passes undigested into the large intestine and is fermented and digested by one
or a limited number of good bacteria (called probiotic) in the colon into short-chain fatty acids, and
the latter (short-chain fatty acids) increase the acidity of the colon thereby selectively favoring the
growth of good bacteria including Lactobacilli and Bifidobacteria and suppression of undesirable
bacteria such as E. coli. There is no such thing as prebiotic proteins.
Prebiotics provide health benefits indirectly by promoting the growth and health of intestinal
microflora that in turn can prevent constipation and diarrhea and stimulate mineral absorption and
immunomodulatory properties. A prebiotic keeps the probiotic alive and fighting bad bacteria.
At present, oligosaccharides, fructooligosaccharides, and galactooligosaccharides are the best-
known prebiotics. There are numerous examples of prebiotic-rich foods in human diet including
artichoke, chicory, green banana, chestnut, garlic, onion, asparagus, fenugreek, and pistachio to
mention a few (Figure 17.1a through d). Chicory, artichoke, banana, chestnut, garlic, and onion are
rich sources of fructooligosaccharides; fenugreek is a good source of gums, while pistachio is a
good source of galactooligosaccharide. Lactulol and polydextrose have shown to produce butyrate
that provides energy to mucosal and immune cells [52].
The health benefit of breast milk is mostly ascribed to the compositional ability of human milk
to create an environment in the colon dominated by good live bacteria called “probiotics” that help
keep the colon healthy by fighting bad bacteria such as E. coli. Human milk contains special types
of sugars that cannot be found in cow’s milk and it is believed that those special sugars make human
milk unique for human health. Unfortunately, this is a scientific explanation that is not passed on
to many individuals, leading many to believe that cow’s milk can replace mother’s milk. In recent
years attempts have been made to add fructooligosaccharides and galactooligosaccharides in infant
milk to promote Bifidobacteria growth in the gut.
(a)
(b)
(c)
Figure 17.1 (a) asparagus is a good prebiotic. (b) Banana plantain contains oligosaccharide. (c) Garlic is an
excellent source of fructooligosaccharides. (Continued )
(d)
Figure 17.1 (Continued) (d) onion, like garlic, is a good source of fructooligosaccharide.
A synbiotic is a mixture of prebiotic and probiotic formulated mostly by the dietary supplement
industry with hope that both will work together to enhance the health of the gut. Several probiotics
are being promoted for their ability to demonstrate efficacy in some inflammatory diseases includ-
ing pouchitis and UC; however, the jury is still out for the efficacy of these microorganisms on CD.
Also, immunocompromised individuals may have to be careful with probiotics because they may
cause fungemia and bacteremia.
High-fiber foods are gut healthy foods because the dietary fiber is fermented by the gut micro-
biota into short-chain fatty acids, mostly butyric acid, which is a good source of energy for mucosal
and immune cells. Black beans, red beans, lima beans, adzuki beans, fenugreek, sorghum, mango
skin, Brussels sprouts, and okra are typical examples of high-fiber foods (Figure 17.2a through e).
Amaranth and quinoa flour are good sources of dietary fiber for healthy gut.
Foods rich in resistant starch are good for healthy gut. Baked and cooled sweet potato is a very
good source of resistant starch (Figure 17.3). Similarly, cooked black beans are rich in resistant
starch (Figure 17.4). Green banana is an excellent source of resistant starch.
(a)
Figure 17.2 (a) adzuki beans contain soluble dietary fiber and flavonoids. (Continued )
(b)
(c)
(d)
Figure 17.2 (Continued) (b) fenugreek is a good source of the prebiotic galactomannan. (c) Lima beans
are a good source of soluble dietary fiber. (d) Mango skin can provide soluble
dietary fiber to the diet. (Continued )
(e)
Figure 17.2 (Continued) (e) Brussels sprout contains significant amounts of dietary fiber.
Figure 17.3 Baked sweet potato can provide a significant amount of soluble dietary fiber.
Polyphenols of the class of flavonoids degrade into short-chain fatty acids and improve the
acidic condition of the gut and favor the growth of beneficial bacteria at the expense of the bac-
teria that induce inflammation. Dark and bitter chocolate are good sources of dietary flavonoids
(Figure 17.5a and b). Cooked black beans or adzuki beans are rich in flavonoids that leached in the
cooking water. Swiss chard is also rich in flavonoids and fiber (Figure 17.6).
Dairy products rich in probiotics can improve gut health. Yalkut liquid yogurt and Dan Active
are few to mention (Figure 17.7). The probiotics need the prebiotics mentioned for their survival
in the gut. Upon colonization and if well nourished, these probiotics can compete and eliminate
inflammation-causing bacteria and establish a healthy gut. S. boulardii from LeSaffre (Marcq-
en-Baroeul, France) are also good probiotics. They can be found in capsules and are available
commercially.
Figure 17.4 Cooked black beans are a good source of soluble dietary fiber and flavonoids.
(a)
(b)
Figure 17.5 (a) Dark chocolate provides flavonoids. (b) flavonoids can also be obtained from chocolate.
Figure 17.6 swiss chard is a good source of fiber and flavonoids.
Figure 17.7 Probiotic in liquid yogurt.
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ChAPter 18
Adopting a Diet
18.1 DeFINItION OF DIet
The dictionary defines diet as “a selection of food and beverages consumed by an individual.”
Dietary habit is the habitual decision an individual makes when selecting food to enjoy. It is a
lifestyle. In general, humans are omnivores; however, with time, differences in dietary habits have
developed across cultures. Foods that may be a preference for some cultures may be taboo for oth-
ers; for instance, dog or frog meat or caterpillar is a delicacy in some cultures, while the same type
of food is strictly prohibitive in some others.
The contemporary human diet can be classified as Western, Mediterranean, traditional
Okinawan, West African, Central African, East African, Southern African, Central and South
American, Indian, Chinese, and others. The Western, Mediterranean, and Japanese dietary habits
are briefly described. The other diets are not described, because these diets are complex and require
additional onsite validity and documentation.
18.2 WeSterN DIet
Micronutrient deficiency including folic acid, iron, zinc, iodine, vitamin A, vitamin C, and vita-
min E has been eliminated in the Western diets and helped reduce infant mortality while improving
child growth and development. However, the hallmark of Western dietary patterns is the so-called
sweet–meaty–salty–high-fat diets characterized by daily intake of sweetened solid foods and bever-
ages and highly saturated fat and salty foods, some of which are processed at very high temperatures.
Sweetened solid foods, such as breakfast cereals, yogurts, bread, and chocolate bars, are rich
in reducing sugars, which is a characteristic of Western diets. Refined grains and potato tubers are
rich in simple sugars and major ingredients in food formulations. Pasta, pizza, pies, butter-rich rice
crispy, sweetened cookies, and ice cream are consumed regularly. The Western diets are rich in
saturated fats. Butter, margarine, and solid shortenings are rich in trans fats and saturated acids,
including myristic and palmitic acid, and are very proinflammatory [1,2].
The Western dietary patterns are also characterized by chronic consumption of sweetened bever-
ages that include sweetened flavored water, juice drinks, carbonated drinks, energy drinks, sweetened
milk products, sweetened chocolate milk products, sport dinks, and diet beverages. Fructose is the
preferred sweetener in most of the beverages. Concentrated fruit juices from citrus, berries, or other
fruits may not have added sugar but do contain significant amounts of naturally occurring fructose.
Regardless of its origin, fructose remains a very reactive reducing sugar, too much of which can gen-
erate significant Maillard reactions inside the human body. Honey, which is also high in fructose, is
widely used in breakfast cereals and in other food formulations. Nowadays, agave is in high demand.
Agave contains 90% fructose and can generate more Maillard reaction products than corn syrup.
331
Salt, sodium chloride (NaCl), is a major ingredient in the Western diet. Salt has major functional
properties that justify its use in food formulations (Table 6.1, Chapter 6). However, high consump-
tion of sodium chloride is associated with the development of high blood pressure or hypertension,
especially in blacks and Hispanics [3–6].
Meat from grain-fed poultry and beef, eggs from grain-fed poultry, and grain-fed fish are prob-
ably a major component of the Western dietary patterns. Eggs are major components of breakfasts,
pasta, and desserts. Processed poultry and red meats, and fish are cooked at high temperatures
where the Maillard reaction is accelerated. The Maillard reaction occurs when a reducing sugar and
a protein with epsilon amine group react. Ribose is a naturally occurring reducing sugar in meat.
Ribose reacts with proteins to generate the Maillard reaction. Ribose is not mentioned as a naturally
occurring reducing sugar in meat suggesting that its side effects are mostly underestimated.
Broiling, frying, grilling, roasting, searing, and microwaving are preferred cooking methods.
Around the clock, from breakfast to dinner time or movie time including snack time, a combination
of processed foods; dried fast foods high in sodium, fats, carbohydrates, and butter; grilled, broiled,
bricked, or seared foods; more than four cups of coffee per day; foods low in health-enhancing
nutrients; beverages sweetened mostly with fructose; consumption of molecules instead of the whole
food including fish oil pills, vitamin pills, and antioxidant pills; a tendency to sweeten anything that
goes into the mouth including green tea and soymilk; and energy-dense foods such as sweetened
chocolate, potato chips, fried foods, pies, butter-loaded rice crispy cookie bars, sweetened cookies,
ice cream, and egg-, meat-, and cheese-loaded pizza and lasagna are consumed regularly.
The driving force behind the popularity of sweetened, meaty, salty, and high-fat foods is a
combination of “cost, convenience, and taste.” These foods are inexpensive, affordable to almost
anyone, very tasty and flavorful, and easy to find. Since humans crave sugar and salt, these types
of diets are very popular worldwide and gaining momentum in every corner of the planet. Western-
style fast-food restaurants that serve Western-style foods and beverages are being built in several
countries around the world where their popularity is increasing.
The Western diet is not a “one size fits all”; it has variations depending on which part of the
Western world one lives, such as France, Germany, the United Kingdom, Canada, or the United
States. Even within each country, there are individuals who follow a healthy diet and do not suc-
cumb to the temptation of fast foods. The promise and realization of the industrial revolution has
led people to drive more and walk less. People are living longer than ever before. Life expectancy is
76 years for men and 78 years for women across most Western nations.
18.2.1 Western Dietary Patterns and the risks of Chronic Diseases
Adoption of the Western diet has been shown to increase the risk of developing the diseases
of civilization including obesity, type 2 diabetes, hypertension, autoimmune disease, osteoporosis,
coronary heart disease, and certain types of epithelial cancer [7]. The Western dietary patterns are
known to be proinflammatory [8]. The incidence of inflammatory bowel diseases, such as Crohn’s
disease, celiac disease, is on the rise and higher in the Western world than in developing nations [9].
The genetic component of inflammatory bowel diseases has been established; however, genetic drift
alone cannot explain the high incidence of these diseases in today’s population because this high
incidence was absent 50 years ago in the 1960s. The composition of the Western diets has led to a
shift in the structural and functional composition of the gut microbiota. The high-carbohydrate and
high–saturated fat composition of the Western diets promotes the expansion of pathological diseases
or pathobionts in the gastrointestinal tract and leads to the gut’s increased exposure to a microbiota
that favors the production of proinflammatory hydrogen sulfite instead of a gut microflora that pro-
motes the production of anti-inflammatory short-chain fatty acids [10,11].
The Western dietary patterns are associated with an increase in the prevalence of child and
adolescent obesity, obesity in women of childbearing age during pregnancy and after birth, and
aDoPtInG a DIet 333
adult obesity [12,13]. Type 2 diabetes is a major risk factor for the Western diet and has already
been globalized as a result of global trade and communication [14]. The sweet–meaty–salty diets are
associated with maternal deficiencies in health-enhancing compounds that translate into impaired
growth in utero during fetal life. The adverse effects of Western diets in childbearing mothers affect
the utero during the early stages of child development and have been suspected to be a harbinger of
health disorders later in the life of the offspring. The fetal origins of metabolic syndrome in adults
in the Western world have been linked to maternal and utero under- or overnutrition. At present,
over a quarter of the U.S. population has the metabolic syndrome. The incidence of hypertension,
macular degeneration, cancer (breast, prostate, and colorectal), and central nervous system (CNS)
diseases including multiple sclerosis, and Parkinson’s and Alzheimer’s disease (AD) is also on the
rise. Dental materials including mercury and nickel and the presence of anaerobic bacteria from
root canals have also been associated with the development of these chronic diseases. The preva-
lence of these chronic degenerative diseases adds significant costs to healthcare systems and put
severe strains in the economies in Western countries. The diseases such as hypertension that long
ago affected adults only are expanding and affecting even children [15]. The globalization of the
Western diets has led and will lead to the globalization of fetal origin of metabolic syndrome.
18.2.2 regions of Longevity in the West
However, despite the occurrence of chronic degenerative diseases, there are pockets of regions
in the West, known as parts of the “Blue Zones,” where individuals live strong past age 90 years old
and remain physically active past 100 years old [16] (Figure 18.1). These regions include the Nicoya
Peninsula in Costa Rica, the Nuoro province of Italy, Ikaria Island of the coast of Turkey, Sardinia,
and the Seventh-day Adventists of Loma Linda, CA. The hallmarks of the Blue Zones include fam-
ily coherence, no smoking, plant-based diets, community involvement for people of all ages, social
activities, physical activity as a daily routine, and avoidance of sugar. These populations have a low
risk of developing chronic diseases including diabetes, cancer, and cardiovascular and cerebrovas-
cular diseases. The dietary patterns of the people of Ikaria are described under the Mediterranean
diets and will not be described here.
Figure 18.1 Blue zones.

18.2.2.1 Dietary Patterns in Nicoya Peninsula, Costa Rica, and Longevity
The Nicoya Peninsula of Costa Rica is known to harbor individuals who enjoy exceptional lon-
gevity (>80 years of age); some of them become and die centenarians [17]. The long-lived individu-
als in this region have mean leukocyte telomere longer than individuals in other regions of Costa
Rica [17]. The diet of the Nicoyans revolves around calcium- and magnesium-rich hard water for
drinking and cooking, rice, fiber-rich corn tortilla, plantain, antioxidant-rich and fiber-rich black
beans, fried eggs, and local fruits such as maroñon that is rich in vitamin C; squash; chayote; anona,
which is like a pear; papaya; pineapple; guava; passion fruit; coconut; cantaloupe; lemons; limes;
star fruit; mango; and blackberries.
Nicoyans eat meat less frequently, but chicken and pork are the most consumed meat. Breakfast
is the biggest meal. Lunch is moderate. Dinner is light and consumed early in the evening. Coffee
is sweetened with raw cane sugar. Lifestyle also includes regular light physical activity and 8 h of
sleep every night. Close family ties along with plenty of socializing and community interactions
make part of the social activities in the peninsula.
A typical meal for the Nicoyans include black beans and rice, corn tortilla, fried plantain, fried
eggs, and lots of fruits. Black beans are rich sources of anti-inflammatory proanthocyanidins. Serra
et al. [18] showed that protocatechuic acid is bioavailable and accumulate mostly in the heart, intes-
tine, kidney, liver, spleen, and plasma. Protocatechuic acid has anti-inflammatory and chemopre-
ventive properties [19]. The abundance of fruits in the diet of the Nicoyans contributes significant
anti-inflammatory activities in body tissues. The mineral water contributes calcium and magnesium
that strengthen bones. Banana plantain is a very good source of fructooligosaccharides and resis-
tant starch. Fructooligosaccharides are prebiotics that are good for the growth and maintenance
of probiotics in the gut. The banana plantain resistant starch is metabolized into short-chain fatty
acids, such as butyrate, which is good to maintain an acidic pH in the gut and contributes anti-
inflammatory activity in the gut. The corn tortilla also contributes calcium to the diet of Nicoyans.
Nicoyans are the only Blue Zone individuals who consume lots of meat, including chicken and pork,
and fried foods, including banana plantain and eggs, and lots of fruits. However, their diet is loaded
with fiber, fruits, and vegetables that are all protective against inflammation. Their longevity is the
lowest of the Blue Zone regions.
18.2.2.2 Dietary Patterns of the Seventh-Day Adventists,

Loma Linda, CA, and Longevity
The Seventh-day Adventists eat mostly plant-based or lacto-ovo-vegetarian diets, nuts, and less
red meat and avoid smoking, coffee, and hot condiments such as hot pepper or ginger, tea, and
spices [20]. The Seventh-day Adventists believe that hot condiments irritate the gastrointestinal
tract and kidney, and produce hypertension and physical effects similar to marijuana. The lacto-
ovo-vegetarians’ diet consists of less than once a week consumption of red meat, poultry, or fish
and no restriction for dairy or egg products. The sera, or clear yellow liquid obtained when blood
is coagulated, from 466 (172 males and 294 females) Seventh-day Adventist vegetarians and non-
vegetarians were analyzed for cholesterol content, and the vegetarians had less cholesterol than the
nonvegetarians [21]. Serum cholesterol levels of true vegetarian Seventh-day Adventists were signif-
icantly lower than lacto-ovo-vegetarian Seventh-day Adventists and significantly lower than serum
cholesterol levels of the U.S. general population regardless of sex [22]. The difference in blood
pressure between 418 vegetarian Seventh-day Adventists from Western Australia and 290 nonveg-
etarian Seventh-day Adventists from Narrogin, Western Australia, was measured [23]. The mean
blood pressure for the Seventh-day Adventists was 128.7/76.2 mmHg and was significantly less than
the mean blood pressure for the omnivores from Narrogin, which was 139.3/84.5 mmHg. The study
also found that the average blood pressure was higher in Seventh-day Adventists who consumed
aDoPtInG a DIet 335
eggs than those who did not and the mean diastolic pressure for Seventh-day Adventists who drank
coffee or tea was higher than those who did not [23]. The vegetarian diet has been found to protect
the Seventh-day Adventists [24]. The fecal microbial flora of Seventh-day Adventist members was
compared to the fecal microbial flora of non-Adventists. The non-Adventists included Americans
and Americans of Japanese descent. The non-Adventists of non-Japanese descent were on conven-
tional American diet. The Japanese-Americans were either on Japanese or Western diet [25]. The
Adventists had high counts of lactobacillus and low counts of C. perfringens and Fusobacterium
compared to non-Adventists on the Western diet or a conventional American diet. The combination
of abstinence from smoking and diet was associated with low mortality rate in Dutch Seventh-day
Adventists during a 10-year period between 1966 and 1977 [26]. The vegetarian diet appears to
protect against the risk of developing obesity and type 2 diabetes [27].
The Adventist Health Study-2 conducted in 2002–2006 enrolled 22,434 men and 38,469 women
to compare the prevalence of type 2 diabetes in nonvegetarians and lacto-ovo-vegetarian, pescov-
egetarian, semivegetarian, or vegetarian individuals. The study reported that vegetarians had lower
BMI (23.6 kg/m2) than lacto-ovo-vegetarians (25.7 kg/m2) than pescovegetarians (26.3 kg/m2) than
semivegetarians (27.3 kg/m2) than nonvegetarians (28.8 kg/m2). Pawlak and Sovyanhadi showed
that the prevalence of overweight and obesity was lower in all Seventh-day Adventist students
regardless of ethnic group compared to non-Adventist students [28].
Seventh-day Adventists consistently have lower levels of cholesterol, the prevalence of obesity,
and the risk of diabetes and hypertension and a lower rate of coronary disease compared to non-
Adventists [29,30]. As a result, there is strong evidence of inverse association of the vegetarian diet
and risk of coronary disease and even some types of cancer.
18.3 trADItIONAL MeDIterrANeAN DIet
The Mediterranean diet refers to the dietary patterns of 21 olive-growing countries/areas that
encompass the Mediterranean region including southern Italy, Crete, coastal Greece, Morocco,
Tunisia, Algeria, Libya, Egypt, Israel, Lebanon, Syria, Turkey, Montenegro, Spain, Malta, Monaco,
Albania, Slovenia, Croatia, and southern France. In this region, the traditional diet is centered on
the following:
• Regular consumption of dark green vegetables and legumes in meals.

• High consumption of whole grains (bread, pasta, rice, polenta, bulgur) and potato.
• Regular and daily consumption of fruits and raw nuts for desserts.
• Regular use of olive oil in meals.
• Regular, moderate consumption of wine (a glass or two of wine per day) with meals.
• Low consumption of grilled or steamed chicken.
• Moderate (few times per week) to high consumption of fish, egg (up to four eggs a week), poultry,
and sweets.
• Very low (few times per month) consumption of red meat mostly lamb meat.
• Moderate consumption of cheese and yogurt, regular use of fresh fruits for dessert, and customary
daily walks.
• The main heavy meal is consumed during daytime, sometimes around noon time, while supper is
often light.
The significance of the Mediterranean diet is that by essence food ingredients are loaded with
all the desired nutrients for good health, no need for supplements, and as a result, these ingredi-
ents work synergistically to enhance health resulting in a naturally reduced rate of cardiovascular
disease, cancer, and other chronic diseases and above all an almost disability-free old age. Virgin
olive oil is rich in oleic acid, which may be associated with enhanced cardiovascular health.
Virgin olive oil is also rich in squalene and polyphenolic antioxidants that have antioxidative and
anti-inflammatory properties to protect against cholesterol and low-density lipoprotein oxida-
tion and, at the same time, aid in reducing the levels of low-density lipoprotein. Hydroxytyrosol,
taxifolin, oleuropein, and oleic acid are also found in extra virgin olive oil and have inhibi-
tory activities against the formation of new blood vessels or angiogenesis, which is associated
with more than seventy chronic degenerative diseases [31]. The Mediterranean diet provides
high amount of dietary fiber and monounsaturated fats and low amounts of saturated fats. High
amounts of dietary fiber help the body fight insulin resistance making people healthier and visit-
ing doctors’ offices less often.
Physical activity is a daily routine for people who live the traditional Mediterranean culture.
It consists of walking for miles to the fields for agricultural work, walking to catch up commuters to
get to work, or walking to visit relatives.
As a result, disability-free old age is associated with a life expectancy in the upper 80s or 90s.
The Mediterranean diet appears to protect against cancer development [32]. However, the globaliza-
tion of world economy and trade has led to the slow but continuous disappearance of the traditional
diet of the Mediterranean region. Three islands, Ikaria, Sardinia, and Crete, have so far maintained
their traditional Mediterranean diets. The diets in these three islands are briefly described below.
18.3.1 Clusters of Longevity in the Mediterranean region
In the Mediterranean region, there are some regions with a high frequency of centenarians
compared to the country national or world average. These regions, further discussed later, include
Sardinia, Nuoro and Sicily in Italy, Crete Island in the Aegean Sea, and Greek island of Ikaria off
the coast of Turkey.
18.3.1.1 Traditional Sardinian and Nuoro Dietary Pattern
Sardinia is an Italian island with about 1.6 million residents. Sardinia has the world’s
highest number of healthy Centenarians. According the UK Guardian magazine, there were 371
Centenarians on the island as of August 23, 2012. The ratio of centenarians in Sardinia compared to
the United States is astonishingly and surprisingly about 20–1. The people in this region are known
for being less or not prone to depression and dementia [16]. Sardinia and Crete are two regions of
the Mediterranean region where the heart healthy diet has been maintained until at least recently.
The traditional diets of these islands will be described because in most parts of the Mediterranean
region including Sardinia and Crete, the metabolic syndrome including high obesity prevalence is
gaining ground and the traditional diet is confronted by the globalization of TV commercials where
Western-style diets including pizzas and sugary soft drinks are becoming popular.
The association of the Sardinian diet and cognitive impairment and AD development is weak
because the Sardinian dietary patterns revolve around food ingredients, meals, and cooking prac-
tices that are not in the Western dietary patterns. The traditional Sardinian dietary patterns include
low-temperature cooking, high consumption of vegetables (rich in folates), fruits (antioxidants), nuts
(melatonin and monounsaturated fats), whole grain bread (folate, betaine, and fiber), whole grains
including whole wheat, fava beans and pulses (low in methionine, rich in micronutrients), virgin
oils, such as olive oil (rich in monounsaturated fats), lemon (rich in terpenes), garlic (rich in sulfur),
small-size meals, moderate consumption of sheep milk (rich in monounsaturated fatty acids, fat-
soluble vitamins A and E—45 times more vitamin D—and whey protein compared to cow’s milk),
oily fish (rich in omega-3 fatty acids), clam (rich in omega-3 fatty acids, carotenoids, potassium),
mussels (omega-3 fatty acids, carotenoids), sheep cheese Pecorino and ricotta eaten as dessert and in
small amounts, goat milk, and dark red wine with meals during daylight. Meat consumption is once
or twice a week and mostly lamb meat, which is low in AGEs, lean pork, oily fish, and shellfish.
aDoPtInG a DIet 337
Lots of minestrone, beans, zucchini, artichoke, aubergine, tomato (good source of lycopene), garlic,
basil, saffron (rich in carotenoids), and salad to end meals, little meat, and lots of physical activity
appear to be the secret to longevity in Sardinia.
Centenarians are in high number in Sardinia and Nuoro province of Italy where old men and
women aged 100 and over or 105 and over, respectively, live. These people move less between their
places of birth and current residence. Nuoro province harbors more than 50% of the centenarians
compared to other regions and more individuals aged 105 and over than other Blue Zone regions.
In Sardinia, male centenarians live as long as female centenarians, and there are more male cen-
tenarians in Sardinia than in any other region of the Blue Zone [33,34]. The dietary habits revolve
around milk and cheese, pasta, roast pig and lamb, and red wine, shellfish, garlic, olive oil, wild
asparagus, eggplant, fennel, mushrooms, and tomatoes.
Sardinians are not completely immune from diseases. Type 1 diabetes is prevalent on the island
[35]. Ethnic homogeneity has been maintained for centuries on the island.
18.3.1.2 Sicilian Diet
In the Sicani Mountains located in western Sicily, Italy, there are more centenarians than the
national Italian average [36]. Centenarians in this region show no sign of age-related disease and
moderate sensory disability and adhere closely to the Mediterranean diet. Blood chemistry of the
centenarians in this region was far better than blood chemistry of age-matched old controls and
very similar to young people used as controls and showed values of anthropometric measurements
within normal limits.
18.3.1.3 Cretan Diet
Crete is an Aegean island in the Mediterranean region. Like Sardinia, centenarians are also
commonly found in the island of Crete. The dietary pattern and lifestyle in Crete revolves around
lots of whole wheat bread, vegetables, beans, lentils, peas, herbs, sun and exercise, and moderate
consumption of fish and shellfish. Olive oil is highly consumed in Crete and more than any other
islands in the Mediterranean region. Meats are rarely consumed, sometimes once or twice a week
but cooked with herbs. Rosemary, sage, thyme, and oregano are herbs that are regularly used in
the Cretan cuisine. Greens are boiled and smothered with olive oil and lemon. A wide variety of
vegetables including wild ones are consumed. Among the ones commonly available in the West are
green beans, runner beans, zucchini, artichoke, tomato, green peppers, grape leaves, and chickpea.
Almond, hazelnut, chestnut, and walnut are among the most commonly consumed nuts [37].
18.3.1.4 Ikarian Diet
Ikaria is a Greek island near the coast of Turkey. The New York Times once described Ikaria as
an island where people forget to die. The diet is mostly nutrient-dense. Herb teas are popular and
regularly and highly consumed in Ikaria. Herbs include rosemary, sage, mint, oregano, marjoram,
chamomile, and dandelion, all of which are very rich in terpenes and other powerful antioxidants.
Sugar is used only in morning coffee and never used in other foods or beverages. Unpasteurized
honey in a teaspoon is consumed in the morning. Breakfast revolves around herbal teas with lemon,
goat milk, wine, whole wheat bread, honey for sugar, and tahini. Main ingredients for lunch are
lentils and garbanzo beans, potato, dark green vegetables (fennel, dandelion, sorrel, and chicory
leaves), pumpkin, and squash.
Bread or pasta is consumed again at dinner along with unpasteurized goat milk (rich in probiot-
ics) and freshly harvested olives. Meat, preferably goat, or lean pork is rarely consumed and in small
amounts mostly once a week and on special holidays such as Christmas. Nuts including almonds,
walnuts, and chestnut are plentiful in Ikaria and are consumed raw. Almond is rich in melatonin,
walnut is a good source of monounsaturated fats, and chestnut is a good source of oligosaccharides.
Blackberries, apples, stone fruits, oranges, pear, kalamata olives, figs, and grapes are commonly
consumed fruits in Ikaria.
The biochemical composition of the traditional Sardinian, Cretan, and Ikarian food ingredients
and foods suggests that most of the dietary risk factors for AD appear to be absent or low for indi-
viduals who use and consume the ingredients or foods from these islands.
18.3.2 Some Differences between the Western and Mediterranean Diets
Grain-fed cows, beef, poultry, and farm-raised fish as it is custom in the West are good sources
of inflammatory saturated fatty acids including myristic and palmitic [38]. The proinflammatory
nature of these two saturated fatty acids has been associated with the development of cardiovascular
diseases and other diseases including obesity and diabetes.
Red meat and poultry, whether raw or cooked, are rich sources of advanced glycation end prod-
ucts (AGEs). While in the West red and white meats are part of a regular diet, in the Mediterranean
region, they are consumed rarely and in moderation. By reducing the consumption of red and white
meat, the people in the Mediterranean region automatically cut on their AGE ingestion. Poultry is
the best source of methionine. High consumption of poultry in any form leads to accumulation of
methionine, which is metabolized into homocysteine, and the latter in excess is a risk factor for
cognitive impairment and later on AD development.
Butter contains saturated fat and high levels of ALEs. Yet it is used abundantly in Western diets
including rolls, mashed potato, Caesar salad dressing, and popcorn. Butter flavor is associated with
the presence of the flavorant diacetyl. Recent studies have identified diacetyl as a proinflammatory
and proapoptotic compound that can exacerbate the toxicity of amyloid beta associated with the
development of AD [39,40]. Questions have risen if the butter flavorant can be considered a risk
factor for AD development [41]. Above all, more than 50% of fatty acids in butter is made of satu-
rated fatty acids of myristic and palmitic acid, which are major components and well-established
proinflammatory saturated fatty acid. Butter also contains about 2.9% trans fat, which is also pro-
cardiovascular disease. Cooking foods in butter is popular because it generates exceptionally tasty
flavor, the consequence of which is underestimated by the cook and the consumer.
Macaroni and cheese, a favorite and inexpensive food in the West, is a good combination of
protein already rich in AGEs and refined carbohydrate. Baked macaroni and cheese is a good source
of AGEs [42]. The products add sufficient amounts of AGEs to the bodies of individuals who chroni-
cally consume these items.
Pizza and lasagna are probably some of the best sources of AGEs that ever existed. Pizza con-
sumption in the West is higher than in the Mediterranean suggesting that people in the West who
consume pizza regularly ingest more AGEs on a regular basis than people in the Mediterranean
region. Pizza is also a good source of refined sugars that are susceptible to undergo the Maillard
reaction inside the human body. Lasagna is known for its content of refined flour, lots of red meat,
and cooking at more than 400°F, thus creating all the favorable conditions for Maillard reaction
and AGE formation. All the variations of pizza or lasagna that undergo high-temperature cook-
ing are also good sources of exogenous AGEs or ingredients for endogenous AGE formation.
Substantial amounts of carcinogenic heterocyclic amines can be found in pizza containing meat
toppings such as salami and ham [43]. Pizza and lasagna contain tomato paste; however, the anti-
oxidants in tomato paste are not heat stable at the temperature of 450°F (232.2°C) at which pizza
or lasagna is cooked. These bioactives, including lycopene and other antioxidants, are stable at
temperatures below 140°C [44].
Raw nuts are a part of the Mediterranean diet. In the West, people eat mostly roasted nuts. This
is a major difference between the Mediterranean diet and the Western diet. Raw nuts have low levels
aDoPtInG a DIet 339
of AGEs, while roasted nuts are rich sources of high levels of AGEs [42,45]. High-temperature
roasting and asparagine content have been associated with the levels of acrylamide in roasted nuts;
low asparagine nuts are associated with low levels of acrylamide, which is a known carcinogen and
neurotoxin [46–49].
Olive oil is used on a daily basis in the Mediterranean diet. Olive oil is rich in oleic acid, which
counteracts the effects of palmitic acid. In the Western diet, cooking oils include peanut, corn, sun-
flower, safflower, and canola, all of which are low in oleic and high in palmitic acid. Oleic acid is
cardioprotective while palmitic acid is cardio-inflammatory.
Lamb meat is preferred in the Mediterranean region. We were also curious to notice that the
level of AGEs in raw lamb meat is higher than raw tuna, raw chicken breast, or red beef meat, raw
pork chop, or raw turkey meat [42]. Yet broiled lamb meat has the lowest AGE levels of all broiled
white or red meat. Since lamb meat is the preferred delicacy in the Mediterranean diet, lamb meat
contributes fewer amounts of AGEs and predisposes individuals who eat lamb meat to less proin-
flammatory factors.
Vegetable and fruit consumption is very high in the Mediterranean region compared to the
Western region. In the West, fruit juice consumption surpasses vegetable consumption. Dark green
vegetables are good sources of chlorophylls, lutein, vitamin K, and phenolics, all of which are
anti-inflammatory.
Peanut butter is popular in the West and most other countries. It is made from roasted peanut.
Peanut is one of the best examples of a food that can undergo the Maillard reaction if not handled
properly. Peanut contains high amounts of proteins, plenty of oil, and some sugar. Roasting pea-
nut creates a favorable environment for the Maillard reaction to take place and the resulting
product whether it is peanut butter or just roasted peanut delivers high levels of AGEs to the body.
Unfortunately, peanut tastes so good and provides so much energy that it is above and beyond
scrutiny.
Chickpea, the ingredient for humus, on the other side has protein, sugar, and less oil than pea-
nut. Therefore, humus has low levels of AGEs if any compared to peanut butter. Uribarri et al. [42]
found significant amounts of AGEs in humus, which is strange because traditional humus is made
from boiled chickpea; however, due to the enzyme-linked immunosorbent assay (ELISA) methods
used to obtain their data, it is not impossible that some false positive may have been obtained in the
course of evaluating hundreds of food items for AGE levels. However, if their results are as good as
presented, then consuming peanut butter and humus throughout the day may not be wise.
Feta cheese is produced from goat or sheep milk or a combination of the two milks. Like any
other cheese, feta cheese does contain saturated fats that make about 70% of the fat in the cheese,
and therefore, it is as good or bad as any other cheese. Feta cheese contains very high levels of
AGEs. Actually, mozzarella is better than feta or any other cheese out there. It is important to sig-
nal that cheese consumption and the way cheese is used as a food ingredient in the West may have
dire implications on cheese effect on health. Fried cheese is probably one of the worst foods ever in
terms of AGEs beside the grilled and seared foods.
Fried cheese absorbs a large amount of oil, which if oxidized is also ingested with the cheese
(Figure 18.2). Cheese is already a good source of AGEs. When cheese is added to pizza, the cooking
temperature accelerates the formation of undesirable Maillard reaction products. Therefore, using
feta cheese to create Western recipes, such as pizza and lasagna, that require very high cooking
temperatures does not solve anything but gives the user a false impression of healthy eating.
Herbs are regularly used in the Mediterranean cuisine. While parsley is used for decoration
around foods in the Western world, parsley is a significant ingredient in tabouli and falafel. Parsley
contains special lipids known as sulfoquinovosyls that inhibit the formation of new blood ves-
sels or angiogenesis and also inhibits enzymes, such as telomerase, that are associated with can-
cer progression and immortality [50,51]. Sage, rosemary, and bay leaves are regularly used in the
Mediterranean cuisine. The health benefits of sage and rosemary are associated with their contents
Figure 18.2 fried cheese is a good source of aGes.
of terpenes, such as oleanolic and ursolic acid, which are anti-inflammatory [52–54], cardioprotec-
tive [55–57], and neuroprotective [58–62].
Meal time and portion size have always been reported as critical factors in the Mediterranean
healthy lifestyle. The portion size is another big difference between the Western diet and the
Mediterranean diet. In the West, meals are often supersized, while in the Mediterranean region,
portion control is a de facto daily routine.
18.4 trADItIONAL OKINAWAN DIet
Okinawa, Japan’s poorest prefecture, has a unique geographical and historical background from
which the people of the island developed their attitude toward food [63,64]. Okinawa is 630 km east
of Taiwan, 1200 km south of Seoul, 750 km southeast of Shanghai, 3240 km northeast of Bangkok,
and 1450 km northeast of Manila. The Chinese belief in longevity through food has strongly influ-
enced Okinawan adherence to food for longevity. The average life expectancy of Okinawans is
82 years and the island harbors some of longest living centenarians [65]. The traditional diet of
Okinawa is nutrient-dense, calorie-restricted (1785 kcal/day compared to 2068 kcal/day Japanese
average), rich in vegetables and legumes, rich in traditional herbs and spices, rich in fruits and
carbohydrate, moderate in fish/fish products and alcohol consumption, low in dairy products and
meat, low in glycemic carbohydrates, low in fat, low in sodium (about 1113 mg/day), and very high
in potassium (5199 mg/day) [66,67]. Traditional Okinawan foods include sweet potatoes, seaweeds,
soy, bitter melon, turmeric, mugwort, fish, and fish products [68].
A comparison between the Okinawan diet and the American Dietary Approaches to Stop
Hypertension (DASH) eating plan shows similarities in both diets. Both diets promote nutrient-
dense foods; reduced intakes of red meat, sweetened beverages, and sweets; high intake of fruits and
vegetables; and consumption of whole grains and fish.
In 2005, the life expectancy for Okinawan men and women born before World War II was higher
than the Japanese national average for men or women [69]. Recent studies have shown that young
Okinawans are losing their longevity advantage as a result of the westernization of the Okinawan
diet, alcohol, and suicide [70]. Life expectancy for Okinawans is now lower than the Japanese aver-
age life expectancy [69].
aDoPtInG a DIet 341
18.5 COMPArISON OF the DIetArY PAtterNS

AND LONGeVItY IN the BLUe ZONeS
The Blue Zones are places including Sardinia in Italy, Okinawa in Japan, Loma Linda in
California, and Nicoya Peninsula in Costa Rica where people easily live long and remain active as
centenarians. There seems to be very few similarities in dietary patterns among these groups. Sugar
or honey is definitely less used by all groups. Diet is mostly plant-based. People eat food from what
is grown or raised in their regions. Processed and refined foods such as butter, bacon, or cola drinks
are not part of their diet. Dietary supplements are probably unheard of in all these regions. Long-
term caloric restriction or energy restriction without malnutrition is common across the Blue Zone
regions. While it is not easy to find specific data for each region of the Blue Zone, studies of the cen-
tenarians in Okinawa have shown consistent correlations between calorie restriction and life span.
Caloric intake of Okinawan school children in the early 1960s was 38% lower than other Japanese
school children [71]. Caloric intake of Okinawan adults in the early 1970s was 17% lower than the
national Japanese average energy intake [72]. Caloric intake restriction has also been observed in
older Okinawan septuagenarians and centenarians [73].
Most centenarians sleep at least 8 h a night without insomnia, are physically active, very active
in their communities, live with their families, and have low prevalence of cardiovascular disease
and its risk factors. Each of these factors and the dietary patterns of centenarians, although different
in composition from one region to another, reduce the risk of cardiovascular disease and increase
longevity.
18.6 CONFUSION AND DISAPPOINtMeNt IN the SUPerMArKet
18.6.1 Introduction
The Western diet is under intense scrutiny by all including the media, consumers, and scientific
community because there appears to be a strong evidence of association with chronic diseases such
as obesity, diabetes, cardiovascular disease, cancer, and AD. The traditional Western diet has been
blamed, sometimes without convincing proof of evidence, for containing food ingredients or foods
that are calorie-, pesticide-, recombinant growth hormone-, and contaminant-rich. However, tradi-
tional diets in some regions of the world are being touted as healthy and good for disability-free
adult and old age. To satisfy consumer’s demand for healthy foods, vendors of worldwide healthy
foods that are supposedly calorie-, pesticide-, recombinant growth hormone–, synthetic ingredi-
ent–, and contaminant-free foods have emerged.
18.6.2 Western Diet, Natural Ingredients, and Organic Foods
The purported association of Western diet and chronic diseases has led consumers to seek natu-
ral ingredients and organic foods. Organic farming is a worldwide trend. It helps maintain soil
fertility, avoid pollution, make use of crop rotation, and sustain local economies. The environmental
impact of organic farming versus conventional farming is a major subject of debate. Compared to
conventional farming, organic farming reduces the release of pesticides to the environment, uses
less energy, produces less waste, sustains diverse ecosystems including soil and water conservation,
and maintains high environmental quality soil.
Organic products are more appealing to families with young children, some educated younger
individuals and environmentalists for several reasons. Most antibiotics allowed for use in animal
husbandry are similar to antibiotics allowed for use in humans. Chronic use of these agents leads to
the development of drug resistance by animals and humans alike. It is believed that organic farm-
ing may reduce the development of drug resistance by both animals and humans. However, studies
on the health risks associated with synthetic pesticides or fertilizers are controversial and often
inconclusive.
Organic farming can produce food products of higher quality or similar quality to conventional
farming. Adler et al. [74] compared milk fat composition of 14 conventional farms and 14 organic
farms and found higher proportions of saturated fat in organic milk. Milk from organic farming
had higher fat proportion of C18:3n-3, C18:1 trans-11 and C18:2 cis-9, trans-11, polyunsaturated
fatty acids, and lower concentrations of n-6 fatty acids and monounsaturated fatty acids than milk
produced by conventional agriculture. Outdoor grazing was associated with higher concentrations
of α-tocopherols and β-carotene in organically produced milk compared with feeding silage used in
conventionally produced milk. The production efficiency of organic farming is lower than the pro-
duction efficiency of conventional farming. Studies have shown that, area for area, organic farming
can produce between 20% and 50% lower yield than conventional farming. If organic farming is
adopted on a worldwide scale, the big losers will be the World Food Program and other international
food relief agencies. As a result of the low yield that can be obtained using organic farming, there
will not be enough food to store and donate to relief agencies involved in fighting hunger or food
shortage around the world.
The potential major benefits of the proliferation of the so-called healthy food stores are fourfold:
1. The shopping carts in these food stores are smaller than the shopping carts in traditional grocery stores,
food is more expensive and packed in smaller size containers than in traditional grocery stores,
people walk through the aisles but take less food home and hopefully this will translate into people
gaining less weight and staying healthy.
2. Some exotic ingredients that have demonstrated health benefits overseas can be found in these
stores.
3. It brings more competition and price discounts on the food market making the consumer the big
winner.
4. The psychology of eating healthy is helping people develop a positive attitude toward the food they
purchase and consume and their health.
However, there is confusion in grocery stores. In the so-called health-conscious grocery stores
and conventional grocery stores, the so-called calorie-, pesticide-, synthetic-, and growth hormone–
rich foods and so-called healthy foods including organic foods are sold side by side. The consumer
is given the choice to select and pick what he/she can afford. Not long ago, consumers were used to
enter grocery stores, pick up food items, go to the cashier, pay and check out. Nowadays, the con-
sumer has to spend some time in front of almost every food item of interest and read to find out which
one may be healthier than the other before picking up items to take to the register. Surprisingly, a
quick glance on the composition of most food items shows that the same kinds of foods with almost
the same composition can be sold under different labels at different prices in the same store. At least
80% of the weight of organic apple chips in Figure 18.3a is sugar. Organic mango (Figure 18.3b) has
9 g of sugar per 10 g of serving. Organic pineapple (Figure 18.3c) has at least 7 g of sugar per 10 g
of serving. Organic raspberries (Figure 18.3d) contain 1 g sugar per 10 g of serving.
18.6.2.1 Gluten Free
What is gluten? Very few people know exactly what gluten is, yet manufacturers and consumers
have all gone crazy about gluten. Gluten-free water, gluten-free butter, gluten-free tea, gluten-free
oil, gluten-free rice bread, gluten-free corn bread, gluten-free peanut butter, gluten-free oatmeal and
oatmeal cookies, gluten-free kettle-baked potato chips, gluten-free corn flakes, gluten-free quinoa,
gluten-free nut, and gluten-free yogurt are commonly available.
aDoPtInG a DIet 343
(a)
(b)
(c)
Figure 18.3 (a) organic apple chips, (b) mango chips, and (c) pineapple chips of which at least 80% of the
product weight is sugar. (Continued )
(d)
Figure 18.3 (Continued ) (d) Dried raspberry of which at least 80% of the product weight is sugar.
Gluten is an elastic mixture of alcohol-/water-soluble storage proteins known as gliadins and

salt-soluble proteins known as glutenins that are formed when the two proteins are combined with
moisture. Gluten traps air bubbles and gives the desirable lift and height to baked products. The
proteins of wheat, kamut, titricale, or spelt that form gluten are termed gliadins and glutenins; the
gluten proteins of barley and rye are known as hordeins and secalins, respectively. Barley contains
18.8–45.0 g of gluten per kg; wheat contains 44.0–68.0 g of gluten per kg, rye and spelt contain
41.6 and 21.2 g of gluten per kg, respectively [75]. The gluten concentration in alcohol-free beer is
< 3.0 ppm, lager beers have < 3.0–8.7 ppm gluten, stout beers contain 9.0–15.2 ppm of gluten, and
wheat beers contain 10.6–41.2 ppm gluten [75].
When marketing trumps science and the people who know the science of foods or beverages
better, the result is that the consumer spends more money on unnecessary food items and the food
scientists who develop the food products look like people who do not know what they are really
offering (products) to the consumers. For instance, butter is made from churning milk cream to
obtain buttermilk and solids. In the United States, butter sold on the market must contain at least
80% fat. The rest is made of water, milk solids, and salt and no gluten at all. So why are butter
manufacturers spending money on labels that declare that their products are gluten-free?
Yes, gluten is a problem to susceptible individuals and some individuals who for some reason
have developed sensitivity to gluten. However, the panic the gluten-free trend has created has left
the scientific community unable to help consumers make educated choices. Rather, gluten-free has
become the very simple answer to a problem that is sometimes overblown because of lack of leader-
ship from the people who are supposed to be the defenders of food science and nutrition.
The economic burden of gluten-free foods is huge, but at the same time, it should not be as huge
as it is. It is big for individuals whose diets are centered on wheat-based food products. And it should
not be big for individuals who do not regularly rely on wheat-based food products for their meals.
Individuals whose staple diets are developed around corn, rice, cassava, or sorghum should not be
concerned. For populations whose diets contain significant amounts of wheat-based food products,
food manufacturers have the daunting tasks of developing products using gluten-free ingredients.
These would include corn, rice, sorghum, quinoa, amaranth, and millet to mention a few. However,
the training provided to food scientists and technologists in universities around the world should be
sufficient for these individuals to address gluten in food through inhibition of its deleterious effects.
aDoPtInG a DIet 345
This is a great challenge to colleges that claim to provide high-quality education to their students
because this is a real-world food science problem that food scientists should solve.
18.6.2.2 Calorie-Free Water
Water provides zero calories. Any water that has calories added to it is not pure water anymore;
rather, it is a sweetened or calorie-rich beverage. Calorie-rich beverages have been on the market
for decades and have never been called water. Yet the consumer is being lured into products with
misleading definition. Artificial or natural dyes used to color water do not provide calories.
18.6.2.3 Bread
Bread has been consumed by humans since ancient time and remains one of the most consumed
foods in the world. The major ingredients that make conventional or organic bread are given in
Table 18.1.
Conventional bread is fortified with several micronutrients that are critical for child and human
development. Micronutrient deficiency including deficiencies in iron, zinc, vitamins A and B, iodine,
and folic acid is a hidden malnutrition that affects more than 2 billion people worldwide [76,77].
Micronutrient malnutrition is a risk factor for several diseases and has profound implications for health,
cognitive development, education, economic development, and productivity [78–81]. It is widespread
in Southeast Asia and Africa and undermines development in these regions [82,83]. It is not known
how much of these micronutrients are available in organic bread. The amount of micronutrients in
organic bread will probably not match the amount of added micronutrients to meet daily intake.
Conventional or organic bread is a Maillard reaction product. When corn syrup is not used in
bread making, it is good to know that lactose in milk is a source of two reducing sugars glucose
and galactose. Both glucose and galactose can undergo the Maillard reaction. As long as a reducing
sugar source, such as corn fructose syrup or honey or lactose, is used to make bread, such bread
will undergo the Maillard reaction. Whole wheat bread is the same across town. Similarly, white
wheat bread from refined flour is the same. As long as both types of bread are baked at temperature
≥375°F for at least 25 min, the Maillard reaction occurs in any bread suggesting that organic bread
is just bread and does not escape the Maillard reaction. Confusion has been created in the con-
sumer’s mind that leads people to purchase expensive bread for the same quality that can be found
in bread from conventional food stores.
Organic gluten is not different from conventional gluten. Both have similar properties. Both
can sensitize people allergic to gluten. Therefore, adding the so-called organic gluten in the bread
formulation is not an answer to people sensitive to gluten. Similarly, organic honey is not different
from honey that is not labeled “organic.” Both honeys contain similar amounts of fructose and may
also contain similar amount of methylglyoxal. Fructose and methylglyoxal are reactants for the
advanced glycation end products formation. The consumer is once again misled by the confusion
created by individuals with no or very low understanding of the reactivity of sugars used in human
food products development.
table 18.1 Major Ingredients Used in Bread Formulations
Conventional Bread Organic Bread
enriched wheat flour, barley malt, ferrous sulfate as iron source, B vitamins (niacin, organic whole wheat
thiamine, riboflavin, folic acid), water, high-fructose corn syrup or cane sugar, flour, water, salt, organic
yeast and yeast nutrients, whole wheat flour, wheat gluten, molasses, soybean oil, gluten, organic honey,
flour and lecithin, salt, dairy whey, butter, maltodextrin, calcium sulfate, dough organic sugar, organic
conditioners, mono- and diglycerides, corn and wheat starch, vinegar, natural cow’s milk whey, organic
flavors, beta-carotene, compounds to retain freshness oil, organic emulsifier
Figure 18.4 oily seeds on bread exacerbate the Maillard reaction.
It has become customary to sprinkle oily seeds on breads (Figure 18.4). Seeds are added to
bread for flavor but not necessarily for health. Baking occurs at temperature higher than 400°F for
at least 20 min. During baking of seed-sprinkled bread, the oil in the seed undergoes a reaction and
heat initiates the interaction between the oil in the seeds and proteins in the seeds, and this may
expand to proteins in the bread. Prolonged baking generates radicals that react with proteins or
amino acids in the seeds or bread and reduce their biological value.
Any cheese added on bread (Figure 18.5) exacerbates the Maillard reaction because it induces
more AGEs on the bread and decreases the health benefit of the bread. Unfortunately, traditional or
conventional as well as healthy food stores are all selling cheese-covered bread. Organic cheese and
organic bread do not escape the Maillard reaction. There is no difference in terms of AGE forma-
tion and load between and among ciabatta or Focaccia bread sold by traditional or new comers in
the grocery store business.
Figure 18.5 Cheese on bread increases the levels of advanced glycation end products in the final product.
aDoPtInG a DIet 347
Rolls are eaten with meals. They can be formulated with butter, margarine or vegetable oil and
can also be consumed with or without butter or margarine. Despite public concerns about butter,
rolls are still being made with butter because butter makes flavorful rolls.
18.6.2.4 Yogurt
To obtain yogurt, pasteurized milk is fermented with bacteria or yogurt cultures including
Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus acidophilus, Lactobacillus bifidus,
Lactobacillus casei, and Streptococcus thermophilus. During yogurt preparation, lactose is
fermented to lactic acid that lowers the pH of the milk and develops a curd. Several lactobacilli
have been identified, patented, and added to dairy yogurts to improve gut health. These good
bacteria are also known as probiotics and require prebiotics for their growth and survival in
the gut. Onion, garlic, chestnut, and artichoke contain inulin or other types of fructans, includ-
ing fructooligosaccharides or galactooligosaccharides, that are excellent prebiotics. However,
it has been shown that most ingested probiotics do not survive for a long period of time in the
human gut.
It is suggested that humans regularly ingest probiotics in order to maintain stability inside the
gut. The results of 11 clinical trials involving 464 subjects have shown that certain probiotics such
as Bifidobacterium lactis HN019 and B. lactis DN-173 010 reduce gastrointestinal transit time [84].
Tulk et al. showed that consumption of 200 g per day of yogurt with B. lactis Bb12, L. acidophilus
La5, and L. casei CRL431 with inulin for two 15-day treatments did not reduce the gastrointestinal
transit time [85].
Consumers evaluate organic yogurt as healthier than conventional yogurt and are willing to pay
a premium of 15%–40% more suggesting that the market potential for organic yogurt is very good
[86]. Tulk et al. [85] designed a crossover study and compared the health benefits of probiotics-
loaded yogurt by feeding 200 g per day of control yogurt versus 200 g per of yogurt containing a
mixture of probiotics, including B. lactis Bb12, L. acidophilus La5, and L. casei CRL431, and 4 g of
prebiotic inulin to 65 healthy individuals for two 15-day periods with a washout period. The deliv-
erables were the gastrointestinal transit time. Results showed that the combination of probiotics did
not improve gastrointestinal transit time. It appears that no probiotics have yet shown the purported
benefits ascribed to the aforementioned probiotics. Table 18.2 shows the compositional difference
between conventional and organic yogurt. The organic yogurt appears to contain all the different
types of yogurt cultures mentioned by Tulk et al. [85].
The ingredient lists of eight different types of “healthy Greek yogurts” from eight different
vendors and manufacturers are presented in Table 18.3. While the compositions of original Greek
yogurts are not known, a look at the eight different Greek yogurts shows that some yogurts are
organic and others are not. Once again confusion is being created in the mind of consumers who
are interested in buying these products.
table 18.2 Comparative Composition of Conventional and Organic Yogurts

Conventional Yogurt Organic Yogurt
Grade a pasteurized nonfat or low-fat milk, fructose Grade a pasteurized reduced fat or skim milk, cane
(± sucralose), modified starch, gelatin, natural and sugar, kosher gelatin, organic flavor, live and active
artificial fruit flavors, fruits, citric acid, vitamin a and yogurt cultures including Bifidobacterium longum,
D3, active yogurt cultures including Lactobacillus L. casei, S. thermophilus, L. bulgaricus,
acidophilus L. acidophilus
Calories: 170–175 Calories: 120–210
Price: $0.50–$0.80 Price: $1.00–$1.80
table 18.3 “healthy” Greek Yogurts Available on the U.S. Market

Yogurt A Yogurt B Yogurt C
Ingredients: Grade a pasteurized skim Cultured grade a milk, water, nonfat yogurt cultures (cultured
milk, fruit, cane sugar, water, corn sugar, natural flavor, gum, pasteurized milk), evaporated
starch, gum, vitamin a, vitamin D3, pectin, potassium sorbate, cane juice, pectin, live and active
live active yogurt cultures contains active yogurt cultures including S. thermophilus,
(L. bulgaricus, S. thermophilus, cultures L. bulgaricus, L. acidophilus,
L. acidophilus, Bifidobacterium, Bifidobacterium, L. casei
L. casei)
serving size: 150 g serving size: 160 g serving size: 150 g
Calories: 170 Calories: 120 Calories: 120
Price: $1.60 Price: $1.00 Price: $1.50
Yogurt D Yogurt e Yogurt F
Low-fat yogurt cultured pasteurized aLL naturaL InGreDIents. Grade a pasteurized skim milk,
grade a reduced fat milk, sugar, milk Cultured grade a nonfat milk, cane sugar, live and active
protein concentrate, whey protein water, sugar, fructose, active S. thermophilus, L. bulgaricus,
concentrate, corn starch, kosher cultures added L. acidophilus, L. casei, Bifidus
gelatin, fruits, gum, caramel, no
specific cultures
serving size: 150 g serving size: 150 g serving size: 150 g
Price: $1 Price: $1.80 Price: $1.80
18.6.2.5 Muffins
In the United States, muffins rank third among commonly consumed breakfast products for peo-
ple who grab meals on the go [87]. Muffins are baked goods that contain carbohydrates, proteins,
and oil and are baked at high temperature. These products undergo the Maillard reaction regardless
of the type of sugar added in the formulation because sugars added are mostly reducing sugars.
Rosales-Soto et al. [87] showed that when anthocyanin-rich raspberries were added to muffin for-
mulations, baking reduced the levels of anthocyanins in the final products. There are more varieties
of muffins with a wide range of flavors on the market; however, it does not translate into products
that are better than products available in traditional grocery stores.
Whether honey or agave is used in the muffin formulation, agave is worse than corn syrup and
does not necessarily bring better health than honey or corn syrup. Agave contains almost twice
the amount of fructose in corn syrup. Too much agave will do the same as too much corn syrup.
Moderation in the use of sugar is the answer rather than jumping from one type of sugar to another.
18.6.2.6 Sweetened Beverages
The beverage industry is a multibillion dollar business. The beverage industry provides consum-
ers with a wide range of unsweetened and sweetened products, including teas, coffees, chocolate
drinks, dairy drinks, energy drinks, sport drinks, cola drinks, juices, nectars, syrups, ciders, fruit
powders, sparkling drinks, and fruit-flavored waters.
Sweetened beverages are energy-dense and have been identified as a risk factor for metabolic
syndrome. The cola drinks were first to be blamed because of their high contents of fructose per
serving size. Then other sweetened beverages, including fruit-flavored beverages and smoothies,
were also considered as risk factors for metabolic syndrome because these products contain high
amounts of fructose per serving. Sweetened beverages containing cane juice are as bad as beverages
sweetened with corn syrup. Beverages sweetened with stevia do not suffer the potential contribution
of sugar to health problems.
aDoPtInG a DIet 349
Tea is the number two beverage consumed in the world after water. Tea is mostly consumed
unsweetened but can also be sweetened to contain significant amounts of reducing sugar, for exam-
ple, 31 g per serving size. The polyphenols, including theaflavins, in black and oolong tea and
catechins in green tea possess antioxidative and antimutagenic activities with potentials depending
on usage for the prevention of metabolic syndrome, cancer, and other inflammatory diseases [88].
Short-term studies have shown that high doses of flavonoids (30–900 mg/day) from black or green
tea inhibit selected biomarkers of oxidative stress, inflammation, and cardiovascular disease [89,90].
A study was conducted to determine whether consumption of green tea beverage or green tea
extract could affect the biomarkers of metabolic syndrome and cardiovascular risk in the U.S. popu-
lation with metabolic syndrome [91]. Obese subjects (n = 35) consumed four cups of green tea
beverages containing a total of 440 mg epigallocatechin gallate (EGCG), 220 mg epigallocatechin
(EGC), 180 mg epicatechin gallate (ECG), and 88 mg epicatechin (EC) daily for 8 weeks and
showed no significant changes in the biomarkers of inflammation and features of metabolic syn-
drome. The same participants who consumed green tea capsules containing 1600 mg of catechins
and 1000 mg of EGCG for 8 weeks also showed no significant changes in the biomarkers of inflam-
mation and features of metabolic syndrome. However, both green tea and green tea capsules signifi-
cantly lowered serum amyloid alpha in the obese subjects compared to matched controls.
The tea or capsules were well tolerated, and it was suggested that at the levels used green tea
or capsules could be used as dietary supplements along with healthy diet and exercise, which can
help reverse the biomarkers of inflammation. Regular and long-term studies using controlled diets
are needed to determine cost-effective low doses of tea bioactives that can be anti-inflammatory
because animal studies have shown that 1% EGCG diet can be proinflammatory [92]. The amounts
of tea bioactives in small tea bags or commercial tea beverages are very small, and the plasma lev-
els of these bioactives are in the nanomolar concentrations and are not sufficient enough to inhibit
advanced inflammation. Consumers may quick be disappointed when they see no improvement
after weeks of regular consumption of commercially available teas in bags or as supplements.
Liver cancer, also known as hepatocellular carcinoma, is a fatal cancer for the majority of
patients in Africa, Asia, Europe, and even the United States. Most individuals diagnosed with liver
cancer have a life expectancy of less than 1 year. The polyphenols of green tea, specifically its bio-
active EGCG, are being studied as a potential effective and promising alternative for the prevention
and treatment of liver cancer in high-risk individuals [88,93], esophageal cancer [94], or ovarian
cancer [95].
Coffee is one of the world’s most popular beverages. It can be consumed unsweetened, sweet-
ened, with milk or cream. Coffee contains the stimulant caffeine and can be decaffeinated. Caffeine
is also present in tea and several cola beverages. Studies with coffee have been all over the map with
some data showing health-enhancing effects and others showing the opposite. Coffee has been said
to be good for people with type 2 diabetes, especially women [96]. The incidence of type 2 diabetes
was shown to decrease by 12% for every 2 cups of coffee consumed per day, by 11% for every two
cups of decaffeinated coffee consumed per day, and by 14% for every 200 mg of caffeine ingested
per day [96].
Japanese employees (n = 1440) were evaluated through diet history questionnaire for the associ-
ation of coffee consumption and insulin resistance, and it was shown that coffee may decrease insu-
lin resistance in overweight individuals [97]. However, coffee and caffeine at high dose increases
anxiety, keeps people awake through insomnia, reduces the quality of sleep, and increases calcium
loss and the risk of fractures [98].
The effect of caffeine on fetal active sleep or wakefulness in near-term fetuses of non- or low-
coffee drinkers and regular coffee consumers was compared [99]. Mothers (n = 13) consumed
two cups of regular coffee containing about 330 mg of caffeine on day 0, nothing on day 1, and
again coffee on day 2. It was shown that 90–180 min post coffee consumption, fetuses of regular
coffee drinkers were tolerant to caffeine but fetuses of non- or low-coffee drinkers experienced
active wakefulness. It has been known for decades that caffeine reduces the quality of sleep. Twelve
people with senile dementia in a nursing home consumed decaffeinated or regular coffee [100].
There was no statistical difference between the decaffeinated and regular coffee consumption in
terms of sleep induction time, quality of sleep, total length of sleep, or time awake during the night.
Reduction in coffee consumption improved anxiety, irritability, and sleep disturbance [101]. One
cup of regular coffee at night reduced sleepiness similar to the effect of two to four cups of regular
coffee [102]. Consumption of four cups of regular coffee or four cups equivalent of caffeine by
18 normal young subjects 30 min before bedtime induced symptoms similar to insomnia [103].
Caffeine intake from coffee or sweetened soft drinks delayed the time to sleep and reduced sleep
duration in some Portuguese adolescents [104]. Coffee is probably a good beverage for morning
time and a sleep retardant beverage when consumed late in the day the effect of which may show
later after several months or years of regular intake.
Chocolate drinks are popular because the flavonoids in chocolate have been reported by many
investigators to be health enhancing. Chocolate milk is a widely consumed beverage. Chocolate
milk was reported to attenuate muscle damage in endurance sports and recommended as an effec-
tive or superior postexercise beverage [105,106]. The mechanism underlying this effect is not
known. However, in food chemistry, it is known that multimeric flavonoids in chocolate bind to and
precipitate proteins, sometimes irreversibly [107]. Pectin and polygalacturonic acid form a ternary
complex protein/polyphenol/carbohydrate and gum Arabic competes with protein for binding to
the polyphenols [108]. The bioavailability of such complex is not known. The effect of gut micro-
biota on such complex is not known. The health benefits of such complex are not known. In the
presence of milk proteins, whether it is cow’s milk or soymilk, chocolate polyphenols bind to pro-
teins and form nondigestible complexes that are structurally, functionally, and nutritionally differ-
ent than the protein or polyphenol alone. The complex chocolate flavonoid-milk protein decreases
the solubility and digestibility of the protein and the ability of the polyphenol to act as antioxidant
or radical scavenger [109]. This may be a less reported dark side of the popular chocolate milk. The
beverage is tasty but the chocolate has no health effect. Roura et al. [110] strongly suggested that
“milk does not affect the bioavailability of cocoa powder flavonoid in healthy humans” because
they were able to detect and quantify significant amounts of cocoa (−) epicatechin in the plasma of
21 healthy human following consumption of 40 g of cocoa powder dissolved in 250 mL of cow’s
milk. It is important to mention that Roura et al. [110] investigated the wrong and least important
flavonoid in cocoa powder. The health benefits of cocoa are not associated with (−) epicatechin;
rather it is the effect of dimeric, trimeric, or polymeric flavonoids, which are good antioxidants
and radical scavengers. While epicatechin glucuronide was detected and measured in the plasma,
there is no mention of the fate and levels of polymeric flavonoids, which are the most important
bioactives in cocoa powder. Therefore, their study has no value when evaluating the functionality
of cocoa flavonoids added to milk.
Similarly, chocolate soymilk beverage has the same problem as cow’s milk chocolate. Soymilk
is a mixture of soy proteins. Similar to cow’s milk proteins, soymilk proteins bind to chocolate
dimeric, trimeric, or polymeric phenolics, and as a result, the benefits of chocolate are lost. The best
way to benefit from chocolate is to drink it without any protein.
There are countless varieties of sweetened cola and diet cola drinks on the world market.
The sweetened colas all differ in taste but have in common too much reducing sugar per serv-
ing size. Several alternatives have been introduced to the beverage market. Unfortunately,
some of the new products brought in have more fructose, and others have been developed with
sweeteners that are not fructose but are also reducing sugars. Sugar cane juice is a mixture of
two reducing sugars glucose and fructose. Agave is 90% fructose. Dextrose is also a reducing
sugar. Chronic consumption of sugar cane juice–sweetened beverage or agave-sweetened bever-
age in large serving sizes is as bad as consuming traditional fructose-sweetened colas in large
serving sizes. Similarly, chronic consumption of dextrose is as bad as chronic consumption of
aDoPtInG a DIet 351
fructose-sweetened beverage. The diet colas are unsweetened but contain high levels of methyl-
glyoxal, a very reactive molecule that is a precursor of AGEs.
Fruit juices have naturally occurring sugar called fructose. Most juices also contain vitamin C
and little amounts of bioactives such as flavonoids in citrus or anthocyanins and proanthocyanidins
in most berries. Juices are good sources of fructose. Fructose is a reducing sugar regardless of its
source, whether it is a fruit, corn, honey, or agave. Chronic consumption of large portion sizes of
fruit juices adds more reducing sugar to the body, and while inside the body, these sugars will react
with proteins to generate AGEs.
18.6.2.7 Milk
Juskevich and Guyer [111] reported in 1990 that U.S. Food and Drug Administration (FDA) sci-
entists concluded after reviewing the evidence that “recombinant bovine growth hormone (rbGH) in
dairy cattle presents no increased health risk to consumers.” The FDA concluded that the hormone
is not biologically active in consumers. However, consumer’s fear of ingesting growth hormone has
not totally subsided and a segment of consumers believe that cow’s milk from conventional farming
may not be good for human health. Melnik [112] wrote that cow’s milk raises serum levels of insu-
lin-like growth factor-1 (IGF-1), a potent mitogen known for its ability to induce cell proliferation
and prevent cell death. It is thought that several chronic diseases common to the Western society are
the result of a diet rich in animal products including cow’s milk and its hormones [112–115]. As a
result, organic milk has been touted as healthier than conventional milk. However, scientific litera-
ture shows insignificant difference in composition between organic and conventional milk. Studies
have reported higher levels of α-tocopherols, β-carotene, and α-linolenic acid in organic milk than
in conventional milk [116–118].
Milk from organic (n = 17) and conventional farms (n = 19) in the United Kingdom was com-
pared for fatty acid composition [119]. Throughout the year, polyunsaturated fatty acids (PUFA)
levels were higher in organic milk than conventional milk, the levels of conjugated linoleic and
vaccenic acid were similar, and the n-6:n-3 FA ratio was lower in organic than conventional milk.
Stiglbauer et al. [120] evaluated milk quality on three different grazing systems, including organic
farms (n = 196), conventional nongrazing farms (n = 64), and conventional grazing farms (n = 36).
Cows from conventional grazing farms produced more milk than other cows. There was very little
effect of grazing on somatic count or standard plate count. Organic farms used fewer vaccinations
than conventional farms.
Rey-Crespo et al. [121] evaluated essential trace (Co, Cr, Cu, Fe, I, Mn, Mo, Ni, Se, and Zn) and
toxic (As, Cd, Hg, and Pb) mineral contents in milk samples from conventional and organic farms.
Milk samples from conventional farms had higher levels of essential minerals compared to organic
milks. There was no statistical significance difference in toxic minerals between organic and con-
ventional milks. Seasonal variation in mineral content was significant in organic milk. Significantly
higher concentrations of arsenic were found in organic milk in the winter as a result of grazing.
18.6.2.8 Butter and Like-But-Not-Butter
Butter is obtained by churning cultured cream. It is at least 80% fat, full of saturated fat, solid
at room temperature. It contains at least 6 g of saturated fat per serving. It is an excellent flavorant
and can be used in cooking, baking, or on baked products, including bread rolls, fried foods, pop-
corns, croissants, scones, chocolate chip cookies, pretzels, corn, and green beans. The saturated fats
include more than 50% of palmitic acid, and the latter is well known for being proinflammatory at
plasma concentration. Despite reports from research community that show the side effects of pal-
mitic acid, vegetable oil containing palmitic acid, such as palm oil, is on almost every food products
that have vegetable oil. Butter has been an ingredient of human foods since ancient times.
The United States produces 1.86 billion pounds of butter per year and butter production has
increased in recent years. Similarly, the U.S. butter per capita consumption has increased signifi-
cantly and has gone from 4.60 lb in 1992 to an estimated 5.56 lb in 2012. Werner et al. [122] per-
formed a double-blind randomized parallel design whereby 38 healthy subjects consumed 39 g
of butter from mountain-pasture grazing cows and from conventionally fed cows. Butter from
grazing cows or conventionally fed cows had no effect on blood lipid or inflammation suggest-
ing that the butter from the pasture was not healthier than butter from conventionally fed cows.
Phytanic acid derived from chlorophyll was shown to increase total and low-density lipoprotein
(LDL) cholesterol. However, Wendlinger and Vetter reported that butter from grass-fed cows
contained more antioxidant furan fatty acids than butter from conventionally raised cows [123].
Whether butter is obtained from conventional milk or organic farming, chronic consumption of
such butter is not good for health. The problem with butter is not where the butter is from, sold, or
which store carries it, the problem with butter is its chemical composition, which is the same regard-
less of the cow it is obtained from. After all, most cows spend a great deal of time outside and this
may explain the difficulty of finding major differences among butters. Butter has a low smoke point
and cannot be used more than once for frying.
Olive oil added to butter does not solve the health problem associated with butter. Confusion is
created in the mind of the consumer that butter with added olive oil or sea salt may be better than
conventional butter. There is no one single ingredient in olive oil that can counteract the detrimental
effects of saturated fats in butter.
Like-but-not-butter is a product with the look of butter but is not butter. This type of products is
on the market. While like-but-not-butter has less saturated fats, it does contain palm oil, an ingredi-
ent whose addition in foods has been posing questions in the research community.
18.6.2.9 Cheese
Cheese can be made in two ways: with rennet or with acid. Similarly, organic cheese can be
made using rennet or acid precipitation. However, cheese makers use rennet more often than acid
when making cheese because it is cheaper. Rennet is obtained by recombinant technology. In gen-
eral, organic food consumers are willing to pay top dollar or euro for organic cheese.
Fish oil–enriched cheese is presumed to add health benefits to cheese. However, not all fish
oils were created equal. Because fish oil is isolated from oily fish, most of these fish tend to accu-
mulate persistent organic pollutants (POPs) that can enter the food chain through addition of the
oil to human foods. The oil may need to undergo extensive cleaning before it is declared good for
human consumption. The oil may be worse if it comes from polluted waters that do not meet inter-
national standards. Dairy products, beverages, and pills are major carriers of fish oil into the human
body. A study was conducted to determine the levels of POPs in conventional and fish oil–enriched
cow’s milk and Italian cheeses [124]. All the omega-3-enriched milk and cheese samples analyzed,
including Stracchino, Pecorino, and ricotta, contained higher levels of POPs than conventional milk.
Similar results were obtained from cheese samples from Spain, Belgium, France, and Finland sug-
gesting that organic or nonorganic cheeses may not be as healthy as some people pretend. Regular
consumption of organic cheese is similar to regular consumption of conventional cheese, and in the
event the cheese contains even trace levels of POP, these compounds will accumulate in the body
over time and cause health problems.
18.6.2.10 Margarine
Napoleon Bonaparte wanted a low-cost butter substitute that would be rancidity-free like butter
for his army and fellow poor French people. Hippolyte Mege-Mouries (1817–1880) invented marga-
rine by mixing skim milk and processed beef fat. The invention was patented in 1869. The physical
aDoPtInG a DIet 353
appearance and physical properties of margarine are similar to the appearance and physical prop-
erties of butter. It is made from vegetable or fruit oil such as palm oil and contains at least 80%
fat. Palm oil has several technological and processing advantages that make it the preferred oil for
margarine formulations and distributions around the world. The oil crystallizes better than any
other oil making it excellent for margarine production. The oil contains stearin, which crystallizes
like palm oil and can be used as substitute of hydrogenated oils. It is also promoted as an excellent
source of vitamins A, D, E, and K and a good source of beta-carotene, tocopherols and tocotrienols,
and linoleic and linolenic acid. Because palm oil is never used as is and is often used as cooking oil,
the vitamins and antioxidants are destroyed after heat treatment above 100°C, making the argument
about the presence of vitamins and antioxidants in palm oil useless. Palm oil is usually cooked at
high temperature during which none of the bioactives survive the heat suggesting that the benefits
of palm oil cannot be realized for populations that use the oil for frying and other high-temperature
food processing operations.
Table margarine contains on average 38% palm oil, 32% palm olein, 5.6% palm stearin, 2.4%
palm kernel oil, and 4% sunflower oil [125]. This formulation is variable, and in some countries,
palm oil is the major ingredient, while in other countries, vegetable oils are major ingredients.
However, recent data show that the health benefits of palm oil and palm oil products are question-
able. Clifton concluded that several studies have associated palmitic acid in palm oil with increased
levels of LDL cholesterol [126].
The levels of saturated fats in palm oil are very high and make margarine from palm oil one of
the worst food products for human consumption. Palm oil–derived margarine fills the shelves of
grocery stores and local markets in many developing countries of Africa, Asia, and Latin America,
exacerbating the poor health conditions of those who already cannot afford expensive medical treat-
ments. Chen et al. [127] reported that chronic consumption of palm oil increases mortality from
ischemic heart disease and stroke by 68 deaths and 19 deaths per 100,000, respectively in develop-
ing countries. In developed countries, the increase is by 17 deaths per 100,000 for ischemic heart
disease and 5.1 deaths per 100,000 for stroke. Combination of palm oil with other saturated fatty
acid–rich sources, including butter, cheese, coconut oil, chicken, pork, or beef, had no effect on
palm oil–induced ischemic heart disease mortality in developing countries. In brief, palm oil is
killing people in developing countries and should be banned for human or pet consumption and be
diverted to nonfood uses such as biodiesel.
Labeling palm oil margarine as “cholesterol and trans fatty acid–free” misleads consumers
because the problem with palm oil is not only cholesterol but a combination of cholesterol and
saturated fatty acids.
Organic palm oil is not different from conventional palm oil; both oils contain saturated fats
that are not good for human health. Conventional or organic palm oil does not contain trans fat.
Trans fat is obtained after processing. Organic palm oil may be odorless and tasteless but does not
increase HDL better than conventional palm oil. Organic palm oil does not have more antioxidant
than conventional palm oil. The antioxidants in organic palm oil are destroyed during heating the
same way antioxidants from conventional palm oil are inactivated by heat. Organic palm oil does
not have antioxidative superiority vis-à-vis conventional palm oil. Therefore, baking with organic
palm oil gives the same unhealthy products that can be obtained using conventional palm oil.
18.6.2.11 Agave, Honey, High-Fructose Corn Syrup, Maple Syrup, Dextrose,

Glucose, Cane Sugar, Cane Juice, or Evaporated Cane Juice
Another unfortunate confusion has been brought on the sweeteners market. Running away from
high-fructose corn syrup, consumers have been introduced to a wide range of so-called natural sugars.
What are the differences among these naturally occurring sugars or sugar from agricultural products?
Agave contains 90% fructose. Some agave syrups are just plain fructose while other types of agave
contain agave inulin, which is a polymer of fructose called fructans similar to inulin [128,129]. Some
agave fructans have prebiotic potentials [128,130]. The reactivity of fructose in Maillard was explained
early in the book under the chapter on Maillard reaction. The National Honey Board provides the fol-
lowing information on U.S. honey. Honey contains two reducing sugars, including fructose that aver-
ages 38.38% (range 30.91–44.26) and glucose that averages 30.31% (range 22.89–40.75), and total
content of reducing sugars that average 76.65% (range 61.39–83.72). Fructose and glucose are the two
major components of honey. Water is the third major component of honey. Despite the wide range of
honey varieties available on the market including clover, orange blossom and chestnut, honey remains
a major source of reactive reducing sugars. High-fructose corn syrup contains less than 60% fructose.
Maple syrup is a major source of sucrose, which is a mixture of glucose and fructose. It is unfor-
tunately often promoted as having fewer calories and more minerals mostly manganese and zinc
than honey. Manganese can be easily obtained from hazelnut, spelt, garbanzo beans, brown rice,
spinach, or oat. The daily intake of zinc is 11 mg per male adult aged 19 years or older and 8 mg for
females aged 19 years or older and can easily be obtained from a combination of nut, fortified cere-
als, crab, lobster, beef, or pork chop. Maple syrup is not one of the best sources of zinc. Too much
zinc exacerbates the activities of enzymes matrix metalloproteinases that catalyze tissue degrada-
tion and cancer proliferation and metastasis. Men with prostate cancer or prostate problems should
avoid food rich in zinc and not consume these foods as it is common to find that zinc is promoted
to strengthen the prostate. Similarly, matrix metalloproteinases catalyze the metastasis of several
types of cancer, including breast and pancreatic cancer, and certain types of brain tumors. Matrix
metalloproteinases are also associated with the progression of hypertension and atherosclerosis.
Maple syrup should be used for its flavor while knowing that this is another reducing sugar that is
being added to the food and being ingested.
Dextrose is another scientific name for glucose. Fructose and glucose are both reducing sugars
and fructose is more reactive than glucose or dextrose when interacting with proteins through the
Maillard reaction. Because agave is almost only fructose, using it as a substitute for high-fructose
corn syrup or glucose promotes more Maillard reaction instead of avoiding it.
Evaporated cane juice is similar to cane sugar, which is a combination of glucose and fructose.
Evaporated cane juice contains some traces of molasses, while cane sugar is devoid of molasses.
In the presence of reactive amine groups, the reactivity of evaporated cane juice is similar to the
reactivity of cane sugar.
The glycemic index is a misleading criterion when it comes to evaluating the reactivity of sugars.
Reducing sugars have low glycemic index, yet these sugars are very reactive and lead to Maillard
reaction products formation, the most fearful products for individuals with diabetes and those who
want to prevent diabetes development. Consuming baked products containing significant amounts
of dextrose is similar to consuming the same baked products containing fructose and the Maillard
reaction has taken place or will occur in vivo. Baked goods containing organic or conventional
agave are not better than baked goods containing other reducing sugars.
18.6.2.12 Pizza
Pizza is a world classic food that is too good and enjoyed the world over. According to
Pizza Magazine PMQ, pizza sales totaled more than $36 billion for the business period end-
ing September 30, 2012. There were more than 71,856 pizzerias as of the end of September 2012.
Sales of pizza have significantly increased in recent years. Pizzerias or pizza restaurants have bour-
geoned around the United States and are in every city or town. Thin crust pizza was a specialty
of the northeast but has been accepted and enjoyed throughout the United States. It is made of
high-gluten durum wheat with a layer of tomato paste, cheese, herbs, and meat or mushroom. It is
often stone-baked at very high temperatures that can reach 900°F. The thick crust has a doughy and
chewy crust and can have a variation of toppings that can go from chicken to red meat to salmon.
aDoPtInG a DIet 355
There are so-called health pizzas for health conscious pizza lovers. The worldwide popularity of
pizza makes it almost impossible to find a negative report on pizza in the scientific literature. Some
consider it a nutritionally complete food that is above criticism. The almighty pizza!
However, for the food chemist, pizza is a classic example of Maillard reaction products that can
also go wrong. The ingredients for making pizza include a special type of high-gluten refined durum
wheat flour, red or white meat, yeast, lots of cheese, tomato paste, mushrooms, pineapple for some, and
sometimes vegetables and fish. The refined flour is a good source of reducing sugars. The ingredients
are cooked at very high temperatures between 350°F and 450°F for at least 15–20 min and sometimes
at temperatures higher than 850°F when the pizza is stone-baked or wood-fire cooked. The Maillard
reaction is initiated at any temperature at which pizza is baked suggesting that it does not make a
difference whether the pizza is from a conventional grocery store or a so-called healthy food store.
Stone-baking pizza does not make it healthier than oven-baking it because stone baking does not
prevent the Maillard reaction to occur especially if the stone temperature reaches 900°F. The bottom
line is that the ingredients in the pizza and baking temperature deliver AGE-rich pizza regardless of
where the pizza is baked. Pizza is pizza; it may have all the so-called good food ingredients for human
development such as cheese and meat, and the baking process develops a product whose regular con-
sumption leads to the accumulation of AGEs in the body and potential health hazards.
18.6.2.13 Flamed or Rotisserie Chicken
Poultry is one of the best dietary sources of methionine, an amino acid that in the body is con-
verted into homocysteine. A high level of homocysteine is termed hyperhomocysteinemia. Clinical
data and laboratory research have shown that hyperhomocysteinemia is a major risk factor for car-
diovascular disease. Hyperhomocysteinemia has also been shown to weaken the blood–brain bar-
rier, which may lead to leaky blood–brain barrier and cognition impairment. Flamed chicken is
not exempt from the Maillard reaction because like any vertebrate, chicken meat contains proteins
and reducing sugar ribose that can easily drive the Maillard reaction inside the oven. Rotisserie
chicken is a good source of carcinogenic heterocyclic amines PhIP (2-amino-1-methyl-6-phenyl-
imidazo [4,5-b]pyridine) (not detected 7.9 ng/g) and MeIQx (2-amino-3,8-dimethylimidazo [4,5-f]
quinoxaline) [131]. Rotisserie chicken skin contained more heterocyclic amine (16.3 ng/g) than
rotisserie chicken meat (1.9 ng/g) than cooked ham (1.1 ng/g) than hot dogs (0.5 ng/g) than pep-
peroni (0.05 ng/g) [131]. Rotisserie adds homocysteine and heterocyclic amines to the human body.
Therefore, purchasing flamed or rotisserie chicken from any stores does not make much differences,
the consumer is mocked once again.
18.6.2.14 Parsley
Parsley is the major vegetable ingredient of tabouli or tabbouleh, the Middle Eastern salad that
also contains bulgur, tomato, onions, olive oil, and lemon juice. Parsley is rich in a lipid that has
the ability to inhibit the formation of new blood vessels (angiogenesis) and inflammation [132].
Parsley is an herb good for liver diseases [133]. Several biomedical properties, including carmina-
tive, gastro tonic, diuretic, inhibition of urinary tract infection, antiurolithiasis, antidote and anti-
inflammatory, and inhibition of amenorrhea, dysmenorrhea, gastrointestinal disorder, hypertension,
cardiac disease, urinary disease, otitis, sniffle, diabetes, and also various dermal disease, have been
ascribed to parsley [134]. Parsley is rich in apigenin, apiin and 6″-acetylapiin, essential oils mainly
myristicin and apiol, and coumarins. Several pharmacological applications, including antioxidant,
hepatoprotective, brain protective, antidiabetic, analgesic, spasmolytic, immunosuppressant, anti-
platelet, gastroprotective, cytoprotective, laxative, estrogenic, diuretic, hypotensive, antibacterial,
and antifungal, have been ascribed to parsley [134]. However, several Western restaurants use pars-
ley for plate decoration instead.
18.6.2.15 Fish Oil
The health benefits of consuming fish oil have been reported and documented. Infant neurologi-
cal development is a health benefit ascribed to fish oil. Omega-3 fatty acid is commonly referred to
as fish oil. Omega-3 fatty acids are obtained from oily fish, some of which are harvested from areas
contaminated with POPs such as polychlorinated biphenyls (PCBs), dioxins, organochlorine pesti-
cides [124], and polybrominated diphenyl ethers (PBDEs) [135]. POPs are oil-soluble and enter the
human body through the food chain including meat, dairy, and fish products. Although efforts are
made to ensure that fish oils and products containing fish oils are safe, there have been cases where
contaminated fish oils entered the food chain. Therefore, any food enriched with such oils may not
be as healthy as the label may claim. While fish oil is good for infant and children development,
parents are not giving fish to their children. Rather fish oil is more of a supplement for adults than
children who actually need it the most.
18.6.2.16 Fruit Jams
The ingredients for making fruit jams include fruit, pectin, sugar, acid, and occasional salt.
Pectin derives from fruits such as apple, strawberry, and citrus peel. Pectin is a long molecule
that is not synthesized in the laboratory. Commercial pectins are obtained from fruits. While
conventional jams often contain commercially available pectin, healthy food stores prefer fruits
rich in pectin instead. There is no difference between pectin purchased individually and pec-
tin in fruit such as strawberry. There is no difference between citric acid purchased commer-
cially and citric acid in lemon. Since corn syrup is not used to make jam, there is no difference
between cane juice and crystal sugar in making jam. Individuals with diabetes should watch out
for the type of reducing sugar used when making jam. Organic sugar does not make any differ-
ence when used in jam.
18.6.2.17 Roasted Nuts
In general, most nuts are healthy. Large cohort studies have shown that increased consumption
of nuts is associated with reduced risk of cardiovascular disease, type 2 diabetes, pancreatic cancer,
and total and cause-specific mortality [136,137]. Nuts are good sources of magnesium, selenium,
and monounsaturated fatty acids. There are several types of edible nuts, including almond, walnut,
pistachio, Brazil nut, peanut, cashew nut, hazelnut, chestnut, macadamia, coconut, pine nut, pecan,
and pili nut. Raw nuts are healthy. Lightly roasted nuts should also be healthy.
Roasted nuts are very susceptible to contain acrylamide and AGEs. Acrylamide is human car-
cinogen. Temperatures higher than 130°C encountered during almond roasting favor the conversion
of asparagine to acrylamide, and acrylamide has been detected in roasted almonds [46,49,138].
Acrylamide concentration in nut is associated with asparagine levels and roasting temperature sug-
gesting that some nuts, such as almonds, that are rich in asparagine are prone to acrylamide for-
mation when roasted at temperatures of 130°C or higher, while others such as hazelnuts that are
asparagine-deficient are less prone to generate acrylamide following roasting [47]. Mild roasting
temperature below 130°C and short roasting time of less than 15 min reduce acrylamide formation
in susceptible almond nuts [139].
Honey is a good source of fructose. Roasting nuts with honey generates more Maillard reaction
than nuts roasted without honey. Conventional and healthy grocery stores all sell honey-roasted nuts
and consumers pay more for these acrylamide and AGE-rich products. Confusion leads consumers
to purchase expensive roasted nuts with no health benefits. Organic or inorganic nuts when roasted
will undergo the Maillard reaction. There are no data showing that organic almonds do not contain
asparagine.
aDoPtInG a DIet 357
18.6.2.18 Dried Fruits
The health benefits of fruits are well established because fruits contain a wide range of health-
enhancing bioactives. Fresh fruits contain mostly water and very small amounts of bioactives.
Drying concentrates bioactives in fruits. Depending on the drying conditions, bioactives such as
vitamin C may be lost. Sun-dried and heat-dried fruits have less vitamin C than fresh fruits. Several
dried fruits, including berries, raisins, papaya, pineapple, and mango, are loaded with sugar. The
serving size of most dried fruits is 40 g. However, 28–32 g of the serving size is reducing sugar.
Only 8–12 g of the serving size is real fruits. Consumers who purchase dried fruits take home more
sugar than they had wanted. Traditional grocery stores often carry fructose-loaded dried fruits.
Other stores carry fruit juice–sweetened dried fruits. The sugar in fruit juices is fructose. Adding
fruit juices to dried fruits makes the dried fruit a rich source of reducing sugars. Consumers walk in
these stores, grab all these so-called healthy dried fruits feeling good but take home products simi-
lar to those found in traditional grocery stores. Organic or not, sugar- or fruit juice–sweetened dried
fruits contain more sugar and less bioactives. An organic sugar has the same chemical composition
as conventional sugar suggesting that once in the body these two types of reducing sugars react sim-
ilarly and can lead to inflammation and diabetes if consumed in excess over a long period of time.
18.6.2.19 Milk Chocolate Bars
Milk chocolate bars have been around for a long time. These are real energy-dense foods. Rich
in calories, saturated fats, hydrogenated fats, and chocolate, these bars contain on average 36 g of
sugars and this amount is similar to drinking a can of sweetened cola drink. The phenolics from
chocolate are bound to milk proteins, and the benefits from these bars come from their high sugar
and calorie content.
18.6.2.20 Cookies and Chips
Cookies are good snacks. All cookies contain reducing sugars. Different sugars are used by dif-
ferent manufacturers to develop the same types of cookies giving consumers the impression that one
type of sugar is better than the other and some types of cookies are better than others. Because most
of these sugars are reactive, the bottom line is that all sugar-containing cookies should be consumed
in moderation. There are no healthier cookies than others.
Various chips, including dark chocolate chips, milk chocolate chips, white chocolate chips,
peanut butter chips, butterscotch chips, mint chocolate chips, or bittersweet chocolate chips, can be
used to add flavor to cookies. Butterscotch, milk chocolate, and white chocolate chips are probably
the least healthy of all the chips. Butterscotch is a combination of brown sugar, butter, syrup, and
flavorings. The combination of milk and chocolate gives a product that has less bioactive pheno-
lics because the phenolics in chocolate bind to the proteins in milk forming a complex that has no
health-enhancing value. White chocolate is cocoa butter, milk, and sugar and hardly contains the
purported health benefits of chocolate phenolics.
All chocolates were not created equal and very few of them provide the health benefits ascribed
to phenolics in chocolate without milk. The presence of the same types of chocolate chips in tradi-
tional and healthy food stores confuses consumers.
18.6.2.21 Kettle-Baked and Gluten-Free Potato Chips
Kettle-baked potato chips are baked at the same temperature as conventionally baked potato.
As a result, these chips are as good or as bad as conventionally baked potato chips. The cooking
process of kettle-baked potato does not prevent acrylamide formation if asparagine is present in
the potato. However, a big confusion has been created and consumers often think that kettle-baked
potato chips are healthier and more natural than potato chips from big vending stores. Potato is not
a source of gluten and wheat flour is never used in the manufacture of potato chips. Marketing again
confuses the consumer with labels that are gimmicks.
18.6.2.22 Sea Salt, Iodized Salt, or Salt
Sea salt is not an answer to blood pressure. First of all, it is obtained following evaporation of sea
water and contains some additional minerals that should not be construed as an important dietary
contribution from sea salt. Sea salt is not chemically different from regular table salt. Both salts
contain sodium chloride as major component. Many varieties of sea salts do not contain less sodium
than Kosher salts and do not show differences in taste intensity compared to Kosher salt [140]. Sea
salt consumption is not treatment for high blood pressure. Sea salt is not iodized. Regular table salt
may contain iodine that is very much needed to avoid the development of goiter.
18.6.3 traditional Western-Style Food Stores versus ethnic Food Stores
18.6.3.1 Traditional Western-Style Food Stores versus Ethnic Food Stores
For more than 200 years, the United States has been a country of immigrants. Many other
Western nations including the United Kingdom, France, and Canada are among the countries with
a long history of immigration. The history of ethnic foods in most of these countries is as old as
the history of immigration itself. There are currently more than 37 million new immigrants in the
United States and immigrants make less than 10% of the people living in the U.S. population [141].
However, from 2050, new immigrants will make about 20% of the people living in the United States
[141]. In the Arab Emirates, for instance, there are more than 3.5 million expatriate workers [142].
It has been suggested that upon arrival to the host nation, new immigrants from Latin America,
Eastern Europe, Middle East, Southeast Asia, and Africa adopt an “obesogenic diet” character-
ized by consumption of affordable supersized energy-dense ready-to-eat meal and ready-to-drink
beverage portions to which they were not exposed to in their native lands [143–145]. In general, the
new immigrants regardless of their native lands often adopt a sedentary lifestyle and engage in less
physical activities as opposed to regular long walks in their native environments [146,147]. Studies
have consistently shown a strong association between length of residency for new immigrants in the
United States, Canada, or rich Arab countries and weight gain or obesity [142,148,149]. However,
this relationship is weak in most European countries [145,150]. In Spain, studies have shown a strong
association between length of residence for all immigrants from Eastern Europe, Latin America,
and Africa and obesity; the same studies have shown no association between length of residence for
immigrants from Western nations and obesity [150,151]. Migrant workers often perform work that
involves physical activity that spares them from gaining weight.
Immigrants who moved to the United States or Canada before 1990 may have adopted an obe-
sogenic Western diet because they were mostly exposed to Western diets. However, it may not be
entirely true in recent years from 1990 onward. The time to blame the host countries is over. Here
is a tentative explanation. Since 1990, there has been a proliferation of ethnic food stores all across
the United States, Canada, and Europe. More new immigrants shop at ethnic food stores than native
United States, Canadian, or European consumers. Immigrants shop at both traditional U.S. food
stores and ethnic food stores. The need for healthy foods is driving consumers including new immi-
grants and nonimmigrants to shop at ethnic food stores for exotic ingredients such as spices and
herbs, produce such as fruits and vegetables, and processed food products that add diversity and new
food experience in their diets [152]. For immigrants in particular, ethnic ingredients or foods also
add “homeland taste” to the diet.
aDoPtInG a DIet 359
The majority of food items including ingredients in ethnic food stores are imported; produce
is locally grown or shipped from another part of the country. Exotic spices, herbs, soups, canned
foods, confectionaries, chocolates, smoked and dried fish, flours, frozen vegetables, processed meat,
salted foods, sweetened beverages, dairy products, bakery products, fruits, fresh fruits and veg-
etables, snacks, and stimulants are available in most ethnic stores. It needs to be demonstrated that
all these imported foods are a solution to healthy, old age disability-free and long life.
The globalization of the world economy has been associated with the globalization of pro-
cessing technologies that transform food ingredients in different countries into processed food
ingredients and pre-prepared and ready-to-eat foods for local consumption and export for use by
immigrants as they criss-cross continents to new residencies. These foods that are being devel-
oped in developing and other developed countries are shipped around the world and sold wherever
new immigrants have settled. It is important to recognize here that the ethnic food stores give the
local communities opportunity to appreciate and evaluate foods from other parts of the world.
Immigrants, nonimmigrants, and informed natives are buying into this new trend that “ethnic food
stores sell healthier food ingredients and products than traditional food stores in town.” A close
examination of food ingredients or food products that rank high in consumer shopping lists in
these proliferating stores across the Western world shows that often consumers are paying more for
foods sold in these stores than in traditional Western-style food stores but are taking home ingre-
dients or foods that are worse than, equally worse, or similar to ingredients available in traditional
Western food stores:
1. Fruit juices in ethnic food stores often contain more sugar than fruit juices processed in the West.
While fructose is being associated with obesity development in the West, fructose-rich fruits in eth-
nic food stores are risk factors for obesity development for immigrants or those who purchase these
fruit juices. Whether fructose corn syrup or regular sugar is being added, sugar is sugar and any
excess of it is not good for the body. Agave has 90% fructose and is worse than corn syrup; however,
because it is natural, consumers thrust it more than corn syrup.
2. Cola and sweetened beverages sold in ethnic stores across the United States often have more sugar
than domestically bottled sweetened beverages. Sugar levels of more than 40 g per serving size are
not uncommon. It can be seen that cola and sweetened beverages bottled outside the United States
and specially in developing countries contain more sugar per serving size than colas or sweet-
ened beverages bottled in the United States. However, occasionally, domestically bottled sweetened
beverages contain more than 40 g of sugar per serving. Colas and sweetened beverages are good
sources of inorganic phosphates. The findings from the Framingham Offspring study that followed
3368 individuals free of cardiovascular and chronic kidney disease for 16 years concluded that high
serum levels of inorganic phosphate is a risk factor associated with increased mortality for individu-
als without history of cardiovascular or kidney disease or the general population [153].
3. Ultrahigh-temperature (UHT) milk was developed to give a product that is shelf stable. It is sold in
ethnic food stores. The high temperature applied to milk to develop UHT milk destroys immuno-
globulins and most valuable bioactive compounds in the milk making this type of milk a beverage
that delivers less than it was intended for.
4. Nonalcoholic beverages contain more sugar than cola drinks or other sweetened beverages pro-
cessed in the West. Chronic consumption of these products at home and evening gatherings do not
make the immigrants who consume these products healthier than if they were to drink sweetened
beverages from the West. These beverages all contain sugar and too much sugar like too much of
anything is not good for the body.
5. Cow’s milk contains lactose and casein, a sugar and protein whose chronic consumption has been
suspected of being associated with chronic diseases prevalent in the Western societies. While the
use of hormones has been touted as the mother of certain diseases prevalent in the West, it is not
known if the same hormones are not present in cow’s milk purchased from ethnic food stores.
It is not known if the cow’s milk from ethnic stores necessarily comes from certified organic farms.
It is presumed that people buy these products to enjoy homeland milk flavor.
6. Canned milk from an ethnic food store is not different from canned milk from a traditional Western-
style food store. Sweetened condensed milk is prepared the same way around the world, it contains
a large amount of sugar, and it is an excellent source of AGEs regardless of point of manufacture
or purchase. Evaporated milk is a rich source of AGEs and inorganic phosphates. While inorganic
phosphate is food grade and approved for use in foods [154] and there are no studies looking at phos-
phate levels in human serum and vascular disease, there is a need for evaluating the health benefits
of phosphates as ingredients in foods and beverages [155,156].
7. Goat’s milk is a good alternative for individuals who are allergic to cow’s milk, although the chemi-
cal composition of goat’s milk suggests very little difference in lactose and casein between cow’s
milk and goat’s milk. While goat’s milk and milk products are consumed in moderation in most part
of the world where these products are largely consumed, immigrants who move to the West often
have a better buying power than in their countries of origin. As a result, immigrants tend to consume
more goat milk and milk products. The contribution of large portion size consumption of goat milk
to long-term human health is not known.
8. Cow’s cheese versus feta cheese versus goat cheese or fromage de chèvre: There are several variet-
ies of cheese on the market. The discussion will be limited to the chemical composition of cheese.
Original feta cheese is from sheep milk. However, nowadays, feta cheese has been made from goat
milk. Feta cheese is to the Mediterranean diet what cow’s cheese is to the Western diet. Goat cheese
has a strong flavor and is tasteful, but taste and flavor do not make goat cheese healthier than cow’s
cheese. The science is not there yet. The only potential explanation to the purported superior health
benefits of goat cheese is associated to the fact that in the Mediterranean diet goat cheese is not con-
sumed in large quantities the way cow’s cheese is used in the Western diet. In recent Western meals,
cow’s cheese is on almost every meal from breakfast to midnight sandwiches. Goat cheese, whether
handmade, organic or conventional, contains more saturated fats than cow’s cheese. Because the
chemical composition of cheese is almost similar whether it is from cow or goat, chronic consump-
tion of goat cheese may lead to the same inflammatory process generated by high levels of AGEs,
oxidative stress, inflammation, and the subsequent diseases that may ensue. Research in this area is
lacking and will not need to be established sooner or later. Table 18.4 shows the compositional dif-
ferences between goat and cow’s cheese.
9. Red and processed meat whether it is from a cow, goat, or lamb, it is red meat, and wherever it
is bought, the meat carries the characteristics of red meat. Ethnic sausage is sausage and has the
characteristics of sausage. Longevity and disability-free old age has often been associated with
reduced red meat consumption and not the excessive consumption of one type of meat over another.
The long-lived people of Sardinia, Nicosia, or Okinawa generally eat meat less than twice a week.
Processed meat has been associated with the increased prevalence of Western diseases. Processed
meat is a good source of inorganic phosphates and inorganic phosphates have been identified as a
health risk factor for cardiovascular disease [157,158].
10. Frozen pizza from an ethnic food store is not different from frozen pizza developed in a Western-
style food store (Figure 18.6). Pizza is made of flour dough, lots of cheese, meat such as pepperoni
table 18.4 Compositional Differences between Sheep, Goat, and Cow’s Cheese
Feta Cheese Goat Cheese Cow’s Cheese
total fat: 20–30 g total fat: 20–30 g total fat: 20–30 g
saturated fat: 1–5 g saturated fat: 1–5 g saturated fat: 1–5 g
trans fat: 0 g trans fat: 0 g trans fat: 0 g
Cholesterol: 20–30 mg Cholesterol: 10–25 mg Cholesterol: 10–30 mg
sodium: 60–200 mg sodium: 60–300 mg sodium: 60–500 mg
total carbohydrate: < 1 g total carbohydrate: < 1 g total carbohydrate: < 1 g
Dietary fiber: 0 g Dietary fiber: 0 g Dietary fiber: 0 g
sugars: < 5 g sugars: < 5 g sugars: < 5 g
Protein: < 15 g Protein: < 15 g Protein: < 15 g
aDoPtInG a DIet 361
Figure 18.6 Indian pizza has similar ingredient as Western-style pizza.
or salami, and/or vegetables. All pizzas are backed at 450°F for at least 15 min during which the
Maillard reaction occurs because of the proteins and sugar in the dough, cheese, and meat. Immigrant
consumers often think that the pizzas from ethnic stores are healthier than the pizzas from Western-
style kitchen or fast-food restaurants. Pizzas from ethnic stores contain processed meats and are
good sources of AGEs similar to pizzas that are home delivered or purchased from supermarkets.
Ethnic pizzas may have different shapes, but they are chemically the same as conventional pizzas.
Organic flour does not escape the Maillard reaction as long as the cooking is done at temperature at
which pizzas are commonly baked. Ethnic pizzas are as good risk factors for the rampant obesity in
ethnic communities as pizzas that immigrants order for home delivery like anybody else.
11. Baked goods in ethnic food stores are not healthier than baked goods in traditional Western-style
food stores. Cheese-layered breads, butter and cream–filled pastries, and sugar-layered pastries are
available in ethnic food stores (Figure 18.7). With a better purchasing power than at the time of their
arrivals in their new homes, new immigrants are often ready to enjoy these delicacies without con-
sideration of the potential health side effects of these baked goods. For instance, baklava is a popular
sweet that may have an ethnic character and significance (Figure 18.8). Yet this food is full of sugar
that makes it probably one of the worst foods for people with diabetes. It is worse than a glazed
donut. The immigrants or those shopping in ethnic food stores look at these imported products as
secrets to healthy life. Baklava is not one of them.
12. Canned foods available in ethnic stores (Figure 18.9) are processed the same way as canned foods
sold in Western-style food stores. It is not known how much bisphenol A is present in these canned
products. Therefore, prejudging these canned products as healthier than others without a chemical
analysis performed on it is premature.
13. Imported dry soups available in ethnic food stores often have more sodium and cost more than
canned soups with less sodium produced locally. Imported dry soups contain very high levels of
sodium that can reach 890 mg per serving size, and this is by far more than the sodium levels in
canned soups from domestic processors (Figure 18.10). Most of these soups have no potassium as
opposed to domestic soups for which processors are making an effort to reduce sodium and add
potassium.
14. Bouillons are dehydrated soup stocks that have been compressed into small cubes (Figure 18.11).
Before use, the bouillon needs to be dissolved in water and added to meal for flavoring. Different
bouillon flavors, including chicken, beef, crayfish, vegetables, and fish, are available on the mar-
ket. Bouillons are classic examples of Maillard reaction products. Mutagens other than benzo[a]
pyrene have been detected at a level of 0.1 part per million in beef bouillon [159]. High levels
(380–670 µg/kg) (2650–4840 µg/kg fat) of 3-chloropropane-1,2-diol fatty acid esters were measured
Figure 18.7 Baked goods from ethnic stores are not necessarily healthier than baked goods from traditional
Western-style bakeries.
Figure 18.8 Baklava is loaded with sugar.
in bouillon cubes; however, the health significance of these compounds has never been investigated
[160]. Heterocyclic compounds have been identified in chicken bouillons [161]. Bouillons are also
good sources of unwanted sodium.
15. Fried flours that can be called ethnic donuts are not different from fried flour served with coffee
or tea in Western shopping outlets. These products are fried for minutes in oil and absorb enough
heated oil. Shih et al. [162–164] developed a range of cereal flours that absorb up to 45% less oil,
provide 32% fewer calories than traditional flours and can be used for donut, beignet, cake, and
other baked product formulations. These types of flours that mark a technological breakthrough are
important for developing food products that are tasty, absorb less oil, and are good for local consum-
ers and travelers who enjoy donuts. Ethnic products like these Indian donuts (Figure 18.12) would
greatly benefit from Shih et al.’s work.
aDoPtInG a DIet 363
Figure 18.9 Imported canned sardines from ethnic food stores.
Figure 18.10 Imported soups are saltier than commercial soups produced in the united states.
16. Palm oil is the favorite of ethnic food cuisines and international industrial food processing applica-
tions where it can be fried for more than 8 h a day and 5 days a week for making potato chips and
crisps, preparing prefried frozen French fries, and in fast-food restaurants [165]. It is the major
source of saturated fat in the diets of billions of people in developing countries where it is used for
making margarine and cooking. Palm oil is an ingredient in many ethnic food products including
some Korean noodles. Palm oil contains carotenoids that are very susceptible to sunlight-induced
oxidation. Yet, palm oil is transported across oceans in very clear transparent bottles like drinking
water. When this oil reaches the ethnic stores and remains on the shelves until it is purchased, it is
already oxidized and the antioxidant carotenoids that have been inactivated are not protective any-
more (Figure 18.13). There are several publications that hail or promote the health benefits of palm
oil [166] and its antioxidants, such as tocotrienols, in fresh and well-preserved palm oil [167,168],
suggesting a wide range of applications of the oil in various food products. The consumers who like
and use palm oil buy whole palm oil and not tocotrienol-rich palm oils that were very well kept
and protected in the laboratory settings. Palm oil investigators who are developing hypotheses that
this oil is healthy should use palm oil samples from local markets in developing countries or ethnic
Figure 18.11 Bouillon imparts good flavor but does not impart good health.
Figure 18.12 an Indian delicacy that is just fried flour.
stores across the Western world and verify their hypotheses instead of publishing findings that use
fresh oil or parts of fresh oil to support data that are not consistent with the reality on the field where
real people are using the oil in their diets and developing chronic diseases such as atherosclerosis
[169–171]. Palm oil is fried at a temperature higher than 150°C for several minutes during which
most of the antioxidants, including beta-carotene, tocotrienols, and tocopherols, present in the oil
are destroyed, a phenomenon those who promote this oil do not take into consideration. Moreover,
palm oil contains about 45% palmitic acid, a saturated fatty acid that probably survives frying and
is known for its ability to promote inflammation and insulin resistance [172] and alters the gut
microbiota and indirectly contributes to the development of saturated fatty acid–induced obesity
[173]. Higher mortality from ischemic heart disease and stroke in developing countries has been
associated in part to increased palm oil consumption [127]. Recently, Basu et al. [171] reported
palm oil to contribute to hyperlipidemia and cardiovascular disease in India and suggested that a
tax on palm oil may curtail the use of this unhealthy oil and modestly reduce hyperlipidemia and
cardiovascular mortality. However, if palm oil is a good source of olein [174] and tocotrienol [167],
aDoPtInG a DIet 365
Figure 18.13 Palm oil is oxidized before consumption.
these health-enhancing bioactives should be separated from palmitic acid and be tested for health
benefits in animals before using them in human food formulations. The best use of palm oil may be
in biodiesel preparation [175–177], and those who produce this oil should divert all productions to
biodiesel production and/or fractionationate the oil into compounds such as glycerin [178], tocotri-
enols, and beta-carotene.
17. Tempura is a deep-fried seafood or vegetable in a special flour mix known as tempura batter
(Figure 18.14). Tempura originated in Portugal, was introduced in Japan in the sixteenth century
by Portuguese missionaries, and has since become a Japanese specialty. The seafood can be large
shrimp, fish, or shellfish. The vegetable can be carrot, cauliflower, eggplant, sweet potato, pumpkin,
green beans, parsley leaves, or any other vegetable. The batter contains wheat and rice flour and
eggs. Deep frying is done at 356°F or higher until the food has turned golden brown. In the process
of making tempura, healthy food ingredients or foods are covered with fried flour and destroyed by
heat. The fried oil is similar to fried oil in fried cheese. Despite all the positive comments on tem-
pura, this deep-fried food is no exception; it is a fried food and carries all the negatives associated
with fried foods.
18. Samosa is a triangle-shaped Indian snack that has conquered the world (Figure 18.15). It is seasoned
vegetables or meat wrapped in flour turnover and deep-fried in oil until it turns golden. The veg-
etables can be spiced mashed potatoes, onion, lentils, peas, spinach, or anything else. The meat is
ground beef, lamb, or chicken. Butter can be used. Spices including turmeric, coriander, chili, or
cumin can be used. There is literature on the efficacy of antioxidants in cumin, coriander, or tur-
meric against AGE formation under deep-frying conditions. Samosa may be tasty and flavorful to
some, but this is a fried food whose health benefits may need to be known.
19. Are immigrants or others shopping in ethnic food stores slimmer than nonimmigrants shopping for
traditional Western foods? Probably not.
Figure 18.14 tempura is fried shrimp.
Figure 18.15 samosa is fried flour with some vegetables or meat.
18.6.3.2 Microbial and Other Chemical Safety of Ethnic Food Stores
Foodborne illness outbreaks occur in ethnic restaurants around the world. In the United States,
the increased number of ethnic stores is associated with high numbers of outbreaks. Lee et al.
[179] summarized that ethnic restaurants in the United States account for 66% of foodborne illness
occurrence out of 48 million cases reported annually.
The safety of packaging materials used for some frozen foods available at ethnic stores needs
to be evaluated. Cassava leaves (Figure 18.16), sweet potato leaves (Figure 18.17), and salted fish
(Figure 18.18) are delicacies for many immigrants including Asians and Africans, and these individu-
als from time to time prefer to prepare meals and consume foods the way it is done in their native
countries. Cassava leaves, sweet potato leaves, and salty fish are imported and kept frozen until it is
cooked. None of the packaging materials used for cassava, sweet potato leaves, or salty fish are freezer
aDoPtInG a DIet 367
Figure 18.16 frozen cassava in a bag that may leak bisphenol a into the frozen cassava.
Figure 18.17 sweet potato leaves stored in bags that may leak bisphenol a into the food.
Figure 18.18 salted fish stored in plastic bags that is not freezer-proof.
safe. Rather, these three products shown in the pictures were packaged in plastic bags that can easily
leak BPA into the food during storage and be consumed when the food is served. BPA is an endocrine
disrupting chemical that can induce promiscuous neurobehavioral disturbances [180,181]. BPA is toxic
and carcinogenic [182,183], yet many immigrants dine and party with these foods all year around.
18.6.4 traditional Western-Style Fast-Food restaurants and

the Westernization of ethnic (Fast-Food) restaurants
Consumer desire for healthy foods has created another shift at the dining outlets where restau-
rants are moving away from traditional Western-style fast foods to serve foods with a healthy look.
New fast-food restaurants, some of which do not want to be regarded as fast-food outlets, have erupted
all over the cities around the world. The original fast-food outlets are mostly those who have been
around in the last 50 years. These restaurants have offered consumers a variety of foods that include
fried and grilled bacon, French fries, fried chicken, toast, bacon, grilled meat or fish, roasted meat or
fish, burgers, scrambled eggs, fried eggs, and others. These restaurants serve beverages that include
water, sweetened fruit juices, coffee and all versions of strong coffee, sweetened and diet cola, and
punches. Cookies, ice cream, sugar-loaded smoothies, and sugar-loaded fruit treats are the desserts.
The so-called new global-minded healthy restaurants offer French fries, bacon, chicken bar-
becues, grilled meat, roasted meats, and almost anything one can find in traditional Western-style
fast-food restaurants. Cola and diet cola are served along with newly developed cola drinks that
sometime have more reducing sugars than the cola and diet cola served by traditional Western-style
fast-food restaurants.
aDoPtInG a DIet 369
18.6.4.1 Westernization of Ethnic Foods, Frying and Grilling in Ethnic Restaurants
In the United States and most parts of the world, restaurants are gatherings for good meals,
planning, romance meals, and meetings. Traditional as well as ethnic restaurants are social eat-
ing houses where middle- and upper-class people experience traditional or exotic fine cuisines.
Ethnic restaurants are expected to serve ethnic foods with ethnic flavors and expose locals to tastes
and communities different from their own. A Mediterranean restaurant is expected to offer real
Mediterranean cuisine. Similarly, an Indian, Thai, or Japanese restaurant should serve Indian, Thai,
or Japanese meals, tastes, and flavors. For years, ethnic restaurants were gatherings for new immi-
grants, visitors, and tourists in search of homeland flavor and taste and locals in search of exotic
meals and gatherings.
Recent interests in healthy eating and the reports on “Blue Zones,” Okinawan diet, and Indian
spices are driving many locals to join immigrants in ethnic eating outlets to experience ethnic
cuisines. However, while some ethnic restaurants strive to be authentic to their names, others
have completely westernized their meal preparations and offer meals that are ethnic only by
name. Food connoisseurs wonder about the authenticity of the restaurants. World travelers are
confused when visiting these restaurants, others expect exotic flavors and taste and are offered
westernized ethnic meals. The psychology of eating healthy exotic meals remains one big reason
people keep coming to ethnic restaurants where confusion is part of the menu. While meal tastes
and flavors in westernized ethnic restaurants are often excellent, the chemistry in foods served in
these outlets is a copy of the chemistry of foods in traditional Western restaurants. The Maillard
reaction for which Western restaurants are blamed is recreated and sometimes exaggerated in
these restaurants.
Frying is common to all people, some do it for a short period of time and call it stir-fry, and
others fry for several minutes. While Western restaurants are criticized for offering unhealthy
fried foods, it is common in some culture to consume fried foods. Ethnic restaurants not only
westernize their recipes but also offer fried foods that are traditional to their homeland culture.
Fried foods offered by ethnic restaurants can be as unhealthy as fried foods offered by tradi-
tional Western restaurants:
1. Fried cheese (Figure 18.2) can be found in many cultures and countries. Fried cheese can be found
in restaurants in Finland (leipäjuusto), Greece (saganaki), India (paneer), Middle East (halloumi),
Central America (queso blanco, queso fresco, or queso frito), and the United States (mozzarella
sticks or cheese curd). Cheese sometimes blended with eggs with or without bread croutons is fried
in oil at a high temperature giving a tasty and flavorful food product whose health value in a society
ravaged by metabolic syndrome is questionable. However, some people love it so much that it is too
good to be investigated. The ingredients and cooking conditions create favorable environment for
the Maillard reaction to occur. With or without gluten-rich flour, these types of products may not be
healthy for individuals with inflammatory bowel disease. Fried ethnic foods create a real confusion
in consumer’s mind because as ethnic foods they escape the criticism of being risk factors for the
metabolic syndrome and are tasty, flavorful, yet proinflammatory. Low-income individuals walk
into these food outlets for a change from their fries- and burger-loaded diets to meals they believe
are healthier. Unfortunately, the psychology of eating healthy once again drives people to these stir-
fried food outlets where they end up purchasing foods whose safety is similar to traditional fried
Western meals. Beverages offered in these outlets include sweetened and unsweetened drinks giving
the consumer the opportunity to choose.
2. Fried tofu (Figure 18.19) is obtained from the healthy soybean curd from soymilk that is coated
with flour and fried in oil at very high temperatures to generate a delicious and flavorful product.
Fried tofu is full of AGEs and not as healthy as tofu. Tofu is a good source of antioxidative pro-
tein Bowman–Birk inhibitor and antioxidative peptide lunasin. Fried tofu has none of the bioactive
Bowman–Birk inhibitor or lunasin.
Figure 18.19 fried tofu.
3. Olive oil French fries are among the latest confusion offered by ethnic restaurants. French fries are
deep-fried potato. Olive oil is among the worst oils for frying because the smoke point of olive oil is
very low and makes the oil prone to generate smoke after few reuse. Fried olive oil is not as healthy as
fresh olive oil. Olive French fries are worse than French fries prepared using sunflower or safflower oil.
4. Fried and grilled foods in Mediterranean restaurants: Mediterranean restaurants that offer Middle
Eastern foods also offer fried broccoli, calamari, cheese, chicken, dough, eggplant, fish, kubbeh,
and others. The psychology of eating healthy once again trumps over the reality of eating unhealthy.
5. Fried and grilled foods in Greek-type restaurants: Fried foods are offered in Greek-type restaurants.
Fried Batzos, broccoli, calamari, cheese, chicken, eggplant, fish, octopus, pork, potato, prawn, san-
torini, shrimp, zucchini, and French fries, grilled calamari, and kabob are served. While chicken
nuggets are being considered as unhealthy, the range of fried foods listed earlier and available in
Greek restaurants is not better than chicken nuggets. These foods are fried in oil and carry the same
proinflammatory factors that are common to fried foods containing sugar and proteins.
6. Westernized Chinese foods: Chinese fast-food restaurants in the West offer a wide range of meals
including stir-fried foods (Figure 18.20) that by no means resemble Chinese cuisine in Mainland
Figure 18.20 Westernized Chinese foods.

aDoPtInG a DIet 371
Figure 18.21 fried Indian foods.
China, Taiwan, or other parts of Asia. Steamed and boiled foods are also offered. Fried foods from
Chinese fast-food restaurants are not different from fried foods from traditional Western fast-food
restaurants. High levels of AGEs are characteristics of these types of foods.
7. Fried Indian foods: Indians fry foods a lot, probably more than many other cultures (Figure 18.21).
Food is stir-fried or fried, spices are roasted or stir-fried, and everything can be stir-fried. India is
probably the spice capital of the world. However, it needs to be shown if fried spices maintain their
contents of anti-inflammatory bioactive compounds. The “Indian” system of medicine, named as
Ayurveda, uses plant products as herbal medicine, food supplement, or spices, in everyday cook-
ing. While data in the laboratories in models of chronic diseases in vitro show excellent results,
these compounds have not always been as efficacious at the translational level as they are in vitro.
Curcumin has been touted as Indian Solid Gold or cure mine [184]. Curcumin has been compared
to some of the most potent modern cancer and other disease drugs including Humira, Remicade,
Enbrel, Avastin, Erbitux, Erlotinib, and Gefitinib, and Herceptin [184]. Cinnamon [185,186], fenu-
greek [187–189], and amla [190,191] are very good against diabetes mellitus. While the rate of
age-adjusted all cancer-related deaths are very low in India, age-adjusted coronary heart disease
death rate is among the highest in the world, diabetes mellitus and dementia death rates are not low
(http://www.worldlifeexpectancy.com/). Actually, India has been dubbed as the diabetes capital of
the world because the country leads the world with the largest number of patients with diabetes
[192], although China has recently taken the number one spot in the world. Stroke-related mortality
is higher in India and China than in Europe or North America [193]. Asian Indians living in the
United States, Canada, and Europe are at higher risk of developing type 2 diabetes, obesity, and
coronary artery disease compared to non-Hispanic Whites and other Asians in the regions men-
tioned [194].
18.7 CONCLUSION AND FUtUre DIreCtION
While individuals are free to opt for whatever eating habits they would like to choose, at the end
of the day it boils down to the economics of diet adoption. In a world where tax money is shrink-
ing because of the many services taxpayers would like to have, responsible consumer education
becomes paramount. Instead of leaving consumers be at the mercy of merchants of foods, it may
be time for consumer advocates to know more about the major differences in food offerings on the
markets. Then the same consumer advocates, whether it is the government or nonprofit organiza-
tions, should reach out to consumers through networks where the most vulnerable consumers can be
reached. Television networks are some typical ones because it can be seen by the most vulnerable
consumers or low-income consumers that do not have regular access to the Internet. These popula-
tions can still afford TV channels where programs of interest to them are broadcasted. This way
healthy eating habits and healthy eating choices can be easily taught to millions if not billions of
consumers and healthcare costs can be reduced.
While people cannot be deprived of the joy of experiencing diverse types of cuisine and foods,
moderation in eating habits should be the message to all consumers. However, consuming a wide
range of AGE-rich in moderation will not solve the problem. Consumer advocates can focus on this.
Eating AGE-less foods in moderation is the message.
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ChAPter 19
thinking Outside the traditional Box and

Setting Up and Maintaining a healthy
Pantry, refrigerator, and Freezer
19.1 INtrODUCtION
It is not uncommon to run into people who simply say that they do not have time to fix a meal for
themselves at home. As a result, some people say that they do not have time to fix breakfast for them-
selves. Others skip lunch because of job-related or social activities. Individuals want convenient foods
or beverages that may be grabbed on the go. Therefore, increasingly people are eating more away from
home than at home. Providers or venders of convenient foods or beverages do their best to provide
tasty and flavorful foods or beverages in hope to retain the clientele. To do so, the cook or food vendors
will use ingredients that make the food tasty and look good in order to keep the clientele.
The previous chapters of the book have shown that most ingredients for convenience cooking
are proinflammatory. These ingredients are consumed regularly on a daily basis because most of
these ingredients can be used for breakfast, lunch or dinner, or found in snacks.
Most people in the Western world including children, adolescents, and adults do not eat well both
at and away from home for several reasons. (1) Most children in the Western world, if not all of them,
are born from parents whose diets are centered on sweet and salty foods, sweetened beverages, and
less vegetables and fruits. The children start their lives ingesting processed sweet and salty foods and
drinking sweetened beverages all day long. Very few of them are breastfed. Parents fill the pantry
with sweet and salty foods and sweetened beverages. (2) When the children start school, they have no
option; the cafeterias offer advanced glycation end product (AGE)-rich foods and beverages includ-
ing glazed doughnuts, pizzas, macaroni and cheese, and sweetened beverages and desserts. (3) The
convenience stores as well as the supermarkets offer the same types of foods: AGE-rich and poten-
tially proinflammatory, oven-baked, hot and salty, frozen and too sweet, cold and sweet, or glazed
and sweet. Pure water is less consumed; however, some manufacturers sweeten water and slightly
add artificial flavor making children drink sugar all day long thinking that they are drinking water.
(4) Low-income parents can’t afford produce for their children. Healthy foods such as sweet potato or
okra are fried or cooked with butter because fried foods taste better. Fried chicken and potato taste
better than stewed chicken or potato. (5) Children are a good target for new food products; sweet and
salty new food products in the supermarket target kids. All these reasons, sweet, salty foods, and so
forth, leave the children and even adults exposed all day and year round to less healthy foods.
The prevalence of too much sweet and salty food products at the disposal of the children and
young often leads to obesity. More than 75% of adolescents who develop obese remain obese
throughout their adult lives. As adults these individuals are prone to develop chronic degenera-
tive diseases including insulin resistance, diabetes, hypertension, atherosclerosis, cardiovascular
disease, cancer, Alzheimer’s, Parkinson’s, gallbladder, and other rare diseases. The kids and young
381
with obesity, abnormal levels of blood pressure, and cholesterol tend to have “difficulty in concen-
tration,” “undesirable eating habits,” and also develop fatigue symptoms early during school hours.
These kids and young persons are prone to become less productive later in life.
For some children the side effects of such exposure show through weight gain, fatigue, and
reduced productivity at school and home. For other children, symptoms will wait and show up later
in life as shown by the AGE-related chronic degenerative diseases in Chapter 3.
Knowing that the prevalence of some of the chronic degenerative diseases including cancer and
AD is in part the result of unhealthy eating habits, it is important that every effort be made to pro-
mote healthy eating at home and away from home. Parents or guardians set the tone in households.
It has been shown that individuals who skip breakfast tend to gain more weight than those who eat
healthy breakfast. Infant nutrition begins in the mother’s womb suggesting that maternal nutrition
is quintessential for healthy child development.
19.2 thINKING OUtSIDe the trADItIONAL BOX AND SettING UP AND

DeVeLOPING A heALthY PANtrY, reFrIGerAtOr, AND FreeZer
The industrial revolution brought about several improvements in human lives. Agricultural products
can keep longer if stored at refrigeration or freezing temperatures. The pantry, refrigerator, or freezer is
the storage or housekeeping of ingredients or food products that in part determine the quality of snacks
or meal and foods that show up on the dining table. Households, academic institutions, healthcare insti-
tutions, restaurants, and government are examples of entities that all build and rely on storages such as
pantries, refrigerators, and freezers to provide meals to their families, students, patients, or personnel.
The cooking temperature is also a critical factor in the quality of foods that humans ingest.
Eating healthy involves thinking outside the traditional family pantry and grocery store and
thinking outside the box (Figure 19.1). Eating healthy involves breaking the traditional habit of
consuming commonly used food items. It requires understanding the benefits and risks of using
traditional methods of procuring food ingredients and developing recipes. It involves critical think-
ing that takes one away from the comfort zone of traditional flavor. It starts with the pantry where
ingredients and foods are stored for meal preparation. The following is a short discussion on what
would constitute a healthy pantry, refrigerator, or freezer for healthy life.
Figure 19.1 thinking outside the traditional box.

tHInKInG outsIDe tHe traDItIonaL BoX anD settInG uP 383
1. Beverages
Store More Also Store Store Less or Not at All

Water including spring water fruit juices (≤45 g sugar per day Carbonated beverages
and mineral water, cow’s milk, for adult men and ≤30 g sugar per (sweetened or diet),
goat milk, soymilk, almond day for adult women) punches, fruit drinks
milk, ciders
tea bags (green, oolong, black,
hibiscus, sage, mint)
unsweetened chocolate without
milk powder
unsweetened cinnamon
Coffee
2. Appetizers
Store More Store Less Store Less or Avoid

Celery, cauliflower, spinach, and Processed meat Liquid cheese or cheese sauces, baked
artichoke dip, proportioned products cheese products, fried cheese, baked
quantities of guacamole, bean dip cream cheese products, butter, bacon,
with celery, humus, lima bean dip, meat balls, prosciutto or prosciutto-
kale dip, yogurt dip, mushroom, wrapped foods, roasted seeds, hot
crab meat, onion dip, crudites with dogs, sugar cookies, sugar tortillas,
blue cheese dip, eggplant humus, bacon pizza, bacon cheese, bacon
pistachio dip, cherry tomatoes, sugar crackers, glazed products,
boiled edamame sugar-coated fruits, fried pickles, hush
puppies, cheese sticks
3. Cereals
Store More Also Consume Store Less

Minimally processed whole grain cereals Minimally processed Phosphate-rich
including Quaker oats, quinoa, amaranth, processed cereals,
sorghum, corn, brown rice, wild rice, buckwheat, white rice, refined
whole wheat pasta bread (whole wheat) flour-rich cereals
4. Flours
Store More Store Less

Whole grain unbleached flours including flours from almonds, amaranth, brown Bleached and
rice, buckwheat, chestnut, chickpea, corn, coconut, sorghum, spelt, tapioca, very refined
quinoa, wheata flours
a not for gluten intolerant people
5. Bread
Store More Store Less

Whole wheat bread, whole wheat dinner rolls, gluten-free White bread, butter-rich dinner rolls,
(corn, potato, sorghum, rice) bread butter-rich croissants
6. Pastries
Consume in
Store and Use More Moderation Store Lessa
Gluten-free and sugar-free unsalted pretzels Buttery croissants, glazed or honey-rich
pastries, whole wheat pastries, baklava, calzone, sugar-rich fruit or
sugar-free and glazed- nut pies, fig rolls, empanada, spicy fried
free pastries, coconut pastries with savory filings such as ground
powder, cinnamon meat, vegetables, vegetable proteins,
powder streusel toppings, jelly doughnut, toaster
pastry such as Pop-tart, salted pretzels,
brownies, donuts, muffins, twinkies
a not good for diabetics
7. Spices, Seasonings, and Flavorings
Store and Use More Store Less or Avoid

turmeric, ginger, cinnamon, anise, basil, black pepper, cayenne Hot chili capsaicin-rich pepper,
pepper, chili powder, caraway, celery flakes, cilantro, cumin, Worcestershire sauce,
curry powder, dill seeds, dill weed, garlic, mace, marjoram, fructose- or syrup-rich sauce
mustard, nutmeg, onion, oregano, paprika, poppy seeds, any bouillon (meat, vegetable
sesame seeds, tarragon seeds, thyme, orange peel, allspice, or seafood)
saffron, vanilla extract
8. Herbs
Store and Use More Consume rarely

sage, rosemary, basil, thai basil, thyme, oregano, mint, chives, cilantro/ Catnip, patchouli
coriander, dill, fennel, lemongrass, mint, parsley, saffron, tarragon,
peppermint, marjoram, sorrel, sassafras, lemon balm, savory, lemon
verbena
9. Oils
Store and Use for Salad For Baking and Sauteeing Consume Occasionally
Virgin olive, avocado oil, canola safflower, sunflower, sesame Palm oil
10. Fruits
Watch for Consume

Store and Use More Sugar Occasionallya
apples, oranges, whole berries (blueberries, cranberries, Grapes, sugar-sweetened
raspberries, blackberries, boysenberries, cranberries), watermelon dried fruits
cherries, banana, cantaloupe, citron, figs, mango, kiwi,
papaya, plums, pears, pomegranate, pineapple, avocado,
apricots, lemon/lime, persimmon, grapefruit, squash
a not good for diabetics
11. Vegetables
Store and Use More Consume rarely

Kale, endive, spinach, broccoli, broccolini, asparagus, Brussels Chard, canned sweet corn,
sprout, turnip, carrots, artichoke, cucumber, celery, snow pea, canned sweetened vegetables
cabbage, whole tomatoes, bell peppers, red beets, sweet
potato leaves, cauliflower, eggplant, fennel, green onion,
rhubarb, okra, watercress radish
12. Mushrooms
Store and Use More

White button, shiitake, maitake, oyster, portabella, king trumpet, brown or white beech
13. Nuts
Consume
Store and Use More Less Beware Of
raw almonds, walnut, cashew, pine, nut butter aflatoxin-contaminated nuts including
peanut, hazelnut, coconut, chestnut, peanut and pistachio in most developing
pecan, pili nut, macadamia, pistachio countries, Brazil nut (allergen)
14. Pulses and Legumes
Store More Pulses Also Store More Also Store

Dry beans including black, red, pinto, navy, white, sprouted pulses frozen legumes
garbanzo, lima, and adzuki dry peas, lentils,
chickpeas
15. Grains
Store and Use More Avoida

sorghum, millet, corn Gluten-forming cereals such as wheat, rye, buckwheat, oat
a for gluten sensitive individuals
16. Roots and Tubers
Store and Use More Beware Of

sweet potato, yam, purple potato, potato, red beets, carrot, Manioc or cassava, yucca
rutabaga, turnip, ginger, radish, malanga, parsnip
17. Seeds
Store and Use More Avoid

raw sunflower, pumpkin salted-roasted seeds
18. Fish, Seafood, and Marine products
Store and Use More Also Store Store Less or Avoid

Wild-caught oily fish (salmon, Canned fish including farm-raised grain-fed fish, tilapia,
trout, herring, sardines, pilchards, wild or alaska mercury-rich fish (king mackerel,
atlantic mackerel, kipper, eel, salmon, sardines, fresh tuna, yellowfin (ahi), bluefin,
anchovies, bloaters), freshwater anchovies albacore (white) tuna, swordfish)
fish, seaweed
19. Dairy Products
Store and Use More Also Store Moderately Store Less or Avoid
yogurt Cheese Condensed-sweetened milk, spray-dried milk
20. Animal Products
Consume Once a Week Also Store Moderately Consume rarely

red meat Bacon, processed red meat, grilled, fried,
barbecued
21. Poultry Products
Consume Once a Week Also Store Moderately Consume rarely or Avoid

Poultry meat Processed poultry meat, grilled, fried,
barbecued
22. Sweeteners
Store Also Store Moderately Consume rarely or Avoid

Cane sugar, stevia artificial sweeteners agave, all syrups, fructose-rich syrups such
as honey
23. Snacks
Store and Use More Consume Occasionally
Baby carrots, orange segments, apple sauce, dried fruits, jerkies, protein bars, meat fruit
strawberries, raspberries, cherries, pies, chocolate chip cookies, ice cream, chocolate
sugar-free dehydrated fruits, frozen drinks, peanut butter products, popcorn including
yogurt microwave ones, cheese-flavored potato chips
24. Vinegars and Condiments
Store and Use More Consume Occasionally

red wine, white wine, rice or rice wine, apple cider, Dijon mustard Balsamic
25. Lunch or Dinner Meals
Store and
Use More Use Occasionally Avoid/Significantly reduce Consumption
salad, brisket smoked white or red meat, meals cooked at more than
350°f for more than 15 min. Melted cheese, fried
chicken, poultry, or red meat grilled with olive oil,
canned soups, processed meats, nut butter sandwiches
26. Canned Foods
Store and Use More Avoid

Meatless canned beans, low-salt canned tuna, low-salt Canned red or white meat, canned
canned salmon, canned sardines, anchovies soups, instant noodle cups, broths
ChAPter 20
Food Preparation techniques and

Potential health Benefits
20.1 INtrODUCtION
Cooking or fixing raw foods is the final step in food preparation before nutrients are consumed
and released in the body. Cooking is necessary for carbohydrate-rich foods, meat, and certain vege-
tables. Cooking has a great influence, which can be positive or negative, on the eating quality includ-
ing appearance, sensory attributes, antinutrient inactivation, and nutrient bioavailability. Cooking
by blanching, boiling reduces the levels of pesticides or natural toxicants such as the insecticide
rotenone in foods [1]. Most nutrients in foods are soluble either in water or in oil. Depending on
the cooking method, cooking can either concentrate or reduce the levels of nutrients in the cooked
foods. The following paragraphs analyze the association of cooking methods and health. First, the
relationship of Western cooking practices and health is analyzed. Second, a variety of cooking
practices some of which are as old as human civilization are presented with their advantages and
disadvantages.
20.2 ASSOCIAtION OF WeSterN COOKING StYLe AND heALth
Since 1850, advances in public health and medical interventions have led to decreased mortality [2].
This progression in life expectancy has led some scientists to suggest that life expectancy in the
United States and most Western nations will rise to reach 100 years by the year 2060 [3]. For the
United Nations, life expectancy of 100 years for males and females in most countries was projected
for the year 2300 [4]. However, these forecasting and projections have not taken into account current
trends in health and mortality as affected by lifestyle and environmental conditions.
Western cooking often involves barbecuing, frying, grilling, charbroiling, smoking, toasting,
roasting, and steaming or stewing. Frying releases and destroys lipid-soluble compounds such as
vitamins A, D, E, and K. Similarly, lipid-soluble toxicants can be released in the frying oil. Grilling
releases bioactive compounds including lipid-soluble ones and develops some unwanted toxicants
if any. Smoking releases water but accumulates unwanted compounds from the smoke and most of
them are carcinogenic. The high temperature associated with these cooking techniques favors the
Maillard reaction in all cases.
The downside of the Western cooking style has been identified through the development of meta-
bolic syndrome and other chronic degenerative diseases. The rise in metabolic syndrome in the Western
nations and worldwide threatens the health and life expectancy of current and future generations.
Obesity is a risk factor for type 2 diabetes, cardiovascular disease, cancer, and several other health
problems. The rise in obesity worldwide is expected to have a negative effect on life expectancy
389
and longevity. Severely obese people may have a life expectancy that is 5–20 years shorter than
nonobese healthy individuals of the same age [5]. It has been suggested that obesity may cause the
current youth and young people to live shorter and less healthy lives than their parents [4]. Increased
exposure to food toxicants generated during Western-style cooking, including Maillard reaction
products, acrylamide, heterocyclic amines (HCAs), nitrosamines, and polyaromatic hydrocarbons,
has negative effects on health, life expectancy, and longevity.
Sixty-two healthy volunteers participated in a 1-month randomized crossover diet-controlled
study that compared the effect of a diet based on food prepared by mild steam and a diet based
on food cooked at a very high temperature [6]. The content of Maillard reaction products based on
Nε-carboxymethyllysine content was higher in the food cooked at high temperature compared to the
food cooked by steam. High-temperature-treated foods induced insulin resistance, reduced plasma
levels of antioxidant vitamin C and E, and increased plasma levels of cholesterol and triglycerides,
all of which are markers of increased risk of type 2 diabetes development.
Acrylamide, a neurotoxin harmful to humans, has been detected and quantified in several pro-
cessed foods and food cooked at temperature higher than 120°C (248°F) [7]. Acrylamide-rich foods
include French fries (200–12,000 µg/kg), crispy potato chips (170–3700 µg/kg), onion soup and dip
mix (1184 µg/kg), crispy bread (800–1200 µg/kg), biscuit crackers (30–3200 µg/kg), gingerbread
(90–1660 µg/kg), cooked Taco shell (559 µg/kg), nuts and nut butter (64–457 µg/kg), and baked
products including breads, bagels, cakes, cookies, and pretzels (70–430 µg/kg) [8]. Some wheat
flours contain significant amounts of asparagine and during baking or frying acrylamide can be
formed from the interaction of reducing sugars in the flour and asparagine.
In vitro studies have shown that acrylamide or its metabolite glycidamide is proinflammatory
[9,10]. In vitro studies have also shown that proteins targeted by acrylamide are associated with
neurodegeneration, diabetes, and atherosclerosis [10]. Increased consumption of acrylamide-rich
foods is also expected to have a negative effect on longevity and life expectancy.
HCAs are toxic compounds formed in grilled, broiled, pan-fried, roasted, baked, barbecued,
deep-fat fried, smoked, and grilled meat and fish [8,11]. High levels of the heterocyclic amine
2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine were detected and quantified in pan-fried
chicken cooked with skin on, pork, and salmon cooked with skin on using Brazilian cooking meth-
ods such as churrasco whereby food is cooked without oil on a grid over charcoal for a long period
of time [12]. Jahuru et al. [13] reported that in Malaysia fried and grilled chicken were the major con-
tributors to dietary sources of HCAs. Sardines and salmon are good sources of omega-3 fatty acids
known for their health-enhancing activities. However, sardines or salmon grilled at 280°C–300°C
or 180°C–200°C contained significant amounts of HCAs [14].
Nitrosamines found in processed meats are genotoxic and increase the risk of gastric cancer
development. A large European study followed 448,568 men and women between the age 35 and
69 years old at baseline without prevalent cancer to examine the association of meat consumption
with cause of death [15]. The study found that consumption of 20 g of processed meat or higher was
moderately associated with cardiovascular disease- and cancer-induced mortality. Pan et al. [16]
used a validated food frequency questionnaire that was updated every 4 years to follow 37,698 men
from the Health Professionals Follow-up Study (1986–2008) and 83,644 women from the Nurses’
Health Study (1980–2008) to evaluate the association between meat consumption and mortality.
The study documented 23,926 deaths of which 5910 were cardiovascular disease-related and 9464
were cancer deaths.
It was concluded that the risk of total cardiovascular and cancer mortality increases with increased
consumption of red meat. Sinha et al. investigated the relationship of red, white, and processed meat
consumption to mortality risk by following for 10 years over 500,000 people aged 50–71 years old
enrolled in the NIH-AARP Diet and Health Study [17]. Total of 71,252 deaths of which 47,976 men
and 23,276 women occurred. The study found a modest association between red and processed meat
consumption and total mortality including cancer-related and cardiovascular-related mortality.
fooD PreParatIon teCHnIQues anD PotentIaL HeaLtH BenefIts 391
Polycyclic aromatic hydrocarbons (PAHs) are formed at very high temperature in the range of
400°C–1000°C and are found in smoked or charcoal broiled foods [18]. PAHs are formed when
wood undergoes thermal decomposition at high temperature. The International Agency for Research
on Cancer has concluded that some of these high-temperature-generated toxicants are potential car-
cinogens for humans [19].
Several attempts have been made to reduce the formation of HCAs, acrylamide, nitrosamines, and
PAHs. Marinades of tomatoes [20], tart cherry tissue [21], onion and garlic [22], or a combination of
lemon juice, soy sauce, minced garlic, clover, and honey [23] have been identified as potential inhibi-
tors of toxicant formation. Beer and wine marinades have been investigated for their ability to reduce
toxicant formation during high-temperature cooking. Beer marinades have been reported as better
than wine marinades [24]. However, neither beer nor wine marinades can completely prevent the for-
mation of toxicants when protein-rich foods such as poultry, red meat, or fish are grilled, charbroiled,
barbecued, baked, or fried. Also, marinating does not have a significant effect on Maillard reaction
formation because the components of marinate are often made of reducing sugars and others that in
fact exacerbate the Maillard reaction and the formation of advanced glycation end products (AGEs).
20.3 ASSOCIAtION OF DIetArY BIOLOGICALLY

ACtIVe COMPOUNDS AND heALthY LIVING
Longevity and life expectancy is a combination of several factors that include, among others,
nutrition. Dietary bioactives are promoted for their health-enhancing properties suggesting that
individuals who consume it should be healthier than individuals who consume less or none of it. India
is a nutritional paradox with relatively wide range of health-enhancing spices but low life expec-
tancy. The same can be said of several countries in Africa, Latin America, and Asia. In Western
nations, dairy and animal bioactives are promoted as health enhancing, life expectancy is higher
than in most developing economies, but advanced ages are not disability-free. In countries where
fermented foods are consumed regularly, advanced ages are not disability-free. It appears that there
is no correlation between
• The health benefits of spices and life expectancy in spice capitals of the world
• The health benefits of dairy bioactives and disability-free adult life in Western nations
• The health benefits of meat and poultry products and disability-free adult life in Western nations
• The health benefits of fermented vegetables and longevity in countries where fermented vegetables
are consumed daily
There is a correlation between traditional cooking habits and longevity and disability-free old
age in populations of Ikaria, Nicoya, Seventh-day Adventists of Loma Linda, Okinawa, Crete, and
Sardinia. The ingredients may be good but the cooking conditions/methods are also very important.
Several factors including ingredient types and cooking parameters such as water activity and acidity
affect the outcome of cooking foods. Cooking habits throughout young and adult age may correlate
with the quality of adult life.
20.4 ASSOCIAtION OF trADItIONAL COOKING teChNIQUeS

AND DIetArY BIOACtIVe AVAILABILItY
The early chapters of this book have focused on high-temperature cooking. The side effects of
high-temperature cooking have been mentioned. Traditional cooking methods have often involved
steaming, boiling, poaching, blanching, or stewing foods. The nutritional advantages and disadvan-
tages of consuming steamed, boiled, poached, blanched, and stewed foods are briefly discussed.
20.4.1 Steaming
Steaming is a traditional cooking technique that involves the use of steam in a steam cooker. The
temperature of the water steam reaches 212°F. Steaming has been used in Chinese cuisine to cook rice
for more than 3000 years. Similarly, the Japanese and Indians have been consuming steamed rice for
centuries. The Songhai communities in Gao, Mali, used steaming during the Iron Age to cook cous-
cous, a semolina dish, and rice [25]. Ibn Battuta, the fourteenth-century Arab explorer, extensively
described steamed couscous as a main staple in West and North Africa thousands of years ago [26].
Tamale is an example of steamed or boiled food regularly prepared in Central America for centuries.
In steaming, the food is placed on a bamboo or stainless steel basket with openings, inserted into
a pot and suspended above a small amount of water. The water is brought to a simmer or boil, the
steam from the water reaches a maximum temperature of 100°C or higher by pressuring the water
(Figure 20.1). During steaming, only the steam contacts the food, the food is not submerged and as a
result micronutrients as well as macronutrients do not leach from the food. Steaming can be used for
any food, for breakfast, lunch, or dinner meals. Flavor retention and texture and appearance of the
original food product are excellent compared to raw uncooked food. Nutrient loss is very minimal
for minerals and heat-stable vitamins such as vitamin B1 and B2 [27].
Vitamin C is highly heat-sensitive and susceptible to leaching in water that can be thrown away.
Vitamin C retention in steamed carrot was 86%, water C leach in water boiled carrots was 40% of which
11% was loss in the cooked water [28]. Retention of vitamin C in steamed broccoli was 83%–100% in
5 min steaming and 45%–63% in boiled broccoli and acceptability of steamed broccoli was higher
than boiled broccoli [29]. The same study showed that the retention of folic acid in steamed broccoli
was better than in boiled broccoli. Steaming broccoli is associated with less leaching and increases the
extractability and availability of sulforaphane from broccoli tissue [30,31]. Sulforaphane is the major
health-enhancing bioactive compound associated with the health benefits ascribed to broccoli.
Vitamin K1 is mostly found in green vegetables such as broccoli. Steaming broccoli nearly
doubles vitamin K1 bioavailability compared to fresh broccoli [32]. Steaming vitamin C-rich foods
such as berries prevents further vitamin decrease during storage [33]. In general, vitamin loss in
steamed food is minimal compared to other conventional cooking techniques such as baking, bar-
becue, stewing, microwaving, frying, or roasting. Lysine is an important amino acid for growth.
Wheat is a poor source of lysine but the major ingredient for bread, which is the most consumed
Figure 20.1 steamed vegetables.

food in the world. Baking destroys the amino acid lysine, whereas steamed bread preserves the
little amounts of the amino acid lysine available in wheat [34]. Steaming like other conventional
cooking methods including grilling, boiling, frying, and microwaving is associated with about 50%
vitamin B12 loss [35]. Steam blanching and cooking of white cauliflower causes less reduction of
phytochemicals compared to boiling or blanching with water [36].
Steamed bread (Figure 20.2) does not contain acrylamide because acrylamide is generally gen-
erated in food containing the amino acid asparagine and cooked at high temperature of 150°C or
above. Recently as early as July 2, 2014, the European Food Safety Authority (EFSA) has con-
firmed that animal studies link acrylamide consumption to increased risk of developing cancer
regardless of age group and children are the most vulnerable. Animal studies have also shown that
acrylamide may also have harmful effects on the nervous system [37–40], pre- and postnatal devel-
opment [41,42], and male reproduction [43–45]. Dietary sources of acrylamide include fried potato
products, coffee, certain baby foods, and baked wheat products including soft bread, crisp bread,
crackers, and biscuits. Acrylamide is easily absorbed in the body from gastrointestinal tract and dis-
tributed to all organs where it is extensively metabolized. Acrylamide is neurotoxic and mutagenic.
One of acrylamide metabolite known to date is called glycidamide and the latter is harmful to
DNA and reproductive system [46,47]. Human studies have shown that glycidamide is also formed
in the human body [48,49]. EFSA has recommended future research on acrylamide in humans and
in June 2015 there will be a final adoption of recommendation that will allow the EFSA’s experts to
develop approaches to help decision-makers take appropriate actions to reduce consumer exposure
to acrylamide in food.
Steaming involves heat and mass transfer to and from the food product, produces loss of fat, an
increase of water content at the center of the food product. In stewing, heat transfer occurs by con-
vection. In the case of proteinaceous red meat or fish, in the event there are precursors of HCA such
as quinolones and quinoxalines in the meat or fish, stewing favors the transport of HCA precursors
to the surface of the food and finally in the cooking liquid leaving behind in the meat or fish a lower
amount of precursors of HCA.
In general, stewing, boiling, stir-frying, or roasting leads to lower amounts of HCA formed com-
pared to griddling, pan-frying, barbecuing, and deep-frying because of lesser heat transfer in the for-
mer mode of cooking. Fried chicken contains more HCA than griddled than roasted chicken meat.
Antioxidants do not help reduce the formation of HCA. Steaming including microwave steaming of
vegetables is generally associated with more vitamin and phytochemical retention than boiling in water.
Figure 20.2 steamed bread.

20.4.2 Decoction and Boiling
Decoction refers to boiling any herb such as tea and water together. Decoction is commonly
used in many parts of the world except for the Western countries where infusion is the most com-
mon practice for preparing tea beverages. In curing infusion, only the water-soluble compounds
leak into the water and will be consumed. However, during decoction, all compounds including
soluble and nonsoluble constituents are in contact with the boiling water. Tea including black, green
oolong, or any other type can carry contaminants such as pesticides, environmental pollutants,
mycotoxins, microorganisms, toxic heavy metals, radioactive isotopes (radionuclides), and plant
growth regulators [50]. As a result, contaminant leakage into the brew prepared by infusion is dif-
ferent from contaminant transfer from tea to tea beverage prepared by decoction. Overboiling of tea
beverage favors the transfer of more contaminants into the beverage.
After 20 min of processing, boiled carrots contained a lower amount of β-carotene (19%) com-
pared to steaming, which retained about 40% of β-carotene [51]. Boiled peanut is less allergenic
than roasted peanut [52].
Common beans require cooking before consumption. Boiling destroys antinutrients such as lec-
tins. During boiling, water-soluble bioactive compounds such as the proanthocyanidins and phytic
acid are leached to the soaking and cooking water suggesting that consumption of the bean and
cooking water is encouraged because the beans are significantly depleted of bioactives after boil-
ing. Boiling kale (Brassica oleracea var. sabellica) at 100°C for 2 or 4 h was not associated with
phytochemical loss [53]. However, boiling or blanching white cauliflower causes significant mineral
and phytochemical losses [36].
Garlic, shallot, and onions are the best dietary sources of polysulfides. Garlic and shallot are
commonly used in Asian cuisines. In most Asian countries, shallot is preferred over onion because
of its pungency and usage in pickles or as a flavorant [54]. Baking and deep-frying reduce the forma-
tion of healthy bioactives.
Pressure-cooking increased the concentration of polyphenols in chickpea [55] and reduced fin-
ger millet polyphenols by 50% [56]. Pressure-cooking or open-pan boiling reduces total flavonoids
and significantly reduces finger millet polyphenol bioaccessibility [56].
Saponins and phytic acid are antioxidants and anticarcinogens. The health benefits of phytic
acid for humans have been demonstrated [57,58]. The old time unsubstantiated antinutrient property
ascribed to saponins and phytic has been debunked by several publications that have shown that these
compounds that are also part of the Mediterranean diet enhance health and reduce cancer cell viability
and proliferation [58–60]. Boiling reduces saponins and phytic that leak into the boiling water [61].
Aflatoxins are associated with high incidence of liver cancer in Asia and Africa. Decreasing
aflatoxin concentration in foods before consumption is desirable because of the toxic effects of these
mycotoxins in human health. Pressure-cooking of green vegetables was associated with significant
reduction of aflatoxin compared to boiling in water [62].
Xanthophylls, specifically zeaxanthin and lutein, prevent age-related macular degeneration.
Egg yolk is an excellent source of xanthophylls including lutein and zeaxanthin. Xanthophylls
are heat-sensitive and it is important to know the effects of heat treatment on the retention of
xanthophylls. Boiling of egg yolk was associated with 22.5% lutein reduction while 16.7% of
lutein was lost during microwave cooking of egg yolk and frying of egg yolk reduced lutein by
19.3% [63]. Orange and yellow peppers are also good sources of lutein, neoxanthin, and zea-
xanthin. Boiling orange or yellow pepper enhances the bioavailability of the carotenoids [64].
Boiling of the peppers showed a decrease in carotenoid contents of some samples but because
the micellar content processed peppers was not reduced the bioaccessibility of the processed
peppers was enhanced compared to raw peppers. This phenomenon is also applicable to carot-
enoid-rich foods such as tomatoes.
20.4.3 Stewing
Stewing refers to cooking solid foods in water; stewing occurs at a temperature less than 100°C
and does not generate more AGEs than frying, broiling, or grilling. However, mineral (calcium,
sodium, potassium, magnesium, and phosphates) and vitamin loss is a significant disadvantage
associated with stewing. Stewing decreases the vitamin content of beef cuts and thiamine leaching
between 70% and 100% into the cooking water has been reported [65]. It has been suggested that
mineral loss can be minimized by (1) eating the cooked foods with the soup generated, (2) adding
about 1% sodium chloride to the meat during cooking, or (3) reducing boiling time [66]. Unlike
other cooking methods that result in vitamin inactivation, stewing does not because the leaked
micronutrients can be recovered in the cooking water.
Vegetable can be cooked in small amount of water mixed with cooking oil to avoid frying
at high temperature and still develop a flavorful meal (Figure 20.3a through 20.3c). In such an
(a)
(b)
Figure 20.3 (a) Vegetables cooked in water and oil. (b) Vegetables cooked in water and oil. (Continued )
(c)
Figure 20.3 (Continued ) (c) Mushrooms cooked in water and oil.
environment, the vegetable is cooked below or at water boiling temperature and the food will never
reach temperature higher than 100°C as long as water is present in the food system. High quality
meal can be prepared this way.
However, in a study conducted in Uruguay, stewed meat was a strong risk factor for esophageal
cancer development [67]. It has been suggested that the onset of disease may be due to ingestion of
very hot food that may cause thermal injury leading to the disease. Breast and colorectal cancers
rank third and sixth as cause of death in Uruguay and in Argentina breast cancer ranks fourth while
colorectal ranks seventh as cause of death (www.worldlifexpectancy.com). Breast and colorectal
cancer rates in these countries are among the highest in the world. Meat consumption has been
identified as risk factor for these cancer-related mortalities [68]. Leaking of toxic metals such as lead
and aluminum has been observed in foods cooked in aluminum cookware and can pose potential
health hazards [69].
20.4.4 Poaching
Poaching is a cooking technique where food is cooked in liquid at temperature less than 100°C,
generally between 60°C and 82°C (140°F–180°F). While traditionally poaching is used for delicate
eggs, fish, chicken occasionally, and vegetables, this method of cooking results in healthier cooked
foods than other methods such as frying. The formation of AGEs is absent in poached foods and
remains a major advantage for this cooking method [70]. Poaching can be extended to other types
of foods including beef, lamb, and goat for healthy cooking.
20.4.5 Vacuum-Packed Pouch Cooking or Sous-Vide Cooking
Sous-vide cooking refers to “cooking individually packaged foods inside a heat-stable vacu-
umized package in water under controlled time-temperature conditions such as an immersion cir-
culator to maximize the organoleptic characteristics of the foods while destroying all vegetative
pathogens” [71–73]. It is often defined as “under vacuum” cooking. Cooking time may be as long as
1, 2, or 72 h. The sous-vide cooking technique has been a favorite of high-end restaurant chefs since
the 1970s [74]. In the food industry, interest in sous-vide cooking was developed in part as a way to
extend the shelf life of minimally processed foods [75]. In recent years, restaurants and households
have adopted sous-vide cooking [76,77]. Sous Vide Supreme and Anova Precision Cooker are some
of the home sous-vide machines available on the market.
The fundamentals of sous-vide cooking are different from traditional cooking techniques.
In sous-vide cooking, the food is kept in heat-stable and vacuum-sealed plastic pouches and the
cooking is performed under very well-controlled heating conditions. Some but not all chefs prefer
sous-vide cooking over other techniques because of the precisely controlled heating temperature
and time that allow controlling food doneness. The food can be cooked at temperature below 100°C,
may not be well done, but will still be safe. Following cooking, the food is chilled or frozen, stored
refrigerated or frozen, and warmed up before consumption.
A major and very significant advantage of sous vide over other techniques is that it cooks
restaurant-quality meal and the Maillard reaction is slow and hence the formation of AGEs. Other
technical advantages of sous vide include
1. Efficient transfer of heat from the water or steam to the food

2. Increased food shelf life by reducing the potentials for contamination during storage
3. Inhibition of off-flavor from oxidation
4. Prevention of loss of flavor volatiles and moisture
5. Reduction of aerobic bacterial growth
6. Good for restaurants and mass catering
7. Extended shelf life that can reach 12 weeks [78]
8. Reduced need for additional flavor enhancers
9. Reduced Maillard reaction and formation of AGEs
10. Development of a flavorful and nutritious food with little risk of overcooking [74]
Chicory stems cooked sous-vide retained total phenolics and antioxidant activity when com-
pared to stems cooked using other cooking techniques including baking, steaming, and microwav-
ing [79]. Chicory stems cooked sous vide scored very high for sensory and visual attributes such as
color retention and flavor compared to other cooking techniques.
Despite all the advantages mentioned, concerns about the microbial safety of sous vide have
been raised [78]. Positive bacterial counts including staphylococci were detected in both cook
chilled and hot filled foods. However, the counts of clostridia and salmonella were negative.
20.4.6 Fermentation
Fermentation involves the use of microorganisms to predigest the food and convert it into a
more digestible one. Fermented foods are mostly prebiotics and help with the growth and intestinal
colonization of healthy bacteria in the gut. Sauerkraut, kimchi, kefir, natto, fermented corn prod-
ucts, and cultured milk products make the list of fermented food products. Regular consumption
of fermented foods can enhance gut health as these products overpower disease-causing bacteria in
the gut and favor the survival of probiotics. Fermentation can be good or bad to certain nutrients.
Fermented dairy products including yogurts and cheeses have health benefits that do not need
to be discussed anymore. Lactic acid bacteria–fermented dairy products contain bacteriostatic
compounds that can outcompete the growth of Escherichia coli. Fermentation can decrease or
remove allergens, degrade lactose and galactose, and prevent lactose intolerance, and galactose
accumulation develops antibacterial compounds including peroxide, bacteriocins, and lactic acid
[80]. However, in some cases fermentation may be associated with loss of nutrients good for human
health. For instance, fermented broccoli contains less glucosinolates than their unfermented coun-
terpart [31].
20.4.7 Sprouting/Germination
Vegetable sprouts or seed sprouts are excellent sources of bioactives including polyphenols,
amino acids, proteins, minerals, vitamins, and dietary fibers for humans (Figure 20.4). Sprouts of
soybean, mung bean, chickpea, broccoli, buckwheat, and vegetables contain more antioxidants than
the parent seeds or vegetables [81]. Sprouts have gained interest in recent years among consumers
in the United States, Europe, and Asia. Sprout flours are richer in bioactives than nonsprout flour.
Broccoli sprouts contain more sulforaphane than broccoli. Sulforaphane-rich broccoli sprout con-
taining the equivalent of sulforaphane in 100–200 g broccoli reduced the impact of diesel exhaust
particles in 29 individuals who received an intranasal challenge with diesel exhaust particles [82].
Peanut sprout has laxative effect that is totally absent in peanut seeds.
20.4.8 Baking
Baking is an ancient cooking technique that goes back to biblical time. Hot stones, hot ashes,
and hot oven can be used to bake foods. Meat, vegetables, mushrooms, and above all, bread and
bakery products are baked to develop desirable taste and flavor. Baking can be done home or com-
mercial levels. When baking is simultaneously followed by grilling, the whole process becomes bar-
becue. Baking in the oven can be done by convection or thermal conduction. The Dutch oven is also
used for baking and has several names including bread oven, fire pan, and ou feu de champagne.
The Maillard reaction develops easily in baked bread when the conditions such as temperature and
time are ripe. The crust on bread is the classical example of the Maillard reaction when it is taught
in college.
20.4.9 Frying/Broiling
Frying is a cooking technique during which the food is immersed in about three-quarts of an
inch (pan-frying) or completely immersed in oil (deep-frying). In deep-frying cooking tempera-
ture can reach 204°C (400°F) or higher. The resulting cooked food tastes very good (Figure 20.5).
During and after frying, susceptible molecules in the foods undergo oxidation, polymerization, and
sometimes hydrogenation. During frying, acrylamide can be formed in the fried food. French fries
Figure 20.4 Bean sprouts.

Figure 20.5 fried foods.
are good sources of acrylamide. Stir-fried vegetables and cereals are major sources of acrylamide
[83]. Fried tofu may not be as healthy as standard tofu. Regular consumption of fried foods has
been associated with the development of type 2 diabetes mellitus and coronary artery disease,
and in association, this is mediated by body weight, hypertension, and hypercholesterolemia [84].
Frying can also lead to the formation of trans fatty acids. Health problems associated with frequent
consumption of trans fatty acid–rich foods include cardiovascular, insulin resistance, infertility in
women, compromised fetal development, and cognitive decline [85].
However, a Spanish cohort of the European Prospective Investigation into Cancer and Nutrition
followed 40,757 adults aged 29–69 and free of coronary heart disease at baseline (1992–1996),
until 2004. The study found that in this region where olive and sunflower oils are used for frying,
there was no association between fried food consumption and coronary heart disease [86]. The
smoke point of olive oil suggests that the oil may not be good for frying, yet several studies in
the Mediterranean region show that extra virgin olive oil contains significant amounts of health-
promoting antioxidants that make the oil suitable for frying. Pan-frying of olive oil is associated
with more reduction of antioxidants compared to deep-frying. Frying in olive oil is also associated
with the migration of antioxidants from the oil to the potato.
Marinating meat or fish with olive oil before frying is a traditional practice in the Mediterranean
cooking style. Marinating meat or fish with extra virgin oil may reduce the formation of hetero-
cyclic aromatic amines as has been shown in model systems where phenolic extracts from extra
virgin oil inhibited the formation of heterocyclic aromatic amines [87]. In biscuits, the formation of
acrylamide was reduced when extra virgin olive oil was added to the formulation [88]. Convincing
epidemiological evidence suggests that olive oil has cardioprotective effects and limited and sugges-
tive evidence exists for olive oil protection against cancer especially hormone-independent breast
cancer [89].
Cooking and removing skin has been identified as one way to alter the concentration of pollut-
ants such as dioxins, heavy metals, and polychlorinated biphenyls (PCBs) in fish. Heavy metals tend
to accumulate with cooking because these metals are bound to proteins. Frying white fish until well
done increased the risk of prostate cancer formation while water boiling of the same fish developed no
PHA [90]. Recent studies indicate that regular consumption of fried foods including French fries, fried
chicken, fried fish, doughnuts, and snack chips may increase the risk of developing prostate cancer [91].
In some rare cases, frying may not affect human health. The levels of omega-3 fatty acids includ-
ing EPA and DHA are not significantly affected by frying, baking, or broiling of Chinook salmon,
common carp, lake trout, or walleye for 10 min [92]. Peanut is commonly fried in some countries
including China. It has been shown that fried peanut is less allergenic than roasted peanut [52].
Broiling involves exposing one side of the food in lightly oiled pan about 3 in below the broiler
wire and cooking at temperature as high as 500°F. Broiling (225°C) generates more AGEs than fry-
ing or roasting (177°C) or boiling (100°C) [70].
20.4.10 roasting
Roasting is a dry cooking technique during which the food is cooked in an open pan in the
oven. The food, meat, or vegetable is cooked in dry air and a small amount of oil can be used as a
base. Roasting can be at 160°C for slow roasting, 170°C–180°C for moderate roasting, and 200°C
for high-temperature roasting. The level of marbling may also dictate the type of roasting to adopt.
Meat cuts with high marbling are best roasted at low temperature to avoid shrinkage and obtain
better yields. The high temperature associated with roasting is a risk factor for the generation of
mutagenic heterocyclic aromatic amines.
Roasting can be developed in the oven in the presence of steam and as a result of the convec-
tion of heat the temperature on the surface of the meat is low and generates low levels of mutagenic
heterocyclic aromatic amines [93]. Keeping the meat in the microwave before frying reduces the
levels of heterocyclic aromatic amines [94]. Roasting of legumes showed improved levels of health-
enhancing bioactives in foods.
20.4.11 Braising
Braising is also known as pot roasting, oven-steaming, or bake-poaching. Braising is a slow

cooking process that combines frying and boiling of food, mostly less tender cuts of red meat, poul-
try, or fish, to make the meat cut savory and tender for consumption. Braising is commonly used for
less tender beef cuts such as chuck (chuck pot roast, shoulder steak, and short ribs), round (bottom
round rump roast and round steak and shank/brisket) (Figure 20.6). The best cooking device for
braising include crock pot, pressure cooker, large sauté pan, or Dutch oven.
Steps for braising include (1) searing or browning the meat in oil in a pan over medium heat
followed by addition of corn syrup or brown sugar, (2) seasoning the browned meat with spices and
Figure 20.6 Brisket.

herbs, (3) adding small amounts of liquid including beer, broth, juice or wine, and finally (4) sim-
mering the meat in a closed vessel for a long time sometimes on the stove top or at 325°F in a
preheated oven until the meat is fork-tender. This cooking technique delivers a delicious meal if a
tight-fitting lid is used to avoid the generation of too much steam that dilutes the rich sauce.
Braised chicken is a traditional cooking technique that is popular in Asian countries. Braised
chicken is produced by coating chicken with honey or maltose, frying the coated chicken and boil-
ing it in a soup.
Fish can also be braised in any form including steak, fillet, or as a whole. Similar to meat, larger
and firmer fleshed fish can be braised to desired flavor. The seared fish can be simmered in a liquid
made of milk, wine, broth, tomato sauce, or soup. Catfish or cod are tender and can be braised in
shorter time than firm-fleshed salmon or striped bass.
Traditionally, during the braising process, carrot, celery, and onion can be added to the oil drip-
pings left behind by the meat, poultry, or fish stirred for a short period of time and added to the
meat, poultry, or fish for simmering. However, other aromatic vegetables or zest such as garlic, rose-
mary, fennel, orange, lemon or lime, ginger, lemongrass, cabbage, curry, mushrooms, or anchovy
can be braised or sautéed in the oil used for browning and added to the meat or fish for simmering.
Braising is described by many in the culinary area as a cooking technique that is good or very
suitable for busy individuals and still can deliver delicious meals at the table. However, braising
combines the Maillard reaction and caramelization and results in a flavorful yet carcinogen-rich
sauce. Several carcinogenic HCAs are generated during the searing/browning process, and these
HCAs are released in the boiling water or sauce [95]. The addition of spices takes place after the
Maillard reaction and cannot remove or inhibit the heterocyclic compounds.
20.4.12 Searing
The meat, poultry, fish, or shellfish is seasoned with salt and sugar or marinated and charred or
scorched at very high temperature reaching 500°F or higher in a stainless steel or cast iron skillet
or hard-anodized aluminum that was heated with butter or oil (Figure 20.7). The higher the sear-
ing temperature, the shorter the cooking time. A crust is formed that seals the juice in the cooked
meat providing a very flavorful and delicious meal. Wine, vinegar, or aromatic vegetables including
chopped green onions, shallots, and scallions can be added to the seared meat. The Maillard reaction
Figure 20.7 seared meat.

and caramelization take place in seared foods. The juice is not retained by the crust. Despite all the
claims about the taste and flavor of seared food, it is important to remember that the same heterocy-
clic and unhealthy compounds formed during braising can be formed in this process.
20.4.13 Microwave Cooking
Cooking food in a microwave has its advantages including short cooking time, energy effi-
ciency, and apparently a product high in nutritional attributes. Microwave cooking does also have
disadvantages as far as nutrient qualities and quantities are concerned. Microwave ovens tend to
cook foods unevenly due to uneven temperature distribution that is sometimes prone to be a cause
of foodborne illness.
Microwave cooking is desirable for pasteurization and blanching. Microwave cooking destroys
Shigella toxin 2 in milk [96]. Cooking peas in a microwave significantly increases the amount of
polyphenolic compounds but reduces the amount of flavonoids.
Microwave cooking followed by deep frying of chicken or beef satay produced significantly less
heterocyclic aromatic amines than charcoal-grilling or microwave-grilling [97]. Oven-baked and
microwave reheated breaded fish contained less toxic furanic compounds compared to deep-fried
breaded fish [98]. Microwaved egg yolks contained more lutein and zeaxanthin than boiled or fried
egg yolks [63]. Cured meats often contain harmful N-nitrosamines, biogenic amines, and residual
nitrites. Microwave cooking or boiling of cured meats contained less harmful compounds than pan-
fried or deep-fried cured meats [99].
Aflatoxin contamination of corn is a tough problem for corn growers and consumers. Corn with
20 ppb or more is not accepted for human consumption and has to be discarded. It is not always
easy to detect such a low levels of contamination and there are times when false negative results are
obtained. In Mexico, aflatoxins are commonly detected in maize as a result of preharvest contami-
nation or poor postharvest management. In Mexico, most of the maize produced is processed into
tortillas. Microwave cooking of corn tortilla during the nixtamalization step may reduce the levels
of aflatoxins and its cytotoxicity [100].
The levels of hydroxymethylfurfural (HMF) increased faster when honey was microwaved for
6 min compared to conventional heating in a water bath for 90 min without affecting the antioxidant
potential of microwaved honey [101]. Honey is mostly fructose and it is evident that HMF formation
is accelerated when honey is placed under the best condition to accelerate the formation of furfurals.
20.4.14 Canning
Nicolas Appert, a chef in Chalons-sur-Marn, France, invented canning as a technique to pre-

serve foods for Napoleon’s army scattered throughout Europe. Appert won the prize offered by
Napoleon Bonaparte to anyone who could develop a method of preserving foods for his soldiers.
In 1811, Appert published his method in “L’Art De Conserver, pendant plusieurs années, Toutes
les Substances Animales et Vegetales” (The Art of Preserving All Kinds of Animal and Vegetable
Substances for Several Years). Canning was born. The food was put in a jar or bottle, the air was
removed, the bottle or jar was tightly closed with a lid, and the food was cooked for several hours in
boiling water. While Napoleon used jars that could break, in 1810 the British Peter Durand patented
a process whereby metal containers were used instead of jars or bottles. By 1813, Peter Durand had
developed canned meat for the Royal Army.
Canning keeps fresh-like characteristics of the foods, provides an acceptable and convenient
shelf life, and assures microbial safety and nutritional value. Canned milk, meat, and vegetables last
long and can be transported all over the world.
Canned foods are good sources of bisphenol A (BPA). DVDs and CDs are also good sources
of BPA. Avoiding canned foods can reduce exposure to BPA by as much as 50% [102]. Recent
studies in China have shown that the levels of BPA in canned foods are from highest to lowest are
canned foods including vegetables > canned fish and seafood > canned milk and milk products >
cooking oils > and eggs [103]. Foods in metal containers contain more BPA than foods in glass
containers. BPA-reduced cans have been developed and are contributing to reduced BPA levels in
canned foods [104].
Low-acid canned meats, vegetables, and butter are common vehicles of clostridium [105,106].
While commercially canned foods produced in the United States have a low prevalence of botulism,
home-canned foods can be good sources of clostridium [106–108]. Clostridium has been isolated in
commercial canned foods in Europe [109,110].
20.4.15 Double-Sword Nature of Black Pepper
Black pepper contains piperine. Several biological activities have been ascribed to piperine
including antioxidant, anti-inflammatory, immunomodulatory, and antitumor [111–113], preven-
tion of cholesterol gallstone formation in mice [114], inhibition of acetylcholinesterase and butyl-
cholinesterase activities [115], and antiobesity [116]. Piperine also enhances the permeability of
compounds that do not easily cross the intestines to the circulation. The use of piperine in an
environment rich in AGEs may increase the absorption and bioavailability of unwanted AGEs. It is
advised to avoid using black pepper in foods rich in AGEs including barbecues, fried foods, grilled
foods, roasted foods, and smoked or seared foods (Figure 20.8). The foods will be tasty but the
term effect on the body may be the promotion of diseases for which there are no cures including the
metabolic syndrome and several central nervous system inflammatory diseases.
Black pepper is a double sword

ingredient. It is a good antioxidant. It
also enhances the absorption of
compounds that connot enter the
bloodstream alone. In doing so, if
added to fried, grilled, or roasted food
it will help dangerous compounds,
formed during high heat cooking,
enter the bloodstream, and be bad for
the body. Therefore, adding black
pepper to barbecued, fried, grilled,
roasted, bricked, seared, or
smoked foods will do more harm
than good.
Figure 20.8 the double-sword nature of black pepper.

Each cooking technique described in this chapter offers a meal with distinct characteristics such
as flavor and taste. They enhance food enjoyment but each technique has its pros and cons. Flavor
and aroma developed during cooking is sometimes the bottom line for others. The burden of health
problems/diseases associated with each cooking technique is the bottom line for health-conscious
individuals. This burden of disease measures population health outcome looking at mortality and
morbidity associated with the cooking technique. This chapter has slightly touched on the burden
of disease associated with the different cooking techniques presented. As well, the health benefits
associated with each cooking technique were presented.
Food is part of enjoying life. Tasty, aromatic, and flavorful foods make life enjoyable. Often
taste, flavor, aroma, and health do not go hand in hand. This has created a dilemma when public
health authorities or consumer advocates try to promote healthy eating. The multiplicity of tasty,
flavorful yet unhealthy foods around the town makes healthy eating choice a difficult and expensive
task. Healthy foods may be in general very expensive. A fruit is more expensive than juice from the
fruit, and the juice may be just colored, sweetened water with very low levels of health-enhancing
bioactive compounds. Stews are less accepted by many than fried foods; yet most people know very
well that fried foods taste good but are not healthy when consumed regularly.
The burden of disease susceptibility as it can be associated with the different food preparation tech-
niques mentioned earlier implies that continuous efforts must be deployed to remind consumers about
the health benefits associated with the food preparation methods they choose to adopt. Moderation is
the key to avoid ingesting excessive amounts of unhealthy compounds through foods or beverages.
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ChAPter 21
Addressing Children, Youth, and

Consumer education
21.1 SIGNIFICANCe OF heALthY eAtING
Infant nutrition begins in the mother’s womb. Maternal dietary lifestyle during pregnancy can
have a significant impact on the mother and child’s health. Studies have shown that dietary prefer-
ences for individuals develop early in life and children’s dietary preferences are influenced by their
mother’s [1,2]. Studies have shown that children of obese mothers are already predisposed to obesity
because their bloods are overloaded with preobesity factors [3–5]. Studies have also shown that
diabetic mothers are at high risk of giving birth to children with higher systolic blood pressure than
children from nondiabetics mothers [6,7]. Less than half of women with type 2 diabetes plan their
pregnancy and only about half of type 1 diabetic women plan their pregnancy making periconcep-
tional glycemic control difficult [8]. When the glycemic control is poor, the health risks for both the
diabetic mother and the child are very high [9].
After birth, two scenarios are possible: either the infant is breastfed and continues to ingest
whatever the mother is ingesting or the infant is exposed to infant formulas. Several health benefits
have been associated with breastfeeding including a lower risk of acute otitis media, gastroenteritis
and diarrhea, severe lower respiratory infections, asthma, sudden infant death syndrome, and obe-
sity. Breastfeeding also protects the obese, gestational diabetic, diabetic, or nondiabetic mother in
reducing the incidence of type 2 diabetes, the metabolic syndrome, cardiovascular disease, pre-
menopausal breast cancer, and ovarian cancer [7,10]. It is suggested that healthcare professionals
encourage obese, diabetic, and nondiabetic mothers to adopt breastfeeding for their health benefits
and the benefits of their children [7,10].
However, if the mother is on high-AGE foods, the infant will share the load of advanced gly-
cation end products (AGEs) with the mother through breastfeeding [11]. The mother’s milk will
be loaded with AGEs. If the mother eats healthy, the infant will also be well-fed. If the infant is
exposed from breakfast to dinner time to processed infant foods including processed milk products
which are well known to be rich in AGEs, then levels of AGEs in the infant body will increase as the
infant grows older. If the mother decides to take better care of her child by feeding the child healthy
foods then the infant will have a better start in life. It is rare that mothers consuming junk foods
will feed their children with healthy foods. While the microbial safety of processed infant foods is
never an issue of public concern, the continuous exposure of children to AGEs from early on in life
is a silent killer that consumer advocates including the World Health Organization and Food and
Agriculture Organization of the United Nations need to address.
411
21.2 ADDreSSING heALthY eAtING tO ChILDreN AND YOUth
“You are what you eat” is the message that all adults should have for the children and young.
Most kids and young adults do not eat healthy both at and away from home. Children are not eating
healthy for many reasons:
1. Most children if not all of them are born around sweet and salty foods and start their lives ingesting
processed sweet and salty foods all day long. Very few of them are breastfed. Parents fill the pantry
with sweet and salty foods without even taking a minute to read the nutrition facts on food labels.
2. When the children start school, they have no option, the cafeterias offer AGE-rich foods and bever-
ages, and the convenience stores as well as the supermarkets offer the same types of foods: fried,
oven-baked, hot and salty, frozen and sugar-rich, cold and sweet, or glazed and sweet everything.
Water is probably the only beverage out there that is neither sweet nor salty; however, some manu-
facturers sweeten water and slightly add artificial flavor making children drink sugar all day long
thinking that they are drinking water.
3. Children are exposed to too many AGE-containing or AGE-promoting foods including soft drinks
and processed and fried foods.
4. Children are often offered large portion sized foods. Observational and experimental studies have
shown that portion size has a major influence on food intake and appetite control [12]. The more
food is given to children, the more they will eat. When more unhealthy foods are given to children,
their health is threatened.
5. Low-income parents can’t afford fresh produce for their children. Even if they bought sweet potato
or okra, frying is the preferred cooking method because fried foods taste excellent. While low-
income parents cannot afford expensive produce, well-to-do children and parents ingest AGE-rich
foods away from home because the cooking methods are a problem at outlets where most people get
their meals.
6. Children are a good target for new food products; sweet and salty new food products in the super-
market target children.
7. Healthy products that can sustain the tests of time like Pemmican are rare to be found.
8. Products are put into commerce using consumer taste panels designed around “like” or “dislike”
science. There is even a trend to sell dietary supplements to children. All these reasons leave the
children exposed all day and year around to less healthy foods. The prevalence of too much sweet
and salty food products in children’s environment often leads to obesity with more than 75% of
obese adolescents remaining obese until their adult lives and being prone to developing chronic
degenerative diseases including insulin resistance, diabetes, hypertension, atherosclerosis, car-
diovascular disease, cancer, Alzheimer’s, Parkinson’s, gallbladder, and other rare diseases. The
children and young with obesity, abnormal levels of blood pressure, and cholesterol tend to have
“difficulty in concentration,” “undesirable eating habits,” and develop fatigue symptoms early dur-
ing school hours. These kids and young are prone to become less productive later in life.
For some children the side effects of such exposure do not wait too long and show through
weight gain, fatigue, and reduced productivity at school and home. For other children who may be
resistant for a while, symptoms will wait and show up later in life as AGE-related chronic degenera-
tive diseases.
Knowing that the prevalence of some of the chronic degenerative diseases including cancer and
Alzheimer’s disease, may be the result of inadequate eating habits, it is important that every effort be
made to the point where kids eat well 7 days a week and 365 days a year. We suggest the following:
1. Parents, guardians, or adults in charge of raising or feeding children are encouraged to rely more on
minimally processed but microbially safe foods. Parents, guardians, or adults in charge of purchas-
ing foods for children are also encouraged to read the labels on food products before the food is
purchased and fed to the children. It is important to know how many calories per serving there are
in the portion size.
aDDressInG CHILDren, youtH, anD ConsuMer eDuCatIon 413
2. Cook it yourself. It is suggested that parents and all guardians take time to know what is going to
be on the dinner table in the evening. Cooking is fun and can be fun for many. Parents are encour-
aged to help children develop time management that includes healthy eating. When people demand
healthy foods, the restaurant industry will respond positively because it is a win-win situation for
both sides. The notion that we are living in a different time and busy society is not always true.
21.3 CONSUMer eDUCAtION
Overconsumption, overweight, obesity, diabetes, cancer, and Alzheimer’s disease are the concern
of the entire world including developed and developing nations. The world has now about 1.4 billion
overweight people [13]. Governments, the food industry, and consumer advocates have initiated cam-
paigns to motivate consumer to eat healthy, but in many cases, the effects are short term for several
including the presence of the very same foods and beverages that cause obesity and all other chronic
degenerative diseases. In some cases, it becomes very difficult to design effective dietary strategies
or new products because of environmental and/or socioeconomic factors. It will take all including
government, food industry, university researchers, stakeholders, and the consumers to identify and
accept strategies that are good for all involved. Consumer education is a lifelong process that should
not be around for a season and disappears. Only by keeping the message permanent that it will sink
in the consumer’s mind. The food industry also has the responsibility to make healthy foods more
available than unhealthy products. The industry can also regulate the amount of unhealthy products
and ingredients such as saturated fats, high fructose corn syrup (HFCS), and monosodium glutamate
(MSG) that can be added to any food products. This way, the daily intake gets very low and the health
risks are reduced. The same can be applied to other AGE-rich foods that are on the market.
Consumer education is very important because food is a complex system. Food derives from
biological systems and undergoes transformation using the fundamentals of chemistry, biochemis-
try, microbiology, engineering, physics, computer science, molecular biology, and bioinformatics.
Due to the fact that foods are consumed to fuel and maintain the body, it is important that consum-
ers select the best appropriate foods on the market. However, because the food industry with its food
scientists and marketing teams know better about the foods that they put on the market, the industry
should have the responsibility to help people eat healthy. It is also the responsibility of the food
industry to warn consumers on unhealthy products so that consumers can use moderation to enjoy
the products that are on the market. The industry should provide clearer information regarding their
products and address the parents and young.
It is very important to establish healthy eating patterns including adequate portion size of energy-
dense foods and beverages early on in children development. Obesity control has to start early in the
child’s life. Weight control has to be a family-, school-, and restaurant-based intervention.
Extension programs at land grant institutions do a good job reaching out and educating consum-
ers. It is suggested that extension agents be more versed in the fundamentals of food chemistry in
order to help them bring the right messages to the consumers as far as the effects of molecules in
foods on human health and performance. It is also suggested that retired food science and nutrition
faculty get involved in youth food science and nutrition education. It is better to have the experts help
the young understand this complex area of food science than to have people with no food science or
nutrition background all over the media to address the young. Similarly, these individuals who are
numbered and can be found around can also educate consumers on topics such as gluten-free diets,
calories in foods, and the side effects of cooking food at very high temperature. Consumer educa-
tion is very much needed because consumers get easily lost and confused between commercials and
the reality of the foods they consume.
In many countries, eating-out has become an important part of modern lifestyle due to sev-
eral factors including advances in delivering microbially safe foods to customers. Very often taste
triumphs over health in foods offered away from home. It is the responsibility of the food providers
to stay on the “healthy eating message” and develop the expertise required to offer quality products
to consumers regardless of their levels of understanding of the chemistry of foods. Nutritional infor-
mation that is aimed at promoting healthy meal choices at every food outlet is very much needed.
Efforts should be made by governments, consumer advocates, and food providers to ensure that the
food is cooked and served by qualified individuals. The food has to be healthy every day of the year
and served in appropriate portions.
reFereNCeS
1. Skinner JD, Carruth BR, Wendy B, Ziegler PJ. Children’s food preferences: A longitudinal analysis.
2. Skinner JD, Carruth BR, Bounds W et al. Do food-related experiences in the first 2 years of life predict
dietary variety in school-aged children? Journal of Nutrition Education and Behavior 2002;34:310–315.
3. Tenenbaum-Gavish K, Hod M. Impact of maternal obesity on fetal health. Fetal Diagnosis and Therapy
2013;34:1–7.
4. Thompson AL, Bentley ME. The critical period of infant feeding for the development of early dispari-
ties in obesity. Social Science & Medicine 2013;97:288–296.
5. Yang Z, Huffman SL. Nutrition in pregnancy and early childhood and associations with obesity in
developing countries. Maternal & Child Nutrition 2013;9(Suppl 1):105–119.
6. Aceti A, Santhakumaran S, Logan KM et al. The diabetic pregnancy and offspring blood pressure in
childhood: A systematic review and meta-analysis. Diabetologia 2012;55:3114–3127.
7. Trout KK, Averbuch T, Barowski M. Promoting breastfeeding among obese women and women with
gestational diabetes mellitus. Current Diabetes Reports 2011;11:7–12.
8. McCance DR. Pregnancy and diabetes. Best practice & research. Clinical Endocrinology & Metabolism
2011;25:945–958.
9. Voormolen DN, DeVries JH, Evers IM et al. The efficacy and effectiveness of continuous glucose moni-
toring during pregnancy: A systematic review. Obstetrical & Gynecological Survey 2013;68:753–763.
10. Gouveri E, Papanas N, Hatzitolios AI, Maltezos E. Breastfeeding and diabetes. Current Diabetes
Reviews 2011;7:135–142.
11. Mericq V, Piccardo C, Cai W et al. Maternally transmitted and food-derived glycotoxins: A factor pre-
conditioning the young to diabetes? Diabetes Care 2010;33:2232–2237.
12. Fisher JO, Goran MI, Rowe S, Hetherington MM. Forefronts in portion size. An overview and synthesis
of a roundtable discussion. Appetite 2015;88:1–4.
13. Oostindjer M, Amdam GV, Egelandsdal B. Getting Norway to eat healthier: What are the opportunities?
Scandinavian Journal of Public Health 2015;43:66–75.
ChAPter 22
22.1 INtrODUCtION
The “Do-It-Yourself” series is one of America’s best guides in home repair, gardening, auto
repair, and you name it. The series is credited for providing all the helpful tips, shortcuts, and sav-
ings on materials, tools, technology, and instructions needed to perform any household project with
ease and confidence. Millions of copies have been sold since its original printing in 1973. Those
who bought copies and used it remember the good time, the savings made, and satisfaction com-
ing from using the books. The last three decades (1990–2010s) saw a shift from “do-it-yourself” to
“do-it-for-me” for reasons that are beyond this chapter.
The title of this section is more of a reflection of any enjoyable meal one can have at home or
away from home involving foods and beverages. The analogy to champagne and caviar (Figure 22.1)
is just synonymous of one of life’s supreme pleasures. Champagne and caviar are one of the great-
est combinations ever beside peanut butter and jelly. Champagne and caviar is also the pursuit and
applications of healthy gastronomy trends with more use of knowledge of food chemistry rather
than the mere combination of ingredients and flipping of pans to create a good flavor that may be
a health risk or disaster as seen on most media ads or programs. So the idea is to have a lasting
and memorable meal and pleasure time with loved ones or friends at home or away from home.
Champagne and caviar is the mind-set that helps set the tone for anyone to be in good mood at home
and away from home all year round. Globalization and convenience in every sector of life have cre-
ated an unprecedented opportunity for the entire food industry from farm to the cells in the body.
Eating is no longer for sweet tooth. Rather, eating is for health and includes eating for good mood
and eating to stay in good physiological and physical shape. Let us start and end the day with good
cuisine and foods for good mood.
22.2 ChAMPAGNe AND CAVIAr
Champagne is an effervescent white wine that is supersaturated with gaseous carbon dioxide
and about 12.5% ethanol, a pair that makes this beverage unique. Liger-Belair et al. [1] wrote that
approximately five liters of carbon dioxide is dissolved in and escapes from a typical 750 mL bottle
of champagne. The gas bubbles make champagne unique. The continuous flow of huge ascending
bubbles that characterize champagne makes champagne very appealing.
It is fair to say that on average champagne wines contain health enhancing hydroxybenzoic
acids, hydroxycinnamic acids, flavonoids, phenolic alcohols, phenolic aldehydes, and phenols [2].
Tyrosol and caffeic acidic are the major phenol in champagne wines. Tyrosol is also one of the main
health enhancing compounds in extra virgin oil [3]. Other health benefits associated with tyrosol
include the suppression of low-density lipoprotein (LDL) cholesterol synthesis, thereby delaying
415
Figure 22.1 Champagne and caviar.
the development of atherosclerotic plaques and cardiovascular disease and inhibition of oxidative
stress in kidney cells [4,5]. Recently, the European Union has approved a health claim on olive oil
hydroxytyrosol and its derivatives [6].
Forty healthy young volunteers ingested a moderate dose of champagne to determine the effect
of white wine on neurotransmitters such as serotonin, dopamine, cholecystokinin, and β-endorphin
during the first hour after ingestion of champagne [7]. Individuals with low serotonin levels
(<620 nmol/L) responded with an increase in serotonin and individuals with higher basal serotonin
showed a decrease in serotonin. Champagne consumption increased the level of the neurotransmit-
ter dopamine but had no effect on cholecystokinin or β-endorphin. Since dopamine helps positively
control communication in the brain, it appears that a moderate dose of champagne is good for
healthy living. The neuroprotective effects of phenolic compounds such as caffeic acid, tyrosol,
and gallic acid found in champagne have been demonstrated in vitro [8]. Parkinson’s disease is
characterized by a progressive and selective loss of neurons in the brain region that produces dopa-
mine. It has been suggested that the pathogenicity of Parkinson’s disease may in part be associ-
ated with the formation of neurotoxic compounds such as the 5-S-cysteinyl-dopamine. Cell culture
studies have shown that tyrosol and caffeic acid potently protect neurons against injury induced
by 5-S-cysteinyl-dopamine [9]. Champagne consumption in moderation may be helpful against
Parkinson’s disease development.
Caviar is processed salted roe delicacy from sturgeon fish. There are Russian (Acipenser guel-
denstaedtii), beluga (Huso huso), sevruga (Acipenser stellatus), and Persian sturgeon (Acipenser
persicus) [10]. The beluga caviar is the finest and most expensive of all types of caviar. The Caspian
Sea provides more than 90% of world caviar supply. Caviar is mostly harvested from wild stur-
geon, while farmed-raised sturgeons are also a source of the roe. Wild-caught sturgeons are rich in
CHaMPaGne, CaVIar, GooD CuIsIne, anD ICe WIne 417
omega-3 polyunsaturated fatty acids (PUFAs), commonly known as fish oil [11]. As fish roe, caviar
de facto also contains fat-soluble vitamins and phosvitin, and the latter is the most phosphorylated
protein in nature. Phosvitin binds iron tightly and is responsible for the stability of egg/roe oil to
oxidation [12]. The combination of omega-3 PUFAs and phosvitin makes caviar a healthy product.
Caviar has health benefits for the brain and heart [13].
Champagne and caviar are premium products that sell at a high price because of their poten-
tial health benefits and consumer demand. Champagne is effervescent and caviar is salty and yet
champagne and caviar is one food and wine combinations that appeals to many food connois-
seurs. The science of champagne phenolics and bubbles and the science of caviar omega-3 fatty
acids and phosvitin set this combination apart. It is important to say that other food connoisseurs
would love to go for a combination of Cabernet Sauvignon and lamb, Sauternes and foie gras,
Chardonnay and lobster, or Fume Blanc and lemon-seasoned seafood. However, champagne and
caviar is unique.
22.3 ANtIDePreSSING AND GOOD MOOD FOODS
Food can regulate human temperament and emotions. Depressive disorders and cognition func-
tion are interrelated [14–16]. The ingestion of food can have a very significant influence on an indi-
vidual’s mood throughout the day and week. Nutrients extracted from foods are used by different
tissues in the body, including the brain and central nervous tissues for growth and development.
Since the brain and central nervous system are the centers of emotion and mood regulations, it is
important to understand what the brain and central nervous system need in order to keep the body
in good mood.
The brain needs energy from food. Food is the major and often the sole source of nutrients
needed for brain health. About 30% of PUFAs in the human body are concentrated in the brain,
making the brain the largest deposit of PUFAs. The PUFAs exist under two different forms, namely,
omega-3 fatty acids and omega-6 fatty acids. With exposure to foods cooked mostly with omega-6
fatty acids and deficient in omega-3, the levels of omega-3 decreases with aging leaving the brain
more concentrated in omega-6 fatty acids. It is also known that omega-3 fatty acids inhibit the
production of inflammatory cytokines, which the omega-6 fatty acids do not do. The omega-3 fatty
acids have calming effects in the brain. Because of the presence of and need for PUFA in the brain,
it is simply reasonable that the brain in turn needs enough antioxidants to protect the PUFA from
oxidation.
The brain also needs vitamins for optimal functioning. Niacin or vitamin B3 is very much
needed in the brain for healthy aging. The brain needs most of the vitamins and minerals but the
B-vitamin group is much needed to maintain good emotional health. Low levels of vitamin B6 are
associated with increased levels of homocysteine, increased risks of cardiovascular disease, and
impaired immune function. Chicken is a rich source of methionine. Foods that are good sources of
B6 vitamins include banana, cooked or steamed (not fried) salmon, cooked or steamed (not fried)
chicken, baked (not fried) potato, raw nuts, beans, and vegetable juices. Most processed cereals are
good sources of vitamin B6. Spinach is a good source of vitamin B6 but is not recommended for
people with kidney problems.
Serotonin, dopamine, and noradrenaline are neurotransmitters that regulate behavior. Serotonin,
a neurotransmitter obtained from the metabolism of the amino acid tryptophan plays a major role in
sleep, depression, appetite, mood, anxiety, depression, concentration levels (focusing), and memory
and has a calming effect. People with low levels of serotonin may suffer from chronic fatigue syn-
drome. Serotonin can be boosted by a high intake of foods rich in tryptophan, but the tryptophan has
to be properly metabolized into serotonin. Rice, whole grains, beans, banana, raw nuts, fish, eggs,
soymilk, humus, lentils, legumes, tofu, sunflower seeds, and turkey are good sources of tryptophan.
However, under disease conditions, including chronic inflammation, cancer, Alzheimer’s, and
HIV/AIDS, consumption of foods rich in tryptophan may not be enough to help maintain the level
of tryptophan at the optimal level in the body. Under these disease conditions, the body has high
levels of the enzymes indoleamine 2,3-dioxygenase (IDO) and tryptophan dioxygenase that metab-
olize tryptophan into kynurenine instead of serotonin, thereby reducing the levels of tryptophan
needed for serotonin synthesis. Inflammatory biomarkers associated with depression include IDO,
C-reactive protein, COX-2, prostaglandin E2, and the proinflammatory cytokines IL-1, IL-6, tumor
necrosis factor α (TNF-α), and interferon-γ (IFN-γ) [17].
Higher levels of IDO lead to cachexia and insomnia both of which are characterized by low
tryptophan levels. High levels of IDO also allow cancer cells to escape the immune surveillance and
localize in lymph nodes. The level of IDO is very high in the brains of individuals with Alzheimer’s
disease. Individuals affected by one of these diseases may not always be in good mood. This is
to suggest that IDO is a good target for good mood. For individuals with chronic diseases such
as cancer, HIV/AIDS or AD, foods rich in compounds that prevent the degradation of tryptophan
including compounds that inhibit IDO expression are badly needed to allow tryptophan conversion
to serotonin. Some of the food compounds have been mentioned early and include almond and
peanut skin, apple skins, adzuki beans, unsweetened and bitter cocoa, green tea, rosemary, ginger,
and sage.
Oxygen is a major resource for life. The brain needs a good supply of oxygen-rich blood to
help individuals think and manage emotion and stress better. Foods that supply oxygen are foods
that prevent the generation of a low-oxygen environment in the brain, and these types of foods
are needed for the brain. Typical foods in this category include fresh fruits and vegetables, whole
grains, and food low in protein. Regular aerobic exercise is an excellent way of delivering oxygen-
rich blood to the brain cells.
Low level of blood sugar is a common cause of bad mood or moodiness. Since sugar obtained
from food has to travel to the brain in order to keep the body in good mood, anything that affects
blood sugar levels (whether it is sugar transport or storage) will affect human’s mood. Insulin resis-
tance increases the susceptibility to bad mood and suicide. Insulin resistance is a common denomi-
nator to several chronic diseases, including the metabolic syndrome, cancer, multiple sclerosis, and
AD. Beverages containing high sugar, including soft drinks and chocolate drinks, rapidly raise the
level of sugar in the blood. When there is a drop in sugar level, then individuals experience a craving
for a sweet food or beverage or snack. It has been shown that individuals experiencing carbohydrate
cravings tend to feel distressed. In some cases, such emotional instability can be misdiagnosed and
treated with tranquilizer drugs.
Instead of relying on highly sweetened foods or beverages as sources of good mood, foods rich
in complex carbohydrates, such as whole grain cereals, have a pacifying effect because they do
help enhance the absorption of tryptophan. Consumption of whole grain cereals including oatmeal
is therefore advised as an early start in the day (Figure 22.2). Goat milk (Figure 22.3) has been
credited for good mood. Pope Leon XIII (1810–1903) who reigned for 32 years, the longest reign-
ing Pope, breakfasted on coffee and goat’s milk, milk supplied by goats that the Pope kept in the
Vatican garden. This Pope loved goat and spent time watching after the goats. He consumed goat
milk, coagulated goat milk, goat milk whey, and goat cheese that apparently kept him in good mood
and health throughout his pontifical life.
Consumption of foods containing high levels of proteins that are easily digested including meat
and eggs leads to excessive acidity in the body and has been thought by some to promote aggres-
sive behavior in the long run. Meat- and egg-rich foods, although being good sources of tryptophan,
should probably not be good for breakfast.
The stomach–brain axis or the cross talk between the stomach and brain has been estab-
lished. The stomach influences the brain function, and disturbances in the interactions between
the stomach and the brain may lead to altered satiety, behavior, and mood. Gastric bacterial
Figure 22.2 oatmeal is a good food to start the day with because it is a good source of tryptophan.
Figure 22.3 Goat milk.

composition affects normal brain functions and through the stomach–brain axis can induce
changes in behavior. Due to the fact that proinflammatory cytokines such as the IFN-γ and
TNF-α alone can elicit symptoms of depression and their levels are associated with the popu-
lation of good bacteria in the gut, it is reasonable to associate mood disorders with foods. For
instance, consumption of probiotic-rich yogurts has shown to improve mood of individuals who
were initially in poor mood [18].
22.4 GOOD CUISINe
Good cuisine translates into good food and healthy eating. In this book, it has been shown that
most of the time the human palate has been accustomed to a cuisine that generates AGE-rich foods.
Yet simple cooking techniques can generate good foods that can be very tasty and healthy for the
consumer. The association of AGE-rich foods and chronic diseases has been explained in this book.
Good cuisine should focus on developing AGE-free or AGE-reduced foods. Cooking techniques
that can deliver such foods were mentioned in the preceding pages. It is suggested that chefs and
cooks adhere to this new paradigm of healthy eating to deliver foods that can help prevent the onset
and progression of the dozens of diet-related chronic diseases discussed in the preceding chapters.
Good cuisines can be developed by adhering to the following recommendations:
1. Avoid the use of colored sodium salt seasonings including sea salt that are conducive to raising blood
pressure.
2. Avoid as much as possible weekly cooking and consumption of seared, brick-cooked, stone-cooked,
blackened, broiled, fried, grilled, and roasted foods made at home or fancy outlets away from home.
3. Lemon juice added to barbecued, grilled, fried, or roasted foods can significantly reduce the levels
of AGEs.
4. Cook foods at temperatures equal or less than 300°F for a long time instead of frying foods. Brisket
is cooked at temperatures lower than 300°F and contains the lowest levels of AGEs among cooked
red meat (Figure 22.4).
5. Steam and flavor foods with the numerous flavoring materials available on the market (Figure 22.5).
The world’s most popular food pizza will be healthier when pizza developers adopt whole grains,
AGE-free or reduced ingredients, and cooking techniques that do not generate significantly higher
levels of AGEs in the final products. Steamed pizza can be made tastier than oven-baked pizza.
Figure 22.4 Brisket.

Figure 22.5 steamed foods can be flavored and make a tasty meal.
As the saying goes “Build and they will come,” develop it and consumers will enjoy steamed cooked
pizza. Due to the popularity of lasagna, pasta developers are encouraged to offer consumers steamed
and well-seasoned lasagna.
6. Promote and/or perfect stove top cooking in water also known as stewing of foods that contain no or
very low levels of AGEs. Stewed foods contain fewer AGEs than oven baked foods (Figure 22.6).
7. Steam- or low-temperature sautéed vegetables deliver more nutrients than ingested raw vegetables
(Figure 22.7).
8. Consumption of raw vegetables may be a health hazard for the elderly because produce can harbor
Clostridium difficile that can cause life-threatening diarrhea.
9. Eat and encourage others to eat more vegetables than fruits and whole grain foods and less methio-
nine-rich foods and palmitic acid-rich foods (Figures 22.8 through 22.10).
Figure 22.6 stove top–cooked rice and vegetables.

Figure 22.7 Low-temperature sautéed vegetables.
Figure 22.8 Vegetables for healthy living.
10. Fish bones are an excellent source of calcium. Retorted whole fish or fish bones can provide more
calcium than low-fat milk. The combination of fish, low-fat milk, vegetables, and soy is a better
source of calcium. Osteoporosis is a lesser problem among populations that consume fish bones and
soy than those that rely mostly on dairy products alone [19,20].
22.5 ICe WINe
Ice wine (Figure 22.11) is a dessert wine made from grapes that stayed on the vine at deep
freezing temperatures below −8°C during the winter until the first frost hit. These grapes concen-
trate sugar to above 35°Brix and phenolics and make an especially sweet wine with a minimum
residual sugar of 125 g/L that can be tailored into a Merlot, Chardonnay, Riesling, Vidal Blanc,
Gewurztraminer, Pinot Blanc, or Pinot Noir. First developed in Germany in the 1700s under the
Figure 22.9 Vegetables and fruits for healthy living.
Figure 22.10 fruits for healthy living.
name of “eiswein” and rooted in Australia, ice wine is fermented at 15°C–17°C in the presence of
high sugar content, which slows the yeast fermentation because of the combination of high sugar
and increasing alcohol concentration. The fermentation process stops prematurely giving a sweet
wine.
Ice wine is a specialty wine for which the Niagara peninsula in Ontario has become the Canadian
and world flagship of ice wines with some of the best varieties including Riesling, Vidal Blanc, and
Cabernet Franc. The province of British Columbia, Canada also has a good signature on a variety
of rich and flavorful wines including Merlot, Chardonnay, Riesling, Vidal Blanc, Gewurztraminer,
Pinot Blanc, or Pinot Noir coming from the Okanagan Valley and other parts of British Columbia.
Ice wine is a trademark and refers to wine produced under much regulated conditions and quality
control that is enforced by the Vintners Quality Alliance (VQA) [21]. Minimum residual sugar of
125 g/L, juice of ≥35°Brix, and temperature at harvest of ≤−8°C are strictly enforced. Ice wine is
sold in special bottles
Figure 22.11 Ice wines.
In the United States, ice wine is making its road to Washington State, New York, and Michigan.
In Washington State, the varieties en vogue are Chenin Blanc and Semillon. Ice wines can pair with
several deserts including blue cheeses, custards, fruit-based sweets, foie gras, lobster, cream sauces,
or can work well as stand-alone dessert. Laissez le bon temps rouler with healthy cooking, eating
and drinking.
reFereNCeS
1. Liger-Belair G, Polidori G, Jeandet P. Recent advances in the science of champagne bubbles. Chemical
Society Reviews 2008;37:2490–2511.
2. Chamkha M, Cathala B, Cheynier V, Douillard R. Phenolic composition of champagnes from
Chardonnay and Pinot Noir vintages. Journal of Agricultural and Food Chemistry 2003;51:3179–3184.
3. Rosignoli P, Fuccelli R, Fabiani R et al. Effect of olive oil phenols on the production of inflamma-
tory mediators in freshly isolated human monocytes. The Journal of Nutritional Biochemistry
2013;24:1513–1519.
4. Waterman E, Lockwood B. Active components and clinical applications of olive oil. Alternative
Medicine Review: A Journal of Clinical Therapeutic 2007;12:331–342.
5. Loru D, Incani A, Deiana M et al. Protective effect of hydroxytyrosol and tyrosol against oxidative
stress in kidney cells. Toxicology and Industrial Health 2009;25:301–310.
6. Mastralexi A, Nenadis N, Tsimidou MZ. Addressing analytical requirements to support health claims
on “olive oil polyphenols” (EC Regulation 432/2012). Journal of Agricultural and Food Chemistry
2014;62:2459–2461.
7. Boyer JC, Bancel E, Perray PF et al. Effect of champagne compared to still white wine on periph-
eral neurotransmitter concentrations. International Journal for Vitamin and Nutrition Research
2004;74:321–328.
8. Vauzour D, Vafeiadou K, Corona G et al. Champagne wine polyphenols protect primary cortical neurons
against peroxynitrite-induced injury. Journal of Agricultural and Food Chemistry 2007;55:2854–2860.
9. Vauzour D, Corona G, Spencer JP. Caffeic acid, tyrosol and p-coumaric acid are potent inhibi-
tors of 5-S-cysteinyl-dopamine induced neurotoxicity. Archives of Biochemistry and Biophysics
2010;501:106–111.
10. Hosseini SV, Hosseini SM, Rad SFM et al. Heavy metal bioaccumulation and risk assessment for wild
and farmed beluga sturgeon caviar. Environmental Monitoring and Assessment 2013;185:9995–9999.
11. Shin JH, Oliveira AC, Rasco BA. Quality attributes and microbial storage stability of caviar from culti-
vated white sturgeon (Acipenser transmontanus). Journal of Food Science 2010;75:C43–C48.
12. Losso JN, Bogumil R, Nakai S. Comparative studies of phosvitin from chicken and salmon egg yolk.
Comparative Biochemistry and Physiology: B, Comparative Biochemistry 1993;106:919–923.
13. Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmacological Research:
The Official Journal of the Italian Pharmacological Society 1999;40:211–225.
14. Phelps EA. Emotion and cognition: Insights from studies of the human amygdala. Annual Review of
Psychology 2006;57:27–53.
15. Weightman MJ, Air TM, Baune BT. A review of the role of social cognition in major depressive disor-
der. Frontiers in Psychiatry 2014;5:179.
16. Joormann J, Quinn ME. Cognitive processes and emotion regulation in depression. Depression and
Anxiety 2014;31:308–315.
17. Muller N, Myint AM, Schwarz MJ. Inflammatory biomarkers and depression. Neurotoxicity Research
2011;19:308–318.
18. Benton D, Williams C, Brown A. Impact of consuming a milk drink containing a probiotic on mood and
cognition. European Journal of Clinical Nutrition 2007;61:355–361.
19. Hirota T, Hirota K. Diet for lifestyle-related diseases to maintain bone health. Clinical Calcium
2011;21:730–736.
20. Chan R, Woo J, Leung J. Effects of food groups and dietary nutrients on bone loss in elderly Chinese
population. The Journal of Nutrition, Health & Aging 2011;15:287–294.
21. Soleas GJ, Pickering GJ. Influence of variety, wine style, vintage and viticultural area on selected chem-
ical parameters of Canadian icewine. Journal of Food Agriculture and Environment 2007;5:97.
Food & Culinary Sciences
The Maillard Reaction Reconsidered

C O O K I N G A N D E A T I N G F O R H E A LT H
Cooking involves chemical reactions that can make food smell and taste better.
However, the same process that is responsible for creating the aroma, flavor,
palatability, color, and taste of grilled and seared foods has also been linked to
the development of chronic degenerative diseases. The Maillard reaction produc-
es advanced glycation end products (AGEs) which are associated with diabetes
complications and several other chronic degenerative diseases including obesity,
chronic inflammation, erectile dysfunction, cardiovascular disease, cancer, and
Alzheimer’s.
Regardless of whether you are a chef, a food scientist, a dietician, a culinologist,

or simply a home cook, The Maillard Reaction Reconsidered: Cooking
and Eating for Health will help you understand the link between the Maillard
reaction, the AGEs, and resulting physiological conditions. Written in nontechni-
cal terms, it elaborates on dietary factors that can help you prevent the develop-
ment of chronic degenerative diseases as well as the factors that pose dietary risk.
The book is divided into three parts. Part I describes the Maillard reaction in
layman’s terms to help you understand the chemistry that takes place when
food ingredients are mixed in the presence of heat. Part II links the Maillard
reaction products to chronic inflammatory degenerative diseases and discusses
the consumption of protective foods. Part III covers champagne, caviar, good
cuisine, and ice wine, and shows you how to develop a healthy pantry both
at home and away from home. The author also gives you some healthy
cooking and eating strategies and discusses the advantages associated with
each strategy.
K23664
ISBN: 978-1-4822-4821-0
90000
9 781482 248210

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Losso, Jack N - The Maillard Reaction Reconsidered _ Cooking and Eating for Heal

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JACK N.

Boca Raton London New York

CRC Press is an imprint of the

A PRODUCTIVITY PRESS BOOK

No claim to original U.S. Government works

International Standard Book Number-13: 978-1-4822-4822-7 (eBook - PDF)

3.5 Processed Meat ..................................................................................................................... 32

4.5.4 Restaurant and Food Service Industry..................................................................... 71

5.5.5 The Restaurant Industry ..........................................................................................94

6.4.2 The Family Doctor................................................................................................. 137

8.4 Dietary Approaches to Healthy Kidney .............................................................................. 169

9.6.6 Reducing Inorganic Phosphate Load in Foods ...................................................... 189

13.3 Dietary and Aromatheraphy Management of Insomnia ..................................................... 237

15.4.5 Insulin Resistance .................................................................................................. 272

16.5.3 Dietary Approach to Alzheimer’s Disease ............................................................ 299

18.6.2.7 Milk ...................................................................................................... 351

the Maillard reaction and Foods

Introduction to the Maillard reaction

1.2 the MAILLArD reACtION IN FOOD PrOCeSSING AND COOKING

table 1.1 reducing Sugars and Some of their Dietary Sources

table 1.3 Dietary Sources of and reducing Compounds

Figure 1.1 Classical example of Mr.

1.2.3 Desirable Attributes of the Maillard reaction

1.2.3.1 Improved Aroma and Flavor of Cooked Foods

1.2.3.2 Improved Colors and Increased Palatability

1.2.4 Undesirable Attributes and health Significance of the Maillard reaction

1.2.4.1 Loss of Color and Darkening of the Final Product

1.2.4.2 Loss of Protein Biological Value

1.2.4.3 Effect on Allergenicity

1.2.4.4 Hydrogen Peroxide

Acrylamide is a well-known bioavailable neurotoxin [15,16]. Several investigators have docu-

1.2.4.7 Reactive Dicarbonyl Compounds

1.2.4.8 Pyridines and Heterocyclic and Mutagenic Compounds

1.2.4.9 Advanced Glycation End Products

The MR generates AGEs such as carboxymethyllysine (CML), pyrraline, pentosidine, and

Figure 1.2 fried foods combo.

Eye disease Stroke

Homogenized milk Butter Condensed milk Cheese Powder milk

Pasta, soups, desserts

Breakfast Snack Lunch Snack Dinner Snack

Raw low AGEs Roasted high AGEs

Breakfast Snack Lunch Snack Dinner Snack

Red meat or poultry

Breakfast Lunch Dinner

Corn ﬂour Corn oil High fructose corn syrup

Breakfast Snack Lunch Snack Dinner Snack

serum albumin or glycolaldehyde-modified β-lactoglobulin are unable to bind to their receptor

1.2.4.10 Insulin Glycation

Birth Old age

Figure 1.8 reduced insulin sensitivity due to insulin glycation.

1. Sodium hydroxide (class I)

1.4 CUrreNt AND FUtUre DIreCtIONS IN MAILLArD reACtION

Basic Understanding of Inflammation

2.2 INFLAMMAtION IN heALth

2.3 INFLAMMAtION IN DISeASe

2.4 MAterNAL AND UterO INFLAMMAtION

Endogenous sources of Exogenous sources of

Oxidative stress Oxidative stress

Figure 2.1 risk factors for maternal inflammation.

2.5 MAILLArD reACtION PrODUCtS-INDUCeD INFLAMMAtION

Allergy and Chronic inflammation

Insomnia Rheumatoid arthritis Erectile dysfunction

So tasty and Yet Proinflammatory

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