Basic Mechanisms of Disease

Basic Nutritional Science and Nutritional related Diseases

Aminuddin
Department of Nutrition
Faculty of Medicine
University of Hasanuddin
2021
 Learning Objectives

After completion of this lecture, students will be able to:

• Identify macro- and micronutrients, their dietary sources and human

macro-and micronutrients requirement

• explain basic techniques or procedures in clinical nutrition

– Nutritional assessment:
• Clinical assessment
• Dietary assessment
• Anthropometric assessment
• Lab assessment

• Explain types and pathophysiology of nutritional related diseases

– Protein Energy Malnutrition (PEM)
– Specific Nutrient Deficiency Diseases
INTRODUCTION
 Are you familiar with these sayings or
quotes?
• You are what you eat
• “Let food be thy medicine and medicine be thy food”  ~Hippocrates
• “The doctor of the future will no longer treat the human frame with
drugs, but rather will cure and prevent disease with nutrition.”
 ~Thomas Edison
• “An apple a day keeps the doctor away”  ~Proverb

Some quotes are taken from http://www.globalhealingcenter.com/natural-health/quotes-

about-health/
Evolution of Human Diet

Modern societies:
Eat more refined and
highly refined foods:
• More fat
• More sugar
• More salt
• Less fiber
Can you answer the following questions?
• What are macronutrients?
• Which macronutrient affects blood glucose the most?
• What is the best dietary source of Vitamin A?
• What is body mass index (BMI)?
• Explain relationship between BMI and health risks
• What is malnutrition? How do we know that someone has malnutrition?

• As a doctor, you need to be able to answer those

questions for a better service to your patients
• This lecture will help you answer those questions,
so stay tuned
 Pictures are taken from http://www1.msjc.edu/hs/nutr100/nutr100_section2a.html

Part I
MACRO- AND MICRONUTRIENTS
 Class of Nutrients
• Carbohydrates
• Proteins
• Fats/Lipids
• Vitamins
• Minerals
• Water
 Carbohydrates
• Empirical formula: Cx(H2O)y
• Example: Glucose: C6(H2O)6
• They are the main source of energy in human
Types of Carbohydrate in our diet (FAO/WHO
1998)
Glycemic Non Glycemic
Monosaccharides Oligosaccharides
• Glucose • Raffinose, Stachyose, verbascose
• Fructose • Human milk oligosaccharides
• Fructo-oligosaccharide

Disaccharides
• Sucrose
• Lactose
• Maltose
• Trehalose

Polysaccharide Non Starch Polysaccharides

Starch (dietary fibers)
• Amylopectin • Cellulose (insoluble)
• Amylose • Hemicellulose (soluble and insoluble)
• Modified Food starch • Beta Glucans (mainly soluble)
• Fructans, e.g. Inulin
• Gums (soluble)
• Mucilages (soluble)
• Algal polysaccharides (soluble)

Why do you think galactose is absent in glycemic monosaccharide?

Brand-Miller, J: Carbohydrates in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd editionc
 Sugars (simple carbohydrate)
• Mono-, Di-, oligosaccharides
• free glucose and fructose exist in small amount in natural foods
– fruit, vegetables, honey
• Galactose is not found free in nature
• Corn syrup (glucose syrup and high fructose corn syrup) is often
used in beverage and food industry as sweeteners
• Maltose (glucose+glucose)- used in alcohol production,
hydrolysis of starch, small amount in our diet
• Sucrose (glucose+fructose)- table sugar
• Lactose (glucose+galactose)- found in milk and dairy products
 Sugars (Oligosaccharide)
• Galactosylsucrose
– Raffinose (trisaccharide: glucose, fructose, galactose)
– Stachyose (tetrasaccharide: glucose, fructose, 2 galactose)
– Verbascose (pentasaccharide: glucose,fructose, 3 galactose)
– major source: peas, beans, lentils
• Fructo-Oligosaccharide (FOS)
– combination molecules of fructoses and one glucose at the end
– Major source wheat, jerusalem artichokes, shallot and onion,
asparagus
• Both are not digestible in human small intestine but fermented
by bacteria in large intestine gas, bloated abdomen
 Starch (complex carbohydrate)
• Starch is homogenous polymers which
consist of only glucose molecules
• Starch polymers:
– Amylose
– Amylopectin
• Natural starches consist of both amylose
(10-30%, may be lesser) and amylopectin
(70-90%)
• Less amylose in starch will make starch
more glutinous and more digestible Amylose molecule

https://ricediversity.org/outreach/gen/
Amylopectin molecule
Pictures taken from
https://chem.libretexts.org/LibreTexts/Sacramento_City_College/SCC
%3A_Chem_309_(Bennett)/Chapters/14%3A_Carbohydrates/14.7%3A_P
olysaccharides
 Carbohydrate Digestion
• starch and sugars absorbed in monosacharide forms: glucose, fructose,
galactose
• the process of having these monomers: hydrolysis
• carb hydrolysis starts in the mouth by alpha-amylase secreted by
salivary gland
• starch extensive hydrolysis occur in the small intestine by amylase
secreted by pancreas---> maltose, maltotriose, alpha-dextrine
• final hydrolysis of disaccharide is at brush border of microvilli by
glucoamylase ie. sucrase, alpha-dextrinase, maltase, lactase
• non starch polysaccharide, undigested resistant starch and
oligosaccharides fermented by bacteria---> gas + short chain fatty aci
( acetate, propionate, butyric acid)
– Butyric acid is thought be for colonocytes
 Carbohydrate Absorption
• Carbohydrate is absorbed in
monosaccharide forms
– Glucose and Galactose absorbed actively
through Sodium dependent glucose
transporter (SGLT1)
– Fructose absorbed by facilitated diffusion
through Glucose transporter 5(GLUT5)
– fructose asorption is slower--> large
amount at one time may exceed gut
absorptive capacity--> diarrhea e.g Toddler
diarrhea caused by excessive apple juice
drink whose sugar is mostly fructose
– fructose is absorbed better with glucose---
> sucrose is rarely cause diarrhea
• adult consume 50 gram fructose may cause
diarrhea, whereas 250 gram sucrose does not
cause diarrhea
 Carbohydrate digestion and absorption
disorder
• Lactase deficiency-->lactose intolerance
– is quite common
– as people get older--> lactase is decreasing except for
people of north european origin
– lactose remain in intestine--> gas production, explosive
diarrhea, abdominal pain
• other disaccharidase deficiency
– rare: sucrase, maltase, isomaltase, trehalase
– maybe genetic or acquired e.g intestinal infection may
cause those disaccharidase deficient--> diarrhea
– many Inuit people in North America genetically lack
sucrase-isomalte
Resistant starch and dietary fiber absorption
Brand-Miller, J: Carbohydrates in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition

Resistant Starch Oligosaccharide

NSP (Fiber) Polydextrose

Colon

Microbial metabolism

Gas +NH4+ SCFA

CO2 Microbial growth Acetate
H2O Propionate
CH4 Butyrate

Flatus Faeces Blood

 Carbohydrate Metabolism
Dietary carbohydrate

Glucose Glycogen

Glucose Phosphate
Penthose Phosphate pathways
Glycolytic pathwy

Triose phosphate Ribose phosphate

Pyruvate Lactate
Amino acids CO2
Protein Acetyl CoA

Amino acids Citric

Acid
cycle

CO2

Brand-Miller, J: Carbohydrates in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
Inborn Errors of carbohydrate metabolism
Inborn Errors consequence

absence of fructokinase prevents fructose metabolism, fructosuria

absence of fructose-I-phosphate inhibition of glycogenolysis, hypoglycemia

galactokinase deficiency galactose not phosphorylated, cataracts

G6PDdeficiency erytrocyte hemolysis, anemia

Brand-Miller, J: Carbohydrates in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
Diseases related to carbohydrate metabolism

• Type 2 Diabetes
– Macronutrient which affects blood glucose the most is
carbohydrate
– Fat and protein effects are minimal e.g.:
• Dietary fat slows glucose absorption, hence delaying BG peak after
ingestion of carbohydrate
• Ingestion of fat and protein augment insulin release hence accelerate
BG clearance
– Quantity and type carbohydrate influence BG response
• Large quantity will increase BG more
• Food with high glycemic index will increase BG more quickly and higher
• Quantity and glycemic of index of foods will influence glycemic load
 Glycemic Index (GI)
• Ranking of carbohydrate containing food
according to post-prandial blood glucose
response
• High GI food will increase BG quicker and
higher
 How to measure GI of foods?

• Comparing Blood glucose response of a test

food with reference food (usually glucose 50
gram, or foods that contain 50 gram available
carbohydrate such as white bread)
• Measuring area under the curve (AUC) of
blood glucose response between test food
and reference food
• GI= AUC of test food
X 100
AUC of Reference food
How to measure GI of foods?
BG response of Reference Food
BG response of test food
250 180
160
200 140
120
150
100 B
A 80
100
60

50 40
20
0 0
0 30 60 90 120 0 30 60 90 120

GI test food : AUC (B) X 100

AUC (A)
Food Categories based on GI
Category Glycemic Index

Low GI < 55

Medium 55-69

High > 70

Venn BJ, Green TJ: Glycemic index and glycemic load: measurement issues and
their effect on diet-disease relationship . Eur. Jour. Of Clin. Nutrition (2007)61
(suppl. 1), S122-S131

For a extensive list of Food GI and GL, you can download the table from:
International Tables of Glycemic Index and Glycemic Load Values: 2008
Diabetes Care 2008 Dec; 31(12): 2281-2283
 Glycemic Load (GL)
• Glycemic load takes into
account GI and quantity of
carbohydrate containing
food eaten
• GL is calculated indirectly by
multiplying GI and available
carbohydrate in one serving
sizes of food
• Directly measured GL is
termed Glucose Equivalent
Venn BJ, Green TJ: Glycemic index and glycemic load: measurement issues and
their effect on diet-disease relationship . Eur. Jour. Of Clin. Nutrition (2007)61
(suppl. 1), S122-S131
Food categories based on GL
Category Glycemic Load

Low GL < 10

Medium GL 10 - < 20

High Gl > 20

Venn BJ, Green TJ: Glycemic index and glycemic load: measurement issues and
their effect on diet-disease relationship . Eur. Jour. Of Clin. Nutrition (2007)61
(suppl. 1), S122-S131

For a extensive list of Food GI and GL, you can download the table from:
International Tables of Glycemic Index and Glycemic Load Values: 2008
Diabetes Care 2008 Dec; 31(12): 2281-2283
 Requirement of glucose
• Glucose is irreplaceble energy source for brain,
kidney (medulla), red blood cells
• Brain needs 140 g/day, kidney needs 40 g/day
• Gluconeogenesis can supply 130 g/day
• So absolute minimum requirement of glucose is
about 50 g/day
• FAO/WHO expert consultation in Human
Nutrition recommends 55% of total energy is
derived from carbohydrate
 LIPIDS
• Dietary fat includes all lipids from plant and
animal tissue in our diet
• Lipids are compound insoluble in water but
soluble in in organic solvent
Lipid categories (FAO/WHO expert consultation
on fats and fatty acid in human nutrition, 2008)
 Triglycerides (TAG)
• Major source of dietary lipids in human nutrition from
both plant and animal foods
• At room temperature exist in two forms ie. Solid (fat,
butter, margarine etc) and liquid (oil)
• It consists of glycerol and three fatty acids
• Physical and biological properties of TAG depend on the
nature of its fatty acid contituents

Fatty acid (Oleic

Triglyceride: Olive Oil acid) Glycerol
Glycerol + 2 Oleic acids + 1 Palmitic acid
 Fatty acids
• Fatty acids consists of even number of carbon
atom chains with hydrogen attached, with
methyl group at one end and carboxylic acid at
one end
• Carboxylic end by convention is where carbon
atom number is started
• Methyl end is known as n minus (n-) or Omega
carbon atom
Classification of fatty acids based on number
of double bonds
• Saturated fatty acids
• Monounsaturated fatty acids
• Polyunsaturated fatty acids
• Trans fatty acids
Common fatty acids and their structures

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
Fatty acid names and occurence

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
 Fatty acid composition of common fat source: Percent
by weight of total fatty acid
Mono
Poly
Saturated unsaturate
unsaturated
d
Unsat./Sa
Lauri Linolei Alpha
Oil or Fat t. Capri
c
Myristi Palmiti Steari
Oleic c
ratio c c c c Linoleni
Acid Acid Acid c
Acid Acid Acid Acid
(ω6) Acid
C12: C18:1 (ω3)
C10:0 C14:0 C16:0 C18:0 C18:3
0 C18:2
Almond Oil 9.7 - - - 7 2 69 17 -
Beef Tallow 0.9 - - 3 24 19 43 3 1
Butterfat (cow) 0.5 3 3 11 27 12 29 2 1
Butterfat (goat) 0.5 7 3 9 25 12 27 3 1
Butterfat (human) 1.0 2 5 8 25 8 35 9 1
Canola Oil 15.7 - - - 4 2 62 22 10
Cocoa Butter 0.6 - - - 25 38 32 3 -
Cod Liver Oil 2.9 - - 8 17 - 22 5 -
Coconut Oil 0.1 6 47 18 9 3 6 2 -
Corn Oil (Maize Oil
6.7 - - - 11 2 28 58 1
)
Cottonseed Oil 2.8 - - 1 22 3 19 54 1
Flaxseed Oil 9.0 - - - 3 7 21 16 53
Grape seed Oil 7.3 - - - 8 4 15 73 -
Lard (Pork fat) 1.2 - - 2 26 14 44 10 -
Olive Oil 4.6 - - - 13 3 71 10 1
Palm Oil 1.0 - - 1 45 4 40 10 -
Palm Olein 1.3 - - 1 37 4 46 11 -
Palm Kernel Oil 0.2 4 48 16 8 3 15 2 -
Peanut Oil 4.0 - - - 11 2 48 32 -
Safflower Oil* 10.1 - - - 7 2 13 78 -
Sesame Oil 6.6 - - - 9 4 41 45 -
Soybean Oil 5.7 - - - 11 4 24 54 7
Sunflower Oil* 7.3 - - - 7 5 19 68 1
Walnut Oil 5.3 - - - 11 5 28 51 5
 Trans fatty acid
• Trans fatty acid is unsaturated fatty acid with trans configuration
• Naturally occurring fatty acids are mostly in Cis configuration
• Cis and Trans are terms used to describe the relative position of hydrogen atoms in respect to the
double bond
• Trans fat is usually a product of hydrogenation of unsaturated fatty acid to have a higher melting
point. Usually oil form is hydrogenated to produce more solid form suitable for industrial use
• Trans fat biologically acts more like saturated fat

Cis-9-octadecenoic acid Trans-9-octadecenoic acid

(Oleic acid) (Elaidic acid)
 Other forms of lipids
• Phospholipids
– Small proportion of dietary lipids
– Consists of glycerol, fatty acids, and either of base
groups (choline, inositol, serine, ethanolamine)
– Most abundant form is phosphatidyl choline
(lechitine)– good emulsifier

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
 Other forms of lipids
• Sterols
– Cholesterol is the principal sterol and only found in animal tissue
– Sterol in plant is called phytosterol: sitosterol, campesterol,
stigmasterol

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
 Digestion
• Stomach helps in fat digestion by forming emulsion
• Further emulsification occur in intestine with the help
bile acids to form fat droplets small enough to have
more surface area for digestive enzymes
• Pancreatic lipase hydrolyzes TAG into glycerol and fatty
acids
• Phospholipids are hydrolyzed by phospholipases
• Cholesterols are hydrolyzed by cholesterol ester
hydrolase
• The end product of digestion is micelles
 Absorption

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
 Lipid transport
• Lipid transported by lipoproteins in the blood

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
 Lipoprotein
• Chylomicron transports dietary triglycerides
• Short live in circulation (15-30 minutes), soon
metabolized by lipoprotein lipase in capillary
wall vessels
• 90% TAG removed from chylomicron
chylomicron remnant transported to liver
• Vitamin A. D, E, K are transported to the liver
in chylomicron remnants
 Lipoproteins

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
 Lipoproteins

Mann, J., Skeaff, M. : Lipids in Mann, J and Truswell, AS, Essentials of human nutrition, 2nd edition
 Protein
Amino acid Three-letter abbreviation One-letter abbreviation
• Amino acids molecules Alanine Ala A
Arginine Arg R
linked by peptide bonds Asparagine Asn N

• There 20+ AA in human diet Aspartic Acid

Cysteine
Asp
Cys
D
C

• Protein is needed for Glutamine

Glutamic Acid
Gln
Glu
Q
E

structural and functional Glycine Gly G

Histidine His H
role Isoleucine Ile I
Leucine Leu L
Lysine Lys K
Methionine Met M
Phenylalanine Phe F
Proline Pro P
Serine Ser S
Threonine Thr T
Tryptophan Trp W
Tyrosine Tyr Y
Valine Val V
Asparagine or aspartic Asx B
acid

Glutamine or glutamic Glx Z

acid
 Protein Digestions
• Activation of zymogen in small
• Daily protein load: intestine
– Dietary sources:70-100 g/day
– Endogenous sources: 35-200
g/day
• Digestion (based on source
of enzymes):
– Gastric: HCl+ pepsin
– Pancreas: trypsin,
chymotrypsin, elastase,
carboxypeptidase
– Intestinal (surface):
Peptidase +dipeptidase
NUTRITIONAL ASSESSMENT
 Nutritional assessment objectives
• Measuring individual physical dimension
– To determine nutritional status:
• Comparing measurement result to certain standards
– To evaluate nutrition prevention over a period of
time
– To evaluate effects of nutrition intervention to
patients
Common sites for skinfold measurement