PREMATURE AGING IN THE DISEASE

CONSTELLATION OF METABOLIC
SYNDROME X
OR SYNDROME X,Y,Z…
Stephen Holt MD, LLD (Hon.) DSc, ChB., PhD, DNM, FRCP
(C), MRCP (UK), FACP, FACG, FACN, FACAM, OSJ

Distinguished Professor of Medicine (Emeritus)

Scientific Advisor, Natural Clinician LLC
 SUPER-SIZING AMERICA
• Americans exude
complacency about their
overweight status.
• Obesity is part of
Metabolic Syndrome X
• Syndrome X is under
diagnosed and often
mistreated by both
conventional and
alternative medicine.
 FACT
• OBESE KIDS BECOME UNHAPPY,
UNHEALTHY OBESE ADULTS
THE UNKNOWN EPIDEMIC
 REDEFINING SYNDROME X
• Classic Definition: Obesity,
Hypercholesterolemia, High Blood
Pressure, Linked by Insulin
Resistance.
• Syndrome X, Y and Z….., an
expanded definition incorporating a
novel unifying concept of common
diseases
 THE PUBLIC HEALTH RISK

• Syndrome X increases risk for :

Type II Diabetes Mellitus
Cardiovascular Disease
Cardiovascular Deaths
Deaths from ALL CAUSES
Am.J.Epidemiol, 148, 958, 1998.
INTEGRATIVE MEDICINE FOR SYNDROME X

“While proper management of the

individual abnormalities of this
syndrome can reduce morbidity and
mortality, it seems unlikely that
management of the individual
abnormalities of this syndrome provides
better outcomes than a more integrated
strategy” CDC, Atlanta, Ga.,
JAMA 2002
 FACTS
• Obese people die young
• Obese people develop premature
disability
• Obese people are modern, metabolic
dinosaurs
• Obese people are generally mismanaged
in clinical practice
 BACKGROUND
• Studies imply that the physically active
person of normal body weight outlives
the overweight, inactive individual.
• Obesity related disease, most notably
Metabolic Syndrome X, presents unifying
concepts of premature aging.
• Retention of body functions and survival
are clearly associated with calorie
restriction.
LOOKING AT OBESITY AND RELATED DISEASE
FROM NEW SCIENTIFIC PERSPECTIVES
CREATES NEW THERAPEUTICS
 A LITANY OF NEW PERSPECTIVES: 2009
• Greater understanding of the epidemiology of obesity.
• The fat cell regulates energy balance and metabolism.
• Neuro-hormonal control of appetite.
• Incretins: GLP-1 and GLP.
• Fuel sensing by the CNS.
• Obesitis
• Insulin Resistance: The core of Syndrome X
• Cancer propagation (colon, prostate, pancreas)
• Evidence base for positive lifestyle change.
• Drug and nutraceutical approaches to treatment.
• The role of bariatric surgery
 NEW PERSPECTIVES ON EPIDEMIOLOGY
• Global problem, 1.6b overweight (BMI>25)
400m obese (>30)
• 32.9% of U.S. adults (age 20-74y) are obese,
17% of teenagers (age 12-19) are overweight.
70M US citizens, Syndrome X.
• Obesity and Syndrome X increase risk of death
from all causes.
• The data support a gene-environment
interaction where the genetically predisposed
respond to energy-dense foods, combined with
reduction in energy expenditure. “Farmyard
Science”
ENERGY BALANCE AND METABOLISM: REGULATED BY ADIPOCYTES

• New discoveries of circulating factors that

signal energy reserves which also signal the
brain, adipose tissue, liver, muscle and the
immune system.
• Research surrounding the discovery of leptin
led to the discovery of other chemical signals.
• Signaling compounds: leptin, adiponectin,
resistin, retinoid binding protein 4, visfatin,
etc.
• Appetite supression: Hoodia etc.
 GUT HORMONES AND APPETITE

• Gut hormones influence eating behavior.

• Ghrelin: “The Hunger Hormone” increases
food intake and body weight (OREXIGENIC).
• In contrast, all other peripheral factors that
regulate energy balance act to restrain
eating.
• Ghrelin secretion is promoted by insomnia.
The “Nocturnal Fridge Raiding Syndrome”.
• The concept of “Sleep Naturally.”
 OBESITIS
• Epidemiological links between obesity and
inflammation have been proposed for >40y.

• Glucose and fat intake induce inflammation by

oxidative stress or the activation of transcription
factors.

• Reductions in macronutrient intake in obese

subjects reduces oxidative stress and the
production of inflammatory mediators
(1000kcal/day, 4 weeks or 48 hr fast).

• Managing weight control must include anti

inflammatory tactics
 INSULIN RESISTANCE

• New concepts of inflammation-induced insulin

resistance.
• Two pathways: the NF-kB pathway and the c-Jun
NH2-terminal kinase (JNK) pathway which are
transcription-factor-signaling-pathways that are
linked to the pro-inflammatory effects of obesity
and insulin resistance.
• Pathways are activated by pro-inflammatory stimuli
e.g. cytokines (TNF-alpha).
• Potential mediators of insulin resistance include IL-
6, IL-10, TNF-alpha, CRP, IL-8, PAI-1 etc.
POTENTIAL MECHANISMS OF OBESITIS
OBESITIS
 CANCER: OBESITY AND SYNDROME X

• Obesity and Syndrome X increase

mortality from several cancers e.g. colon,
prostate, breast and pancreas.
• Consistent risk factors for colon cancer
(or adenoma) include obesity, inactivity,
pot-belly, hyperglycemia and
hyperinsulinemia (Syndrome X)
• Obesity linked to fatal prostate cancer.
• Type II diabetes increases risk of
pancreatic cancer by approximately 50%.
 LIFESTYLE CHANGE AND NUTRITION:
FIRST LINE OPTION
• Face to face lifestyle advice performs
about 50% better than comprehensive
internet-based programs for weight loss.
(inference: the same applies to books?)
• Continued patient-practitioner contact
with compliance promotes sustained
weight control.
• Managing weight loss without managing
Syndrome X is nihilistic.
DRUGS AND NUTRACEUTICALS
 WEIGHT MANAGEMENT
• Not only a function of diet
• Calorie Control
• Behavior Modification
• Exercise
• Management of Syndrome X
• Treatment of obesity related disease
• Obesitis
• Detoxification
UNREALISTIC WEIGHT
LOSS EXPECTATION
COMMON CAUSES OF OBESITY

• The Double Whopper Brain

• Sedentary Lifestyle
• Genetic Tendency
• Social Gluttony (Appetite)
• Sleeplessness
• Body Toxicity
 THE GLYCEMIC INDEX
• Calculations of the glycemic index of food is
probably a waste of time.

• Understanding factors that control gastric

emptying rate can result in inference about
the glycemic index.

• Slowing gastric emptying slows glucose

absorption – relevance in acute dosing
GLUCOSE TOLERANCE WITH SOLUBLE FIBER

Holt S, et al
Effect of Gel
Fiber…
Lancet,
March 24th,
1979.
 DIETARY PRINCIPALS
• Calories Count
• Watch Macronutrients CHO, Fat,
Protein
• Healthy Fat (EPA)
• Salt Restriction
• Fiber Intake
• Nutrient Density
SYNDROME X NUTRITIONAL FACTORS
•OBESITY: Hoodia, fiber, green coffee bean extract,
starch blocker, chromium, fat blockers
•HYPERTENSION: fiber, botanicals unpredictable
•OXIDATIVE STRESS: alpha lipoic acid, AGES, redox
balanced, hydrophilic and lipophilic
•HOMOCYSTEINE: B6, B12, folate, TMG
•INSULIN RESISTANCE: fish oil (EPA), alpha lipoic acid,
vitamin and mineral support
•BLOOD LIPID: soy, fish oil, guggul, garlic etc.
•INFLAMMATION: EPA, curcumin, C etc.
 SYNDROME X NUTRITIONAL FACTORS
•A healthy blood glucose level
•A healthy blood cholesterol level
•A healthy blood homocysteine level
•Healthy immune function
•Healthy digestive function
•Antioxidant function
•Calorie control by induction of satiety
•Inhibition of fat and sugar absorption
 SYNDROME X NUTRITIONAL FACTORS
• Soluble fiber e.g. oat beta glucan
• Omega 3 fatty acids (EPA) ENTERIC COATED
• Chromium
• Alpha lipoic acid
• Vanadium
• Antioxidants e.g. ellagic acid, bioflavonoids
• Starch blockers
• Cinnamon
• Maitake
• Green tea or coffee bean extract
• Hoodia gordonii
• Fucoxanthin
 SYNDROME X PROTOCOL
• Lifestyle change: diet, exercise,
limitation of substance abuse,
behavior modification
• Nutritional insurance: mixtures of
fruit, vegetable, berries and greens
powders with full RDI of vitamins,
mineral enrichment.
 CONCLUSIONS
• Weight management involves holistic medicine and
education on new perspectives.
• There is no successful, sustainable stand alone
intervention for weight control
• Failing to manage Metabolic Syndrome X and its
complex pathophysiology is a common mistake.
• Sleep, inflammation, nutrition etc. must be addressed.
• Nutraceuticals are preferred first line adjunctive
options: the concept of “Syndrome X Nutritional
Factors,” Clinical EPA/DHA.
• The “Integrative Approach” must be favored.