METABOLIC SYNDROME X

Transcription

1 METABOLIC SYNDROME X The Most Important Anti-Aging Initiative Stephen Holt MD, LLD (Hon.) ChB., PhD, ND, FRCP (C), MRCP (UK), FACP, FACG, FACN, FACAM, OSJ Distinguished Professor of Medicine, NYCPM,

2 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.

3 FACT OBESE KIDS BECOME UNHAPPY, UNHEALTHY OBESE ADULTS

4 THE UNKNOWN EPIDEMIC

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6 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

7 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.

8 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

9 FACTS Obese people die young Obese people develop premature disability Obese people are modern, metabolic dinosaurs Obese people are generally mismanaged in clinical practice

10 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 partial food restrictions, at least in rodents.

11 LOOKING AT OBESITY AND RELATED DISEASE FROM NEW SCIENTIFIC PERSPECTIVES CREATES NEW THERAPEUTICS

12 A LITANY OF NEW PERSPECTIVES: 2007 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

13 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. Obesity increases risk of death from all causes. The data support a gene-environment interaction where the genetically predisposed respond to increased availability of palatable, energy-dense foods, combined with reduction in energy expenditure. Farmyard Science Modern accounts of obesity are polite ways of telling western nations that they are fat and idle. A message that is neither novel nor new!

14 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, visceral adipose-tissue derived serine protease inhibitor, plasminogen activator inhibitor 1, adipsin, angiopoientin-like peptide/fasting induced adipose factor, cytokines and chemokines, adipose production of corticosteroids and complex interrelationships.

15 LEPTIN PRODUCTION IN ADIPOCYTES

16 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. These Satiety Signals include: CCK, PYY, PP, Oxyntomodulin, GLP-1(Incretin). These gut hormones may be safe, logical drug or nutraceutical targets for changing eating behavior. Ghrelin secretion is promoted by insomnia. The Nocturnal Fridge Raiding Syndrome.

17 INCRETINS: GLP-1 AND GLP Incretin peptides include glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GL). Secreted within minutes of oral nutrient intake. Incretin receptor activation leads to glucosedependent insulin secretion, and a variety of other metabolic consequences. GLP-1 and GAP integrate nutrient-derived signals to control food intake, energy absorption and assimilation. GLP-1 and GIP actions are a basis for innovative treatments of Syndrome X and Type II Diabetes Mellitus.

18 PERIPHERAL ACTIONS OF GLP-1

19 FUEL SENSING BY THE CNS Highly complex neurohormonal controls underpin hunger, appetite, satiety and eating behavior. Socio-behavioral factors may operate with dominance. Lipostatic, Glucostatic and Aminostatic theories of appetite control. A function of the hypothalamus: the promise of Hoodia gordonii, Caralluma etc.

20 HOODIA GORDONII

21 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 without managing inflammation may be malpractice?

22 : Fat tissue, normal weight mouse :Fat tissue, from fat mouse (ob/ob)

23 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 proinflammatory 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.

24 POTENTIAL MECHANISMS OF OBESITIS

25 OBESITIS Obesity is an inflammatory disorder 30% of blood cytokine IL-6 from adipose tissue, decrease CRP and IL- 18 with weight loss Naïve Zones, but EPA valuable Adipocytokines [leptin, adiponectin and visfatin], adiponectin lowers TNF-alpha Final common pathway oxidative stress

26 OBESITIS

27 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%. Hyperinsulinemia or oxidative stress initiated by hyperglycemia appear to be the mechanism.

28 CANCER: OBESITY AND SYNDROME X PUTATIVE MECHANISMS

29 LIFESTYLE CHANGE AND NUTRITION: FIRST LINE OPTION Randomized controlled trials on the use of lifestyle or diet changes for inducing and maintaining weight loss are few and far between: The Banting, Yudkin, Atkins Diets and others involve restriction of simple sugar. This fits the bill - at least in the short term. 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, high levels of physical activity and the long term use of drugs (supplements?) with positive lifestyle change promote sustained weight control. Managing weight loss without managing Syndrome X is nihilistic. Reason for failure of the Atkins Diet, in long term.

30 DRUGS AND NUTRACEUTICALS

31 WEIGHT MANAGEMENT Not only a function of diet Calorie Control Behavior Modification Exercise Management of Syndrome X Treatment of obesity related disease Obesitis

32 HOODIA-PEER REVIEW ARTICLES NOVEMBER AND DECEMBER 2006 TOWNSEND LETTER

33 UNREALISTIC WEIGHT LOSS EXPECTATOIN

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35 WHICH ARE QUICK FIX PROMISES? Drugs: Phentermine, Fen-phen, Sibutramine, Orlisat OTC: Phenylpropanolamine Dietary Supplements: Pyruvate, Chromium Picolinate, Conjugated Linoleic Acid, Hydroxycritic Acid, Omega 3 Fatty Acids, GLA, Hoodia Gordonii etc? [SYNERGY] ALL OF THE ABOVE!

36 COMMON CAUSES OF OBESITY The Double Whopper Brain Sedentary Lifestyle Genetic Tendency Social Gluttony (Appetite) Sleeplessness

37 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

38 GLUCOSE TOLERANCE WITH SOLUBLE FIBER Holt S, et al Effect of Gel Fiber Lancet, March 24th, 1979.

39 DIETARY PRINCIPALS Calories Count Watch Macronutrients CHO, Fat Protein Healthy Fat (EPA) Salt Restriction Fiber Intake

40 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.

41 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

42 SYNDROME X NUTRITIONAL FACTORS Soluble fiber e.g. oat beta glucan Soy Protein 25 g/day Omega 3 fatty acids (EPA) Chromium Alpha lipoic acid Vanadium Antioxidants eg ellagic acid, bioflavonoids Starch blockers Cinnamon Maitake Green coffee bean extract Hoodia gordonii

43 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 in the overweight person is malpractice. Sleep, inflammation,nutrition etc. must be addressed. Nutraceuticals are preferred first line adjunctive options: the concept of Syndrome X Nutritional Factors. The Integrative Approach must be favored.