Diet & Healthy Living

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Diet & Healthy Living Zhaoping Li, M.D., Ph.D. Professor of Medicine David Geffen School of Medicine, UCLA VA Greater Los Angeles Health Care System TIME Feb. 23, 2004 Neurological diseases Role of Inflammation in Human Diseases Pulmonary diseases Autoimmune diseases Cancer INFLAMMATION Arthritis Cardiovascular diseases Diabetes II Alzheimer s disease

The epidemiology of inflammatory environments Western Life Style Over Nutrition Inactivity Industrial waste Pollution Diabetes CVD Cancers Spare Tire Intra-Abdominal fat Medical Complications of Obesity Pulmonary disease Asthma obstructive sleep apnea hypoventilation syndrome Nonalcoholic fatty liver disease steatosis steatohepatitis cirrhosis Gall bladder disease Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Osteoarthritis Skin Gout Idiopathic intracranial hypertension Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension Severe pancreatitis Cancer breast, uterus, cervix colon, esophagus, pancreas kidney, prostate Phlebitis venous stasis

A New View of the Adipocytes Current view: Adipose tissue as active endocrine organ Adipose tissue secretes adipokines regulate energy homeostasis, glucose and lipid metabolism Inflammatory response Appetite Angiogenesis Blood pressure Reproduction system Adipocytes also produce factors that participate in the acute phase reaction and in immune surveillance. Adiposity Excessive total body fat mass Increased abdominal visceral fat Ectopic fat deposition Intramuscular lipid stores Non-alcoholic liver fat Pancreatic lipid infiltration Cardiac muscle lipid infiltration Abnormal fat tissue metabolism Macrophage Ingress Mediates the Inflammatory State of Adipose Tissue

Integration between Macrophages & Adipocytes Weight Stability Masks Sarcopenia Gallagher, D. et al. Am J Physiol Endocrinol Metab 279: E366-E375 2000 1

Muscle Loss with Age: Inadequate Protein & Exercise, Same Weight, Different Muscle Mass 73 year old Female (BMI = 24.5 kg/m 2 ) 21 year old Female (BMI = 24.3 kg/m 2 ) Prevalence of saroopenia in the New Mexico Elder Health Survey 1993-1995 Weight Loss and Regain Newman, A. B et al. Am J Clin Nutr 2005;82:872-878

nd 22 Annual Fall Symposium Arizona Geriatrics Society All Fat Cells Are Not Created Equal Adrenergic Receptors InsulinInsulin-Mediated Antilypolysis Large InsulinInsulinResistant Adipocytes CatecholamineCatecholamineMediated Lipolysis Small InsulinInsulin-Sensitive Adipocytes Adrenergic Receptors Fatty Acids Fat Distribution Change at Menopause Sedentary Lifestyle

Only in Los Angeles Diets Then and Now 50,000 Years Ago Today Fruits, nuts, seeds, roots, tubers, flowers, leaves, stalks, beans 1/2 the fat 2-3x the protein No dairy or refined flour No processed foods No alcohol, no tobacco Potato, refined pasta & cereals white rice & flour, corn Added fat and sugar High fat proteins Ice cream, cheese and whole milk Processed foods We will be What We Eat 21

We eat these colors High Fructose Corn Syrup Current US annual consumption of HFCS 63 pounds per person 2

Adulteration of Food Supply Addition of fructose palatability (esp. with decreased fat) browning agent Removal of fiber shelf life freezing Cheap, ample supply Fructose is Not Glucose Fructose does not suppress ghrelin Acute fructose does not stimulate insulin nor leptin Hepatic fructose metabolism is different Chronic fructose exposure promotes the Metabolic Syndrome Eliot et al. Am J Clin Nutr Nutr, 2002 Bray et al. Am J Clin Nutr Nutr, 2004 Teff et al. J Clin Endocrinol Metab Metab, 2004 Gaby, Alt Med Rev, 2005 Le and TappyTappy, Curr Opin Clin Nutr MetabMetab Care, 2006 Wei et al. J Nutr Biochem Biochem, 2006, Johnson et al. Am J Clin Nutr 2007 Rutledge and Adeli Adeli, Nutr Rev, 2007 Brown et al. Int. J.Obes Obes, 2008 Fructose Metabolism in Liver Elliott, S. S et al. Am J Clin Nutr 2002;76:911-922

Fructose Increases de novo Lipogenesis Hellerstein et al. Ann Rev Nutr 16:523, 1996 Ascorbic Acid Rich source for vitamins and minerals, low calorie, high fiber Phytochemicals/Phytonutrients Non-nutrient plant compounds Provide health benefits against certain chronic human illnesses such as cancer, heart disease, neurodegenerative diseases, etc.

Diet and Exercise Intervention Controlled Dietary Intervention 30% protein 77 servings of fruits and vegetables 20% fat 50% carbohydrates with 25-35 grams of fiber per day Controlled Exercise Intervention Exercise program individually tailored Weight training Aerobic exercise Exercise training performed on-site at UCLA Fit Center South Gym 0 Leptin ng/ml-10-20 -30-40 -50 Preliminary Results Leptin from Serum 01 02 04 05

Estrone-S ng/ml 2 1 0-1 -2 Preliminary Results Estrone-S S from Serum 01 02 04 05 Preliminary Results Content of Estradiol in Nipple Lavage Fluid 20 15 10 5 Estradiol 0 (pmoll/l) -5-10 -15-20 01 02 04 05 High Intake of Carotenoid-rich rich Vegetables and Fruit Reduces Plasma CRP Watzl et al AJCN 2005

Fruit and Vegetable Intake in Hispanic and Non-Hispanic White Elders Gao et al. J Nutr 2004 Protein is Important Protein helps curb hunger Protein helps build muscle mass Soy protein provide high quality plant protein without the added calories of animal protein Nitrogen Balance (mg N/kg/day) Determining the RDA Egg Protein Intake (g/kg/day) Young et al. 1973

Protein requirements in endurance athletes Meredith et al. 1989 Increased Satiety with Higher Protein Intake Perceived satiety for subjects consuming high-protein (HPLF, n = 9) or highcarbohydrate (HCLF, n = 7) low-fat, energy-restricted diets for 6 wk using a 7-point Likert scale. Maintenance of Lean Body Mass with Higher Protein Intake Treyzon et al Nutr J. 2008 Aug 27;7:23

Increased Saturated Fat 4 4 Polyunsaturated Fatty Acids Omega-6 6 (linoleic) Sunflower oil (70%) Corn Oil (55%) Soybean oil (51%) Omega-3 3 (linolenic) Canola (10%) Walnut oil (10%) Fish (DHA, EPA) Leafy greens Flaxseed

Opposing Roles of 6 s 6 s and 3 s3 Omega-6 6 eicosonoids pro-inflammatory pro-aggregatory pro-vasoconstriction Il-6, TNF-α Omega-3 3 eicosomoids less-inflammatory less aggregatory favor vasodilation Ratio of ω-6 6 to ω-3 Paleolithic Man 2:1 Current American 15:1 to 30:1 WHO recommendation 5:1 to 10:1 Supplements Unknown: optimal therapeutic dosage, effects of chronic use, potential toxicity Single compound works differently from whole food False sense of healthy life style

Diet, Health and Environment Energy Intake (Carcinogen) High Fat/Calories High omega -66 fats Growth Factors Gene-Nutrient Imbalance Genetic Susceptibility (Common Polymorphisms) Energy Expenditure (Phytochemicals) Physical Activity Fruits Vegetables Whole Grains Soy Protein JUNK DIETS ARE OUT OF BALANCE TOO MANY CALORIES TOO MUCH FAT TOO MUCH SUGAR NOT ENOUGH VITAMINS AND MINERALS NOT ENOUGH NATURAL PLANT NUTRIENTS 5 An inflamed body in an inflamed environment Garry Egger, Centre for Health Promotion & Research & Southern Cross University

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