From Science to Life Style Changes. Patana Teng-umnuay, M.D. Ph.D. Phyathai 2 Hospital

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1 From Science to Life Style Changes Patana Teng-umnuay, M.D. Ph.D. Phyathai 2 Hospital

2 Aging Aging is the accumulation of changes in the cells and tissues that increase the risk of death. The aging process produces aging changes at an exponentially increasing rate with advancing age.

3 Anti-aging Medicine The use of multidisciplinary techniques to prevent aging process that leads to disabilities or death. Aesthetic Medicine The use of medical techniques to enhance patient s satisfaction with his/her physical appearance. Regenerative Medicine The process of creating living, functional tissues to repair or replace tissue or organ function lost due to age, disease, damage, or congenital defects.

4 Percent of all individuals reporting the disease who are 65 years and older, USA, 1996 Cerebrovascular disease 68.9% Arthritis 45.6% Hearing impairment 43.7% Diabetes 41.7% Heart disease 41.3% Hypertension 40.8% Visual impairment 32.3% Asthma and emphysema 13.4%

5 Projected Global Deaths for Selected Causes World Health Statistics 2007

9 Theories of Aging

10 Telomere shortening Telomeres are sequences of nucleic acids extending from the ends of chromosomes. Every time the cell divides, telomeres are shortened, leading to cellular damage and death. Telomerase is an enzyme that can repair and replace telomeres, found only in germ cells and cancer cells.

11 Hormonal Theory of Aging

12 Geriatric medicine says

13 Anti-aging medicine says

14 Hormonal Imbalance in Aging INSUFFICIENCY Melatonin Growth hormone Estrogen Progesterone Testosterone DHEA Pregnenolone Thyroid hormone EXCESS Cortisol Insulin

15 Impact of anabolic deficiency on survival rate in men with chronic heart failure (Circulation 2006;114:1829) Hormone Status High levels of DHEA, testosterone, and IGF-1 Deficiency in one hormone (DHEA, testosterone, or IGF-1) Deficiency in two hormones (DHEA, testosterone, or IGF-1) Deficiency in all three hormones (DHEA, testosterone, and IGF-1) Three-year Survival Rate 83% 74% 55% 27%

16 Cross-linkage theory of Aging The formation of advanced glycosylation end products (AGEs) of mainly glucose-protein interactions, which form chemically cross-linked molecules Rate of formation of AGEs is proportional to the blood glucose level. AGEs have been identified in hemoglobin, β-2 microglobulin, β- amyloid protein, collagen, and lens crystalline. Deposition of AGEs results in protein dysfunction and inflammation

17 Approximate mean plasma glucose at different HbA1C levels (MPG change of 35 mg/dl or 2 mmol/l per 1% change in HbA1c) HbA1C mmol/l Approximate MPG mg/dl Rohlfing et al Diabetes Care 25:275

18 Glycated Hemoglobin Not just a risk factor for a diabetic! EPIC-Norfolk Study (Ann Intern Med 2004;141:413) HbA 1C concentrations predict mortality continuously across the whole population distribution in people with or without diabetes.

19 Prediabetic Patients Show Increased CVD Mortality Risk (Circulation 2007, 10:1161) In an Australian cohort study, 10,428 adults were examined at baseline and followed for a median of about 5 years. All-cause mortality was higher among those with known diabetes, impaired fasting glucose, or impaired glucose tolerance than among those with normal glucose tolerance. Cardiovascular mortality was increased among those with diabetes or impaired fasting glucose.

20 To reduce AGEs formation, one must obtain the lowest HbA1c possible without hypoglycemia Caloric restriction Low glycemic index food Exercise Metformin Acarbose, Voglibose PPARγ activator ACEI Telmisartan

Energy intake is minimized, but sufficient quantities of vitamins, minerals, and other important nutrients must be eaten

21 Caloric Restriction (CR) Limiting dietary energy intake to retard aging In human subjects, CR has been shown to lower cholesterol, fasting glucose, and blood pressure. Energy intake is minimized, but sufficient quantities of vitamins, minerals, and other important nutrients must be eaten (caloric restriction with optimal/adequate nutrition (CRAN) diet). Except for houseflies, animal species tested with CR so far, including primates, rats, mice, drosophila, and C. elegans, have shown lifespan extension.

Glycemic Index of Foods Classification GI Range Examples High GI 70 or more White rice, sticky rice, white bread, potato, watermelon, ice cream doughnut, popcorn,

22 Glycemic Index of Foods Classification GI Range Examples High GI 70 or more White rice, sticky rice, white bread, potato, watermelon, ice cream doughnut, popcorn, Medium GI Sucrose, soda pop, carrot, bran rice, pineapple, noodle, orange Low GI 55 or less Banana, mango, apple, strawberry, vegetable, yogurt, milk, fructose, chestnut

23 Lower GI Diet: Three Factors 1. Type 2. Amount 3. Vegetables and protein lower GI

Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydraterestricted diet than on a calorie- and

24 Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydraterestricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. (N Engl J Med 2003; 348: 2074)

25 Replace Higher GI Foods with Lower GI Foods

Life span is determined by the rate of such damage to the mitochondria.

26 Free Radical Theory of Aging Aging is the accumulation of deleterious changes produced by free radical reactions, most initiated by the mitochondria. Life span is determined by the rate of such damage to the mitochondria. Excess nourishment, combined with sedentary lifestyle, results in sugar and fat accumulation within muscle, adipose tissue, and pancreatic cells, and leads to the generation of excess reactive oxygen species.

27 Generation of reactive oxygen species (ROS) (Johansen et al. Cardiovascular Diabetology, 2005)

28 How to Reduce Oxidative Stress Caloric Restriction Losing Weight Diet Exercise Antioxidants Beta-carotene Astaxanthin Vitamin E Vitamin C Co-enzyme Q10 Alpha-lipoic acid N-acetyl cysteine Glutathione Selenium Resveratrol

29 Clinical trials of antioxidants Study Intervention Results HOPE Vitamin E Negative ATBC CARET Physicians Health Study Women s Health Study Beta-carotene Vitamin E Beta-carotene and vitamin A Beta-carotene Beta-carotene Increased risk of ischemic heart disease Increased risk of hemorrhagic stroke Increased risk of cardiovascular disease No effect No effect

among male smokers after five to eight years of supplementation with α- tocopherol or

30 The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group (N Engl J Med 1994;330: ) Alpha-tocopherol No reduction in the incidence of lung cancer among male smokers after five to eight years of supplementation with α- tocopherol or β-carotene. Beta-carotene Higher incidence of lung cancer among the men who received β-carotene

31 ARE YOU TAKING THE WRONG FORM OF VITAMIN E? There are 8 forms of vitamin E α, β, δ, γ tocopherols α, β, δ, γ tocotrienols

32 It is gamma- not alpha- Tocopherol! Low dose alpha-tocopherol improves and high dose alpha- tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits (J( J Clin Invest 1994; 93: 844). Alpha tocopherol (regular vitamin E) displaces critically important gamma tocopherol in the cells (J( J Natl Cancer Inst. 2000; 92:1966). While alpha tocopherol inhibits free-radical radical production, gamma tocopherol is required to trap and neutralize existing free radicals (Proc( Natl Acad Sci USA 1997; 94: 3217).

33 Clinical trials of antioxidants Study Intervention Results Lyon Diet heart Study AREDS Mediterranean-type diet Vitamin C, E, zinc, and β-carotene Reduced coronary events Delayed age-related macular degeneration and visual loss Steno-2 Study ALADIN Study Intensive therapy plus vitamin C, E, folic acid, and chromium Alpha-lipoic acid Selenium Reduced cardiovascular and microvascular incidence by 50 percent Improved symptoms and signs of diabetic neuropathy Prevent lung, prostate, and colorectal cancer

34 Acetyl-L-carnitine carnitine (ALCAR) and lipoic acid supplementation improves metabolic function in old rats (PNAS 2002;99:1870)

35 Coenzyme Q10 (Ubiquinone) Antioxidant, part of electron transport chain in mitochondria. Improves cardiac functions in cardiomyopathy, ischemic heart disease, post-chemotherapy, and sport medicine (proc Natl Acad Sci USA 82: ). Neuroprotective effects in parkinsonism and stroke (Arch neurol 59: ) Precursor of coenzyme Q10, mevalonate, is inhibited by statins (J Clin Pharmacol 3: )

36 Inflammatory Theory of Aging Pathology of many age-related diseases showed immune cells and expression of inflammatory markers. Increased inflammatory markers (hscrp, homocysteine, Interleukin-1, TNF-alpha) expression are associated with the severities of many chronic diseases including atherosclerosis, diabetes, cancer Anti-inflammatory medicine shows reduction in the incidence of cancer and severities of diabetes.

38 How to Reduce Inflammation Caloric Restriction Losing Body FAT Low glycemic index food Exercise Antioxidants Avoid animal fat Fish oil Medicine Low dose aspirin Lowering cholesterol level ACEI, ARB

39 Bad Fat are saturated fat, trans fat, cholesterol Good Fat are unsaturated fat Molecular structure of fatty acid

40 Trans fat increases the risk of coronary heart disease Occur in small quantities in meat and dairy products. Industrially created by partial hydrogenation of plant. The process developed in the early 1900s and first commercialized as Crisco in Considered to be more of a health risk than saturated fat.

41 Sources of Trans Fat in the U.S. Diet Okie S. N Engl J Med 2007;356:

42 Results of Randomized Studies of the Effects of a Diet High in Trans Fatty Acids (Circles) or Saturated Fatty Acids (Squares) on the Ratio of LDL Cholesterol to HDL Cholesterol Ascherio A et al. N Engl J Med 1999;340:

44 Dietary sources of polyunsaturated fatty acids Omega-6 fatty acids LA, linoleic acid 18:2ω6 AA, arachidonic acid 20:4ω6 Omega-3 fatty acids ALA, alpha-linolenic acid 18:3ω3 EPA, eicosapentaenoic acid 20:5ω3 DHA, docosahexaenoic acid 22:6ω3 Food sources Vegetable oils (corn, soybean), animal meats Animal sources (meat, eggs) Food sources Flaxseed, canola oil, walnuts Marine sources, fish oils Marine sources, fish oils, egg, dairy products

DHA, the prominent structural fatty acid in the gray mater of the brain and

45 DHA, the prominent structural fatty acid in the gray mater of the brain and in the retina, is an essential nutrient to provide for optimal neuronal and visual function. Metabolic conversion of omega-3 3 fatty acid Metabolic conversion of ALA to DHA/EPA is very limited in humans. Infants consuming breast milk via supplementation of the mothers with 200 mg DHA had significantly higher outcomes on the psychomotor development index at 30 months of age.

46 Effects of EPA on the production of eicosanoids and inflammatory cytokines

47 DHA/EPA: Reduction in triglyceride level

DHA/EPA and Stroke Increasing fish consumption up to 5 servings or more per week was associated with an approximate overall 31% reduction in stroke mortality (Stroke 2004; 35: 1538).

48 DHA/EPA and Stroke Increasing fish consumption up to 5 servings or more per week was associated with an approximate overall 31% reduction in stroke mortality (Stroke 2004; 35: 1538). Consumption of boiled or baked fish was associated with a lower risk of ischemic stroke while the intake of fried fish or fish sandwiches was associated with a higher risk (Arch. Intern. Med 2005; 165: 683).

49 Cardiac mortality in relation to different treatments (Studer et al. Arch Intern med 2005;165:725)

50 American Heart Association officially recommended one fatty fish meal per day (DHA/EPA of 900 mg/day) in patients with coronary disease and two fish servings/ week ( mg/day of DHA/EPA) for healthy individual (Circulation 2000;102:2284).

51 Omega-3 Fatty Acid Supplement Label Size DHA EPA Omex mg 125 mg 25 mg Blackmore 1000 mg 120 mg 180 mg MorEPA 1000 mg 70 mg 581 mg MorDHA 800 mg 465 mg 64 mg

52 Three Mystery Oil and Health Olive Oil Rice Bran Oil Evening Primrose Oil

53 Antiaging medicine is NOT about one medicine. It is about EVERYTHING

54 Pathway to Wellness Nutrition Exercise Smoking cessation Stress Reduction Vitamin Supplements Hormonal Supplements Risk Factors Identification Medicine

Lipids. PBHL 211 Darine Hachem, MS, LD

Lipids. PBHL 211 Darine Hachem, MS, LD Lipids PBHL 211 Darine Hachem, MS, LD Outline Functions of lipids in our body Types of lipids Sources of lipids Recommendation of fat intake Fat association with heart diseases Provide energy (9Kcal/g