1. The Role of Nutrition in Human Health, Disease, and Aging – A Practical Approach Christopher B. Heward, Ph.D. President – Kronos Science Laboratories, Inc. IABG 10 th Congress - September 2003

2. Physician: “We think you ate something that triggered some primitive genes?” Patient: “But Doc, what do I do?” Physician: “Stop eating so much sh__ …garbage!” Sound Nutritional Advice

3. The Current Scientific Consensus About Nutrition

4. USDA Dietary Guidelines THE USDA FOOD PYRAMID Promotes a grain-based low fat / high carbohydrate diet.

5. 195519621969197619831990 34 42 32 36 38 40 % Dietary Calories as Fat % of Calories from Fat from Amer Dietetic Assoc 95 417-420(1995) Year Dietary Fat Intake and Obesity (US 1955-1990) % Dietary Calories as Fat

6. 35 32 29 26 23 20 195519621969197619831990 34 42 32 36 38 40 % Overweight % of Calories from Fat from Amer Dietetic Assoc 95 417-420(1995) Year Dietary Fat Intake and Obesity (US 1955-1990) % Overweight % Dietary Calories as Fat

7. Actual Causes of Death – United States (1990) Tobacco400,00019% Diet/Activity Patterns300,00014% Alcohol100,000 5% Microbial Agents 90,000 4% Toxic Agents 60,000 3% Firearms 35,000 2% Sexual Behavior 30,000 1% Motor Vehicles 25,000 1% Illicit Use of Drugs 20,000<1% Cause Estimated Number % of Total McGinnis et al. - JAMA, November 10, 1993

8. Actual Causes of Death – United States (1990) Tobacco400,00019% Diet/Activity Patterns300,00014% Alcohol100,000 5% Microbial Agents 90,000 4% Toxic Agents 60,000 3% Firearms 35,000 2% Sexual Behavior 30,000 1% Motor Vehicles 25,000 1% Illicit Use of Drugs 20,000<1% Cause Estimated Number % of Total McGinnis et al. - JAMA, November 10, 1993

9. Major Causes of Death in the US Cardiovascular Disease Cancer Cerebrovascular Disease Chronic Pulmonary Disease Accidents Diabetes Mellitus Influenza & Pneumonia Alzheimers Kidney Septicemia Suicide Chronic Liver Disease/Cirrhosis Hypertension & Hypertensive Renal Disease Not Shown: 17.6 - Other Source: Minino, AM, Arias, E, Kochanek, et al., Summary National Vital Statistics 2000

10. The Problem Visceral Fat Subcutaneous Fat

11. Obesity Trends* Among U.S. Adults BRFSS, 1990 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

12. Height (meters) Height (meters) BMI = [Weight (kilograms)] 2 [Weight (kilograms)] 2 [Height (Inches) / 39.54] [Height (Inches) / 39.54] BMI = [Weight (Pounds) / 2.2] 2 [Weight (Pounds) / 2.2] 2 Body Mass Index (BMI)

13. Body TypeBMI Range Underweight < 18.5 Healthy Weight18.5 - 24.9 Overweight25.0 - 29.9 Obese30.0 - 39.9 Extremely Obese > 40.0 Weight Ranges For Different BMI Scores

14. Obesity Trends* Among U.S. Adults BRFSS, 1991 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

15. Obesity Trends* Among U.S. Adults BRFSS, 1992 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

16. Obesity Trends* Among U.S. Adults BRFSS, 1993 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

17. Obesity Trends* Among U.S. Adults BRFSS, 1994 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

18. Obesity Trends* Among U.S. Adults BRFSS, 1995 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

19. Obesity Trends* Among U.S. Adults BRFSS, 1996 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

20. Obesity Trends* Among U.S. Adults BRFSS, 1997 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

21. Obesity Trends* Among U.S. Adults BRFSS, 1998 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

22. Obesity Trends* Among U.S. Adults BRFSS, 1999 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

23. Obesity Trends* Among U.S. Adults BRFSS, 2000 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

24. Obesity Trends* Among U.S. Adults BRFSS, 2001 Source: Mokdad A H, et al. J Am Med Assoc 1999;282:16, 2001;286:10.

25. What Do The Experts Say? Dr. Atkins’ New Diet Revolution - Atkins Protein Power - Eades Sugar Busters - Steward The Zone - Sears Dieting With The Duchess - Sarah Volumetrics - Rolls The Pritikin Principle - Pritikin Choose To Lose - Goor Eat More, Weigh Less - Ornish

26. Comparison of Popular Diets - Macronutrients

32. The Metabolic Imperative EnergyIntake EnergyExpended =

33. EnergyExpended EnergyIntake >

34. EnergyIntake EnergyExpended <

35. NO! Does That Mean You Should Go On A Diet?

36. Rx For Healthy Nutrition and Weight Control Diet Carbohydrates - 35% (Fruits & Vegetables) Proteins - 30% of Calories (Fish, Poultry, Eggs) Fats - 35% of Calories (Fish, Meat, Nuts, Oils) 1/3 - Saturated 1/3 - Monounsaturated 1/3 - Polyunsaturated Colorful Fruits and Vegetables Supplements Vitamins & Minerals (RDA) Omega-3 FA’s (fish oil)

37. Relative Risk Relative Risk (Age Adjusted) (Age Adjusted) In the 88,000 Nurses Study, Dietary Vitamin E greater than 200 IU per day was associated with a 41% Decreased Risk for Major Coronary Heart Diseases. Vitamin E and Heart Disease

38. Health Benefits: Reduces Risk of Sudden Cardiac Death Reduces Risk of Sudden Cardiac Death Anti-inflammatory Properties Anti-inflammatory Properties Improves Membrane Fluidity Improves Membrane Fluidity Increases HDL (good) Cholesterol Increases HDL (good) Cholesterol Reduces Blood Pressure Reduces Blood Pressure Reduces Risk of Blood Clots Reduces Risk of Blood Clots Lowers LP(a) Lowers LP(a) Eicosapentaenoic Acid (EPA, 20:5w3) Docosahexaenoic Acid (DHA, 22:6w3) Omega-3 Fatty Acids (fish oil)

39. Consume ONLY those foods with a nutritional payoff - NO EMPTY CALORIES! Consume ONLY those foods with a nutritional payoff - NO EMPTY CALORIES! Vitamins Vitamins Minerals Minerals Water Water Amino Acids Amino Acids Fatty Acids Fatty Acids Phytochemicals Phytochemicals X X X X X X X Focus On Essentials - Eat Mostly Nutrient-Dense Foods Avoid “Trans” Fats! Avoid

40. USDA Revising The Food Pyramid?

41. What About Caloric Restriction and Aging?

42. Adapted From: R. Weindruch et al., J. of Nutrition, 116:641, 1986 Fully Fed 50% Calorie Restriction 10% Calorie Restriction 60% Calorie Restriction Typical Survival Curves For Mice On CR Diets

43. Caloric Restriction In Adult Mice 0 61212 Age (months) 12991177941Group 4 1040918808Group 3 129612261057Group 2 941822701Group 1 Maximum10th %ileMedian Length Of Life In Days ad libidum 60% of ad libidum intake 0 6 12 0 6 12 Age (months) Age (months) Data from Yu et al. (1985) Figure from Masoro (1989)

44. Caloric Restriction In Adult Mice 0 61212 Group 4 Lifespan Increase: ~40% Age (months) 12991177941Group 4 1040918808Group 3 129612261057Group 2 941822701Group 1 Maximum10th %ileMedian Length Of Life In Days ad libidum 60% of ad libidum intake 0 6 12 0 6 12 Age (months) Age (months) Data from Yu et al. (1985) Figure from Masoro (1989)

45. Studies of Late-Onset Caloric Restriction Adapted From Walford & Weindruch (1989) 5%13%4135393112M50%Rat5 10%8%4539413614M50%Mouse4 18%30%3330282312M50%Hamster3 15%24%3026 2112M50%Mouse2 0%44%3026301812M50%Rat1 MaxAveMaxAveMaxAveOnsetCRAnimalStudy Ad libidum Restricted % Increase Length Of Life In Months

46. Studies of Late-Onset Caloric Restriction Adapted From Walford & Weindruch (1989) 5%13%4135393112M50%Rat5 10%8%4539413614M50%Mouse4 18%30%3330282312M50%Hamster3 15%24%3026 2112M50%Mouse2 0%44%3026301812M50%Rat1 MaxAveMaxAveMaxAveOnsetCRAnimalStudy Ad libidum Restricted % Increase Length Of Life In Months

47. The Payoff From A Successful Caloric Restriction Diet Constant Hunger Abnormal Focus On Food (24hrs./day) Loss of Libido (reproductive function) Increased Life Expectancy Payoff: –If, starting at age 50, you do CR successfully for 30 years, then when you are 80 years old, you will function as though you were only 70. ~33% Retardation of Aging Rate This is just NOT enough for most people!

48. Adapted From: British Medical Journal, 1997; 314: 1311-1317 0 5 10 15 20 25 <20202224262830 Body Mass Index Deaths/1000/year All Cause Mortality Height (meters) Height (meters) BMI = [Weight (kilograms)] 2 [Weight (kilograms)] 2 BMI and All Cause Mortality

49. Lee CD et al. Am J Clin Nutr 1999. <16%16-25%  25% Risk of Death Fit-Fat & Mortality In Men % Body Fat

50. 173 Sedentary, overweight, post- menopausal women Exercise group: 45 minutes, 5 day/day X 1 year 3 months 3 d/week supervised & 2 days unsupervised 9 months 1 d/week supervised & 4 days unsupervised JAMA- Jan 15, 2003: Vol 289(3) Effect of Exercise On Total and Visceral Body Fat

51. Conclusions Americans are too fat – and getting fatter. The best diet is to reduce caloric intake without reducing nutritional intake. Take high quality dietary supplements that include: – –Vitamins and Minerals (RDA) – –Fish Oil – –Vitamin E The benefits (if any) of serious CR diets are not worth the effort for most people. Exercise may help compensate for some of the negative health affects of obesity.