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Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health

Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013. The concept of positive health.

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Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health

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  1. Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Athens, Greece October 16, 2013

  2. The concept of positive health Positive health requires a knowledge of man’s primary constitution (what today we would call genetics) and of the powers of various foods, both those natural to them and those resulting from human skill (today’s processed food). But eating alone is not enough for health. There must also be exercise, of which the effects must likewise be known. The combination of these two things makes regimen, when proper attention is given to the season of the year, the changes of the winds, the age of the individual and the situation of his home. If there is any deficiency in food or exercise the body will fall sick. ~Hippocrates

  3. Genotype Environment Phenotype Development Childs, B. (1990). Genetic Variation and Nutrition. World Rev Nutr Diet, Vol 63. Relationships between genes, environment, and development are dynamic

  4. Simopoulos AP: Genetic variation and evolutionary aspects of diet. In: Antioxidant Status, Diet, Nutrition, and Health, Papas AM (Editor), CRC Press, Boca Raton, 1999, pp. 65-88. Hypothetical scheme of fat, fatty acid (ω6 and ω3, trans and total) intake (as percent of calories from fat) and intake of vitamins E and C (mg/d)

  5. The desaturation and elongation of ω3 and ω6 fatty acids (FADS 2) (FADS 1)

  6. Ratios of dietary ω6:ω3 fatty acids in the late Paleolithic period and in current Western dietary patterns (g/d) a,b aData from Eaton et al. (1998), World Rev Nutr Diet. bAssuming an energy intake of 35:65 of animal:plant sources.

  7. ω6:ω3 ratios in various populations aData from Eaton et al. (1998), World Rev Nutr Diet. bAssuming an energy intake of 35:65 of animal: plant sources.

  8. The Mediterranean Region

  9. The Mediterranean Diets Although Greece and the Mediterranean countries are usually considered to be areas of medium-high death rates (14.0-18.0 per 1000 inhabitants), death rates on the island of Crete have been below this level continuously since before 1930. No other area in the Mediterranean basin has had as low a death rate as Crete, according to data compiled by the United Nations in their demographic yearbook for 1948. It was 11.3-13.7 per 1000 inhabitants before World War II and about 10.6 in 1946-1948. Cancer and heart disease caused almost three times as many deaths proportionally in the United States as in Crete. The diet of Crete represents the traditional diet of Greece before 1960. Reference: Allbaugh LG. Crete: A case study of an underdeveloped area. Princeton, NJ: Princeton University Press, 1953.

  10. The Seven Country Study

  11. OLIVE OIL CONSUMPTION PER PERSON GREECE SPAIN ITALY PORTUGAL U.S. EEC/OTHER

  12. Olive Oil Samples

  13. Fatty Acid Composition of Olive Oil Ampelistra Olive Oil

  14. Life expectancy and disease rates in the United States and Greece in the 1960’s

  15. Dietary characteristics in the United States and Greece in the 1960s

  16. Reference: National Geographic, September 1969, Vol. 136, No. 3

  17. Per capita consumption of the major food groups in 1962 and 1997 in Greece demonstrating important trends in the nutrition of Greeks over a period of 35 years Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

  18. Per capita consumption of meat from various sources from 1962 to 1997 in Greece showing a steady increase in meat consumption Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

  19. Per capita consumption of fish and other marine products from 1962 to 1997 in Greece Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

  20. Per capita calorie consumption from vegetable and animal products from 1962 to 1997 in Greece Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

  21. Per capita consumption of oils from various sources from 1962 to 1997 in Greece Simopoulos AP, Sidossis L. What is so special about the traditional diet of Greece: the scientific evidence. In: Simopoulos AP, Visioli F (Eds). Mediterranean Diets. World Rev Nutr Diet, vol. 87, 2000, pp. 24-42.

  22. Nature’s nutrients: The purslane plant Simopoulos AP et al . Common purslane: A source of omega-3 fatty acids and antioxidants. J Am College Nutr 1992;11(4):374-382.

  23. Fatty acid content of plants* *mg/g of wet weight Source: A.P. Simopoulos and N. Salem, Jr. New England Journal of Medicine, 315:833 (1986).

  24. Summary: Nutritional value of purslane One serving of fresh leaves (100 g) contains: • 300-400 mg 18:3ω3 • 12 mg alpha-tocopherol • 27 mg ascorbic acid • 2 mg beta-carotene • 15 mg glutathione Simopoulos AP et al. Common purslane: A source of omega-3 fatty acids and antioxidants. J Am College Nutr 1992;11(4):374-382.

  25. Melatonin concentrations in some edible plants Reference: Simopoulos AP, et al. J Pineal Res 2005;39:331-332.

  26. Fatty acid levels in various chicken egg yolks (mg fatty acid/g hard-boiled egg yolk) Simopoulos AP and Salem N Jr: n-3 fatty acids in eggs from range-fed Greek chickens. N Engl J Med 321:1412, 1989.

  27. Fatty acid composition of selected cheeses (amount in grams/100 grams, edible portion) Simopoulos AP. Mediterranean Diets: What is So Special About the Diet of Greece? The Scientific Evidence. J Nutr 2001;131:3065S-3073S.

  28. Fatty acid composition of snails

  29. Fat content and fatty acid composition of wild and cultured salmon*

  30. Fatty acid composition of serum cholesterol esters(Percent, X ± SD)

  31. Omega-3 fatty acids in traditional diets • In traditional diets, omega-3 fatty acids are found throughout the food chain • Eggs have a ratio of omega-6:omega-3 of 1:1 • Pasta made with eggs and milk that is rich in omega-3 fatty acids is enriched in omega-3’s • Pasta made with water and flour, or regular milk, is not enriched in omega-3’s.

  32. Cretan Mediterranean diet for prevention of coronary heart disease Renaud S et al. Am J Clin Nutr. 1995 Jun;61(6 Suppl):1360S-1367S. .

  33. Marchioli R., Barzi F., Bomba E. et al. Circulation 2002; 105: 1897-1903. Early protection against sudden death by ω3 polyunsaturated fatty acids after myocardial infarction: Time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione • 11,323 patients were randomly assigned to supplements of omega-3 PUFAs • 850 mg/d- ratio of EPA:DHA = 2.1 • Vitamin E = 300 mg/d • Both omega-3 and vitamin E • None (control) • On top of optimal pharmacological treatment, lifestyle advice • Survival curves for omega-3 PUFA treatment diverged early after randomization and total mortality was significantly lowered after 3 months of treatment • A similar significant, although delayed pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac and coronary death

  34. ω-3 PUFA + CVD Early benefit of omega-3 polyunsaturated fatty acid (ω-3 PUFA) therapy on total mortality, sudden death, coronary heart disease (CHD) mortality, and cardiovascular mortality. Probability measurements represent relative risk (95% confidence interval). Reprinted, with permission, from Marchioli et al. MI = myocardial infarction.

  35. Marchioli R., Barzi F., Bomba E. et al. Circulation 2002; 105: 1897-1903. Early protection against sudden death by ω3 polyunsaturated fatty acids after myocardial infarction: Conclusion The early effect of low dose 850 mg/d omega-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of omega-3 fatty acids. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, epidemiological and clinical studies.

  36. Metabolic Syndrome The prevalence of metabolic syndrome in the U.S. has been increasing and is particularly high for older adults and certain ethnic groups. Hispanics have the highest reported prevalence of metabolic syndrome, and are more likely to be affected by type 2 diabetes than non-Hispanic whites.

  37. The Components of the Metabolic Syndrome • Abdominal Obesity • waist circumference > 102 cm in Men • and > 88 cm in Women • Dyslipidemia • Increase Trigylcerides > 150 mg/dl • Decrease HDL < 40 mg/ dl in Men • and < 50 mg/dl in Women • Hypertension • Blood Pressure > 130/85 mmHg • Fasting Hyperglycemia • 100 mg/dl

  38. Omega-3s and Insulin Sensitivity Dietary intake of omega-3 fatty acids have insulin-sensitivity actions in adipose tissue and liver and improve insulin sensitivity. Genes involved in insulin sensitivity (PPAR), glucose transport (GLUT-2/GLUT-4) and insulin receptor signaling (IRS-1/IRS-2) are upregulated by omega-3 fatty acids. Moreover omega-3 fatty acids increase adiponectin, an anti-inflammatory and insulin-sensitizing adipokine, and induce AMPK phosphorylation, a fuel-sensing enzyme and a gate keeper of the energy balance.

  39. Simopoulos, AP. Exp Biol Med (Maywood). 2008 Jun; 233(6):674-88 ω-6/ω-3 ratio in chronic diseases In the secondary prevention of cardiovascular disease, a ratio of 4/1 was associated with a 70% decrease in total mortality. A ratio of 2.5/1 reduced rectal cell proliferation in patients with colorectal cancer, whereas a ratio of 4/1 with the same amount of omega-3 PUFA had no effect. The lower omega-6/ omega-3 ratio in women with breast cancer was associated with decreased risk.

  40. Simopoulos, AP. Exp Biol Med (Maywood). 2008 Jun; 233(6):674-88 ω-6/ω-3 ratio in chronic diseases A ratio of 2-3/1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5/1 had a beneficial effect on patients with asthma, whereas a ratio of 10/1 had adverse consequences. These studies indicate that the optimal ratio may vary with the disease under consideration. This is consistent with the fact that chronic diseases are multigenic and multifactorial. Therefore, it is quite possible that the therapeutic dose of omega-3 fatty acids will depend on the degree of severity of disease resulting from the genetic predisposition.

  41. ω-3’s in Development • Maternal intake of W-3’s during pregnancy and lactation may favor the later mental development of children (Helland et al. Pediatrics. 2003 Jan;111:39-44) • important in visual and cognitive development

  42. Metabolic programming of long-term outcomes due to fatty acid nutrition in early life Understanding of the importance of dietary fatty acids has grown beyond a simple source of energy to complex roles in regulating gene expression and cell and intracellular communication. This is important because the metabolic and neuroendocrine environment of the fetus and infant plays a key role in guiding the set point of neural receptors that regulate energy homeostasis and expression of genes that control energy storage and oxidation. Early deviations in these pathways have the potential to lead to lasting adaptations, termed metabolic programming, which may combine to increase the risk of metabolic syndrome in later life. The quality of fatty acids in human diets has undergone major changes in the last 50 years, characterized by an increase in ω-6 and decrease in ω-3 fatty acids. Evidence is accumulating to support the concept that the maternal intake of ω-6 and ω-3 fatty acids in gestation and lactation, possibly involving both excess ω-6 and inadequate ω-3 fatty acids, can impact the developing infant tissue lipids and neuroendocrine and metabolic pathways relevant to metabolic programming. Further work is needed to understand the needs for different ω-6 and ω-3 fatty acids during fetal and infant life, and their roles with respect to development of energy homeostasis and metabolism.

  43. ω-3’s in Healthy Subjects • 33 healthy subjects, 13 M, 20 F, 22-51 yrs (mean =33 ±7yrs) Subjects were tested at the beginning of the experiment and after 35 days. Supplemented with 4 grams of fish oil (1.60g EPA + 0.80 DHA + 0.4g of other W-3’s). Control consisted of 4g olive oil (indistinguishable by packaging, shape or taste). Fontani et al. Eur J Clin Invest. Nov; 35 (11) : 691-699

  44. ω-3’s in Healthy Subjects Olive OilFish Oil Day 1:AA/EPA = 16.39 ± 8.32 mean value vs. 16.17 ± 10.63 Day 35:AA/EPA = 14.26 ± 8.87 mean value vs. 4.29 ± 2.60 P>0.0001

  45. Before ω-3 After ω-3 Profile of Mood States (POMS). Comparison before and after Omega-3 supplementation. Mean ± standard error (subjects n = 33). Paired samples t-test: **** P < 0·0001, *** P < 0·001, ** P < 0·01, * P < 0·04. Fontani et al 2005.

  46. ω-3’s in Healthy Subjects The mood profile improved after W-3’s with increased vigor and reduced anger, anxiety and depression states. An EEG frequency shift towards the theta and alpha band were recorded in all tests after W-3’s Conclusion W-3 supplementation is associated with an improvement of attentional and physiological functions, particularly those involving complex cortical processing.

  47. 25-year CHD mortality in the Seven Countries Study Reference: de Lorgeril, M., Salen, P. Mediterranean type of diet for the prevention of coronary heart disease. A global perspective from the Seven Countries Study to the most recent dietary trials. Int J Vitam Nutr Res 2001; 71(3): 166-172.

  48. Ambring A, Johansson M, Axelsen M, et al., Am J Clin Nutr 2006; 83: 575-81. Mediterranean-inspired diet: Conclusion A Mediterranean-inspired diet (MID) reduces the number of platelets and leukocytes and VEGF concentrations in healthy subjects. This may be linked to higher serum concentrations of omega-3 fatty acids, which promote a favorable composition of phospholipids.

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