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Welcome Cutting Healthcare Costs Through Prevention:

Welcome Cutting Healthcare Costs Through Prevention: Measuring the Efficacy, Safety, and Cost Savings of Dietary Supplements. Richard Sharpee, PhD Symposium Planning Chairman Natural Health Research Institute Scientific Research Manager Now Health Group, Inc. Artemis P. Simopoulos, MD

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Welcome Cutting Healthcare Costs Through Prevention:

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  1. Welcome Cutting Healthcare Costs Through Prevention: Measuring the Efficacy, Safety, and Cost Savings of Dietary Supplements

  2. Richard Sharpee, PhD Symposium Planning Chairman Natural Health Research Institute Scientific Research Manager Now Health Group, Inc.

  3. Artemis P. Simopoulos, MD President The Center for Genetics, Nutrition & Health

  4. Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Economic and Health Implications of Changing America’s Oil: The Omega-3 Opportunity Natural Health Research Institute Symposium Chicago, Illinois October 28, 2011

  5. 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

  6. 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

  7. 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)

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

  9. 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.

  10. 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.

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

  12. The Mediterranean Region

  13. 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. Allbaugh LG (1953). Crete: A case study of an underdeveloped area. Princeton, NJ: Princeton University Press. The Mediterranean Diets

  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. National Geographic, September 1969, Vol. 136, No. 3.

  17. Nature’s nutrients: The purslane plant

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

  19. 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

  20. A.P. Simopoulos and N. Salem, Jr. (1989). New England Journal of Medicine, 321:1412. Fatty acid levels in various chicken egg yolks (mg fatty acid/g hard-boiled egg yolk)

  21. Fatty acid composition of selected cheeses (amount in grams/100 grams, edible portion)

  22. Fatty acid composition of snails

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

  24. 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.

  25. Mediterranean α-linolenic acid rich diet in secondary prevention of CHD: End points (27 months mean follow up) de Lorgeril, M. et al. Lancet 1994; 343: 1454-59.

  26. Values are means of four measurements. Values for each fatty acid with the same letter do not differ significantly (p<0.01) between control and fat-1. Kang, J.X. (2003), World Rev Nutr Diet, Vol. 92. Polyunsaturated fatty acid composition of total cellular lipids from the control heart cells and the transgenic cells expressing a C. elegans fat-1 cDNA

  27. Eicosanoid Formation and Metabolism

  28. Catabolic pathways of arachidonic acid

  29. Lipid Mediators Uncontrolled inflammation is now appreciated in the pathogenesis of many diseases that were not previously considered classic inflammatory diseases- Atherosclerosis, cancer, and several neurological disorders such as Alzheimer’s disease and Parkinson’s disease. EPA Resolvins of E series DHA Resolvins of D series DHA Protectins D DHA Neuroprotectin D1 AA Lipoxins A4, B4

  30. Key cellular actions of lipoxins and resolvins Spite M, Serhan CN. Circ Res. 2010;107:1-15. LXA₄ is generated from AA, whereas omega-3 fatty acids, EPA and DHA serve as precursors for E-series and D-series resolvins, respectively. Lipoxins and resolvins act in a stereospecific manner on distinct cell types through interaction with GPCRs to stimulate nonphlogistic macrophage phagocytosis, increase antiinflammatory cytokines, and decrease proinflammatory cytokine generation in macrophages, neutrophils (PMNs) endothelial cells, and dendritic cells. Lipoxins and resolvins also stimulate endothelial production of nitric oxide (NO) and vasoprotectiveprostacyclin (PGI₂.

  31. IMMUNOLOGY AND INFLAMMATION

  32. Biological activities of interleukin-1 Figure courtesy of Dr. Jos W. M. van der Meer, Nijmegen, the Netherlands

  33. Chronic inflammatory diseases • Rheumatoid Arthritis • Ulcerative Colitis • Psoriasis • Lupus Erythematosus • Diabetes (I & II) • Obesity • Atherosclerosis • Cancer IL-1 (IL-α AND IL-1-β), IL-1ra TNF are elevated

  34. Effect of ω-3 fatty acids on factors involved in the pathophysiology of atherosclerosis, inflammation, and the metabolic syndrome

  35. Effect of ω-3 fatty acids on factors involved in the pathophysiology of atherosclerosis, inflammation, and the metabolic syndrome

  36. Effect of ω-3 fatty acids on factors involved in the pathophysiology of atherosclerosis, inflammation, and the metabolic syndrome

  37. Effect of ω-3 fatty acids on factors involved in the pathophysiology of atherosclerosis, inflammation, and the metabolic syndrome

  38. Effect of ω-3 fatty acids on factors involved in the pathophysiology of atherosclerosis, inflammation, and the metabolic syndrome

  39. PLASMA LIPIDS AND LIPOPROTEINS

  40. THROMBOSIS AND ATHEROSCLEROSIS

  41. Omega-3 fatty acids The antiarrhythmic effects in animal and human studies could explain the reduced mortality of postmyocardial infarction patients given these acids.

  42. CELL MEMBRANE FUNCTION AND METABOLISM THROUGHOUT THE LIFE CYCLE

  43. Effects of PUFA on several genes encoding enzyme proteins involved in inflammation, adhesion molecules, cell growth, early gene expression, β-oxidation, and growth factors Fatty acid Cell growth and early gene expression c-fos, Egr-1 Adhesion molecules VCAM-1 mRNA** Inflammation IL-1B mRNA β-oxidation acyl-CoA oxidase mRNA** Growth Factors PDGF mRNA LA LNA AA *** EPA * DHA *EPA has no effect by itself but enhances the effect of DHA. ** Monounsaturates also suppress VCAM-1 mRNA, but to a lesser degree than DHA, and induce acyl-CoA oxidase mRNA ***AA suppresses VCAM-1 mRNA, but to a lesser degree than DHA suppress or decrease induce or increase Simopoulos AP. Annals of Nutrition and Metabolism 1996;40:303-311.

  44. Mechanisms of Omega-6/Omega-3 Fatty Acids • Linoleic Acid Inhibits Eicosapentaenoic Acid Incorporation from Dietary Fish Oil Supplements in Human Subjects • Linoleic Acid Increases Low-Density Lipoprotein Oxidation and Severity of Coronary Atherosclerosis • As the Omega-6/Omega-3 Ratio Decreases, So Does the Platelet Aggregation

  45. Mechanisms of Omega-6/Omega-3 Fatty Acids • Omega-3 Fatty Acids downregulate the expression of genes involved in inflammation and obesity • A Lower Omega-6/Omega-3 Ratio as part of a Mediterranean Diet Decreases Vascular Endothelial Growth Factor • Decreasing Linoleic Acid with Constant α-Linolenic Acid in Dietary Fat Increases Eicosapentaenoic Acid in Plasma Phospholipids in Healthy Men

  46. Verschuren, W.M. et al. (1995). Serum total cholesterol and long-term coronary heart disease mortality in different cultures: Twenty five-year follow-up of the seven countries study. JAMA, 274 (2). 25-year CHD mortality in the Seven Countries Study

  47. 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

  48. Marchioli R., Barzi F., Bomba E. et al. Circulation 2002; 105: 1897-1903. Early benefit of ω3 PUFA therapy: Total mortality

  49. Marchioli R., Barzi F., Bomba E. et al. Circulation 2002; 105: 1897-1903. Early benefit of ω3 PUFA therapy: Sudden death

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