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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 The Importance of the Omega-6/Omega-3 Ratio in Chronic Disease Risk Functional Forum: The Evolution of Medicine Arlington, Virginia October 10, 2016.

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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 The Importance of the Omega-6/Omega-3 Ratio in Chronic Disease Risk Functional Forum: The Evolution of Medicine Arlington, Virginia October 10, 2016

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Beneficial Effects of OBeneficial Effects of Omega-3 Fatty Acids on Factors Contributing to Metabolic Syndromemega-3 Fatty Acids Robinson LE et al. Appl Physiol Nutr Metab. 2007 Dec;32(6):1008-24.

  8. Wang L et al. Eur J Nutr 2016;55(2):687-97 A Prospective study of erythrocyte polyunsaturated fatty acid, weight gain, and risk of becoming overweight or obese in middle-aged and older women ω3 and ω6 fatty acids (FA) may have divergent effects on the development of obesity. The authors examined the association of baseline erythrocyte ω3 and ω6 FA composition with body weight change and the risk of becoming overweight or obese in the Women's Health Study (WHS) participants. They identified 534 women who had baseline erythrocyte FA measured and a baseline body mass index (BMI) of 18.5-<25 kg/m(2). Body weight was updated at a total of six time points during follow-up. Weight gain during a mean of 10.4-year follow-up increased with increasing quartiles of baseline erythrocyte cis ω6 FA, ω6/ω3 ratio, and trans FA while decreased with increasing cis ω3 FA. CONCLUSIONS: In this prospective study, there is suggestive evidence that erythrocyte cis ω6 FA may be positively associated, and cis ω3 FA inversely associated with weight gain in initially normal-weight women.

  9. The effects of dietary EPA and DHA on the composition of the EPA and DHA in skeletal muscle membrane phospholipids and their relationship to insulin resistance/hyperinsulinemia and chronic diseases (obesity, T2DM, hypertension, coronary artery disease) Simopoulos AP. Nutrients 2013;5(8):2901-23

  10. Conclusions and Recommendations The importance of omega-3 essential fatty acids in the diet is now evident, as well as the need to return to a more physiologic omega-6/omega-3 ratio of about 1-4/1 rather than the ratio of 20-16/1 provided by current Western diets. In order to improve the ratio of omega-6/omega-3 essential fatty acids, it will be necessary to decrease the intake of omega-6 fatty acids from vegetable oils and to increase the intake of omega-3 fatty acids by using oils rich in omega-3 fatty acids and increase the intake of fish to two to three times per week or take supplements.

  11. Conclusions and Recommendations Omega-3 fatty acids have been part of our diet since the beginning of time. It is only for the past 150 years that omega-3 fatty acids have been decreased in Western diets due to agribusiness and food processing. The need to return the omega-3 fatty acids into the food supply has been recognized by industry, which is already producing omega-3 enriched products.

  12. Conclusions and Recommendations Because chronic diseases are multigenic and multifactorial it is essential in designing clinical trials that the background diet, the omega-6/omega-3 ratio and the genetic variants are taken into consideration.

  13. Adequate intakes (AI) for adults 1. Although the recommendation is for AI, the Working Group felt that there is enough scientific evidence to also state an upper limit (UL) for LA of 6.67 g/d based on a 2000kcal diet or of 3.0% of energy. 2. For pregnant and lactating women, ensure 300 mg/d of DHA.3.Except for dairy products, other foods under natural conditions do not contain trans-FA. Therefore, the Working Group does not recommend trans-FA to be in the food supply as a result of hydrogenation of unsaturated fatty acids or high temperature cooking (reused frying oils).4.Saturated fats should not comprise more than 8% of energy.5. The Working Group recommended that the majority of fatty acids are obtained from monounsaturates. The total amount of fat in the diet is determined by the culture and dietary habits of people around the world (total fat ranges from 15-40% of energy) but with special attention to the importance of weight control and the reduction of obesity. Simopoulos AP , Leaf A, Salem N Jr, J Am Coll Nutr 1999;18(5):487-9

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