Artemis P. Simopoulos, M.D. President The Center for Genetics, Nutrition and Health Washington DC, USA Evolutionary Aspects of Diet with the emphasis on Omega-3 Fatty Acids Functional Forum: The Evolution of Medicine Arlington, Virginia October 10, 2016 1

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

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

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) 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. 4

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

n-6 and n-3 fatty acid metabolic pathways n-6 and n-3 fatty acid metabolic pathways. FADS1, fatty acid desaturase 1; FADS2, fatty acid desaturase 2

Ratios of dietary ω6:ω3 fatty acids in the late Paleolithic period and in current Western dietary patterns (g/d) a,b Paleolithic Western LA:ALA 0.70 18.75 AA+DTA:EPA+DPA+DHA 1.79 3.33 Total 0.79 16.74 aData from Eaton et al. (1998), World Rev Nutr Diet. bAssuming an energy intake of 35:65 of animal:plant sources. 8

ω6:ω3 ratios in various populations Reference Paleolithic 0.79 a,b Eaton et al, 1998 Greece prior to 1960 1.00-2.00 Simopoulos, 1999 Current United States 16.74 United Kingdom and northern Europe 15.00 Sanders, 2000 Japan 4.00 Sugano and Hirahana, 2000 India rural 5-6.1 Pella et al, 2003 India urban 38-50 aData from Eaton et al. (1998), World Rev Nutr Diet. bAssuming an energy intake of 35:65 of animal: plant sources. 9

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.

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.

Eicosanoid Formation and Metabolism 12

Catabolic pathways of arachidonic acid

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 14

IMMUNOLOGY AND INFLAMMATION 15

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 16

PLASMA LIPIDS AND LIPOPROTEINS THROMBOSIS AND ATHEROSCLEROSIS 17

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