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A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many chronic diseases, including cardiovascular disease. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of essential fatty acids (EFA) in cell membrane phopholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have strong anti-inflammatory effects, suppress interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids tend to be pro-inflammatory. Because inflammation is at the base of many chronic diseases, including coronary heart disease, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Increased dietary arachidonic acid (AA) significantly enhances the apparent atherogenic effect of genotype, whereas increased dietary intake of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blunts this effect. The diet-gene interaction further suggests that dietary omega-6 fatty acids promote, whereas marine omega-3 fatty acids EPA and DHA inhibit leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation.

Anthropological and epidemiological studies and studies at the molecular level indicate that human beings evolved on a diet with a ratio of omega-6 to omega-3 essential fatty acids (EFA) of approximately 1 whereas in Western diets the ratio is 15/1 to 16.7/1. A high omega-6/omega-3 ratio, as is found in today's Western diets, promotes the pathogenesis of many diseases, including cardiovascular disease, cancer, osteoporosis, and inflammatory and autoimmune diseases, whereas increased levels of omega-3 polyunsaturated fatty acids (PUFA) (a lower omega-6/omega-3 ratio), exert suppressive effects. Increased dietary intake of linoleic acid (LA) leads to oxidation of low-density lipoprotein (LDL), platelet aggregation, and interferes with the incorporation of EFA in cell membrane phospholipids. Both omega-6 and omega-3 fatty acids influence gene expression. Omega-3 fatty acids have anti-inflammatory effects, suppress interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6), whereas omega-6 fatty acids do not. Because inflammation is at the base of many chronic diseases, dietary intake of omega-3 fatty acids plays an important role in the manifestation of disease, particularly in persons with genetic variation, as for example in individuals with genetic variants at the 5-lipoxygenase (5-LO). Carotid intima media thickness (IMT) taken as a marker of the atherosclerotic burden is significantly increased, by 80%, in the variant group compared to carriers with the common allele, suggesting increased 5-LO promoter activity associated with the (variant) allele. Dietary arachidonic acid (AA) and LA increase the risk for cardiovascular disease in those with the variants, whereas dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease the risk. A lower ratio of omega-6/omega-3 fatty acids is needed for the prevention and management of chronic diseases. Because of genetic variation, the optimal omega-6/omega-3 fatty acid ratio would vary with the disease under consideration.

Advances in genetics and molecular biology indicate that susceptibility to chronic diseases such as coronary artery disease (CAD), hypertension, diabetes, obesity, osteoporosis, alcoholism, cancer, etc., to a great extent is genetically determined. Studies have shown that 50% of the variance in plasma cholesterol concentration is genetically determined, whereas 30%-60% of the variance in blood pressure is genetically determined. For fibrinogen, an independent risk factor for CAD, 15%-50% of the variance is genetically determined. In the U.K. population the variance for the fibrinogen level is 15% whereas in the Hawaiian population, the variance is 50%, indicating significant differences between populations. Among Australians, 75% of the variance in bone density is found to be genetically determined. Genetic variation influences the response to diet. For example, individuals with ApoE4 have higher cholesterol levels and a higher risk of CAD than those with ApoE3. Additional studies show that women of the ApoE 3/2 phenotype stand to benefit the least from a high polyunsaturate: saturate (P:S) diet because of reduction in the more 'protective' high density lipoprotein cholesterol (HDL-C), whereas men of the ApoE 4/3 phenotype showed the greatest improvement in the LDL/HDL ratio. Therefore a general recommendation to increase the polyunsaturated content of the diet in order to decrease the risk for CAD is not appropriate for women with ApoE 3/2 phenotype. Thus, specific information is needed to define the optimal diet for an individual.