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.