Dietary polyunsaturated fatty acids and inflammatory mediator production


James, M.J., Gibson, R.A., Cleland, L.G. 2000. Am J Clin Nutr. 71(suppl):343S-348S.


Dietary polyunsaturated fatty acids (PUFA) modulate inflammatory processes through the production of inflammatory and anti-inflammatory eicosanoids and cytokines. The proinflammatory eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are derived from the n-6 fatty acid arachidonic acid which is prevalent in the modern Western diet characterized by high n-6 and low n-3 content. The predominance of n-6 fatty acids is due to the high intake of linoleic acid (LA) in the diet; in contrast to the low intake of alpha-linolenic acid (ALA), which is found in high amounts in flax seed oil. LA is converted to arachidonic acid (AA) and ALA is converted to eicosapentaenoic acid (EPA). EPA is a competitive inhibitor of AA conversion to PGE2 and LTB4, which can occur after flax seed or fish oil supplementation. LA and ALA are both essential fatty acids, whereas the omega-9 fatty acid oleic acid, while consumed in substantial amount, is not an essential fatty acid. Oleic acid converts to eicosatrienoic acid, which can decrease synthesis of leukotriene LTB4. Increasing the n-3 fatty acids through flax seed or fish oil supplementation can shift the balance to eicosanoids to a less inflammatory combination. Dietary fats also influence the cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) which have proinflammatory cellular actions that stimulate the production of collagenases and increase the expression of adhesion molecules, causing inflammation such as inflammatory joint disease and arthritis. Whereas the eicosanoids mediate much of the early pathology of inflammatory joint disease such as swelling, pain, and leukocyte infiltration, the cytokines are implicated in the late, destructive phase of the disease, characterized by cartilage loss, bone resorption, and joint failure. Dietary supplementation of n-3 fatty acids using fish or flax seed oil can suppress the production of both IL-1β and TNF-α. Although the mechanism whereby cytokine production is suppressed is unknown, it may involve altered eicosanoid production. Fish oil supplementation has been observed to provide a beneficial clinical effect on rheumatoid arthritis in at least 11 double-blind placebo-controlled trials, and has been shown to provide partial sparing of nonsteroidal anti-inflammatory drug use. The authors conclude that novel anti-inflammatory therapies can be developed to take advantage of positive interactions between dietary fats and existing or new pharmaceutical products.