Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases
The Center for Genetics, Nutrition and Health, Washington, D.C
Omega-3 fatty acids which possess the most potent immunomodulatory activities, and among the omega-3 those from fish oil—eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—are more biologically potent than -linolenic acid (ALA). Some of the effects of omega-3 are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn’s disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB4 produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn’s disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.
Key words: inflammation, cardiovascular disease and major depression autoimmune diseases, IL-1, IL-6, TNF, background diet, omega-6/omega-3 ratio
Key teaching points:
• In Western diets, omega-6 fatty acids are the predominant polyunsaturated fats. The omega-6 and omega-3 fatty acids are metabolically distinct and have opposing physiologic functions.
• Eicosapentaenoic acid (EPA) is released to compete with arachidonic acid (AA) for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.
• Animal and human studies support the hypothesis that omega-3 PUFA suppress cell mediated immune responses.
• In experimental animals and humans, serum PUFA levels predict the response of proinflammatory cytokines to psychologic stress. Imbalance in the omega-6/omega-3 PUFA ratio in major depression may be related to the increased production of proinflammatory cytokines and eicosanoids in that illness.
• The increased omega-6/omega-3 ratio in Western diets most likely contributes to an increased incidence of cardiovascular disease and inflammatory disorders.
• Patients with autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease and asthma, usually respond to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation by decreasing the elevated levels of cytokines.
The first evidence of the important role of dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) in inflammation was derived from epidemiological observations of the low incidence of autoimmune and inflammatory disorders, such as psoriasis, asthma and type-1 diabetes, as well as the complete absence of multiple sclerosis, in a population of Greenland Eskimos compared with gender- and age-matched groups living in Denmark . Most of these diseases are characterized by inappropriate activation of T cells resulting on and ultimately destruction of host tissues.
In the 1980’s several independent lines of evidence suggested that changes in the natural history of hypertensive, atherosclerotic and chronic inflammatory disorders may be achieved by altering availability of eicosanoid precursors. Native Greenland Eskimos  and Japanese  have a high dietary intake of long chain omega-3 PUFA from seafood and a low incidence of myocardial infarction and chronic inflammatory or autoimmune disorders, even when compared to their Westernized ethnic counterparts. Diets containing omega-3 PUFA have also been found to reduce the severity of experimental cerebral  and myocardial  infarction, to retard autoimmune nephritis and prolong survival of NZB x NZW F1 mice [6,7] and reduce the incidence of breast tumors in rats .
The 1980s were a period of expansion in our knowledge about PUFAs in general and omega-3 fatty acids in particular. Today we know that omega-3 fatty acids are essential for normal growth and development and may play an important role in the prevention and treatment of coronary artery disease, hypertension, arthritis, other inflammatory and autoimmune disorders and cancer . Research has been carried out in animal models, tissue cultures and human beings. The original observational studies have given way to controlled clinical trials.
In this paper, I review the anti-inflammatory aspects of omega-3 fatty acids relative to prostaglandins and cytokines and their clinical effects in inflammatory and autoimmune diseases, such as cardiovascular disease, major depression, arthritis, inflammatory bowel disease, asthma and psoriasis.
Received May 21, 2002. Accepted August 15, 2002.