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Omega-3 Fatty Acids in Inflammation

Artemis P. Simopoulos, MD, FACN

The Center for Genetics, Nutrition and Health, Washington, D.C

 
 Omega-3  fattyacids  which possess the most potent immunomodulatoryactivities, and among the omega-3  those from fish oil--eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologicallypotent than-linolenic acid (ALA). Some of the effects of omega-3 are brought about by modulation of the amount and typesof eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways,transcription factor activity and gene expression. Animal experimentsand clinical intervention studies indicate that omega-3 fattyacids 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 arecharacterized by an increased level of interleukin 1 (IL-1),a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmunediseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB₄ produced by omega-6 fatty acids. There havebeen a number of clinical trials assessing the benefits of dietarysupplementation with fish oils in several inflammatory and autoimmunediseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus,multiple sclerosis and migraine headaches. Many of the placebo-controlledtrials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowereduse 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 theproduction 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 psychologicstress. Imbalance in the omega-6/omega-3 PUFA ratio in majordepression may be related to the increased production of proinflammatorycytokines and eicosanoids in that illness.

* The increased omega-6/omega-3 ratio in Western dietsmost likely contributes to an increased incidence of cardiovasculardisease and inflammatory disorders.

* Patients with autoimmune diseases, such as rheumatoidarthritis, inflammatory bowel disease and asthma, usually respondto eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)supplementation by decreasing the elevated levels of cytokines.

Introduction
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 [1]. 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 [2] and Japanese [3] 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 [4] and myocardial [5] 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 [8].
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 [9]. 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.
 

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Received May 21, 2002. Accepted August 15, 2002.

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