Dietary N-3 fatty acid supplementation in rheumatoid arthritis - Mechanisms, clinical outcomes, controversies, and future directions

Studies on the use of dietary n-3 fatty acids supplementation in patients with rheumatoid arthritis started to appear in the scientific literature in the early 1980's. Interest in n-3 fatty acid-modified diets developed further when it was observed that such diets in animal models partly alleviated autoimmune-induced inflammatory disease. Human studies indicate that n-3 fatty acids may reduce inflammation; however, the mechanism of these effects have not been fully elucidated, Inflammatory stimuli result in cytokine production and free radical release, which may enhance the production of tissue necrosis factor (TNF) and cytokines other than those produced through the cyclooxygenase and 5-lipoxygenase enzyme systems and the platelet-activating factor (PAF) system. Clinical manifestations of rheumatoid arthritis have been established by the American College of Rheumatology. The diagnostic criteria most commonly used in the clinical management of rheumatoid arthritis include prolonged morning stiffness, swelling and pain in more than one joint, commonly involving the hands, wrists, knees, and feet in a symmetrical pattern, and an ESR (erythrocyte sedimentation rate) of at least 28 mm/h. Systemic symptoms associated with active disease include low-grade fever, weakness, and extra articular manifestations such as vasculitis, neuropathy, and pleuritis, There are inconsistencies reported in the literature regarding the effects of n-3 fatty acid supplementation on these clinical parameters. Controversies associated with n-3 fatty acids and rheumatoid arthritis studies may be associated with the crossover design protocol which is not appropriate because of the long carry over effects of fish oils. Also, a study length of less than 12 weeks is insufficient for alteration of cellular lipid levels, Another source of confusion is that the level of supplementation with n-3 fatty acids has nor been dose related, and there has not been any control of linoleic acid levels in the background diet. The purpose of this article is to review the recent studies utilizing n-3 fatty acids in clinical investigations of patients with rheumatoid arthritis and to suggest directions for future research efforts.