Forty-nine patients with active rheumatoid arthritis completed a 24-week, prospective, double-blind, randomized study of dietary supplementation with 2 dflerent dosages of fish oil and 1 dosage of olive oil. Clinical evaluations were performed at baseline and every 6 weeks thereafter, and ipmunologk variables were measured at baseline and after 24 weeks of study. The 3 groups of patients were matched for age, sex, disease Severity, and use of disease-modifying antirheumatic drugs (DMARDs). Subjects continued receiving DMARDs and other background medications without change during the study. Twenty patients consumed daily dietary supplements of n3 fatty acids containing 27 m&g eicosapentaenoic acid (EPA) and 18 mgkg docosahexaenoic acid (DHA) (low dose), 17 patients ingested 54 mg/kg EPA and 36 mgkg DHA (high dose), and 12 patients ingested olive oil capsules containing 6.8 gm of oleic acid. Significant improvements from baseline in the number of tender joints were noted in the low-dose group at week 24 (P = 0.05) and in the high-dose group at weeks 18 (P = 0.04) and 24 (P = 0.02). Significant decreases from baseline in the number of swollen joints were noted in the low-dose group at weeks 12 (P = 0.003), 18 (P = 0.002), and 24 interleukin-1 production decreased by 38.5% in the olive oil group (P not significant), 40.6% in the low-dose group (P = 0.06), and 54.7% in the high-dose group (P = 0.0005). Tritiated thymidine incorporation in peripheral blood mononuclear cells after stimulation with concanavalin A increased significantly in all 3 groups after 24 weeks, compared with baseline values. We conclude that the clinical benefits of dietary supplementation with omega3 fatty acids are more commonly observed in patients consuming higher dosages of fish oil for time intervals that are longer than those previously studied. Dietary supplementation with olive oil is also associated with certain changes in immune function, which require further investigation.Fish oil contains the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (1). EPA (205 n3) competitively inhibits the utilization of arachidonic acid (20:4 n6) and becomes a substrate for the production of alternative biologically active products through the cyclooxygenase and 5-lipoxygenase cellular metabolic pathways (2,3). Omega-3 fatty acid ingestion results in the production of thromboxane A, and prostacyclin I, (4) and a net physiologic shift that favors decreased platelet aggregation (since prostacyclin I, retains its vasodilatory

fish-oil ingestion results in subjective alleviation of active rheumatoid arthritis and reduction in neutrophil leukotriene B4 production. Further studies are needed to elucidate mechanisms of action and optimal dose and duration of fish-oil supplementation.