Suppression of autoimmune disease by dietary n-3 fatty acids

Previous studies have demonstrated that dietary fish oil preparations have anti-inflammatory effects in humans and in experimental animals, but the individual components of fish oils that are responsible for their anti-inflammatory effects have not been documented. We therefore investigated in (NZB x NZW)F1 mice, a model for human systemic lupus erythematosus, the effects of diets containing ethyl esters of two purified n-3 fatty acids, eicosapentaenoic acid (EPA-E) and docosahexaenoic acid (DHA-E), a refined fish oil triglyceride (FO) which contained 55% n-3 fatty acids, and beef tallow (BT) which contains no n-3 fatty acids. The diets were initiated prior to the development of overt renal disease at age 22 weeks, and continued for 14 weeks. The extent of the renal disease was quantified by light microscopy and by proteinuria. Diets containing either 10 wt% FO, 10% EPA-E, or 6% or 10% DHA-E alleviated the severity of the renal disease, compared to the BT diet, whereas diets containing either 3% or 6% EPA-E or 3% DHA-E were less effective. Two diets containing approximately 3:1 mixtures of EPA-E and DHA-E alleviated the renal disease to a greater extent than expected for either of these fatty acids given singly. We believe that these experiments provide the first demonstration of anti-inflammatory effects of individual dietary n-3 fatty acids. The results also indicate that the anti-inflammatory effects of fish oils depend on synergistic effects of at least two n-3 fatty acids.