Omega-3 fatty acids and depression: from cellular mechanisms to clinical care.

Omega-3 fatty acids are the most widely used nonvitamin supplement in the United States by both adults and children. 1 We presently lack data from adequately powered controlled trials to say definitively whether omega-3 (n-3) fatty acids are efficacious as mono-therapy in the treatment of major depressive disorder (MDD). Data are inconclusive regarding their efficacy as adjunctive therapy in MDD; however, a growing literature supports a role for omega-3 fatty acids in depression and neuropsychiatric dysfunction. Basic, translational, and clinical research efforts are moving forward to elucidate the role that this important nutritional component plays in mental illness and health. Convincing epidemiologic data associates diets high in omega-3 fatty acids with a lower risk of major depression, perinatal depression , and bipolar disorder. 2–4 The assessment of a dietary component for a specific indication is difficult, however, and the background diet of individual subjects receiving omega-3 fatty acid supplementation is likely to affect or even drive the overall results. Another area of concern is the enzymatic competition between the metabolic pathways of omega-3 fatty acids and omega-6 (n-6) fatty acids. Omega-3 fatty acids are relatively underrepresented in the Western diet, while the contribution of omega-6 fatty acids has grown enormously, with an emphasis on soy and corn in food production. 5 Factory farming of domesticated animals (including fish) has led to changes in the animals' diets, creating products lower in omega-3 fatty acids than have been produced in the past. Foods high in saturated fats and omega-6 fatty acids comprise a large part of dietary fat intake in the Western diet and are associated with proinflammation. 6 Therefore, the optimal amount of omega-3 fatty acids is a complicated target, subject to the influences of dietary national trends and individual dietary patterns. Most randomized controlled trials have been small and of relatively short duration and have yielded inconsistent findings. 7–9 Most studies have used omega-3 fatty acids as adjunctive treatment to antidepressants or mood stabilizers, and the doses and composition of the omega-3 supplements have varied widely. There have been at least 5 double-blind, placebo-controlled trials 10–15 of omega-3 fatty acids as monotherapy for MDD. Two of those studies, 1 in pregnant women 10 and 1 in children, 11 have demonstrated benefit over placebo and have used combinations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Four studies 12–15 in various populations with MDD used DHA, EPA, or the combination in …