Long-chain omega-3 polyunsaturated fatty acids in depression: from research to recommendations

Abstract

In the early 1990s it was first proposed that the long-chain omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have therapeutic potential in depression. This suggestion was supported by observational studies reporting an association between low dietary omega-3 PUFA intake and increased risk of depression and lower omega-3 PUFA blood levels in those with depression. DHA, EPA, and their bioactive lipid mediators operate via multiple overlapping and independent mechanisms of action, and some of these mechanisms have the potential to improve depressive symptoms, such as enhancing neuroplasticity, modulating of the endocannabinoid system, and exerting anti-inflammatory and proresolving effects. However, although numerous clinical trials and their subsequent meta-analyses have investigated their efficacy, the results have been mixed and inconsistent. These inconsistencies likely stem from heterogeneity and limitations in the design of the clinical trials, including mixed study populations, small sample sizes, lack of appreciation of the differences between DHA and EPA, inappropriate placebo comparators, and a lack of applied standardized diagnostic criteria. This review explores the divergent effects of DHA and EPA on neuroplasticity and inflammation and identifies under which conditions long-chain omega-3 PUFAs may provide the greatest therapeutic effects in depression.