Efficacy of omega-3 PUFAs in depression: A meta-analysis

Summary

This 2019 meta-analysis pooled 26 double-blind randomized placebo-controlled trials of omega-3 PUFA supplementation for depression to ask a specific question: does the EPA-to-DHA ratio matter? The authors found that it does, decisively. Formulations that were either pure EPA or majority EPA (60 percent or more EPA) showed clinical benefit for depressive symptoms at relatively low doses (1 gram per day or less), while pure DHA and DHA-majority formulations did not. The therapeutic effect was specific to EPA-dominant supplementation. The mechanism inference is that EPA's anti-inflammatory effects (via resolvins and reduction of pro-inflammatory eicosanoids) drive the antidepressant signal, while DHA's role in neuronal membrane structure does not similarly translate to mood benefit at supplementation doses. The paper is the most-cited recent meta-analysis on omega-3 and depression and has shaped subsequent dosing recommendations: when omega-3 is used adjunctively for depressive disorders, EPA-dominant formulations at sub-gram doses are the evidence-supported choice. The paper does not claim omega-3 replaces antidepressant medication; it supports adjunctive use.