Efficacy and safety of n-3 fatty acids supplementation on depression: A systematic review and dose-response meta-analysis of randomised controlled trials

Abstract

We aimed to investigate the effectiveness of n-3 fatty acids supplementation on the risk of developing depression, depressive symptoms and remission of depression. We searched PubMed, Scopus and Web of Science from inception to December 2022 to find randomised trials of n-3 fatty acids supplementation in adults. We conducted random-effects meta-analyses to estimate standardised mean differences (SMD) and 95 % CI for continuous outcomes and risk difference and 95 % CI for binary outcomes. A total of sixty-seven trials were included. Each 1 g/d n-3 fatty acids supplementation significantly improved depressive symptoms in adults with and without depression (moderate-certainty evidence), with a larger improvement in patients with existing depression. Dose-response analyses indicated a U-shaped effect in patients with existing depression, with the greatest improvement at 1·5 g/d. The analysis showed that n-3 fatty acid supplementation significantly increased depression remission by 19 more per 100 in patients with depression (low-certainty evidence). Supplementation with n-3 fatty acids did not reduce the risk of developing depression among the general population, but it did improve the severity of depression among patients with existing depression.