Background: Greater dietary intakes of n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for depressed mood.

Objective: This study aimed to systematically review all published randomized controlled trials investigating the effects of n-3 PUFAs on depressed mood.

Design: Eight medical and health databases were searched over all years of records until June 2006 for trials that exposed participants to n-3 PUFAs or fish, measured depressed mood, were conducted on human participants, and included a comparison group.

Results: Eighteen randomized controlled trials were identified; 12 were included in a meta-analysis. The pooled standardized difference in mean outcome (fixed-effects model) was 0.13 SDs (95% CI: 0.01, 0.25) in those receiving n-3 PUFAs compared with placebo, with strong evidence of heterogeneity (I2 = 79%, P < 0.001). The presence of funnel plot asymmetry suggested that publication bias was the likely source of heterogeneity. Sensitivity analyses that excluded one large trial increased the effect size estimates but did not reduce heterogeneity. Meta-regression provided some evidence that the effect was stronger in trials involving populations with major depression-the difference in the effect size estimates was 0.73 (95% CI: 0.05, 1.41; P = 0.04), but there was still considerable heterogeneity when trials that involved populations with major depression were pooled separately (I2 = 72%, P < 0.001).

Conclusions: Trial evidence that examines the effects of n-3 PUFAs on depressed mood is limited and is difficult to summarize and evaluate because of considerable heterogeneity. The evidence available provides little support for the use of n-3 PUFAs to improve depressed mood. Larger trials with adequate power to detect clinically important benefits are required.