Food and Behaviour Research

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Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials

Appleton KM, Hayward RC, Gunnell D, Peters TJ, Rogers PJ, Kessler D, Ness AR. (2006) American Journal of Clinical Nutrition 84(6) 1308-16 The American Society for Nutrition

Web URL: View the abstract via PubMed here



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


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


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.


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).


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.

For a non-tecnical summary of this article's conclusions, see the Reuters news report "Jury still out on fish oils for depression"


The results of this meta-analysis are hardly surprising given the very diverse nature of the studies included. Some trials involved healthy subjects, others patients with conditions other than depression (including chronic fatigue syndrome and obsessive compulsive disorder).

A more positive conclusion was obtained from another recent meta-analysis, which focused only on patients diagnosed with major depression or bipolar disorder.(See Freeman et al 2006) This more focused analysis showed modest benefits for depressed mood in these clinical patient groups when omega-3 were used in addition to standard medications. From those findings, and considering the safety and general health benefits of omega-3, the American Psychiatric Association made a treatment recommendation that all patients with clinical depression should consume at least 1000mg/day of long-chain omega-3 (EPA/DHA) - but it must be emphasised that this recfommendation is in addition to any other treatment, NOT as a substitute.

One conclusion reached by both reviews is that further evidence is needed, i.e. that more good quality randomised controlled trials of onmega-3 for mood disorders are clearly warranted.