Meta-study: only fish oil with high amounts of EPA effective antidepressant

Eicosapentaenoic Acid (EPA) ~ Fish oil supplements can help against depression, but they have to contain the right type of fish oil. Researchers at the New York State Psychiatric Institute drew this conclusion after doing a meta-study where they reanalysed data they collected from 15 trials in which nearly a thousand people suffering from depression had been given fish oil.

Some studies show that fish oil can help prevent depression and that it can even help people who are already suffering from depression, [J Affect Disord. 2007 Aug;101(1-3):245-9.] but others suggest fish oil has no effect on depression. Recent meta-studies have therefore concluded that the anti-depressant effect of fish oil is an illusion. [Mol Psychiatry. 2012 Dec;17(12):1272-82.]

The lack of clarity on the antidepressant effect of fish oil is probably the result of different sorts of supplements being used in experiments with people suffering from depression, the New York researchers discovered. The supplements are only effective if they contain more of the fish fatty acid EPA [structural formula shown above] than the fish fatty acid DHA.


The best results have been achieved in trials where the subjects suffering from depression were given 1-2 g more EPA than DHA every day.


The researchers are not sure why EPA is effective against depression and DHA not. One difference between the two fatty acids is that EPA has a stronger effect on the fat sensor PPAR than DHA does. But the researchers are not sure whether this has anything to do with the antidepressant effect of EPA.

Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression.



Randomized trials of omega-3 polyunsaturated fatty acid (PUFA) treatment for depression have differed in outcome. Recent meta-analyses ascribe discrepancies to differential effects of eicosapentaenoic acid (EPA) versus docosahexaenoic acid (DHA) and to diagnostic heterogeneity. This meta-analysis tests the hypothesis that EPA is the effective component in PUFA treatment of major depressive episodes.


PubMed/MeSH was searched for studies published in English from 1960 through June 2010 using the terms fish oils (MeSH) AND (depressive disorder [MeSH] OR bipolar depression) AND randomized controlled trial (publication type). The search was supplemented by manual bibliography review and examination of relevant review articles.


The search yielded 15 trials involving 916 participants. Studies were included if they had a prospective, randomized, double-blinded, placebo-controlled study design; if depressive episode was the primary complaint (with or without comorbid medical conditions); if omega-3 PUFA supplements were administered; and if appropriate outcome measures were used to assess depressed mood.


Extracted data included study design, sample sizes, doses and percentages of EPA and DHA, mean ages, baseline and endpoint depression ratings and standard deviations for PUFA and placebo groups, and P values. The clinical outcome of interest was the standardized mean difference in the change from baseline to endpoint scores on a depression rating scale in subjects taking PUFA supplements versus subjects taking placebo.


In a mixed-effect model, percentage of EPA in the supplements was the fixed-effect predictor, dichotomized into 2 groups: EPA < 60% or EPA ? 60% of the total EPA + DHA. Secondary analyses explored the relevance of treatment duration, age, and EPA dose. RESULTS: Supplements with EPA ? 60% showed benefit on standardized mean depression scores (effect size = 0.532; 95% CI, 0.277-0.733; t = 4.195; P < .001) versus supplements with EPA < 60% (effect size = -0.026; 95% CI, -0.200 to 0.148; t = -0.316; P = .756), with negligible contribution of random effects or heteroscedasticity and with no effects of treatment duration or age. Supplements with EPA < 60% were ineffective. Exploratory analyses supported a nonlinear model, with improvement determined by the dose of EPA in excess of DHA, within the range of 200 to 2,200 mg/d of EPA. CONCLUSIONS: Supplements containing EPA ? 60% of total EPA + DHA, in a dose range of 200 to 2,200 mg/d of EPA in excess of DHA, were effective against primary depression. Translational studies are needed to determine the mechanisms of EPA's therapeutic benefit. © Copyright 2011 Physicians Postgraduate Press, Inc. The impact of omega-3 fatty acids on depressive disorders and suicidality: can we reconcile 2 studies with seemingly contradictory results? [J Clin Psychiatry. 2011] PMID: 21939614 [PubMed - indexed for MEDLINE] PMCID: PMC3534764 Source: http://www.ncbi.nlm.nih.gov/pubmed/21939614

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