Effects of n-3 Polyunsaturated Fatty Acid Supplementation in the Prevention and Treatment of Depressive Disorders—A Systematic Review and Meta-Analysis

Abstract

N-3 polyunsaturated fatty acids (PUFAs) have been suggested to affect depressive disorders. This review aims to determine the effect of n-3 PUFAs on depressive symptoms in people with or without diagnosed depression. Medline, PsycINFO, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) assessing the association between n-3 PUFAs and depressive symptoms or disorders as outcomes. A random-effects meta-analysis of standardized mean difference (SMD) with 95% confidence intervals (CI) was performed. Twenty-five studies (7682 participants) were included. Our meta-analysis (20 studies) indicated that n-3 PUFA supplementation lowered depressive symptomology as compared with placebo: SMD = −0.34, 95% CI: −0.55, −0.12, I2 = 86%, n = 5836, but a possible publication bias cannot be ruled out. Subgroup analyses indicated no statistically significant difference by treatment duration of <12 vs. ≥12 weeks, presence of comorbidity, or severity of depressive symptoms. Nevertheless, beneficial effects were seen in the subgroups of studies with longer treatment duration and with no depression and mild to moderate depression. Subgroup analysis by eicosapentaenoic acid (EPA) dosage revealed differences in favor of the lower EPA dosage. Sensitivity analysis including studies with low risk of bias seems to confirm the overall result. Supplementation of n-3 PUFA appears to have a modest beneficial effect on depressive symptomology, although the quality of evidence is still insufficient.

Beneficial Outcomes of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on Human Health: An Update for 2021

“…Similarly, EPA (2 g/day for 4 weeks) improved symptoms in patients with unipolar depressive disorder [ 105 ]. There are many meta-analyses of RCTs involving participants with depressive disorders, including a number published fairly recently [ 106 , 107 , 108 , 109 , 110 , 111 ]. One analysis of 26 studies, which included 2160 participants, identified an overall benefit from EPA + DHA [ 108 ].…”

“…Furthermore, the analysis suggests that use of pure EPA formulations or formulations containing >60% EPA was associated with clinical benefits, whereas pure DHA or DHA-rich formulations did not show benefits. Another meta-analysis of 20 RCTs also identified significant benefit from omega-3 PUFAs [ 109 ] but concluded that better quality evidence is needed. Another recent meta-analysis identified no significant effect of EPA + DHA on depressive symptoms in older people (>65 years of age) who “were well”, while there was “a large effect” of EPA + DHA in older people with depression [ 110 ].…”

Exploring the Role of Nutraceuticals in Major Depressive Disorder (MDD): Rationale, State of the Art and Future Prospects

“…Obviously, ω-3 PUFAs are not going to show prompt clinical benefits per se if the patient is not previously well nourished, just like any pharmaceutical or dietary supplement is not going to be successful unless the individual is monitored in a period of few months [ 102 ]. Moreover, more beneficial effects have been seen in patients with longer treatment duration and with mild to moderate depression and with no depression, but more quality evidence is still missing [ 103 ].…”

Omega- 3 Fatty Acids and Major Depression: A Mendelian Randomization Study

“…While observational studies suggest inverse associations between omega-3 fatty acids and depression, 1, 2 trials supplementing omega-3 fatty acids have yielded mixed results. [3][4][5][6][7] Long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are widely regarded as important for brain health. 8 As a major source of long-chain omega 3 fatty acids is sh consumption, observational associations between circulating omega-3 fatty acids and depression are heavily confounded, and reverse causality from poor dietary intake in depressed individuals is likely.…”

“…11 Trials using omega 3 supplements for preventing depression have yielded inconsistent results. 3,4 Good quality trials are expensive and time consuming, especially for depression prevention. However, two recent well powered factorial trials have cast doubt over whether omega 3 fatty acids prevent depression, and by extension their possible role in its aetiology.…”