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

Maike Wolters,Ann-Kristin Baalmann,Maike Wellbrock,Annkathrin Von Der Haar,Thomas L Heise,Stefan Rach

doi:10.3390/nu13041070

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.

Highlights

Depressive symptoms are associated with reduced quality of life, increased morbidity and mortality, and rising utilization of the healthcare system [1]
Our meta-analysis (20 studies) indicated that n-3 polyunsaturated fatty acids (PUFAs) supplementation lowered depressive symptomology as compared with placebo: standardized mean difference (SMD) = −0.34, 95% confidence intervals (CI): −0.55, −0.12, I2 = 86%, n = 5836, but a possible publication bias cannot be ruled out
The role of n-3 PUFAs in inflammation has been confirmed by an randomized controlled trials (RCTs) in adults with high or low inflammatory status, which indicated that supplementation of eicosapentaenoic acid (EPA) resulted in a relevant decrease in depression scores only in those with high inflammatory status [10]

Summary

Introduction

Depressive symptoms are associated with reduced quality of life, increased morbidity and mortality, and rising utilization of the healthcare system [1]. N-3 polyunsaturated fatty acids (n-3 PUFAs) are components of cell membranes and are essential for many aspects of physiological function, such as the general brain metabolism and, in particular, neuronal processes associated with depressive symptoms [6,7,8]. The role of n-3 PUFAs in inflammation has been confirmed by an RCT in adults with high or low inflammatory status, which indicated that supplementation of eicosapentaenoic acid (EPA) resulted in a relevant decrease in depression scores only in those with high inflammatory status [10]. Preclinical results suggest a role of n-3 PUFAs in the function of the hypothalamic–pituitary–adrenal (HPA) axis. Results of previous studies suggested that EPA may be more effective in the treatment of depression [9]

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