Omega-3 fatty acids and depression: epidemiological and experimental evidence
The changes of omega-6/omega-3 polyunsaturated fatty acids (PUFA) in the food supply of Western societies occurred over the last 150 years is thought to promote the pathogenesis of many inflammatory-related diseases, including depressive disorders. Among the biological properties of omega-3 PUFA, their anti-inflammatory effects and their role on the structural changing of the brain should be taken into account to better understand the possible pathway through which they can be effective both in preventing or treating the depressive status. The use of omega-3 supplement in depressed patients reached notable improvements during last years. Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder and patients with depressive symptomatology but no diagnosis of major depressive disorder demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized mean difference in clinical measure of depression severity was 0.56 [95% CI: 0.20, 0.92] and 0.22 [95% CI: 0.01, 0.43], respectively; pooled analysis resulted in 0.38 [95% CI: 0.18, 0.59] standardized mean difference). Use of mainly eicosapentaenoic acid (EPA) within the preparation, rather than docosahexaenoic acid (DHA), influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression, primary disease other than depression (i.e., patients with schizophrenia, Alzheimer disease, cardiovascular disease) and healthy individuals. The systematic review of epidemiological studies exploring the possible relation of fish or omega-3 PUFA consumption resulted in findings much harder to be interpreted. A total of 28 studies, including 251,464 individuals and over 20,000 cases of depression, were examined. Among the 18 studies exploring the possible association between fish consumption and depression, 5 out of 7 cross-sectional and 6 out of 11 prospective studies reported a significant relation. A protective effect of omega-3 PUFA intake on depression was reported in 7 out of 11 cross-sectional and 4 of 9 prospective studies. The high degree of heterogeneity did not allow to support or confute the hypothesis that dietary omega-3 PUFA decrease the risk to develop depression. Future researches should into account the methodological limitations retrieved, such as i) better assessment of depressive cases, ii) detailed consumption of all PUFA and their possible interactions, and iii) consider the possibility of a non-linear relationship between fish or omega-3 PUFA intake and the risk to develop depressive disorders. Whether future findings will confirm that omega-3 PUFA consumption would result effective in prevent depressive disorders, to correct the inadequate supply of omega-3 PUFA in Westernized countries diet is a priority in order to set food and health policies and dietary recommendations for individuals and population groups.
Omega-3 PUFA, depression, randomized controlled trials, epidemiology, meta-analysis
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