Eating Fish May Not Reduce Risk for Depression

Laurie Barclay, MD

April 13, 2011

April 13, 2011 — Long-chain omega-3 fatty acids from fish may not protect against the risk for depression, according to the results of a large longitudinal prospective study reported online April 6 in the American Journal of Clinical Nutrition.

"The associations between different sources of dietary n-3 (omega-3) and n-6 (omega-6) fatty acids and the risk of depression have not been prospectively studied," write Michel Lucas, from the Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, and colleagues. "The objective was to examine the relation between different n-3 and n-6 types with clinical depression incidence."

The study cohort consisted of 54,632 US women from the Nurses' Health Study who were 50 to 77 years old and who had no depressive symptoms at baseline. Validated food frequency questionnaires were used to collect dietary information. Clinical depression was defined as regular use of antidepressant medication for physician-diagnosed depression.

There were 2823 incident cases of depression documented during follow-up from 1996 to 2006. Although long-chain n-3 fatty acid intake from fish was not associated with depression risk, a-linolenic acid (ALA) intake was inversely associated with depression risk. The relative risk (RR) for a 0.3-g/day increment in long-chain n-3 fatty acid intake was 0.99 (95% confidence interval [CI], 0.88 - 1.10), whereas the multivariate RR for a 0.5-g/day increment in ALA was 0.82 (95% CI, 0.71 - 0.94).

Women with low linoleic acid (LA) intake had a stronger inverse association between ALA and depression (P for interaction = .02). A 0.5-g/day increment in ALA was inversely associated with depression in the first, second, and third LA quintiles (RR, 0.57 [95% CI, 0.37 - 0.87]; RR, 0.62 [95% CI, 0.41 - 0.93]; and RR, 0.68 [95% CI, 0.47 - 0.96], respectively, but not in the fourth and fifth quintiles.

"The results of this large longitudinal study do not support a protective effect of long-chain n-3 from fish on depression risk," the study authors write. "Although these data support the hypothesis that higher ALA and lower LA intakes reduce depression risk, this relation warrants further investigation."

Limitations of this study include residual confounding, reverse causation, confounding by indication, outcome misclassification, and statistical limitations because of use of multiple comparisons. In addition, it is impossible to completely separate LA from ALA intake.

"Several biological mechanisms might potentially explain the effect of ALA in depression," the study authors conclude. "Dietary ALA deficiency has been linked with altered brain biochemistry, such as membrane structure and fluidity, ion channels, second messengers, reduced cyclic AMP [adenosine monophosphate] response element-binding protein transcription factor activity and brain-derived neurotrophic factor expression, and increased expression of cytosolic and secretory phospholipase A2 and cyclooxygenase-2. ... However, the mechanism of action of dietary n-3 and n-6 in depression requires further exploration in humans."

The National Institutes of Health supported this study. Two of the study authors have disclosed various financial relationships with the National Alliance for Research on Schizophrenia and Depression and/or the Fonds de Recherche en Santé du Québec (FRSQ).

Am J Clin Nutr. Published online April 6, 2011. Abstract


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