Fish contains two important dietary n-3 long-chain fatty acids, eicosapentanoic acid (EPA, C20:5 (n-3)) and docosahexanoic acid (DHA, C22:6 (n-3)). These fatty acids accumulate in plasma membranes where they may increase membrane fluidity, and can also influence cellular function through the production of signal molecules. The central nervous system relies on the correct supply of these n-3 long-chain fatty acids in order to be able to carry out physiological processes. Low intakes of n-3 long-chain fatty acids are associated with reduced concentrations of dopamine in some areas of the brain and decreased levels of dopamine D2 and serotonin 5-HT2A receptors. Epidemiological evidence shows an inverse association between fish intake and depression, and lower plasma membrane concentrations of n-3 fatty acids are found in individuals with depressive symptoms. Researchers are therefore interested in the effects of n-3 long-chain fatty acids on the mood of people who may have clinical depression.
In a study published in the American Journal of Clinical Nutrition in 20061, researchers reviewed the literature to assess the effects of n-3 long-chain fatty acids on depressed mood. The authors included 12 randomised control trials in their meta-analysis. The pooled results showed a significant benefit in those receiving n-3 long-chain fatty acids compared to the placebo. The effect was greater in those subjects who had the most severe depression. In another meta-analysis published in the Journal of Clinical Psychiatry2, pooled results from 10 clinical trials showed a significant anti-depressive effect for n-3 long-chain fatty acid treatment, which included improvements for those with clinically diagnosed depression and bipolar disorder. interestingly, there was no dose effect for n-3 long-chain fatty acids with regard their beneficial effects. However, both of these meta-analyses noted strong heterogeneity amongst the studies and detected publication bias.
The n-3 long-chain fatty acid EPA had been compared directly to the anti-depressant drug fluoxetine in a clinical trial3, both directly and in combination. The study involved 60 out-patients that had been diagnosed with depressive disorder using the Hamilton Depression Rating Scale (HDRS). Subjects received either 1000mg EPA or 20 mg fluoxetine, or a combination of the two for 8 weeks. The results showed no significant difference between EPA or fluoxetine treatment in terms of their ability to control depressive symptoms. In combination, the EPA and fluoxetine were more effective that when either was given alone. The response rates in the EPA, fluoxetine and EPA plus fluoxetine groups were 56, 50 and 81 %, respectively. While anxiety was reported as a side effect of fluoxetine treatment, the only side effect following EPA treatment was after-taste from the fish oil containing the EPA.
Long chain fatty acids from fish oils therefore appear to be beneficial in the elevation of depressed mood in some individuals, perhaps having the greatest effect in those with the worst depression. In addition, the anti-depressive effects of fish oils appear to be equal to those of the prescription drug fluoxetine. Because the exact cause of depression is unknown, it is difficult to speculate how n-3 long-chain fatty acids may be of benefit. However, it is possible that the condition itself is actually caused by a deficiency of the n-3 long-chain fatty acids in the diet. It is known from animal experiments and experiments investigating the symptoms of α-linolenic acid (ALA, C18:3 (n-3)) deficiency that mood alterations and depression result from low dietary intakes. In animals and humans, ALA is synthesised to EPA and DHA, suggesting that dietary supplementation with these oils may reverse the n-3 deficiency symptoms, and elevate mood.
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