Most individuals living in developed nations now consume a typical Western diet. The slow transition from traditional diets to the typical Western diet has lowered the intakes of long chain omega-3 fatty acids, with long chain omega-6 fatty acids and saturated fatty acids taking their place. Omega-3 fatty acids are important because they form series 3 eicosanoids and series 5 leukotrienes that are able to block the effects of pro-inflammatory series 2 eicosanoids and series 4 leukotrienes derived from omega-6 fatty acids, the latter having pronounced pro-inflammatory effects. The high omega-6 to omega-3 fatty acid ratio characteristic of the typical Western diet results in pro-inflammatory eicosanoid production, and this may be a driver of Western lifestyle diseases such as cancer, cardiovascular disease, obesity and type 2 diabetes. The pro-inflammatory conditions caused by the fatty acid imbalance may increase cytokine production, explaining the high levels of these immunochemicals in depressed individuals.
Docosahexaenoic acid (DHA, C22:6 (n-3)) and eicosapentaenoic acid (EPA, C20:5 (n-3)) are long chain polyunsaturated fatty acid in fish oils. In humans DHA is converted to EPA, the latter forming the series 3 and serie 4 eicosanoids and leukotrienes, respectively. However, DHA can also be converted to other eicosanoids through the non-classical pathway. These ‘docosanoids’ include resolvins of the D series, docosatrienes and maresins (these last two groups also called protectins), some of which may have neuroprotective effects. For example, the docosatriene neuroprotectin D1 may have particular protective effects on neurones against oxidative damage and cell death. Fish consumption is associated with a lower risk of depression. Epidemiological studies suggest that depressed individuals may have low plasma levels of omega-3 fatty acids. This has lead to the formulation of the hypothesis that EPA or DHA may be deficient in such individuals, and that supplementation with EPA or DHA may alleviate that depression.
The antidepressive effects of fish oils have been well studied. A review of the studies investigating the use of fish oils to treat depression was published in 2009 on the relevant clinical trials up to that date1. Only double-blind randomised placebo controlled trials reporting depressive symptoms as a primary outcome were included in the analysis (251 studies in total). The results showed that overall depression scores were reduced with omega-3 fatty acid supplements compared to a placebo. However, there were significant heterogeneity between studies. Analysis of the heterogeneity showed that higher levels of baseline depression coupled to a lower DHA to EPA ratio improved the therapeutic efficacy of the fish oil supplements. Bipolar and major depression saw significant improvements with omega-3 fish oils, while mild to moderate depression and chronic fatigue did not see improvements. Therefore omega-3 fish oils may be useful in the treatment of particular sub-categories of severe depression.
Interestingly the authors of the meta-analysis then analysed the studies using either pure DHA or pure EPA to treat depression. In this regard symptoms of depression were not reduced in the 3 included studies using pure DHA nor in 4 studies using more than 50 % DHA. However, in 13 studies using greater than 50 % EPA and in 8 studies using pure ethyl-EPA, symptoms of depression were reduced. The authors concluded that it might be EPA and not DHA that is responsible for the antidepressive effects of fish oils. This conclusion has also been reached by other authors working in the field2. Therefore studies that conclude that fish oils are not beneficial, may suffer from methodological flaws in that they have not supplied a high enough EPA to DHA ratio in the fish oils used. Some studies have also attempted to recruit depressed individuals, but on testing the depression is only very mild. For fish oils to be beneficial, the baseline levels of depression would appear need to be severe.
RdB
