Omega-3 fatty acids play key roles in health, which includes maintaining cell membrane integrity and fluidity and promoting a normal inflammatory response. There are two main omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Due to the fundamental functions of these fatty acids, many researchers have investigated the potential benefits of increasing omega-3 fatty acid intake on chronic conditions, including depression. 

Inflammation has been found to be associated with depression. Thus, one potential mechanism for the mood benefits of omega-3 fatty acids is that they support a healthy inflammatory response. Both DHA and EPA can decrease the production of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1beta, IL-2, and IL-6. DHA and EPA may also combine with the more proinflammatory arachidonic acid (AA) into membrane-based phospholipids to decrease the activity of AA in the cell. 

EPA may exert more anti-inflammatory actions than DHA. EPA supports the synthesis of anti-inflammatory eicosanoids to balance potentially proinflammatory eicosanoid metabolites derived from omega-6 fatty acids. It also decreases the production of arachidonic acid by inhibiting delta-5-desaturase, the enzyme that converts dihomo-γ-linoleic acid into AA. EPA also competes with AA for phospholipase A2 in the cyclooxygenase enzyme system, blocking the production of proinflammatory eicosanoids, such as prostaglandins, thromboxanes, and leukotrienes.

Neurotransmitter balance may also play a role in depression pathophysiology, especially those involving the serotonergic and noradrenergic systems. Omega-3 fatty acids (particularly DHA) may promote normal neurotransmitter transmission by supporting the membrane integrity and fluidity of cells. This may beneficially alter the receptor number and function to normalize dopaminergic and serotonergic neurotransmission.

Clinical studies have demonstrated the potential for increasing omega-3 intake to benefit depression. Consuming a diet of moderate intake of fish and other sources of omega-3 fatty acids was found to be associated with lower odds of depression in one of the studies. A meta-analysis of double-blind, randomized, placebo-controlled trials found that omega-3 fatty acids led to a therapeutic effect of −0.28. The supplements containing 60% EPA, including those with 100% EPA at a dosage of 1 gram or more, imparted beneficial effects on depression. Formulas that were 60% DHA did not. This suggests that the benefits from omega-3 fatty acids may be due to the mechanisms of EPA rather than DHA, but more research is necessary.

Many factors may be involved in supporting normal neurotransmitter balance and a positive outlook. One aspect may involve managing a balance of omega-3 to omega-6 fatty acids in the diet. This may promote a healthy inflammatory response, which may impact the risk of developing disorders associated with chronic inflammation, such as depression.* Supplementing with omega-3 fatty acids may provide additional support for individuals requiring higher intake.

By Kendra Whitmire, MS, CNS