It is well-known in the scientific literature that omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (both derived from oily fish) possess anti-inflammatory properties. Omega-3 PUFAs are substrates for bioactive lipid mediators that aid in regulating inflammation and promote its resolution. Evidence supports the use of EPA and DHA in various noncommunicable (inflammatory) diseases, including cardiovascular diseases, type 2 diabetes, neurodegenerative diseases, obesity, and certain cancers. 

According to a recent study published in Molecular Psychiatry, evidence from human in vitro and clinical investigations shows that EPA and DHA bioactive lipid metabolites, also known as specialized pro-resolving mediators, may be beneficial in inflammation-associated brain disorders, specifically depression. 

Specialized pro-resolving mediators (SPMs) are endogenously produced lipid-based chemical mediators known as resolvins, maresins, protectins, and lipoxins that have been shown to support the body’s innate immune response during the “resolution phase” of inflammation, accelerating the body’s return to homeostatic balance. SPMs bind to receptors that can modify proinflammatory chemokine, cytokine, and adipokine regulation.

Researchers from the National Institutes of Health Research investigated the effects of high doses of EPA and DHA in depressed patients along with an in vitro human hippocampal cell model labeled “depression in a dish.” Hippocampal cells play a significant role in proper cognitive function, memory, learning, and neuronal synthesis. Using mass spectrometry lipidomics, hippocampal cells that were pre-treated with either EPA or DHA before exposure to proinflammatory cytokine IL-1β, IL-6, and interferon-α prevented increased cell death and reduced neurogenesis induced by these cytokines. Detected for the first time in human hippocampal neurons, the results showed that these neuroprotective effects were mediated by LOX and CYP450 EPA and DHA metabolites, specifically 5-HEPE, 4-HDHA, 18-HEPE, 20-HDHA, 17(18) EpETE, and 19(20) EpDHA.

Similar results were demonstrated in 22 patients with major depressive disorder (MDD) who received supplementation with either 3 grams of EPA or 1.4 grams of DHA daily for 12 weeks. This supplementation results increased the same LOX and CYP450 EPA/DHA metabolites, significantly improving depressive symptoms by an average reduction of 64% and 71% in the EPA and DHA groups, respectively. Moreover, higher plasma metabolite levels were associated with less severe depressive symptoms. The findings suggest that these bioactive mediators produced by the breakdown of EPA and DHA could be neuroprotective molecular targets for patients with depression.  

Depression is a major cause of disease burden worldwide; the percentage of adults with anxiety or depressive symptoms increased from 36.4% to 41.5% between August 2020 and February 2021. Compared to those without the disorder, individuals suffering from MDD have higher levels of inflammation in their bodies, according to research. Findings from previous research demonstrates that increased EPA and DHA concentrations were associated with a greater improvement in depressive symptoms. Additional research showed that 740 mg of EPA and 400 mg of DHA supplementation for 16 weeks significantly reduced depression and anxiety scores compared to a placebo, suggesting a potential role for adjunctive omega-3 PUFAs for depression symptoms.

It’s not as simple as recommending more dietary and supplemental omega-3. However, it may be helpful in supporting a healthy neuronal inflammatory response and positive mental outlook. These molecular mechanisms are complicated and further clinical trials are needed to fully understand the role of omega-3 PUFAs in potentially reducing inflammation and depressive symptoms. Other nutrients to consider for supporting improved mood include Sceletium and saffron extract, 5-hydroxytryptophan (5-HTP), B vitamins, and probiotics, in addition to adopting an anti-inflammatory diet, stress-reduction practices, and incorporating more daily healthy movement.

By Caitlin Higgins, MS, CNS