Depression and mood symptoms impact up to half of the population worldwide (WHO).1 Although there are many pharmaceuticals available to improve general symptoms of depression, often patients want alternative options or desire options that have fewer side effects. Supplementation with omega-3s may be an important alternative for clinicians and their patients who want to improve mood and depression.

Research on omegas-3s and their impact on mood, improved skin, decreased inflammation, and even weight loss have been studied for over two decades. The mechanisms of how omega-3s impact the brain and mood are not fully understood, but a number have been proposed, and likely they involve numerous biochemical processes impacting both cellular function and neurotransmission.2,3 Potential ways that omega-3s may aid in mood improvement of signal transduction and enzyme activity include the production of the proteins ATPase and Kinase C.2,3 The cellular membrane fluidity changes induced by higher concentrations of omega-3s may impact neurotransmission signals by interacting with serotoninergic and dopaminergic transmission and increased receptor binding. Increased serotonin and dopamine have been shown to improve mood. 2,3 Some animal studies have indicated a reduction in dopamine receptors when omega-3 levels are decreased. However, these shifts with omega-3 supplementation show an increase in receptors and binding of dopamine.2,3 Omega-3s may also help regulate hypothalamic–pituitary–adrenal (HPA) axis dysfunction by reducing the corticotrophin releasing factor expression and corticosterone secretion, which has been shown to be higher in depressed individuals.2

There have also been studies linking inflammation and mood alterations, including depression.4,5 A number of studies have shown a relationship between depressive symptoms and level of inflammatory markers.2 Pro-inflammatory cytokines interfere with some of signaling mechanisms that are seen in depression including altering serotonin metabolism and reducing synaptic plasticity.3 Omega-3s have been shown to reduce inflammation, by promoting pro-inflammatory cytokines. Studies show an anti-inflammatory cytokine TGF-β1, is decreased in depressed patients and clinical trials have seen that omega-3 supplementation can increase TGF-β1 synthesis.

Numerous clinical studies have been conducted evaluating the effectiveness of omega-3s for mood and depression; however, the results of these studies are mixed.4,5 Some show significant positive impacts of omega-3 supplementation against placebos.5 However, there are many pooled systematic reviews that do not indicate significance.6 These mixed results are likely from the complexities surrounding depression and depressive mood disorders and diagnosis. A number of studies have examined the use of omega-3 supplementation as an adjuvant with pharmaceuticals, but many of these small trials did not show a significant difference in their participants as compared to just the pharmaceutical.6,7

While the jury is still out on the impact of omega-3 supplementation on mood or symptoms of depression, they are considered to be safe with little to no side effect  and may in fact, have a supportive impact  on therapy for those interested in a more natural approach to improved mood.3

Based on the physiological mechanisms it does appear that omega-3 supplementation may:

  • Increase serotonin and dopamine production and receptor binding
  • Decrease pro-inflammatory cytokines
  • Improve mood and mild depression symptoms
  • Is safe and has little to no major side effects

It is clear that the impacts of omega-3 supplementation on mood impact many different physiological aspects, including some that are not clearly understood. However, the potential benefits and high level of safety make it worth considering for individuals, especially those with mild symptoms of depression and who are adverse to pharmaceuticals.


  1. World Health Organization. Accessed April 12, 2017.
  2. Wani AL, Bhat SA, Ara A. Omega-3 fatty acids and the treatment of depression: a review of scientific evidence. Integrative Medicine Research. 2015;4(3):132-141. doi:10.1016/j.imr.2015.07.003.
  3. Grosso G, Galvano F, Marventano S, et al. Omega-3 Fatty Acids and Depression: Scientific Evidence and Biological Mechanisms. Oxidative Medicine and Cellular Longevity. 2014;2014:1-16. doi:10.1155/2014/313570.
  4. Osher Y, Belmaker RH. Omega-3 Fatty Acids in Depression: A Review of Three Studies. CNS Neuroscience & Therapeutics. 2009;15(2):128-133. doi:10.1111/j.1755-5949.2008.00061.x.
  5. Arnold LE, Young AS, Belury MA, et al. Omega-3 Fatty Acid Plasma Levels Before and After Supplementation: Correlations with Mood and Clinical Outcomes in the Omega-3 and Therapy Studies. Journal of Child and Adolescent Psychopharmacology. March 2017. doi:10.1089/cap.2016.0123.
  6. Sarris J. Clinical use of nutraceuticals in the adjunctive treatment of depression in mood disorders. Australasian Psychiatry. 2017:103985621668953. doi:10.1177/1039856216689533.
  7. Smith DJ, Sarris J, Dowling N, O’connor M, Ng CH. Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial. Nutritional Neuroscience. 2017:1-5. doi:10.1080/1028415x.2017.1283128.

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