EPA reduces inflammation in recurrent depression

eggsApproximately 40–50% of people who experience depression suffer from more than one episode and are therefore categorised as experiencing the recurrent type of this disorder.   Identifying predictors for recurrence in these patients is important for a better understanding of its course and for providing opportunities to improve preventive interventions (1).

The link between diet and depression is one that is gaining considerable interest and it has recently been hypothesised that an unhealthy dietary pattern, one that is low in vegetables, fruits, whole grains and fish, and high in refined grains, fast food, meat and sugar, leads to chronic inflammation which, in turn, could raise the risk for depression and depressive disorders (2).  The products of an inflammatory response, known as cytokines, are produced by a specific type of dietary fat known as the omega−3 and omega-6 polyunsaturated fatty acids.  Importantly, cytokines produced by the omega-6 fatty acid AA are considered pro-inflammatory whilst those from omega-3 EPA are anti-inflammatory.   These polyunsaturated fats are present in our cell membranes where they have important structural and functional roles. The ratio of AA to EPA in the diet therefore influences the composition of cells which, in turn, influences the regulation of inflammation within the body and brain.

Depression is associated with low intake of fish (rich in omega-3), low EPA levels and an imbalance between omega−3 and omega-6 polyunsaturated fatty acids, leading to increased levels of pro-inflammatory products that are linked to many of the somatic symptoms linked to depression, such as gastrointestinal disturbances, complaints of chronic pain, fatigue, and/or other unexplained medical illness3.  Pro-inflammatory cytokines are also known to reduce the availability of the amino acid tryptophan – needed for the production of the mood-enhancing neurotransmitter, serotonin.  Serotonin production and lowered omega-3 fatty acid status are related to dysregulation of the serotonin pathway that is related to mood and cognitive dysfunction in depression.

Low levels of omega-3, and specifically deficiencies in EPA, are consistently observed in patients with depression and recurrent depression.  However, many supplementation studies have given rise to conflicting results and it appears that the efficacy of a ‘fish-oil’ intervention in treating depression is dictated by the EPA content of the oil.  Only oils containing pure EPA appear to offer consistent therapeutic effects on symptoms, with a 1g daily dose of EPA over a period of 3 months providing break-through benefits for depression sufferers (4,5,6).  Whilst there are several hypotheses about the success of pure EPA supplements over conventional oils – which has been EPA shown to be as effective as Prozac in its therapeutic effects (7), – it is believed that 1g  may reduce depressive symptoms, in part via regulation of the key components of the inflammatory cascade that are known to affect the production of serotonin (8).


1.  Lok A, Assies J, Koeter MW, Bockting CL, Wouters LF, Mocking RJ, Schene AH. (2012) Sustained medically unexplained physical symptoms in euthymic patients with recurrent depression: predictive value for recurrence and associations with omega 3- and 6 fatty acids and 5-HTTLPR? J Affect Disord. 136:604-11.

2. Ekmekcioglu C. (2012) Are proinflammatory cytokines involved in an increased risk for depression by unhealthy diets? Med Hypotheses. 78:337-40.

3.  Hoffmire CABlock RCThevenet-Morrison Kvan Wijngaarden E. (2012) Associations between omega-3 poly-unsaturated fatty acids from fish consumption and severity of depressive symptoms: An analysis of the 2005-2008 National Health and Nutrition Examination Survey.  Prostaglandins Leukot Essent Fatty Acids. [Epub ahead of print]

4.  Martins JG, Bentsen H, Puri BK. (2012) Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of Bloch and Hannestad and updated meta-analysis. Mol Psychiatry. 2012 Apr

5.  Sublette ME, Ellis SP, Geant AL, Mann JJ. (2011) Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry. 72:1577-84.

6.  Martins JG. (2009) EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 28:525-42. Review.

7.  Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H, Jalali M, Peet M. (2008) Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry. 42:192-8.

8.  Jazayeri S, Keshavarz SA, Tehrani-Doost M, Djalali M, Hosseini M, Amini H, Chamari M, Djazayery A. (2010) Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder. Psychiatry Res. 178:112-5.


Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.