Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid supplementation: A pilot study

Prostaglandins Leukot Essent Fatty Acids. 2017 Apr;119:38-44. doi: 10.1016/j.plefa.2017.03.004. Epub 2017 Mar 10.


Low omega-3 polyunsaturated fatty acid (PUFA) levels are seen in major depression. We examined effects of six weeks of fish oil supplementation on clinical characteristics in 16 patients with symptomatic major depressive disorder, and tested plasma phospholipid levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as correlates of clinical response. Depression symptoms improved after supplementation (p=0.007). The reduction in depression severity was not predicted by baseline PUFA levels but did exhibit a relationship with endpoint PUFAs, correlating negatively with DHA as a percentage of plasma phospholipids (DHA%; R2=0.60, p=0.004), adjusting for endpoint EPA%; and correlating positively with endpoint EPA% (R2=0.58, p=0.007), adjusting for endpoint DHA%. Thus, the higher the proportion of DHA to EPA, the greater the reduction in depression severity (r=-0.43, p=0.097). Five patients showed a decrease of >50% on the 17-item Hamilton Depression Rating Scale and a final score <7 and were thus not only responders but met standard criteria for remission, and were distinguished from non-responders by higher levels of DHA% (p=0.03). This pilot study suggests that post-supplementation DHA% levels may be a necessary target for antidepressant response to fish oil, and that this may depend to some extent on the efficacy of EPA conversion to DHA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / diet therapy*
  • Dietary Supplements
  • Docosahexaenoic Acids / blood*
  • Drug Administration Schedule
  • Eicosapentaenoic Acid / blood*
  • Fatty Acids, Unsaturated / blood
  • Female
  • Fish Oils / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Severity of Illness Index
  • Treatment Outcome


  • Fatty Acids, Unsaturated
  • Fish Oils
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid