Nutritional Supplements for Depression

It is time to update the information on this site about nutritional supplements that may be effective for people with depression.

An April 2016 review of the literature by Jerome Sarris published in the American Journal of Psychiatry concludes that there is moderately strong data supporting the effectiveness of some supplements for reducing symptoms of depression.

This review, which not only tried to find every relevant article published prior to December 2015, but also subjected those research findings to tests to see if there was evidence of publication bias and to determine whether statistically significant results were actually not meaningful in terms of the extent of improvement in depression symptoms, found that a few nutritional supplements did appear to have good quality evidence supporting their effectiveness.

The authors summarized the results this way:

“Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta-analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies; funnel plots also revealed asymmetry (reflecting potential study bias).”

In other words, the evidence was strongest for omega-3 supplements (and EPA appeared to be the active ingredient, not DHA), was somewhat weaker for SAMe, and was moderate for methylfolate and vitamin D.

There were individual studies suggesting that creatine, folinic acid, and an amino acid combination might be helpful.

There were no consistent findings supporting the use of zinc, folic acid, vitamin C or tryptophan (the latter an especially interesting finding since tryptophan is often recommended as a natural alternative to serotonin antidepressants). And inositol appeared to be clearly ineffective.

For More Information

This review supersedes a previous article that suggests that the evidence is unclear for fish oil.

More information about supplements is available on our sister website.


Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, Ng CH. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016 Jun 1;173(6):575-87. doi: 10.1176/appi.ajp.2016.15091228. Epub 2016 Apr 26. PubMed PMID: 27113121.