The efficacy of zinc supplementation in depression: systematic review of randomised controlled trials

J Affect Disord. 2012 Jan;136(1-2):e31-e39. doi: 10.1016/j.jad.2011.06.022. Epub 2011 Jul 27.


Background: Depression is a significant public health problem. Pre-clinical studies suggest a potential role of zinc in reducing or preventing depressive symptoms. Many epidemiological studies have examined the association of low zinc status with depression; however, clinical trials on the effect of zinc supplementation in depression are limited. This review aimed to synthesise results from all published randomised controlled trials on the efficacy of zinc supplementation for reducing or preventing depressive symptoms.

Methods: Six databases were searched over all years of records until March 2011. All randomised controlled trials with a comparison group, that examined zinc supplementation as the intervention and depressive symptoms as the primary outcome were included. Pairs of reviewers extracted key information of study characteristics and outcomes, and assessed the quality of each study.

Results: Four randomised controlled trials met inclusion criteria. In studies that examined the effects of zinc supplementation as an adjunct to antidepressants drug treatment, zinc significantly lowered depressive symptom scores of depressed patients. There is less clear evidence on the effectiveness of zinc supplementation alone on depressive symptoms of non-depressed healthy subjects. The overall study quality was rated 'moderate'.

Limitations: There are limited trials examining the effects of zinc supplementation on depressive symptoms. An overall pooled estimate of effect for all included studies could not be calculated and evidence was difficult to summarise because of substantial heterogeneity.

Conclusion: Evidence suggests potential benefits of zinc supplementation as a stand-alone intervention or as an adjunct to conventional antidepressant drug therapy for depression. However, there are methodological limitations in existing studies and so further well-designed, adequately powered research is required.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Depression / drug therapy*
  • Depression / prevention & control*
  • Dietary Supplements
  • Humans
  • Male
  • Randomized Controlled Trials as Topic
  • Young Adult
  • Zinc / therapeutic use*


  • Antidepressive Agents
  • Zinc