Zinc in depression: a meta-analysis

Biol Psychiatry. 2013 Dec 15;74(12):872-8. doi: 10.1016/j.biopsych.2013.05.008. Epub 2013 Jun 24.


Background: Zinc is an essential micronutrient with diverse biological roles in cell growth, apoptosis and metabolism, and in the regulation of endocrine, immune, and neuronal functions implicated in the pathophysiology of depression. This study sought to quantitatively summarize the clinical data comparing peripheral blood zinc concentrations between depressed and nondepressed subjects.

Methods: PubMed, Cumulated Index to Nursing and Allied Health Literature, and PsycINFO were searched for original peer-reviewed studies (to June 2012) measuring zinc concentrations in serum or plasma from depressed subjects (identified by either screening or clinical criteria) and nondepressed control subjects. Mean (±SD) zinc concentrations were extracted, combined quantitatively in random-effects meta-analysis, and summarized as a weighted mean difference (WMD).

Results: Seventeen studies, measuring peripheral blood zinc concentrations in 1643 depressed and 804 control subjects, were included. Zinc concentrations were approximately -1.85 µmol/L lower in depressed subjects than control subjects (95% confidence interval: [CI]: -2.51 to -1.19 µmol/L, Z17 = 5.45, p < .00001). Heterogeneity was detected (χ(2)17 = 142.81, p < .00001, I(2) = 88%) and explored; in studies that quantified depressive symptoms, greater depression severity was associated with greater relative zinc deficiency (B = -1.503, t9 = -2.82, p = .026). Effect sizes were numerically larger in studies of inpatients (WMD -2.543, 95% CI: -3.522 to -1.564, Z9 = 5.09, p < .0001) versus community samples (WMD -.943, 95% CI: -1.563 to -.323, Z7 = 2.98, p = .003) and in studies of higher methodological quality (WMD -2.354, 95% CI: -2.901 to -1.807, Z7 = 8.43, p < .0001).

Conclusions: Depression is associated with a lower concentration of zinc in peripheral blood. The pathophysiological relationships between zinc status and depression, and the potential benefits of zinc supplementation in depressed patients, warrant further investigation.

Keywords: Depression; depressive symptoms; major depressive disorder; micronutrient; trace metal; zinc.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Factual / statistics & numerical data
  • Depression / blood*
  • Humans
  • Zinc / blood*


  • Zinc