Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression

Nutr Neurosci. 2014 Feb;17(2):65-71. doi: 10.1179/1476830513Y.0000000066. Epub 2013 Nov 26.


Objective: Zinc is found in abundance in the human brain. Patients with depression may have decreased consumption of food sources rich in zinc, and zinc supplementation may have a potential influence on depressive symptoms. However, clinical trials on the effect of zinc supplementation in depression are limited. The objective of the present study was to determine the effect of zinc supplementation on efficacy of antidepressant therapy. Furthermore, the effect of zinc on plasma levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and brain-derived neurotrophic factor-a (BDNF-a) were assessed.

Design: A single-center, randomized, double-blind, placebo-controlled trial of zinc supplementation was conducted in patients with DSM-IV major depression. Forty-four patients of both sexes aged 18-55 years were recruited for this study from a university hospital. The zinc-supplemented group received zinc sulfate (25 mg elemental Zn/day) orally in addition to their selective serotonin reuptake inhibitor antidepressants for 12 weeks. Symptoms were evaluated using the Hamilton Depression Rating Scale (HDRS) on arrival, weeks 6 and 12. Plasma levels of IL-6, TNF-α and BDNF-a were measured at baseline and at the end of study.

Results: Twenty patients in zinc group and 17 patients in placebo groups completed the study. At baseline, there were no significant differences in any variable between the patients allocated to receive placebo and those taking zinc supplement. Zinc supplementation significantly reduced HDRS compared to placebo (P < 0.01 at 12th week). No significant differences were observed in plasma levels of IL-6, TNF-α, and BDNF-a between zinc-supplemented and placebo-supplemented group.

Conclusion: Zinc supplementation in conjunction with antidepressant drugs might be beneficial for reducing depressive symptoms. However, its effect does not appear to be mediated through impact of zinc on inflammatory processes.

Keywords: HDRS; Major depression; SSRI; Zinc.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents / therapeutic use*
  • Brain-Derived Neurotrophic Factor / blood*
  • Citalopram / therapeutic use
  • Cytokines / blood*
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / drug therapy*
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Fluoxetine / therapeutic use
  • Humans
  • Interleukin-6 / blood
  • Iran
  • Male
  • Middle Aged
  • Placebos
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Tumor Necrosis Factor-alpha / blood
  • Zinc / administration & dosage*


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Interleukin-6
  • Placebos
  • Serotonin Uptake Inhibitors
  • Tumor Necrosis Factor-alpha
  • Fluoxetine
  • Citalopram
  • Zinc