Zinc in depression: From development to treatment: A comparative/ dose response meta-analysis of observational studies and randomized controlled trials

Somaye Yosaee, Cain C T Clark, Zahra Keshtkaran, Mahkameh Ashourpour, Parisa Keshani, Sepideh Soltani

    Research output: Contribution to journalReview articlepeer-review

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    Background: A previous meta-analysis suggested that zinc status may be linked to depression status. However, it remains unclear whether zinc status can predict the risk of depression development, or whether the monotherapy of zinc is superior to the combination of zinc supplementation and antidepressant medications in the treatment of depression. Therefore, this meta-analysis aimed to clarify the impact of zinc status and supplementation on depression development and status across all available evidence. Methods: PubMed, EMBASE, Scopus, and ISI web of science were searched, up to 14 May 2020, for relevant publications. Pooled relative risks (RRs) with 95% confidence intervals (CI) in observational studies, and mean and standard deviation (SD) for the change in depression score in RCTs were calculated using a random-effects model. Results: The meta-analysis of RCTs indicated that zinc supplementation significantly lowered depressive symptom scores of depressed patients [weighted mean difference (WMD = −4.15 point; 95% CI: −6.56, −1.75 point; P < 0.01)], and the improvement in depression status occurred only when zinc supplementation was prescribed as a monotherapy. The cohort studies showed that the highest level of zinc intake was associated with a 28% reduced risk of depression (RR: 0.66; 95% CI: 0.50, 0.82; I 2 = 13.90). Dose-response analyses revealed a significant non-linear effect of baseline mood status on depression score. Conclusion: Current evidence from observational studies and RCT's supports the potential benefits zinc to reduce the risk of, and alleviate, depression. However, further trials are needed to confirm the beneficial effect of zinc as a monotherapy versus adjunctive therapies.

    Original languageEnglish
    Pages (from-to)110-117
    Number of pages8
    JournalGeneral Hospital Psychiatry
    Early online date10 Aug 2020
    Publication statusPublished - 1 Jan 2022

    Bibliographical note

    NOTICE: this is the author’s version of a work that was accepted for publication in General Hospital Psychiatry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in General Hospital Psychiatry, (2020) DOI: 10.1016/j.genhosppsych.2020.08.001

    © 2020, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/


    Larestan University of Medical Sciences , Research committee (IR.LARUMS.REC.1398.003


    • Depression
    • Meta-analysis
    • Monotherapy
    • Zinc

    ASJC Scopus subject areas

    • Psychiatry and Mental health


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