Clinical effectiveness of zinc supplementation on the biomarkers of oxidative stress: a systematic review and meta-analysis of randomized controlled trials

Seyed Mohammad Mousavi, Maryam Hajishafiee, Cain C T Clark, Israel Júnior Borges do Nascimento, Alireza Milajerdi, Mohammad Reza Amini, Ahmad Esmaillzadeh

    Research output: Contribution to journalReview articlepeer-review

    12 Citations (Scopus)
    142 Downloads (Pure)


    Background: Oxidative stress plays an important role in the occurrence of chronic diseases. Zinc supplementation is also known to be an antioxidant agent. While, there is no review on the effects of zinc supplementation on oxidative stress, this study aimed to systematically summarize randomized clinical trials (RCTs) which have evaluated the impacts of zinc supplementation on oxidative stress biomarkers. Methods: Systematic searches were performed using the PubMed/Medline, Scopus, and Google Scholar databases, up to April 2020. All RCTs assessed the effect of oral zinc supplementation on serum malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione (GSH), and nitric oxide (NO) levels, were included. For each variable, mean differences (MD) and standard deviations (SDs) were combined using the random-effects model, and the fractional polynomial model was used to implement the dose-response analysis. Results: Ten RCTs were included. The pooled analysis of data showed that zinc supplementation significantly reduced MDA levels (MD: -0.42 μmol/L; 95 % CI: -0.71 to -0.13), increased serum TAC (MD: 225.96 mmol/L; 95 % CI: 68.42–383.5) and GSH levels (MD: 49.99 μmol/L; 95 % CI: 2.25 t 97.73), compared with the placebo group. In contrast, no significant changes were seen in NO levels following zinc supplementation (MD: -1.66 μmol/L; 95 % CI: -5.89 to 2.57). Dose-response analysis showed a significant non-linear relationship between zinc supplementation dosage and serum levels of MDA (p < 0.01), but not other biomarkers. Conclusions: The current study showed that zinc supplementation would significantly decrease MDA and increase TAC and GSH, but not NO levels. Thus, it encourages the use of zinc supplementation in oxidative stress-related diseases.

    Original languageEnglish
    Article number105166
    JournalPharmacological Research
    Early online date21 Aug 2020
    Publication statusPublished - Nov 2020

    Bibliographical note

    NOTICE: this is the author’s version of a work that was accepted for publication in Pharmacological Research. 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
    Pharmacological Research, 161, (2020)
    DOI: 10.1016/j.phrs.2020.105166

    © 2020, Elsevier. Licensed under the Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International


    • Antioxidants
    • Malondialdehyde
    • Oxidative stress
    • Reactive oxygen species
    • Zinc

    ASJC Scopus subject areas

    • Pharmacology


    Dive into the research topics of 'Clinical effectiveness of zinc supplementation on the biomarkers of oxidative stress: a systematic review and meta-analysis of randomized controlled trials'. Together they form a unique fingerprint.

    Cite this