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

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 mu mol/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 mu mol/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 mu mol/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.