Clinical efficacy of zinc supplementation in improving antioxidant defense system: A comprehensive systematic review and time-response meta-analysis of controlled clinical trials.

Oxidative stress is a contributing factor to many chronic diseases. It has been investigated that zinc (Zn) may enhance the antioxidant defense. The current dose-response and time-response meta-analysis aims to determine the efficacy of Zn supplementation in improving antioxidant defense. Scopus, PubMed/Medline, Web of Science, and Embase databases were searched systematically up to December 30, 2020. Meta-analysis was performed on human controlled clinical trials using random effects method. To find any source of heterogeneity, subgroup analysis and meta-regression were performed. Trim and fill analysis was used for adjusting the publication bias. To find any non-linear relationship between variables and effect size, dose-response and time-response analyses were performed. Cochrane Collaboration's tool was used for evaluating the quality assessment. A total of 23 controlled clinical trials were analyzed. The range of Zn supplementation duration in various studies was within 4-24 weeks. Zn supplementation did not have beneficial effects on glutathione peroxidase (GPx) activity (SMD = -0.34 U/g; 95% CI: -0.93, 0.25; P = 0.258). There were significant increasing effects of Zn supplementation on glutathione (GSH) (SMD = 1.28 μmol/l; 95% CI: 0.42, 2.14; P = 0.003) and total antioxidant capacity (TAC) levels (SMD = 1.39 mmol/l; 95% CI: 0.44, 2.35; P = 0.004). Zn had ameliorative effects on superoxide dismutase (SOD) activity after elimination of publication bias (SMD: 0.84 U/g; 95% CI: 0.12, 1.56, P < 0.05). Zn could also elevate GSH and TAC levels, plus SOD activity after modifying the publication bias. Finally, Zn had no significant effect on GPx activity.