The Effects of Zinc Supplementation on C-Reactive Protein and Inflammatory Cytokines: A Meta-Analysis and Systematical Review.

ABSTRACT

Zinc is known for anti-inflammatory and antioxidant roles. In this meta-analysis, we aim to evaluate the impact of zinc supplementation on inflammatory markers, acute-phase reactants, and serum zinc level during inflammatory and infectious diseases. PubMed, Scopus, and Web of Science databases were screened systematically with the terms "zinc supplementation" AND "CRP" OR "IL-1ß" OR "IL-2" OR "IL-6" OR "IL-10" OR "IL-12" OR "TNF-α" OR "TGF-ß" OR "IFN-γ" OR "WBC (clinical trial)" OR "macrophage (clinical trial)" OR "lymphocyte (clinical trial)" OR "neutrophil (clinical trial)" OR "virus (clinical trial)" OR "antiviral (clinical trial)" for all databases. A total of 2,258 publications were screened, and 73 articles had suitable data for the meta-analysis. Serum zinc level was significantly higher in supplementation group compared with controls [P = 0.0006, mean difference 11.35 (4.84, 17.87)] (n = 37). Zinc supplementation downregulates acute-phase reactants, especially serum C-reactive protein (CRP) in adults [P < 0.00001, mean difference -0.75 (-0.98, -0.52)] (n = 22) and pregnant women [FEM P < 0.00001, mean difference -1.77 (-2.53, -1.00)] (n = 3) but not in children [REM P = 0.10, mean difference -0.85 (-1.86, 0.17)] (n = 3). In subgroups analysis of chronic inflammatory diseases, serum CRP [REM P < 0.00001, mean difference -0.57 (-0.76, -0.38)] were significantly lower in zinc-supplemented patients compared with no intervention group. Zinc supplementation (mg/day) correlated with serum interferon-gamma (IFN-γ) level (P = 0.018, r = 1,000). In the nonsupplemented group, serum zinc correlated with serum interleukin-6 (IL-6) level (P = 0.041, r = -0.829) and serum tumor necrosis factor alpha (TNF-α) level (P = 0.063, r = 0.730). Zinc intake correlated with serum zinc (P = 0.0428, r = 0.5115) and TNF-α (P = 0.0043, r = -0.9461). This meta-analysis shows that zinc supplementation improves CRP levels in adults and pregnant women. It might have modulatory effects on cytokine secretions and blood cells in inflammatory and infectious diseases. For the first time, we investigated the effects of zinc supplementation on inflammatory cytokine.