Blood Trace Element Status in Multiple Sclerosis: a Systematic Review and Meta-analysis

The aim of this meta-analysis was to investigate whether the blood concentrations of patients with multiple sclerosis (MS) are associated with those of the healthy control group in terms of trace elements including zinc (Zn), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), and copper (Cu). A comprehensive search was performed in online databases including PubMed, Scopus, Embase, and Web of Science for studies, which have addressed trace elements in MS up to July 23, 2020. The chi-square test and I² statistic were utilized to evaluate inter-study heterogeneity across the included studies. Weighted mean differences (WMDs) and corresponding 95% CI were considered as a pooled effect size (ES). Twenty-seven articles (or 32 studies) with a total sample comprised of 2895 participants (MS patients (n = 1567) and controls (n = 1328)) were included. Pooled results using random-effects model indicated that the levels of Zn (WMD = - 7.83 mcg/dl, 95% CI = - 12.78 to - 2.87, Z = 3.09, P = 0.002), and Fe (WMD = - 13.66 mcg/dl, 95% CI = - 23.13 to - 4.19, Z = 2.83, P = 0.005) were significantly lower in MS patients than in controls. However, it was found that levels of Mn (WMD = 0.03 mcg/dl, 95% CI = 0.01 to 0.04, Z = 2.89, P = 0.004) were significantly higher in MS patients. Yet, no significant differences were observed in the levels of Mg, Se, and Cu between both groups. This meta-analysis revealed that the circulating levels of Zn and Fe were significantly lower in MS patients and that Mn level was significantly higher than those in the control group. However, it was found that there was no significant difference between MS patients and controls with regard to levels of Mg, Se, and Cu.