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The present meta-analysis was performed to assess the association between MS patients and control subjects in terms of their circulating levels of arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd). We searched Medline/PubMed, Scopus, Web of Science, and Embase up until June 2020 to identify all studies that examined the concentrations of heavy metals in MS patients. Statistical tests used to assess inter-study heterogeneity were Cochrane’s Q test and the I2 statistic. Given the observed significant heterogeneity, the random-effects model was employed to pool the weighted mean differences (WMDs) and the corresponding 95 % confidence intervals (CIs). Out of a total of 1181 articles, 16 studies with 1650 participants (772 patients with MS and 878 controls) were included in this review meta-analysis. Pooled results using random-effects model showed that the levels of Pb (WMD= 0.73 µg/L, 95 % CI= 0.33 to 1.12, P< 0.001), As (WMD= 2.48 μg/L, 95 % CI= 1.44 to 3.53, P <0.001; I2= 98.9 %, P <0.001), and Cd (WMD= 0.17 μg/L, 95 % CI= 0.09 to 0.26, P <0.001) were significantly higher in MS patients than those of the controls. However, there were no significant differences in the levels of Hg (WMD= -0.14 µg/L, 95 % CI= -0.77 to 0.49, P= 0.658) among both groups. Sensitivity analysis indicated that after excluding one-by-one study, the overall pooled WMD of Pb was changed. This meta-analysis showed that patients with MS had significantly higher levels of circulatory As and Cd compared to the controls. Yet, there was no statistically significant difference between circulating levels of Hg and Pb among MS patients and controls.
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