Copper Concentration in Multiple Sclerosis: a Systematic Review and Meta-Analysis

Background A wide range of risk factors, from genetic to environmental, have been identified to play role in the etiology of multiple sclerosis. However, the role of trace element remains mostly unknown. We sought to combine all available evidence to assess the association between copper concentration and multiple sclerosis. Methods This systematic review and meta-analysis was conducted based on PRISMA guidelines. PubMed, Scopus, Embase, and Web of Science were searched since inception till July 2020. Observational studies that assessed copper as exposure in serum, plasma, whole blood, and cerebrospinal fluid were included. Standardized mean differences (SMD), comparing the mean of copper concentration in multiple sclerosis patients versus healthy controls, were considered as the measure of association. The fixed-effect model with inverse variance weighting was used to combine the findings. Results Twenty studies inclusive of 797 multiple sclerosis cases and 875 healthy controls were included in the meta-analysis (all case-control studies). The combined SMDs were 1.25 (95% confidence interval [CI] 0.95 to 1.55, number of included studies [n]=4) in plasma, 0.45 (CI 0.22 to 0.68, n=4) in whole blood, 0.19 (CI 0.06 to 0.33, n=12) in blood serum and 1.23 (CI 0.83 to 1.64, n=4) in cerebrospinal fluid. Conclusions We found a higher concentration of copper in multiple sclerosis patients than healthy controls. The possible causal nature of the observed associations warrants further investigation with prospective data.