Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication




Journal article


Mult Scler Relat Disord

Publication Date





Cerebrospinal fluid, Copper, Meta-analysis, Multiple sclerosis, Plasma, Serum