Copper concentration in multiple sclerosis: a systematic review and meta-analysis

• Published in: Multiple sclerosis and related disorders 2020-10, Vol.45, p.102426, Article 102426
• Main Authors: Sarmadi, Mohammad, Bidel, Zeinab, Najafi, Fereshteh, Ramakrishnan, Rema, Teymoori, Farshad, Zarmehri, Hassan Azhdari, Nazarzadeh, Milad
• Format: Article
• Language: English
• Subjects: Case-Control Studies; Cerebrospinal fluid; Copper; Humans; Meta-analysis; Multiple Sclerosis; Plasma; Prospective Studies; Risk Factors; Serum
• ISSN: 2211-0348; 2211-0356
• DOI: 10.1016/j.msard.2020.102426

•Evidence for the association between copper and multiple sclerosis remains mostly controversial.•Twenty studies inclusive of 985 multiple sclerosis cases and 947 healthy controls from nine countries were included in this meta-analysis.•We found a higher concentration of copper in multiple sclerosis patients than healthy controls.•The magnitude of association was higher in studies that measured copper concentration in the plasma and cerebrospinal fluid. 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. 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. 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. 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. [Display omitted]