Risk of bias assessment for each study.

<div><p>The role of trace elements and toxic metals on human health has been extensively discussed concerning disease pathogenesis and risk factors of diseases. In this systematic review and meta-analysis, we aimed to investigate arsenic (As), cadmium (Cd), lead (Pb), iron (Fe), zinc (Zn), and magnesium (Mg) levels in individuals with multiple sclerosis (MS) and healthy controls. We searched different databases/search engines for this systematic review and meta-analysis, including Web of Science, PubMed, Scopus, and Google Scholar, until June 27, 2024. Out of 5466 studies identified, 65 met our eligibility criteria and were included in the systematic review. For the meta-analysis, 58 studies with 10420 participants (5316 multiple sclerosis patients and 5104 healthy controls) had adequate data for inclusion. Results from the pooled data, analyzed using a random-effects model, revealed higher levels of As (Hedge’s g = 4.00 μg/l, 95% CI = 2.03 to 5.98, P <0.001; I<sup>2</sup> = 97.69%, P<0.001) and Cd (Hedge’s g = 1.20 μg/l, 95% CI = 0.13 to 2.27, P = 0.028; I<sup>2</sup> = 97.99%, P<0.001) in multiple sclerosis patients compared to healthy ones. However, no significant differences were observed in the concentrations of Zn, Fe, Mg, and Pb between the two groups. This study identified elevated As and Cd levels in MS patients, indicating the need for targeted interventions and public health guidelines for toxic metal exposure. Limiting exposure to contaminated environments and maintaining essential element levels through natural resources or supplements is essential, as there may be a possible relationship between multiple sclerosis and the concentrations of these elements in humans.</p></div>