The Association Between Serum α-Tocopherol and Pathogenesis of Multiple Sclerosis: A Systematic Review and Meta-Analysis of Case-Control Studies.

BACKGROUND

Oxidative stress is a key pathological mechanism of multiple sclerosis (MS) and α-tocopherol is recognized as a primary chain-breaking antioxidant. This study is aimed at investigating the relationship between serum α-tocopherol and the pathogenesis of MS

METHODS

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Joanna Briggs Institute (JBI) manual for evidence synthesis. Scopus, PubMed, Web of Science, and Embase were searched in March 2025. The risk of bias was evaluated using the critical appraisal tool developed by JBI. All statistical analyses were performed with comprehensive meta-analysis software (CMA3).

RESULTS

Out of 506 records evaluated during the title/abstract screening phase, five case-control studies were included. Studies encompassed a total of 389 participants, comprising 211 individuals diagnosed with MS and 178 healthy controls. The levels of α-tocopherol were found to be lower in MS patients compared to the healthy group (standardized mean difference [SMD] = -1.17; 95% CI: -2.02, -0.31; p = 0.007, I2 = 91.5%, p < 0.001; predictive values: -3.13, 0.79). Although subgroup analyses were performed based on sample size, sex, and phase of the diseases, the source of heterogeneity was not found.

DISCUSSION: Current evidence supports the possible association of serum α-tocopherol and MS pathogenesis; however, considering the restricted number of included studies (five papers), the retrospective nature of the studies, and substantial heterogeneity in the conducted quantitative synthesis, multicenter and large-scale prospective studies are recommended.