Exploring the Link of Serum Vitamin B12, Folate, and Homocysteine Concentrations in Individuals with Multiple Sclerosis: An Umbrella Meta-analysis of Case-control Studies.

Abstract

Multiple sclerosis (MS) is an inflammatory neurodegenerative condition of the central nervous system resulting in myelin demyelination. Meta-analyses and systematic reviews indicate that serum concentrations of vitamin B12 (VB12), folate, and homocysteine (Hcy) may be associated with MS pathogenesis. This umbrella review aims to investigate the association of serum VB12, folate, and Hcy concentrations in participants living with MS. Databases including PubMed, Scopus and Web of Science were searched to attain meta-analysis and systematic review studies published up to December 2024. For our review the following framework was used: Population (participants diagnosed with MS), Exposure (serum concentrations of Hcy, VB12, and folate), Comparison (healthy control), and Outcome (pooled serum concentrations of folate, VB12, and Hcy). Five meta-analyses (published 2011 to 2022) with 15 effect sizes were eligible for inclusion. Our analyses reveal that lower serum levels of VB12 and folate were detected in participants living with MS (SMD: -0.14, 95 % CI: -0.25, -0.04; SMD: -0.09, 95 % CI: -0.18, -0.00, respectively), while serum concentration of Hcy were meaningfully higher in people living with MS (SMD: 1.02, 95 % CI: 0.37, 1.68). Our umbrella review demonstrates that participants living with MS exhibit significantly elevated serum Hcy levels, along with reduced concentrations of VB12 and folate, compared to healthy controls. Further high-quality research is required to clarify the potential role of these biomarkers in the pathogenesis of MS and to explore if sex-differences exist.