Vitamin D in Multiple Sclerosis: A Comprehensive Umbrella Review

Multiple sclerosis (MS) is an inflammatory neuroimmune disease with a multifaceted etiology and long-lasting adverse effects. Several studies have explored the role of 25-hydroxyvitamin D (25(OH)D) serum levels, vitamin D receptor (VDR) gene polymorphisms, and vitamin D supplementation (VDS) in individuals with MS. The aim of this study was to evaluate the relationship of MS with 25(OH)D serum levels, VDR gene polymorphisms, and VDS. We assessed relevant articles published in PubMed, Scopus, and Web of Science from the inception up to 24 February, 2024. Meta-analyses that investigated the link of 25(OH)D serum levels, VDR gene polymorphisms including Apal (rs7975232), BsmI (rs1544410), Taql (rs731236), and Fokl (rs10735810), and VDS with the risk and clinical manifestations of MS were included. The methodological quality of selected articles was assessed by the Assessment of Multiple Systematic Reviews version 2. The statistical analysis of this umbrella review was carried out using RStudio version 2023.03.1 and R version 4.3.2, simultaneously. A total of 23 of 304 records were entered into this umbrella review with a pooled sample size of 37,567 participants. Eleven articles were rated as high quality, 1 was moderate quality, 1 was low quality, and 10 were critically low quality. The homozygote model of FokI (FF+ff compared with Ff) was significantly associated with an 8% reduction of MS risk (odds ratio: 0.92, 95% confidence interval: 0.86, 0.98; I2 = 0%, P > 0.99). According to existing clinical evidence, the risk of MS may be associated with VDR gene polymorphism. Further studies are needed to explore the association of MS and vitamin D. This trial was registered at International Prospective Register of Systematic Reviews (PROSPERO) as registration number CRD42024521541.