Role of vitamin D as adjuvant therapy on multiple sclerosis: an updated systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Multiple sclerosis (MS) is the most common demyelinating disorder affecting the central nervous system, with multiple risk factors suggested to be involved in the pathogenesis. Many studies have linked vitamin D deficiency to an increased risk of MS. This review aims to comprehensively evaluate the published randomized clinical trials (RCTs) of vitamin D supplements as add-on therapy for MS patients.

Methods: We systematically searched the Web of Science, Scopus, PubMed, and Cochrane databases up to August 2024 for the published RCTs evaluating the use of vitamin D for MS in adults. All included studies were screened and abstracted independently by two authors. Radiological and clinical outcomes were extracted, and the meta-analysis was conducted using Review Manager 5.4.

Results: Our meta-analysis, which included 21 studies with 1,903 patients (20.1% males), found that vitamin D supplementation significantly reduced expanded disability status scale scores (MD = - 0.17, p = 0.03), relapse rates (OR = 0.66, p = 0.02), and new T2 lesion formation (MD = - 0.48, p = 0.03) in patients with MS compared to controls, with minimal to no heterogeneity. However, there was no effect on the annual relapse rate (p = 0.81), timed 25-foot walk (p = 0.54), fatigue severity, or quality of life. Subgroup analysis indicated a relapse rate reduction only in those treated for more than 12 months (OR = 0.53, p = 0.003), suggesting duration-dependent benefits of vitamin D.

Conclusions: Vitamin D supplementation produces statistically significant-yet clinically modest-reductions in disability progression, relapses, and new T2-lesion formation without demonstrable effects on fatigue or quality of life. Accordingly, it should be considered a potentially helpful adjunct pending more definitive evidence. Larger, dose-stratified trials powered for clinically meaningful endpoints are still needed before vitamin D can be endorsed as an efficacy-proven disease-modifying therapy.

Keywords: Cholecalciferol; Disease-modifying therapy; Multiple sclerosis; Vitamin D.

Fig. 1

PRISMA flowchart of included studies

Fig. 2

Cochrane risk-of-bias (RoB 2) tool for randomized trials

Fig. 3

Analysis of Mean difference of EDSS Scores between Vitamin D group and control group

Fig. 4

Analysis of Standardized Mean difference of Annual Relapse Rate (ARR) between Vitamin D group and control group

Fig. 5

Analysis of Odds Ratio for Patients who experience relapses during research with different administration time of vitamin D

Fig. 6

Analysis of Mean difference of New T2 lesions between Vitamin D group and control group

Fig. 7

Analysis of Standardized Mean difference of T25FW, timed 10 foot walk between Vitamin D group and control group

Fig. 8

A Analysis of Standardized Mean difference of 25(OH)D levels between Vitamin D group and control group. B After making Sensitivity analysis by removing One study

Fig. 9

Analysis of Standardized Mean difference of Fatigue Severity Scale (FSS) between Vitamin D group and control group

Fig. 10

Analysis of Standardized Mean difference of Quality of life (QoL) between Vitamin D group and control group