Vitamin D as an adjunct treatment for multiple sclerosis: a systematic review and meta-analysis

Introduction Vitamin D deficiency has been associated to a higher risk of developing multiple sclerosis (MS) and a more disabling disease course. Nonetheless, the efficacy of vitamin D as an add-on to immunomodulatory therapy for MS remains a controversial topic in neurology. Objectives: To perform a systematic review and meta-analysis of randomized controlled trials to assess the impact of adjunct high-dose Vitamin D on clinical and radiological outcomes. Methods: PubMed, Embase, and Cochrane Library databases were queried for relevant articles published until December 18th, 2022. Two authors independently selected RCTs involving patients with MS, that had an intervention group receiving high-dose (?1000 IU/day) Vitamin D, and reporting clinical or radiological outcomes such as EDSS, ARR, and new MRI lesions. Articles not published in English, Spanish, French, or Portuguese, or consisting of study protocols or duplicate records were excluded. Two authors independently extracted data and assessed the risk of bias of studies using a standardized, pilot-tested form. The meta-analysis was conducted using the RStudio software. Results: We included 12 studies with 1009 participants. No significant benefit of EDSS (six studies, 347 participants) or ARR (nine studies, 845 participants) was observed in the high-dose vitamin D supplementation group. Interestingly, a small reduction in the T2 lesion count was seen in subjects treated with high-dose vitamin D (MD -0,71, CI 95% [-1,13;-0,28], I2 = 34%, p = 0,001). We found no evidence of significant heterogeneity or publication bias. Conclusion: The findings of this systematic review and meta-analysis provide novel evidence that vitamin D supplementation has no relevant short-term impact on the clinical outcomes of patients with MS. However, the small, yet significant, benefit on T2 lesions may signal a potential long-term benefit. Thus, long-term follow-up studies are necessary to validate these findings and further clarify potential clinical benefits.