Vitamin D3 as an add-on treatment for multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials

Background: Vitamin D deficiency has been linked to a higher risk of multiple sclerosis (MS) and disease progression. However, the efficacy of vitamin D3 as an adjuvant therapy for MS remains a controversial topic. Objective: To perform a systematic review and meta-analysis of randomized controlled trials to assess the impact of adjunct high-dose vitamin D3 on clinical and radiological outcomes. Methods: PubMed, Embase, and Cochrane Library were searched for trials published until December 18th, 2022. Authors independently selected randomized controlled trials involving patients with MS, with an intervention group receiving high dose (>= 1000 IU/day) cholecalciferol and reporting clinical or radiological outcomes. Authors independently extracted data and assessed the risk of bias using a standardized, pilot-tested form. The meta-analysis was conducted using RStudio for EDSS at the last follow-up, ARR, and new T2 lesion count. Results: We included 9 studies with 867 participants. No significant reduction of EDSS (MD = 0.02, CI 95 % [-0.37; 0.41], p = 0.91), ARR (MD -0.03, CI 95 % [-0.08; 0.02], p = 0.26), or new T2 lesions (MD -0.59, CI 95 % [-1.24;0.07], p = 0.08) was observed at 6-24 months. We found no evidence of publication bias. Conclusion: The findings of this meta-analysis strengthen current evidence that vitamin D3 supplementation has no significant impact on clinical outcomes in patients with MS. However, the non-significant reduction of new T2 lesions could precede long-term clinical benefits and should be validated in additional studies.