High-Dose Vitamin D Monotherapy Reduced Disease Activity in CIS and Early Relapsing-Remitting MS

High-dose vitamin D (cholecalciferol) monotherapy significantly reduced disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS) according to results of the D-Lay MS clinical trial (NCT01817166) published in JAMA. Conducted across 36 centers in France from 2013 to 2020, this study provides compelling evidence supporting vitamin D as a therapeutic option for CIS and early-stage RRMS.

The study enrolled 316 participants with untreated CIS aged 18 to 55 years, who were within 90 days of symptom onset and had serum vitamin D levels less than 100 nmol/L and MRI findings consistent with multiple sclerosis. Following the 2017 update of the McDonald criteria, 247 of the participants met the diagnostic requirements for RRMS. Participants were randomized to receive either 100,000 IU of oral cholecalciferol (n=163) or placebo (n=153) every 2 weeks for 24 months. The primary outcome was disease activity, defined as relapse occurrence and/or MRI evidence of new or contrast-enhancing lesions.

Results showed a significantly reduced incidence of disease activity among patients receiving vitamin D compared to placebo (60.3% vs. 74.1%; hazard ratio [HR], .66; P=.004), and median time to disease activity was notably longer in the vitamin D group (432 days vs. 224 days; P=.003). MRI outcomes also favored vitamin D treatment, with fewer new lesions (46.2% vs. 59.2%; HR, .61; P=.003) and fewer contrast-enhancing lesions (18.6% vs. 34%; HR, .47; P=.001). However, clinical secondary outcomes such as relapse rate and disability progression showed no significant differences between groups. Post-hoc analysis showed similar results for the RRMS group.

The findings suggest that high-dose vitamin D supplementation may be effective in reducing early inflammatory activity in people with CIS who are at high risk of developing MS, as well as in people with early-stage RRMS. Given its favorable safety profile and low cost, vitamin D could represent an accessible therapeutic approach, particularly beneficial for patients with severe vitamin D deficiency or limited access to conventional disease-modifying therapies. Further research into its role as an adjunctive therapy is warranted.