HIGH-DOSE vitamin D supplementation significantly reduces disease activity in patients with clinically isolated syndrome (CIS) and early multiple sclerosis (MS), extending the time to relapse or new brain lesions by over 200 days, according to findings from the D-Lay MS randomised clinical trial.
Vitamin D deficiency is a well-established risk factor for MS development and progression, yet evidence supporting supplementation has been inconsistent. This double-blind, placebo-controlled trial evaluated whether high-dose vitamin D monotherapy could delay or reduce disease activity in early MS patients, addressing a critical gap in non-pharmacological intervention strategies. The findings offer new insights into managing CIS, a precursor to MS, through accessible nutritional supplementation.
The trial enrolled 316 participants (median age 34, 70% female) with recent CIS (≤90 days), low baseline vitamin D levels (<100 nmol/L), and MRI evidence of MS-like lesions. Patients received 100,000 IU oral cholecalciferol or placebo every two weeks for 24 months. Disease activity—defined as relapse or new/enlarging MRI lesions—occurred in 60.3% of the vitamin D group versus 74.1% with placebo (HR 0.66; 95% CI 0.50–0.87; p=0.004), delaying median time to activity from 224 to 432 days (p=0.003). MRI outcomes favoured vitamin D: new lesions reduced by 39% (HR 0.61; p=0.003), contrast-enhancing lesions by 53% (HR 0.47; p=0.001). However, clinical relapse rates showed no significant difference (17.9% vs 21.8%; p=0.16). Safety profiles were comparable, with severe adverse events unrelated to treatment in both groups.
These results position high-dose vitamin D as a safe adjunct therapy for early MS, particularly for reducing subclinical disease activity detectable via MRI. For clinical practice, initiating vitamin D supplementation in CIS patients with deficiency could delay progression, complementing disease-modifying therapies. Future research should explore optimal dosing schedules, long-term outcomes, and synergistic effects with immunotherapies. Guidelines may need updating to incorporate routine vitamin D monitoring and supplementation in early MS care, prioritising patients with deficiency.
Reference
Thouvenot E et al. High-dose vitamin D in clinically isolated syndrome typical of multiple sclerosis: The D-Lay MS randomized clinical trial. JAMA. 2025;DOI:10.1001/jama.2025.1604.
