A groundbreaking clinical trial has demonstrated for the first time that high-dose vitamin D supplementation significantly reduces disease activity in patients with clinically isolated syndrome (CIS) and early multiple sclerosis (MS), delaying disease progression by more than 200 days compared to placebo.
The D-Lay MS randomized clinical trial enrolled 316 participants with recent CIS diagnosis (within 90 days), low baseline vitamin D levels (below 100 nmol/L), and MRI evidence of MS-like lesions. The double-blind, placebo-controlled study addressed a critical gap in non-pharmacological intervention strategies for early MS management.
Significant Reduction in Disease Activity
Participants receiving 100,000 IU of oral cholecalciferol every two weeks for 24 months showed markedly better outcomes than those receiving placebo. 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).
The median time to disease activity was extended from 224 days in the placebo group to 432 days in the vitamin D group (p=0.003), representing a delay of over 200 days before disease progression.
Dr. Eric Thouvenot, co-lead of the trial and neurologist at the University of Montpellier in France, noted that previous vitamin D trials may have failed due to insufficient participant numbers, short monitoring periods, or concurrent use of MS medications that complicated assessment of vitamin D's independent effects.
Stronger Impact on Imaging Than Clinical Outcomes
MRI outcomes strongly favored vitamin D supplementation, with new lesions reduced by 39% (HR 0.61; p=0.003) and contrast-enhancing lesions reduced by 53% (HR 0.47; p=0.001). However, clinical relapse rates showed no statistically significant difference between groups (17.9% with vitamin D vs. 21.8% with placebo; p=0.16).
This disparity between imaging and clinical outcomes suggests that vitamin D may be particularly effective at reducing subclinical disease activity detectable through MRI before symptoms become apparent.
Novel Trial Design Targets Early Intervention
The trial's design was distinctive in focusing on patients with CIS, a precursor condition to MS that represents the earliest detectable phase of the disease. Approximately 85% of MS patients initially present with CIS.
"We had a window in which we could directly investigate the impact of vitamin D supplementation on disease progression before patients started taking other drugs for multiple sclerosis," explained Dr. Thouvenot.
The study population was predominantly female (70%) with a median age of 34, reflecting the typical demographic profile of MS patients.
Safety Profile and Dosing Considerations
Despite administering doses approximately 20 times higher than common over-the-counter supplements, the safety profiles were comparable between groups, with severe adverse events unrelated to treatment in both groups. No participants developed hypercalcemia, a potential concern with high-dose vitamin D supplementation.
Dr. Klaus Schmierer, professor of neurology at Queen Mary University of London, who was not involved in the trial, called this "important research" that supports the use of high-dose vitamin D by patients with multiple sclerosis—a practice many physicians already recommend.
The biweekly administration schedule (rather than daily dosing) may have contributed to the favorable safety profile, though researchers emphasize that such high doses should only be administered under medical supervision.
Implications for Clinical Practice
These findings position high-dose vitamin D as a potential adjunct therapy for early MS, particularly for reducing subclinical disease activity. For clinical practice, initiating vitamin D supplementation in CIS patients with deficiency could delay progression, complementing disease-modifying therapies.
The researchers emphasize that vitamin D supplementation would not replace current disease-modifying drugs but rather provide another therapeutic option, particularly valuable for patients with limited access to conventional MS medications.
Future Research Directions
Future research should explore optimal dosing schedules, long-term outcomes beyond the two-year study period, and potential synergistic effects with immunotherapies. Clinical guidelines may need updating to incorporate routine vitamin D monitoring and supplementation in early MS care, prioritizing patients with deficiency.
The study results were published in JAMA, marking a significant advancement in understanding non-pharmacological approaches to managing this complex neurological condition.
