Written by Peter Liu
Spoon Feed
High-dose vitamin D (cholecalciferol 100,000 IU once every other week) significantly reduced disease activity in patients with a clinically isolated syndrome (CIS) typical for multiple sclerosis (MS).
Vitamin D can “D-Lay” MS activity
Despite a clear association between vitamin D deficiency and worse MS outcomes, RCTs studying vitamin D supplementation in MS have shown lackluster results to date.
The D-Lay MS trial changes this, demonstrating a likely benefit of vitamin D supplementation in patients with a CIS, namely a first presentation with new neurological symptoms typical of MS. This double-blind, placebo-controlled randomized clinical trial investigated whether high-dose cholecalciferol (100,000 IU biweekly) reduces disease activity in patients with CIS. Among 303 participants, disease activity occurred on follow-up over 24 months in 60.3% receiving vitamin D versus 74.1% on placebo (AHR 0.65; 95% CI 0.49–0.87; p = 0.004). Median time to disease activity was 432 days in the vitamin D group vs. 224 days in the placebo group (p = 0.003). MRI outcomes similarly favored vitamin D therapy; for example, fewer patients had new or enlarging lesions (AHR 0.62; 95% CI 0.44-0.86; p = 0.004). Surprisingly, hypercalcemia was only seen in two patients in the placebo group.
Several RCTs have asked similar questions to D-Lay, but have had negative results, including the contemporaneous PREVANZ study.
Why did D-Lay MS show positive results in contrast to other RCTs?
- D-Lay had higher power that PREVANZ.
- D-Lay utilized higher, intermittent dosing of vitamin D compared to the daily dosing in PREVANZ and other RCTs.
- D-Lay (and PREVANZ) studied earlier-stage patients with CIS, compared to previous studies that studied patients with later-stage MS.
How does this change my practice?
The findings of D-Lay MS strongly support high-dose vitamin D supplementation in patients with MS syndromes early in the disease progression. Particularly in MS patients with low vitamin D levels (who benefited even more from supplementation), and those with low risk of harm, I would now favor high-dose cholecalciferol therapy. As for side effects of long-term vitamin D supplementation, no hypercalcemia was seen in the treatment group.
Source
High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial. JAMA. 2025 Apr 22;333(16):1413-1422. doi: 10.1001/jama.2025.1604. PMID: 40063041
