High-Dose Vitamin D Reduces Disease Activity in Early Multiple Sclerosis and CIS: JAMA

"High-dose vitamin D not only reduced disease activity in early MS and CIS compared to placebo but also prolonged the time to disease activity, with patients on vitamin D experiencing a delay of 432 days versus 224 days in the placebo group, without any severe adverse events associated with the supplementation," the researchers reported in JAMA.

Clinically isolated syndrome, the first neurological episode suggestive of multiple sclerosis, requires early intervention to delay disease progression. Among potential risk factors, vitamin D deficiency has been linked to increased disease activity in MS, raising interest in its therapeutic role. However, while supplementation is considered a promising strategy, existing evidence on its effectiveness remains inconclusive.

Against the above background, Eric Thouvenot, CHU Nimes, Service de Neurologie, Univ Montpellier, Nimes, France, and colleagues aimed to assess the effectiveness of high-dose cholecalciferol as a standalone treatment in lowering disease activity in patients with clinically isolated syndrome indicative of MS.

For this purpose, the researchers conducted the D-Lay MS trial, a parallel, double-blind, randomized placebo-controlled study across 36 MS centers in France. From July 2013 to December 2020, they enrolled untreated CIS patients aged 18 to 55 years, with CIS duration under 90 days, serum vitamin D levels below 100 nmol/L, and MRI findings meeting 2010 criteria for dissemination in space or oligoclonal bands. Participants were randomized to receive either 100,000 IU of oral cholecalciferol (n=163) or placebo (n=153) every two weeks for 24 months. The primary outcome was disease activity, defined by relapses or MRI changes.

Key Findings:

• Among 316 enrolled participants (median age 34 years, 70% women), 303 (95.9%) received at least one dose, and 288 (91.1%) completed the 24-month trial.

 • Disease activity was observed in 60.3% of the vitamin D group vs. 74.1% of the placebo group (HR, 0.66).

• Median time to disease activity was longer in the vitamin D group (432 vs. 224 days).

• MRI outcomes favored vitamin D over placebo:

• MRI activity: 57.1% vs. 65.3% (HR, 0.71).

• New lesions: 46.2% vs. 59.2% (HR, 0.61).

• Contrast-enhancing lesions: 18.6% vs. 34.0% (HR, 0.47).

 • There was no significant difference in secondary clinical outcomes, including relapse (17.9% vs. 21.8%).

• There were similar results in 247 patients meeting the 2017 relapsing-remitting MS criteria.

• Severe adverse events occurred in 17 patients in the vitamin D group and 13 in the placebo group, with none linked to cholecalciferol.

"The trial demonstrated that high-dose oral cholecalciferol (100,000 IU every two weeks) effectively reduced disease activity in CIS and early RRMS with a low risk of adverse events. These findings support further research on its potential as an add-on therapy in MS management," the researchers concluded.

Reference:

Thouvenot E, Laplaud D, Lebrun-Frenay C, et al. High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial. JAMA. Published online March 10, 2025. doi:10.1001/jama.2025.1604