by Justin Jackson , Medical Xpress

Credit: Unsplash/CC0 Public Domain

Researchers from CHU Nîmes, Université Montpellier, and multiple MS centers in France have found that oral cholecalciferol in doses of 100,000 IU every two weeks significantly reduced disease activity in clinically isolated syndrome and early relapsing‑remitting multiple sclerosis.

The study is published in the journal JAMA.

Multiple sclerosis (MS) typically starts with an acute episode involving the central nervous system, such as optic neuritis (inflammation of the optic nerve), transverse myelitis (inflammation of the spinal cord), or brainstem syndromes. This combination of initial signs is termed a clinically isolated syndrome (CIS), although CIS does not always convert to MS.

The risk factors for relapse (conversion to clinically definite MS) include the presence of cerebrospinal fluid oligoclonal bands, a high number of T2‑weighted fluid‑attenuated inversion recovery lesions on brain MRI, and younger age at CIS onset.

Vitamin D deficiency is a risk factor for MS and is associated with disease activity, but prior supplementation trials have produced conflicting results. Given its immunomodulatory effects, vitamin D has mostly been tested as an add‑on therapy to interferon beta. The research team aimed to evaluate the safety and efficacy of vitamin D as monotherapy in recent CIS cases.

In the D‑Lay MS randomized clinical trial, investigators conducted a parallel, double‑blind, placebo‑controlled study comparing high‑dose cholecalciferol versus placebo in untreated CIS.

Eligibility criteria included adults aged 18–55 with CIS onset within 90 days, serum vitamin D <100 nmol/L, and MRI evidence of dissemination in space or ≥2 lesions plus positive oligoclonal bands.

A total of 316 participants were randomized 1:1 to receive oral cholecalciferol 100,000 IU (n=163) or matching placebo (n=153) every two weeks for 24 months. The primary outcome was disease activity (first relapse or new/contrast‑enhancing MRI lesions). Of the 316 randomized, 303 (156 vitamin D; 147 placebo) received at least one dose and 288 completed the full 24‑month follow‑up.

Disease activity occurred in 94 of 156 patients (60.3%) receiving vitamin D versus 109 of 147 (74.1%) receiving placebo (HR, 0.66), and median time to disease activity was significantly longer with vitamin D (432 vs. 224 days).

All three secondary MRI outcomes favored vitamin D: overall MRI activity (57.1% vs. 65.3%; HR, 0.71), new or enlarging T2 lesions (46.2% vs. 59.2%; HR, 0.61), and contrast‑enhancing lesions (18.6% vs. 34.0%; HR, 0.47).

Oral high‑dose cholecalciferol reduced disease activity in CIS and early relapsing‑remitting MS. These findings support further investigation, including pulse high‑dose vitamin D as an add‑on therapy. High‑dose vitamin D may offer an inexpensive, well‑tolerated option, especially where access to standard disease-modifying therapies is limited.

The authors recommend future trials of vitamin D add‑on therapy, particularly in patients with severe baseline deficiency.

More information: Eric Thouvenot et al, High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis, JAMA (2025). DOI: 10.1001/jama.2025.1604

Journal information:Journal of the American Medical Association

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