A groundbreaking study from CHU Nîmes, Université Montpellier, and multiple multiple sclerosis (MS) centers across France has revealed that high-dose oral cholecalciferol (vitamin D3) significantly reduces disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting multiple sclerosis (RRMS). The results, published in the journal JAMA, suggest that vitamin D supplementation could serve as an effective, low-cost, and well-tolerated strategy for managing early MS, particularly in regions where access to standard disease-modifying therapies is limited.
Multiple Sclerosis and the Role of Vitamin D
What is Multiple Sclerosis?
Multiple sclerosis is a chronic autoimmune disease that affects the central nervous system (CNS). It occurs when the immune system mistakenly attacks the protective myelin sheath that surrounds nerve fibers, leading to inflammation, nerve damage, and disruption of neural communication. Symptoms vary widely but often include fatigue, vision problems, muscle weakness, numbness, coordination difficulties, and cognitive impairment.
MS typically begins with a clinically isolated syndrome (CIS)—an initial episode of neurological dysfunction that may involve optic neuritis (inflammation of the optic nerve), transverse myelitis (spinal cord inflammation), or brainstem syndromes. While not all CIS cases progress to MS, certain risk factors increase the likelihood of conversion, including specific MRI findings, oligoclonal bands in cerebrospinal fluid, and younger age at onset.
The Link Between Vitamin D and MS
Epidemiological studies have long suggested a connection between vitamin D deficiency and MS risk. Vitamin D is known to have immunomodulatory effects, helping to regulate immune function and reduce inflammation. Low vitamin D levels have been associated with increased disease activity, relapse rates, and lesion development in MS patients.
However, clinical trials evaluating vitamin D supplementation as a treatment for MS have produced mixed results. Many of these studies have examined vitamin D as an add-on therapy to interferon beta, rather than as a standalone treatment. The new French study aimed to fill this gap by investigating the efficacy of high-dose vitamin D as a monotherapy in recent CIS cases.
The D-Lay MS Trial: High-Dose Vitamin D vs. Placebo
Study Design
The D-Lay MS randomized clinical trial was a double-blind, placebo-controlled study designed to assess whether high-dose cholecalciferol (100,000 IU every two weeks) could reduce disease activity in patients with early MS or CIS. The study included 316 participants aged 18–55 who had experienced CIS within the previous 90 days, had serum vitamin D levels below 100 nmol/L, and exhibited MRI findings consistent with early MS (either dissemination in space or at least two lesions with positive oligoclonal bands).
Participants were randomly assigned to receive either:
- 100,000 IU of oral cholecalciferol (vitamin D3) every two weeks (n=163)
- A matching placebo (n=153)
The trial lasted 24 months, with the primary outcome being disease activity, defined as the first relapse or the appearance of new or contrast-enhancing MRI lesions.
Key Findings
The results demonstrated a significant reduction in disease activity among patients receiving high-dose vitamin D compared to those in the placebo group.
- 60.3% of patients in the vitamin D group showed disease activity versus 74.1% in the placebo group.
- The median time to disease activity was longer in the vitamin D group (432 days vs. 224 days in the placebo group).
- Vitamin D was associated with reduced MRI activity:
- 57.1% of patients in the vitamin D group had overall MRI activity versus 65.3% in the placebo group (Hazard Ratio [HR], 0.71).
- 46.2% developed new or enlarging T2 lesions versus 59.2% in the placebo group (HR, 0.61).
- Only 18.6% had contrast-enhancing lesions versus 34.0% in the placebo group (HR, 0.47).
These findings strongly suggest that high-dose vitamin D supplementation reduces MS disease activity and may delay progression in high-risk individuals.
Potential Implications for MS Treatment
A Cost-Effective and Accessible Treatment
One of the most significant aspects of this study is that vitamin D is an inexpensive and widely available supplement. Unlike conventional MS treatments, such as disease-modifying therapies (DMTs), which can be costly and may have significant side effects, vitamin D is well-tolerated and requires minimal monitoring.
For patients in low-resource settings where access to DMTs is limited, high-dose vitamin D could serve as a viable first-line intervention to slow disease progression. Moreover, given the low risk of adverse effects observed in the study, vitamin D may be a safe complementary therapy alongside existing MS treatments.
Future Research and Clinical Applications
The researchers behind the D-Lay MS trial emphasize the need for further studies to optimize dosing strategies and investigate the potential benefits of pulse high-dose vitamin D therapy as an add-on treatment to existing DMTs.
Additionally, targeting patients with severe vitamin D deficiency could yield even greater benefits. Future trials could explore:
- Personalized vitamin D supplementation based on baseline serum levels.
- Combination therapies integrating vitamin D with established MS treatments.
- Long-term outcomes to assess whether sustained high-dose vitamin D supplementation influences disability progression.
Conclusion
The findings from this study represent a major step forward in MS research, reinforcing the critical role of vitamin D in modulating disease activity. High-dose cholecalciferol (100,000 IU every two weeks) significantly reduced relapse rates and MRI lesion development, providing a promising, low-cost intervention for patients with early MS or CIS.
While more research is needed to refine optimal dosing strategies and explore vitamin D’s potential in combination therapies, this study underscores the importance of early intervention and proactive management in MS. For patients and clinicians, high-dose vitamin D supplementation offers a safe, accessible, and effective strategy to potentially delay disease progression and improve long-term outcomes in multiple sclerosis.
As research continues, vitamin D could become an essential component of MS management, providing hope for millions worldwide affected by this debilitating disease.
Reference: Eric Thouvenot et al, High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis, JAMA (2025). DOI: 10.1001/jama.2025.1604