Exploring the Impact of Vitamin D on Brain Atrophy Progression in MS Patients

Recent research presents a more nuanced view of vitamin D supplementation’s role in mitigating brain atrophy and disease progression in multiple sclerosis (MS). While earlier observational studies hinted at potential neuroprotective effects, the latest randomized trials reveal a more complex and context-dependent picture.

A 2025 study published in JAMA evaluated the impact of high-dose vitamin D₃ (100,000 IU biweekly) in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS). Over 24 months, participants who received supplementation demonstrated a statistically significant reduction in disease activity, including fewer relapses and MRI-detected lesions, compared to those in the placebo group. These findings suggest that early intervention with high-dose vitamin D may offer neuroprotective benefits during the initial phase of the disease.

In contrast, the VIDAMS trial (Vitamin D to Ameliorate MS), a randomized controlled study completed in 2023, assessed the effects of daily high-dose vitamin D₃ (5,000 IU) alongside standard disease-modifying therapy in established RRMS over a 96-week period. The trial found no significant differences in MRI lesion burden, relapse rates, or disability progression between high- and low-dose groups, indicating limited additional benefit of supplementation in patients already undergoing standard treatment.

Further complicating the clinical picture, a 2024 meta-analysis published in Multiple Sclerosis and Related Disorders reviewed nine randomized trials involving a total of 867 MS patients. The analysis concluded that high-dose vitamin D supplementation did not significantly impact clinical outcomes such as relapse frequency, Expanded Disability Status Scale (EDSS) scores, or the progression of brain lesions on MRI. These findings highlight the inconsistency of response and underscore the importance of individualized treatment planning.

The divergent outcomes of these trials may be influenced by several factors, including baseline vitamin D status, genetic polymorphisms in the vitamin D receptor, and the timing of intervention relative to disease onset. While the immunomodulatory properties of vitamin D are well established—namely its role in downregulating proinflammatory cytokines and promoting regulatory T cell function—these biological effects may not uniformly translate into clinical or radiological improvements, especially in later stages of MS.

For clinicians, this evolving evidence supports a more targeted approach. Monitoring serum 25-hydroxyvitamin D levels remains prudent, particularly in patients with low baseline levels or those in early stages of disease. Supplementation may be most effective as a preventive or adjunctive measure in CIS or early RRMS, rather than as a primary intervention in longstanding disease.

In conclusion, vitamin D supplementation continues to be a topic of active research in MS care. While promising results have emerged for early disease stages, high-dose supplementation has shown limited benefits in more advanced cases. Until more definitive evidence emerges, incorporating vitamin D level assessments into routine MS care—as part of a comprehensive, personalized strategy—may help identify patients who could benefit most from intervention.