Does Vitamin D Supplementation Slow Brain Volume Loss in Multiple Sclerosis? A 4-Year Observational Study

Background and Aims: Vitamin D is currently well regarded for its pleiotropic effects on the immune system, stimulating an anti-inflammatory response and enhancing immune tolerance. Vitamin D deficiency is an established risk factor for multiple sclerosis (MS). Additionally, lower vitamin D serum levels are associated with worse disease outcomes. However, current randomized clinical trials provide conflicting evidence about the beneficial role of vitamin D on disease progression. Most studies have evaluated the effect of vitamin D supplementation on clinical and radiological activity, yet very few have examined the impact on brain atrophy. Methods: A 4-year observational, non-interventional study design was applied to evaluate the association between vitamin D supplementation and disease progression. Altogether, 132 relapsing&ndash:remitting multiple sclerosis patients were enrolled in the study (97 subjects in the group with vitamin D supplementation and 35 subjects in the group without supplementation). The analyzed groups were similar in terms of age, body mass index, sun exposure, comorbidities, nicotinism, duration of the disease, and current treatment. The number of relapses, Expanded Disability Status Scale assessments, and the number of new/enlarged T2-weighted lesions and gadolinium-enhancing lesions in magnetic resonance imagining analyses, as well as 25-hydroxyvitamin D serum levels, were assessed every 12 months of a 4-year follow-up, whereas brain atrophy was assessed at the baseline and after 36 months using two-dimensional measurements. Results: After 36 months, a significant increase in atrophy was observed in both groups: however, patients without vitamin D supplementation had a significantly higher increase in intercaudate distance, third ventricle width, and bicaudate ratio after 36 months of observation (p &lt: 0.05). Vitamin D supplementation among the studied group did not affect other disease activity outcomes. Conclusions: Our study revealed an observed association between vitamin D supplementation and reduced brain atrophy in patients with MS. Randomized controlled trials are required to establish the impact of vitamin D supplementation on brain atrophy progression.