Serum 25-Hydroxyvitamin D and Neurological Disability in Multiple Sclerosis: A Cross-Sectional Study from the Mediterranean Epidemiological Frontier

Background Vitamin D is widely studied in multiple sclerosis (MS), yet its clinical relevance for disability and relapse activity remains uncertain, especially in underrepresented populations. Objective To examine whether serum 25-hydroxyvitamin D [25(OH)D] levels are associated with disability or relapse activity in a multicenter cohort of Libyan adults with MS. Methods : In a cohort of adults with MS (n = 369), the exposure was 25(OH)D scaled per 10 ng/mL (vitD10). Primary outcomes were the continuous Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR). We prespecified equivalence margins of ± 0.30 EDSS points and ± 0.25 ARR, fit covariate‑adjusted models with HC3 robust standard errors, and conducted two one‑sided tests (TOST). Results For continuous EDSS, estimates were small and the 90% confidence interval lay within the ± 0.30 margin, supporting equivalence; ARR results were similar within ± 0.25. There was little evidence of non‑linearity and measurement‑error sensitivity (SIMEX) had negligible impact. An exploratory threshold analysis at EDSS ≥ 4 suggested a small, cut‑point–dependent increase in odds (OR 1.47, 95% CI 1.01–2.15) that warrants prospective replication. Conclusions In these cross‑sectional data, differences in 25(OH)D were unlikely to correspond to clinically meaningful differences in disability on the continuous scale. Correct vitamin D deficiency for general health and consider potential links with inflammatory activity, but avoid inferring large differences in established disability from a single measurement. Prospective studies with season, supplementation, and treatment information are needed to test effect modification and trajectories.