Vitamin D Status and Its Impact on Disease Activity in Pediatric-Onset Multiple Sclerosis: A Comprehensive Narrative Review

Pediatric-onset multiple sclerosis (POMS), defined as the onset of multiple sclerosis (MS) before the age of 18 years, accounts for approximately 3–5% of all MS cases and is characterized by a markedly inflammatory disease course with high relapse rates and earlier accrual of cognitive and physical disability than adult-onset disease [22–25]. Among the modifiable environmental risk factors implicated in MS susceptibility and activity, vitamin D has attracted sustained scientific attention [3,4,48]. This narrative review synthesizes current evidence on the role of vitamin D in POMS, integrating epidemiological, immunological, genetic (Mendelian randomization), observational and interventional data. Mendelian randomization analyses provide robust evidence for a causal relationship between genetically lowered 25-hydroxyvitamin D [25(OH)D] concentrations and increased POMS susceptibility (OR 0.72, 95% CI 0.55–0.94, p = 0.02 for higher genetically predicted vitamin D) [1]. Observational studies consistently report that each 10 ng/mL (25 nmol/L) increase in serum 25(OH)D is associated with an approximately 34% reduction in subsequent relapse rate in POMS [2], and with comparable reductions in new T2 and gadolinium-enhancing magnetic resonance imaging (MRI) lesions in mixed adult-pediatric cohorts [17,19]. Despite biologically plausible immunomodulatory and remyelinating effects demonstrated in experimental models [36–39], randomized controlled trials of vitamin D supplementation have predominantly failed to meet primary clinical endpoints, with positive signals largely confined to secondary MRI outcomes [5,6,41–43]. Pediatric-specific randomized data remain scarce. Current expert consensus supports avoidance of insufficiency (25(OH)D < 20 ng/mL) and targeting serum levels of 30–50 ng/mL (75–125 nmol/L) using daily doses up to 2000–4000 IU of cholecalciferol, with biochemical monitoring [3,27,28,50]. Future research priorities include adequately powered pediatric trials, harmonized dosing protocols, and long-term safety surveillance.