VITAMIN D STATUS AND ITS IMPACT ON DISEASE ACTIVITY IN PEDIATRIC-ONSET MULTIPLE SCLEROSIS: A COMPREHENSIVE NARRATIVE REVIEW

Justyna Zabicka; Kinga Lichtarska; Michał Gutowski; Cezary Orzechowski; Sviatlana Filitaryna; Monika Kałwak; Magda Marciniak; Aleksandra Foryś; Monika Wiatr; Wojciech Wojas; Patryk Dłubis

doi:10.31435/ijitss.3(51).2026.6487

Authors

Justyna Zabicka Maria Sklodowska-Curie Warsaw Higher School, Poland https://orcid.org/0009-0002-0612-0938
Kinga Lichtarska Lazarski University, Poland https://orcid.org/0009-0004-9319-8323
Michał Gutowski Medical University of Warsaw, Poland https://orcid.org/0009-0006-7865-8736
Cezary Orzechowski Medical University of Warsaw, Poland https://orcid.org/0009-0008-1265-311X
Sviatlana Filitaryna Specialist Hospital of dr. Tytus Chałubiński in Radom, Poland https://orcid.org/0009-0003-8897-0254
Monika Kałwak Independent Public Healthcare Facility of the Ministry of Internal Affairs and Administration of Sergeant Grzegorz Załoga in Katowice, Poland https://orcid.org/0009-0000-4244-3086
Magda Marciniak Specialist Hospital of dr. Tytus Chałubiński in Radom, Poland https://orcid.org/0009-0005-4016-6536
Aleksandra Foryś Provincial Specialist Hospital No. 5 of St. Barbara in Sosnowiec, Poland https://orcid.org/0009-0008-7983-1443
Monika Wiatr Specialist Hospital of dr. Tytus Chałubiński in Radom, Poland https://orcid.org/0009-0000-2038-3174
Wojciech Wojas Maria Sklodowska-Curie Warsaw Higher School, Poland https://orcid.org/0009-0007-4295-0599
Patryk Dłubis Municipal Hospital in Gliwice LLC, Poland https://orcid.org/0009-0009-2952-6675

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6487

Keywords:

Pediatric-Onset Multiple Sclerosis; Vitamin D; 25-Hydroxyvitamin D; Cholecalciferol; Relapse Rate; Magnetic Resonance Imaging; Immunomodulation; Mendelian Randomization

Abstract

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.

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