BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with a multifactorial aetiology, including vitamin D levels, that have been linked to disease activity. Given the inconsistent findings on the vitamin D supplementation in MS, we aimed to analyse the connection between 25(OH)D levels and disease activity and to identify an optimal level of 25(OH)D in MS utilizing our real-world database. METHODS: This study utilized a 10-year dataset from the Czech national multiple sclerosis registry (ReMuS), encompassing 1,861 adult MS patients. Patients had a minimum of one year of follow-up, with subgroup analysis for those with at least five years. A mixed-effects model tested the impact of 25(OH)D and cholesterol levels on relapse incidence. Subgroup analysis categorised patients by average 25(OH)D levels and analysed relapse incidence using the Kruskal-Wallis test and Kaplan-Meier survival analysis. RESULTS: Higher serum 25(OH)D levels and age correlated with reduced relapse risk (p < 0.001 for both). Each 10 nmol/L increase in 25(OH)D levels associated with a 6.7% decrease in relapse risk (p < 0.001). Cholesterol levels and sex did not significantly affect relapse rate. Subgroup analysis revealed that patients with 25(OH)D levels above 100 nmol/L had significantly fewer relapses compared to those with levels below 75 nmol/L. CONCLUSION: Our findings suggest that optimising 25(OH)D levels may reduce the risk of relapse in pwMS. Causation cannot be confirmed. Results highlight the importance of personalized vitamin D supplementation strategies and support the potential benefit of maintaining optimal serum 25(OH)D levels in MS management.

Department of Clinical Biochemistry and Haematology KZ a s Hospital Teplice Teplice Czechia

Department of Economic Statistics Prague University of Economics and Business Prague Czechia

Department of Neurology Centre of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czechia

Department of Neurology Faculty of Medicine and University Hospital in Pilsen Charles University Pilsen Czechia

Department of Neurology KZ a s Hospital Teplice Duchcovska 53 Teplice 415 01 Czechia

ReMuS The Czech Republic Multiple Sclerosis Patient Registry Prague Czechia

Zobrazit více v PubMed

Walton C, King R, Rechtman L (2020) Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler J 26:1816–1821. 10.1177/1352458520970841 PubMed DOI PMC

Simpson S, Wang W, Otahal P et al (2019) Latitude continues to be significantly associated with the prevalence of multiple sclerosis: an updated meta-analysis. J Neurol Neurosurg Psychiatry 90:1193–1200. 10.1136/jnnp-2018-320189 PubMed DOI

Sintzel MB, Rametta M, Reder AT (2018) Vitamin D and multiple sclerosis: a comprehensive review. Neurol Ther 7:59–85. 10.1007/s40120-017-0086-4 PubMed DOI PMC

Pender MP (2012) <article-title update="added">CD8+ T-cell deficiency, Epstein-Barr virus infection, vitamin D deficiency, and steps to autoimmunity: a unifying hypothesis. Autoimmune Dis 2012:189096. 10.1155/2012/189096 PubMed DOI PMC

Houen G, Trier NH (2021) Epstein-Barr virus and systemic autoimmune diseases. Front Immunol 11:587380. 10.3389/fimmu.2020.587380 PubMed DOI PMC

Lorincz B, Jury EC, Vrablik M (2022) The role of cholesterol metabolism in multiple sclerosis: from molecular pathophysiology to radiological and clinical disease activity. Autoimmun Rev 21:103088. 10.1016/j.autrev.2022.103088 PubMed DOI

Laursen JH, Søndergaard HB, Sørensen PS (2016) Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab. Mult Scler Relat Disord 10:169–173. 10.1016/j.msard.2016.10.005 PubMed DOI

Mowry EM, Krupp LB, Milazzo M et al (2010) <article-title update="added">Vitamin D status is associated with relapse rate in pediatric‐onset multiple sclerosis. Ann Neurol 67:618–624. 10.1002/ana.21972 PubMed DOI

Mowry EM, Waubant E, McCulloch CE et al (2012) Vitamin D status predicts new brain magnetic resonance imaging activity in multiple sclerosis. Ann Neurol 72:234–240. 10.1002/ana.23591 PubMed DOI PMC

Muris AH, Smolders J, Rolf L et al (2016) Vitamin D status does not affect disability progression of patients with multiple sclerosis over three-year follow-up. PLoS One. 10.1371/journal.pone.0156122 PubMed DOI PMC

Runia TF, Hop WCJ, De Rijke YB et al (2012) Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology 79:261–266. 10.1212/WNL.0b013e31825fdec7 PubMed DOI

Simpson S, Taylor B, Blizzard L et al (2010) Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 68:193–203. 10.1002/ana.22043 PubMed DOI

Butzkueven H, Ponsonby AL, Stein MS et al (2024) Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome. Brain 147:1206–1215. 10.1093/brain/awad409 PubMed DOI PMC

Cassard SD, Fitzgerald KC, Qian P et al (2023) High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial. EClinMed 59:101957. 10.1016/j.eclinm.2023.101957 PubMed DOI PMC

Derakhshandi H, Etemadifar M, Feizi A et al (2013) Preventive effect of vitamin D3 supplementation on conversion of optic neuritis to clinically definite multiple sclerosis: a double-blind, randomized, placebo-controlled pilot clinical trial. Acta Neurol Belg 113:257–263. 10.1007/s13760-012-0166-2 PubMed DOI

Hanaei S, Sahraian MA, Mohammadifar M et al (2021) Effect of vitamin D supplements on relapse rate and expanded disability status scale (EDSS) in multiple sclerosis (MS): a systematic review and meta-analysis. Int J Prev Med 12:42. 10.4103/ijpvm.ijpvm_208_20 PubMed DOI PMC

Sîrbe C, Rednic S, Grama A, Pop TL (2022) An update on the effects of vitamin D on the immune system and autoimmune diseases. Int J Mol Sci 23:9784. 10.3390/ijms23179784 PubMed DOI PMC

Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281. 10.1056/nejmra070553 PubMed DOI

Spiro A, Buttriss JL (2014) Vitamin D: an overview of vitamin D status and intake in Europe. Nutr Bull 39:322–350. 10.1111/nbu.12108 PubMed DOI PMC

Stastna D, Drahota J, Lauer M et al (2024) The Czech National MS Registry (ReMuS): data trends in multiple sclerosis patients whose first disease-modifying therapies were initiated from 2013 to 2021. Biomed Pap 168:262–270. 10.5507/bp.2023.015 PubMed DOI

Carter GD, Berry J, Cavalier E et al (2020) Biotin supplementation causes erroneous elevations of results in some commercial serum 25-hydroxyvitamin D (25OHD) assays. J Steroid Biochem Mol Biol 200:105639. 10.1016/j.jsbmb.2020.105639 PubMed DOI

Mansoor F, Kumar V, Kumar S et al (2021) Association between serum vitamin D levels and frequency of relapses in patients with multiple sclerosis. Cureus 13. 10.7759/cureus.14383 PubMed PMC

Fitzgerald KC, Munger KL, Köchert K et al (2015) Association of vitamin D levels with multiple sclerosis activity and progression in patients receiving interferon beta-1b. JAMA Neurol 72:1458–1465. 10.1001/jamaneurol.2015.2742 PubMed DOI

Anna AR, Suzan AR, Helmii M (2013) The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. J Rheumatol 40:265–272. 10.3899/jrheum.111594 PubMed DOI

Tang J, Shan S, Li F, Yun P (2023) Effects of vitamin D supplementation on autoantibodies and thyroid function in patients with Hashimoto’s thyroiditis: a systematic review and meta-analysis. Medicine. 10.1097/md.0000000000036759 PubMed DOI PMC