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Multiple sclerosis
Original research
Vitamin D affects the risk of disease activity in multiple sclerosis
  1. Antonino Giordano1,2,3,
  2. Ferdinando Clarelli1,
  3. Béatrice Pignolet4,5,
  4. Elisabetta Mascia1,
  5. Melissa Sorosina1,
  6. Kaalindi Misra1,
  7. Laura Ferrè1,3,
  8. Florence Bucciarelli4,
  9. Ali Manouchehrinia6,
  10. Lucia Moiola3,
  11. Vittorio Martinelli3,
  12. Maria A Rocca1,2,3,
  13. Roland Liblau4,7,
  14. Massimo Filippi1,2,3,
  15. Federica Esposito1,3
  1. 1 Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
  2. 2 Università Vita Salute San Raffaele, Milano, Italy
  3. 3 Department of Neurology and MS Center, IRCCS Ospedale San Raffaele, Milan, Italy
  4. 4 Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, Toulouse, France
  5. 5 Neurosciences Department, Toulouse University Hospital, Toulouse, France
  6. 6 Neuroimmunology Unit, Karolinska Institute, Stockholm, Sweden
  7. 7 Department of Immunology, Toulouse University Hospitals, Toulouse, France
  1. Correspondence to Dr Federica Esposito; esposito.federica{at}hsr.it

Abstract

Background Vitamin D (VitD) affects the risk of multiple sclerosis (MS), but the impact on disease activity is controversial. We assessed whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status at 2 years from disease-modifying treatment (DMT) start, and whether this association is causal or the result of confounding factors. Furthermore, we explored if a genetic predisposition to higher VitD levels affects the risk of disease activity.

Methods 230 untreated relapsing-remitting MS patients underwent serum 25-OH-vitamin-D measurement, and the association between seasonally adjusted VitD and disease activity was tested. Modelling a Polygenic Risk Score from a Genome-Wide Association Study on ~400 000 individuals, we studied the impact of genetic predisposition to higher VitD on the NEDA-3 status in 1408 independent MS patients. Two-sample Mendelian randomisation (MR) was used to assess causality.

Results Lower baseline VitD was associated with decreased probability of NEDA-3 at 2 years (p=0.019). Particularly, VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36, 95% CI 1.30 to 3.88, p=0.0037). Genetic predisposition to higher VitD levels was associated with delayed age at MS onset (p=0.018) and with a higher probability of NEDA-3 status (p=0.034). MR confirmed causality between VitD and the risk of disease activity (p=0.041).

Conclusions VitD levels before DMT start affect the risk of disease activity in MS. Genetic predisposition to higher VitD levels confers a lower risk of disease activity and is associated with delayed MS onset. Our work prompts future prospective studies regarding VitD supplementation and lifestyle interventions to hamper disease activity in MS.

  • MULTIPLE SCLEROSIS
  • NEUROIMMUNOLOGY

Data availability statement

Data are available on reasonable request. Anonymized data of the analyses presented in this study are available upon reasonable request from the corresponding author.

https://doi.org/10.1136/jnnp-2024-334062

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    Data availability statement

    Data are available on reasonable request. Anonymized data of the analyses presented in this study are available upon reasonable request from the corresponding author.

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    Footnotes

    • Contributors Study concept: AG, FC, MS and FE. Data acquisition and analysis: AG, FC, BP, EM, MS, KM, LF, FB, MAR and FE. Interpretation of data: AG, FC, AM, VM, RL and FE. Statistical analysis: AG and FC. Drafting of the manuscript: AG. Revision of the manuscript: all authors. Guarantor of the study: FE.

    • Funding The present study is part of the FindingMS project, which was supported by ERA PerMed-JTC2018 (cofunded by the European Commission).

    • Disclaimer The funding source had no role in design and conduction of the study, or in the analysis and interpretation of the results.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.