Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis

Journal of Neurology volume 262, pages2713–2721(2015)Cite this article

Abstract

Observational studies have suggested that vitamin D may reduce inflammation in relapsing-remitting multiple sclerosis (RRMS), but this has not been clearly confirmed in randomized controlled trials. To further explore the possible anti-inflammatory effects of vitamin D in RRMS, we examined the effect of high-dose oral vitamin D3 on eleven markers of systemic inflammation in 68 RRMS patients enrolled in a double-blinded randomized placebo-controlled trial of vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Serum inflammation markers and 25-hydroxyvitamin D (25(OH)D) were measured at baseline and week 96, and no restrictions were set on additional standard immunomodulatory treatment for RRMS. The mean 25(OH)D level rose from 56 ± 29 to 123 ± 34 nmol/L among patients receiving vitamin D3 supplementation, whereas only a minor increase from 57 ± 22 to 63 ± 24 nmol/L was seen in the placebo group. However, no significant differences appeared between the vitamin D group and the placebo group for any of the inflammation markers. Patients on immunomodulatory therapy had significantly higher levels of interleukin-1 receptor antagonist and chemokine (C–X–C motif) ligand 16 than patients without immunomodulatory treatment, but there were no clear synergistic effects between immunomodulatory therapy and vitamin D3 supplementation on any of the inflammation markers. The rise in 25(OH)D levels after vitamin D3 supplementation was unaffected by immunomodulatory treatment. We conclude that in this study of RRMS patients, high-dose oral vitamin D3 supplementation prominently increased serum 25(OH)D levels without affecting markers of systemic inflammation, while a more anti-inflammatory phenotype was found among patients on immunomodulatory treatment.

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Acknowledgments

This work was supported by the Southern and Eastern Norway Regional Health Authority (Grant Number 2013006).

Author information

Affiliations

  1. Department of Neurology, Akershus University Hospital, Lørenskog, Norway

    Egil Røsjø & Trygve Holmøy

  2. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Egil Røsjø, Jūratė Šaltytė Benth, Annika E. Michelsen, Pål Aukrust, Thor Ueland & Trygve Holmøy

  3. Department of Neurology, University Hospital of North Norway, Tromsø, Norway

    Linn H. Steffensen & Margitta T. Kampman

  4. Department of Clinical Medicine, University of Tromsø, Tromsø, Norway

    Linn H. Steffensen

  5. Department of Health and Care Sciences, University of Tromsø, Tromsø, Norway

    Lone Jørgensen

  6. Department of Clinical Therapeutic Services, University Hospital of North Norway, Tromsø, Norway

    Lone Jørgensen

  7. Helse Sør-Øst Health Services Research Centre, Akershus University Hospital, Lørenskog, Norway

    Jonas C. Lindstrøm & Jūratė Šaltytė Benth

  8. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway

    Annika E. Michelsen, Pål Aukrust & Thor Ueland

  9. Section for Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway

    Pål Aukrust

  10. KG Jebsen Inflammatory Research Center, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Pål Aukrust

  11. KG Jebsen MS Research Centre, Department of Clinical Medicine, University of Bergen, Bergen, Norway

    Øivind Torkildsen

  12. Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital, Bergen, Norway

    Øivind Torkildsen

Authors
  1. Egil Røsjø
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  2. Linn H. Steffensen
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  3. Lone Jørgensen
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  4. Jonas C. Lindstrøm
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  5. Jūratė Šaltytė Benth
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  6. Annika E. Michelsen
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  7. Pål Aukrust
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  8. Thor Ueland
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  9. Margitta T. Kampman
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  10. Øivind Torkildsen
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  11. Trygve Holmøy
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Corresponding author

Correspondence to Egil Røsjø.

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Ethical standards

The Regional Committee for Medical and Health Research Ethics in Northern Norway approved the study protocol and the study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was provided before patient enrollment.

Conflicts of interest

E. Røsjø has received honoraria for participation in a clinical trial from Merck Serono. Ø. Torkildsen has served on a scientific advisory board for Biogen Idec, and received speaker honoraria and travel grants from Genzyme, Merck Serono, Novartis and Biogen Idec. T. Holmøy has received speaker honoraria and travel support from Sanofi Aventis, Biogen Idec, Bayer HealthCare Pharmaceuticals, Novartis, Genzyme and Merck Serono. L. H. Steffensen, L. Jørgensen, J. C. Lindstrøm, J. Šaltytė Benth, A. E. Michelsen, P. Aukrust, T. Ueland and M. T. Kampman report no disclosures.

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Røsjø, E., Steffensen, L.H., Jørgensen, L. et al. Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis. J Neurol 262, 2713–2721 (2015). https://doi.org/10.1007/s00415-015-7902-5

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Keywords

  • Multiple sclerosis
  • Vitamin D
  • Systemic inflammation