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

Abstract

Multiple sclerosis (MS) presents with optic neuritis (ON) in 20 % of cases and 50 % of ON patients develop MS within 15 years. In this study, we evaluated the preventive effects of vitamin D3 administration on the conversion of ON to MS (primary outcome) and on the MRI lesions (secondary outcome) of ON patients with low serum 25 (OH) D levels. Thirty ON patients (15 in each of 2 groups, aged 20–40 years) with serum 25 (OH) D levels of less than 30 ng/ml were enrolled in a double blind, randomized, parallel-group trial. The treatment group (cases) received 50,000 IU of vitamin D3 weekly for 12 months and the control group (controls) received a placebo weekly for 12 months. Finally, the subsequent relapse rate and changes in MRI plaques were compared between the two groups. Risk reduction was 68.4 % for the primary outcome in the treatment group (relative risk = 0.316, p = 0.007). After 12 months, patients in the treatment group had a significantly lower incidence rate of cortical, juxtacortical, corpus callosal, new T2, new gadolinium-enhancing lesions and black holes. The mean number of total plaques showed a marginally significant decrease in the group receiving vitamin D3 supplementation as compared with the placebo group (p = 0.092). Administration of vitamin D3 supplements to ON patients with low serum vitamin 25 (OH) D levels may delay the onset of a second clinical attack and the subsequent conversion to MS.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. 1.

    Dalton CM, Brex PA, Miszkiel KA, Hickman SJ, MacManus DG, Plant GT, Thompson AJ, Miller DH (2002) Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis. Ann Neurol 52(1):47–53

    PubMed  Article  Google Scholar 

  2. 2.

    Voss E, Raab P, Trebst C, Stangel M (2011) Clinical approach to optic neuritis: pitfalls, red flags and differential diagnosis. Ther Adv Neurol Disord 4(2):123–134

    PubMed  Article  Google Scholar 

  3. 3.

    Hickman SJ, Dalton CM, Miller DH, Plant GT (2002) Management of acute optic neuritis. Lancet 360(9349):1953–1962

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Nilsson P, Larsson EM, Maly-Sundgren P, Perfekt R, Sandberg-Wollheim M (2005) Predicting the outcome of optic neuritis: evaluation of risk factors after 30 years of follow-up. J Neurol 252(4):396–402

    PubMed  Article  Google Scholar 

  5. 5.

    No authors listed (1977) The 5 year risk of MS after optic neuritis. Experience of the optic neuritis treatment trial. Optic Neuritis Study Group. Neurology 49(5): 1404–1413

    Google Scholar 

  6. 6.

    Hanwell HEC, Banwell B (2011) Assessment of evidence for a protective role of vitamin D in multiple sclerosis. Biochim et Biophys Acta (BBA)-Mol Basis Dis 1812(2):202–212

    Article  CAS  Google Scholar 

  7. 7.

    Kimball S, Ursell M, O’Connor P, Vieth R (2007) Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 86(3):645

    PubMed  CAS  Google Scholar 

  8. 8.

    Burton J, Kimball S, Vieth R, Bar-Or A, Dosch H, Cheung R et al (2010) A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 74(23):1852

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Etemadifar M, Abtahi SH, Razmjoo H, Abtahi MA, Dehghani A, Salari M, Maghzi AH, Akbari M (2012) 25-Hydroxyvitamin D concentrations in patients with optic neuritis as a clinically isolated syndrome and healthy controls. Int J Prev Med 3(5):313–317

    PubMed  Google Scholar 

  10. 10.

    Wingerchuk DM, Lesaux J, Rice GP, Kremenchutzky M, Ebers GC (2005) A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 76(9):1294–1296

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘‘McDonald Criteria’’. Ann Neurol 58(6):840–846

    PubMed  Article  Google Scholar 

  12. 12.

    Smolders J, Damoiseaux J, Menheere P, Hupperts R (2008) Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol 194(1–2):7–17

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Mahon B, Gordon S, Cruz J, Cosman F, Cantorna M (2003) Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 134(1–2):128–132

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Holdeman NR, Nguyen T, Tang RA (2012) Demyelinating optic neuritis presenting as a clinically isolated syndrome. Optometry 83(1):9–18

    PubMed  Article  Google Scholar 

  15. 15.

    Faridar A, Eskandari G, Sahraian MA, Minagar A, Azimi A (2012) Vitamin D and multiple sclerosis: a critical review and recommendations on treatment. Acta Neurol Belg (Epub ahead of print)

  16. 16.

    Kirbas A, Kirbas S, Anlar O, Turkyilmaz AK, Cure MC, Efe H (2012) Investigation of the relationship between vitamin D and bone mineral density in newly diagnosed multiple sclerosis. Acta Neurol Belg (Epub ahead of print)

  17. 17.

    Munger K, Zhang S, O’Reilly E, Hernan M, Olek M, Willett W et al (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62(1):60

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Munger K, Levin L, Hollis B, Howard N, Ascherio A (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296(23):2832

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Soilu-Hanninen M, Airas L, Mononen I, Heikkila A, Viljanen M, Hanninen A (2005) 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler 11(3):266

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Etemadifar M, Abtahi SH (2012) Multiple sclerosis in Isfahan, Iran: past, present and future. Int J Prev Med 3(5):301–302

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors are very grateful to the patients and their relatives for their collaboration with this research. This survey was conducted by the cooperation of Isfahan University of Medical Sciences (IUMS) and Isfahan Multiple Sclerosis Society (IMSS). The project was supported by IUMS [Grant number: 291041] and SHARNOS research Co. (Knowledge of vision and motion). Also, a specific research grant has been received from CinnaGen Inc. The results of this study are dedicated to the memory of Dr. Afsane Khandan (Iranian internist) who devoted her precious life to knowledge, health development, and, medical research.

Conflict of interest

The authors have no proprietary interest in the materials presented herein.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Seyed-Hossein Abtahi.

Additional information

Clinical trial registration number: IRCT201205319919N1.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Derakhshandi, H., Etemadifar, M., Feizi, A. et al. 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 (2013). https://doi.org/10.1007/s13760-012-0166-2

Download citation

Keywords

  • Multiple sclerosis
  • Optic neuritis
  • Vitamin D3
  • 25 (OH) D
  • Clinical trial
  • Isfahan, Iran