Acta Neurologica Belgica

, Volume 112, Issue 4, pp 327–333 | Cite as

Vitamin D and multiple sclerosis: a critical review and recommendations on treatment

  • Alireza Faridar
  • Ghazaleh Eskandari
  • Mohammad Ali Sahraian
  • Alireza Minagar
  • Amirreza Azimi
Review Article

Abstract

Multiple sclerosis (MS) is an immune-mediated and degenerative disease of nervous system, which affects mostly young adults. Vitamin D deficiency is a well-known environmental risk factor for MS and is considerable in terms of immediate clinical implications. In addition to its classical action on regulation of bone homeostasis, vitamin D may have a potent impact on cytokine profiles and neuro-inflammation. Given the immunomodulatory effects of vitamin D and its high rate of deficiency in MS patients, prescribing vitamin D is a remarkable issue in MS. The results from several experimental and clinical studies indicate that vitamin D supplementation may ameliorate the inflammation during the relapse phase and attenuate disease progression. We present the experimental and clinical studies, which assessed the effects of vitamin D on the pathophysiology, prevalence and management of MS. The authors also discuss current recommendations on prescription of this vitamin to MS patients.

Keywords

Vitamin D Multiple sclerosis Demyelinating Prevention 

References

  1. 1.
    Munger K, Levin L, Hollis B, Howard N, Ascherio A (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296(23):2832PubMedCrossRefGoogle Scholar
  2. 2.
    Giovannoni G (1997) The immunopathogenesis of multiple sclerosis. Baillière’s Clin Neurol 6(3):387Google Scholar
  3. 3.
    Ascherio A, Munger K (eds) (2008) Epidemiology of multiple sclerosis: from risk factors to prevention. Thieme-Stratton Inc., New YorkGoogle Scholar
  4. 4.
    Ramagopalan SV, Ebers GC (2008) Genes for multiple sclerosis. The lancet 371(9609):283–285. doi:10.1016/S0140-6736(08)60145-2 Google Scholar
  5. 5.
    Irizar H, Muñoz-Culla M, Zuriarran O, Goyenechea E, Castillo-Triviño T, Prada A et al (2011) HLA-DRB1* 15:01 and multiple sclerosis: a female association? Multiple Scler JGoogle Scholar
  6. 6.
    Amirzargar A, Mytilineos J, Yousefipour A, Farjadian S, Scherer S, Opelz G et al (1998) HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian multiple sclerosis (MS) patients. Eur J Immunogenet 25(4):297–301PubMedCrossRefGoogle Scholar
  7. 7.
    Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L et al (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476(7359):214–219PubMedCrossRefGoogle Scholar
  8. 8.
    Handel A, Giovannoni G, Ebers G, Ramagopalan S (2010) Environmental factors and their timing in adult-onset multiple sclerosis. Nature Rev Neurol 6(3):156–166Google Scholar
  9. 9.
    Chaudhuri A (2005) Why we should offer routine vitamin D supplementation in pregnancy and childhood to prevent multiple sclerosis. Med Hypotheses 64(3):608–618PubMedCrossRefGoogle Scholar
  10. 10.
    Holick MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80(6):1678SPubMedGoogle Scholar
  11. 11.
    Arnson Y, Amital H, Shoenfeld Y (2007) Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 66(9):1137PubMedCrossRefGoogle Scholar
  12. 12.
    Cutolo M (2009) Vitamin D and autoimmune rheumatic diseases. Rheumatology 48(3):210PubMedCrossRefGoogle Scholar
  13. 13.
    Holick MF, Krane SM, Potts J (1998) Calcium, phosphorus, and bone metabolism: calcium-regulating hormones. Harrisons Princ Intern Med:2214–2226Google Scholar
  14. 14.
    Heaney RP (2008) Vitamin D criteria for safety and efficacy. Nutr Rev 66:S178–S181PubMedCrossRefGoogle Scholar
  15. 15.
    Zittermann A (2003) Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 89(05):552–572PubMedCrossRefGoogle Scholar
  16. 16.
    Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K et al (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117(4):503PubMedCrossRefGoogle Scholar
  17. 17.
    Hollis BW (2004) Editorial: the determination of circulating 25-hydroxyvitamin D: no easy task. J Clin Endocrinol Metab 89(7):3149PubMedCrossRefGoogle Scholar
  18. 18.
    Ross AC, Manson JAE, Abrams SA, Aloia JF, Brannon PM, Clinton SK et al (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96(1):53PubMedCrossRefGoogle Scholar
  19. 19.
    Staud R (2005) Vitamin D: more than just affecting calcium and bone. Curr Rheumatol Rep 7(5):356–364PubMedCrossRefGoogle Scholar
  20. 20.
    Phinney KW (2008) Development of a standard reference material for vitamin D in serum. Am J Clin Nutr 88(2):511SPubMedGoogle Scholar
  21. 21.
    Rafique I, Frederiksen J A (2010) complete literature survey: vitamin D and multiple sclerosis–what is clearly evident? Eur Neurol J 2(2):113–120Google Scholar
  22. 22.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al (2011) Evaluation, treatment, and prevention of vitamin d deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96(7):1911PubMedCrossRefGoogle Scholar
  23. 23.
    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):202–212Google Scholar
  24. 24.
    Penna G, Adorini L (2000) 1, 25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164(5):2405PubMedGoogle Scholar
  25. 25.
    Ponsonby AL, Lucas R, Mei IAF (2005) UVR, vitamin D and three autoimmune diseases—multiple sclerosis, type 1 diabetes, rheumatoid arthritis. Photochem Photobiol 81(6):1267–1275PubMedCrossRefGoogle Scholar
  26. 26.
    Lemire JM (1995) Immunomodulatory actions of 1, 25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol 53(1–6):599–602PubMedCrossRefGoogle Scholar
  27. 27.
    van Etten E, Gysemans C, Branisteanu D, Verstuyf A, Bouillon R, Overbergh L et al (2007) Novel insights in the immune function of the vitamin D system: synergism with interferon-beta. J Steroid Biochem Mol Biol 103(3–5):546–551PubMedCrossRefGoogle Scholar
  28. 28.
    van Halteren AGS, Tysma OM, van Etten E, Mathieu C, Roep BO (2004) 1 [alpha], 25-dihydroxyvitamin D3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis. J Autoimmun 23(3):233–239PubMedCrossRefGoogle Scholar
  29. 29.
    Mark BL, Carson JAS (2006) Vitamin D and autoimmune disease–implications for practice from the multiple sclerosis literature. J Am Diet Assoc 106(3):418–424PubMedCrossRefGoogle Scholar
  30. 30.
    Pierrot-Deseilligny C (2009) Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol 256(9):1468–1479PubMedCrossRefGoogle Scholar
  31. 31.
    Correale J, Ysrraelit M, Gaitán M (2009) Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132(5):1146PubMedCrossRefGoogle Scholar
  32. 32.
    Knippenberg S, Smolders J, Thewissen M, Peelen E, Tervaert JWC, Hupperts R et al (2011) Effect of vitamin D3 supplementation on peripheral B cell differentiation and isotype switching in patients with multiple sclerosis. Multiple Scler JGoogle Scholar
  33. 33.
    Smolders J, Peelen E, Thewissen M, Tervaert JWC, Menheere P, Hupperts R et al (2010) Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One 5(12):e15235PubMedCrossRefGoogle Scholar
  34. 34.
    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):128–132PubMedCrossRefGoogle Scholar
  35. 35.
    Ebers G, Sadovnick A (1993) The geographic distribution of multiple sclerosis: a review. Neuroepidemiology 12(1):1–5PubMedCrossRefGoogle Scholar
  36. 36.
    Acheson E, Bachrach C, Wright F (1960) Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation, and other variables. Acta Psychiatr Scand 35(S147):132–147Google Scholar
  37. 37.
    Smolders J (2011) Vitamin D and multiple sclerosis: correlation, causality, and controversyGoogle Scholar
  38. 38.
    Poppe AY, Wolfson C, Zhu B (2008) Prevalence of multiple sclerosis in Canada: a systematic review. Can J Neurol Sci 35(5):593–601PubMedGoogle Scholar
  39. 39.
    Grønlie SA, Myrvoll E, Hansen G, Grønning M, Mellgren SI (2000) Multiple sclerosis in North Norway, and first appearance in an indigenous population. J Neurol 247(2):129–133Google Scholar
  40. 40.
    Fernandes de Abreu DA, Landel V, Féron F (2011) Seasonal, gestational and postnatal influences on multiple sclerosis: the beneficial role of a vitamin D supplementation during early life. J Neurol Sci 311(1–2):64–68PubMedCrossRefGoogle Scholar
  41. 41.
    Van der Mei I, Ponsonby A, Dwyer T, Blizzard L, Simmons R, Taylor B et al (2003) Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 327(7410):316PubMedCrossRefGoogle Scholar
  42. 42.
    Kampman M, Wilsgaard T, Mellgren S (2007) Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J Neurol 254(4):471–477PubMedCrossRefGoogle Scholar
  43. 43.
    Noonan F, Bucana C, Sauder D, De Fabo E (1984) Mechanism of systemic immune suppression by UV irradiation in vivo. II. The UV effects on number and morphology of epidermal Langerhans cells and the UV-induced suppression of contact hypersensitivity have different wavelength dependencies. J Immunol 132(5):2408PubMedGoogle Scholar
  44. 44.
    Hanneman K, Cooper K, Baron E (2006) Ultraviolet immunosuppression: mechanisms and consequences. Dermatol Clin 24(1):19PubMedCrossRefGoogle Scholar
  45. 45.
    Beretich B, Beretich T (2009) Explaining multiple sclerosis prevalence by ultraviolet exposure: a geospatial analysis. Multiple Scler 15(8):891CrossRefGoogle Scholar
  46. 46.
    Mirzaei F, Michels KB, Munger K, O’Reilly E, Chitnis T, Forman MR et al Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol 70(1):30–40Google Scholar
  47. 47.
    Soilu-Hänninen M, Airas L, Mononen I, Heikkilä A, Viljanen M, Hänninen A (2005) 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Multiple Scler 11(3):266CrossRefGoogle Scholar
  48. 48.
    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):60PubMedCrossRefGoogle Scholar
  49. 49.
    Munger K, Chitnis T, Frazier A, Giovannucci E, Spiegelman D, Ascherio A (2011) Dietary intake of vitamin D during adolescence and risk of multiple sclerosis. J Neurol 258(3):479–485PubMedCrossRefGoogle Scholar
  50. 50.
    Simon K, Munger K (2010) Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis. Multiple Scler 16(2):133CrossRefGoogle Scholar
  51. 51.
    Wüthrich R, Rieder H (1970) The seasonal incidence of multiple sclerosis in Switzerland. Eur Neurol 3(5):257PubMedCrossRefGoogle Scholar
  52. 52.
    Tremlett H, Van der Mei I, Pittas F, Blizzard L, Paley G, Mesaros D et al (2008) Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 31(4):271–279PubMedCrossRefGoogle Scholar
  53. 53.
    Embry A, Snowdon L, Vieth R (2000) Vitamin D and seasonal fluctuations of gadolinium enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 48(2):271–272PubMedCrossRefGoogle Scholar
  54. 54.
    Cantorna MT, Hayes CE, DeLuca HF (1996) 1, 25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA 93(15):7861PubMedCrossRefGoogle Scholar
  55. 55.
    Spach KM, Pedersen LB, Nashold FE, Kayo T, Yandell BS, Prolla TA et al (2004) Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis. Physiol Genomics 18(2):141–151PubMedCrossRefGoogle Scholar
  56. 56.
    Orton S, Morris A, Herrera B, Ramagopalan S, Lincoln M, Chao M et al (2008) Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr 88(2):441PubMedGoogle Scholar
  57. 57.
    Smolders J, Damoiseaux J, Menheere P, Tervaert J, Hupperts R (2009) Association study on two vitamin D receptor gene polymorphisms and vitamin D metabolites in multiple sclerosis. Ann NY Acad Sci 1173(1):515–520PubMedCrossRefGoogle Scholar
  58. 58.
    Mowry E, Krupp L, Milazzo M, Chabas D, Strober J, Belman A et al (2010) Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 67(5):618–624PubMedGoogle Scholar
  59. 59.
    Goldberg P, Fleming M, Picard E (1986) Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 21(2):193–200PubMedCrossRefGoogle Scholar
  60. 60.
    Wingerchuk D, Lesaux J, Rice G, Kremenchutzky M, Ebers G (2005) A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing–remitting multiple sclerosis. Br Med J 76(9):1294Google Scholar
  61. 61.
    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):1852PubMedCrossRefGoogle Scholar
  62. 62.
    Kampman MT, Steffensen LH, Mellgren SI, Jørgensen L (2012) Effect of vitamin D3 supplementation on relapses, disease progression and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Multiple Scler [Epub ahead of print]Google Scholar
  63. 63.
    Soilu-Hänninen M, Ãivo J, Lindström BM, Elovaara I, Sumelahti ML, Färkkilä M et al (2012) A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 83(5):565–571PubMedCrossRefGoogle Scholar
  64. 64.
    van Etten E, Gysemans C, Branisteanu DD, Verstuyf A, Bouillon R, Overbergh L et al (2007) Novel insights in the immune function of the vitamin D system: synergism with interferon-beta. J Steroid Biochem Mol Biol 103(3):546–551PubMedCrossRefGoogle Scholar
  65. 65.
    Nieves J, Cosman F, Herbert J, Shen V, Lindsay R (1994) High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis. Neurology 44(9):1687PubMedCrossRefGoogle Scholar
  66. 66.
    Hiremath G, Cettomai D, Baynes M, Ratchford J, Newsome S, Harrison D et al (2009) Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis. Multiple Scler 15(6):735CrossRefGoogle Scholar
  67. 67.
    Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK et al (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96(1):53–58PubMedCrossRefGoogle Scholar
  68. 68.
    Pierrot-Deseilligny C, Souberbielle JC (2011) Widespread vitamin D insufficiency: a new challenge for primary prevention, with particular reference to multiple sclerosis. La Press MedGoogle Scholar
  69. 69.
    Adams JS, Hewison M (2010) Update in vitamin D. J Clin Endocrinol Metab 95(2):471PubMedCrossRefGoogle Scholar
  70. 70.
    Haroon M, Regan MJ (2010) Vitamin D deficiency: the time to ignore it has passed. Int J Rheum Dis 13(4):318–323PubMedCrossRefGoogle Scholar
  71. 71.
    Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R (2005) Estimates of optimal vitamin D status. Osteoporos Int 16(7):713–716PubMedCrossRefGoogle Scholar
  72. 72.
    Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna J, Lilius E, Mononen I (2008) A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 79(2):152PubMedCrossRefGoogle Scholar
  73. 73.
    Cantorna M, Mahon B (2004) Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med 229(11):1136–1142Google Scholar
  74. 74.
    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):645PubMedGoogle Scholar
  75. 75.
    Mosayebi G, Ghazavi A, Ghasami K, Jand Y, Kokhaei P (2011) Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Investig 40(6):627–639CrossRefGoogle Scholar

Copyright information

© Belgian Neurological Society 2012

Authors and Affiliations

  • Alireza Faridar
    • 1
  • Ghazaleh Eskandari
    • 2
  • Mohammad Ali Sahraian
    • 3
  • Alireza Minagar
    • 4
  • Amirreza Azimi
    • 2
  1. 1.Department of NeurologyUniversity of CaliforniaSan FranciscoUSA
  2. 2.Brain and Spinal Injury Research CenterTehran University of Medical Sciences, Sina HospitalTehranIran
  3. 3.SinaMS Research Center, Brain and Spinal Injury Research CenterTehran University of Medical SciencesTehranIran
  4. 4.Department of NeurologyLSU Health Sciences CenterShreveportUSA

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