Skip to main content
SpringerLink
Log in

Vitamin D und Multiple Sklerose

Der Stellenwert für das Erkrankungsrisiko und die Behandlung

Vitamin D and multiple sclerosis

The role for risk of disease and treatment

  • Übersichten
  • Published:
Der Nervenarzt Aims and scope Submit manuscript

Zusammenfassung

Neben seinen wichtigen Funktionen in Knochenstoffwechsel und Kalziumhomöostase werden Vitamin D weitere positive Effekte bei verschiedenen Erkrankungen zugeschrieben. Aufgrund seiner immunmodulatorischen Eigenschaften könnten beispielsweise ein Mangel an Vitamin D oder Veränderungen im Vitamin-D-Metabolismus Risikofaktoren für die Entstehung von Autoimmunerkrankungen wie der Multiplen Sklerose und eine Vitamin-D-Supplementation eine Option für deren Behandlung sein. Tatsächlich gibt es inzwischen zahlreiche Untersuchungen, die einen Zusammenhang zwischen dem Vitamin-D-Haushalt und dem Erkrankungsrisiko einer Multiplen Sklerose nahelegen, sodass Vitamin D einer der lange gesuchten Umweltfaktoren für die multifaktorielle Entstehung dieser häufigsten chronisch-entzündlichen Erkrankung des Zentralnervensystems sein könnte. Weniger aussagekräftig sind die bislang vorhandenen Daten zur Verlaufsmodifikation einer bereits manifesten Multiplen Sklerose durch Vitamin D.

Diese Übersichtsarbeit beleuchtet die möglichen Zusammenhänge zwischen Vitamin D und Multipler Sklerose. Schwerpunkte liegen dabei auf der kritischen Auseinandersetzung mit der Rolle, die Vitamin D bei der Entstehung einer Multiplen Sklerose spielen könnte, und der Eignung von Vitamin D als therapeutische Option zur Verlaufsmodifikation. Erfreulicherweise wird insbesondere der bislang noch unzureichend untersuchte therapeutische Aspekt derzeit in mehreren methodisch hochwertigen klinischen Studien adressiert.

Summary

In addition to its important role in bone metabolism and calcium homeostasis an increasing number of beneficial effects are being attributed to vitamin D. Because of its suggested immunomodulatory capacity vitamin D deficiency or disturbance in the vitamin D metabolism might be a risk factor for the development of autoimmune diseases, such as multiple sclerosis; but supplementation with vitamin D might also be a therapeutic option. Substantial epidemiologic evidence indicates an association between vitamin D levels and risk of multiple sclerosis, suggesting vitamin D to be one of the long searched environmental factors for the development of this most common chronic inflammatory disease of the central nervous system. Less consistent are the available data for modification of the disease course in already established multiple sclerosis.

This review highlights possible interactions between vitamin D and multiple sclerosis and focuses on its putative involvement in the pathogenesis and its possible role for treatment of multiple sclerosis. In particular the as yet insufficiently investigated therapeutic aspect is currently being addressed in several high quality clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Noseworthy JH, Lucchinetti C, Rodriguez M et al (2000) Multiple scleroris. N Engl J Med 343:938–952

    Article  PubMed  CAS  Google Scholar 

  2. Hein T, Hopfenmüller W (2000) Projection of the number of multiple sclerosis patients in Germany. Nervenarzt 71:288–294

    Article  PubMed  CAS  Google Scholar 

  3. Compston A, Coles A (2008) Multiple sclerosis. Lancet Neurol 372:1502–1517

    Article  CAS  Google Scholar 

  4. Buck D, Hemmer B (2011) Treatment of multiple sclerosis: current concepts and future perspectives. J Neurol 258:1747–1762

    Article  PubMed  CAS  Google Scholar 

  5. Multiple Sclerosis Therapy Consensus Group (MSTCG), Wiendl H, Toyka KV, Rieckmann P et al (2008) Basic and escalating immunomodulatory treatments in multiple sclerosis: Current therapeutic recommendations. J Neurol 255:1449–1463

    Article  Google Scholar 

  6. Holick MF: Vitamin D: A millenium perspective. C Cell Biochem 2003; 88:296–307

    Google Scholar 

  7. Holick MF: Vitamin D deficiency. N Engl J Med 2007; 357:266–281

  8. Peelen E, Knippenberg S, Muris A-Het al (2011) Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun Rev 10:733–743

    Article  PubMed  CAS  Google Scholar 

  9. Fleet JC, DeSmet M, Johnson R, Li Y (2012) Vitamin D and cancer: a review of molecular mechanisms. Biochem J 441:61–76

    Article  PubMed  CAS  Google Scholar 

  10. Souberbielle J-C, Body J-J, Lappe JMet al (2010) Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 9:709–715

    Article  PubMed  CAS  Google Scholar 

  11. Falkenstein E, Tillmann HC, Christ M et al (2000) Multiple actions of steroid hormones--a focus on rapid, nongenomic effects. Pharmacol Rev 52:513–556

    PubMed  CAS  Google Scholar 

  12. Hagenau T, Vest R, Gissel TN et al (2008) Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int 20:133–140

    Article  PubMed  Google Scholar 

  13. Vieth R (2004) Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid Biochem Mol Biol 89-90:575–579

    Google Scholar 

  14. Reusch J, Ackermann H, Badenhoop K (2009) Cyclic changes of vitamin D and PTH are primarily regulated by solar radiation: 5-year analysis of a German (50 degrees N) population. Horm Metab Res 41:402–407

    Article  PubMed  CAS  Google Scholar 

  15. Hintzpeter B, Mensink GBM, Thierfelder W et al (2008) Vitamin D status and health correlates among German adults. Eur J Clin Nutr 62:1079–1089

    Article  PubMed  CAS  Google Scholar 

  16. Fernandes de Abreu DA, Eyles D, Féron F (2009) Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases. Psychoneuroendocrinology.; 34 [Suppl 1]:265–277

  17. Ramagopalan SV, Maugeri NJ, Handunnetthi L et al (2009) Expression of the Multiple Sclerosis-Associated MHC Class II Allele HLA-DRB1*1501 Is Regulated by Vitamin D. PLoS Genet 5:1–6

    Article  Google Scholar 

  18. Sawcer S, Hellenthal G, Pirinen Met al (2011) Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476:214–219

    Article  PubMed  CAS  Google Scholar 

  19. Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) (2009) Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet 41:824-828

    Article  Google Scholar 

  20. Correale J, Ysrraelit MC, Gaitán MI (2009) Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132:1146–1160

    Article  PubMed  Google Scholar 

  21. Lemire JM, Archer DC (1991) 1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest 87:1103–1107

    Article  PubMed  CAS  Google Scholar 

  22. Yu S, Cantorna MT (2011) Epigenetic reduction in invariant NKT cells following in utero vitamin D deficiency in mice. J Immunol 186:1384–1390

    Article  PubMed  CAS  Google Scholar 

  23. Smolders J, Thewissen M, Peelen E et al (2009) Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis. PLoS One 4:e6635

    Article  PubMed  Google Scholar 

  24. Chen S, Sims GP, Chen XX et al (2007) Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 179:1634–1647

    PubMed  CAS  Google Scholar 

  25. 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 U S A 93:7861–7864

    Article  PubMed  CAS  Google Scholar 

  26. Pedersen LB, Nashold FE, Spach KM, Hayes CE (2007) 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking. J Neurosci Res 85:2480–2490

    Article  PubMed  CAS  Google Scholar 

  27. Wergeland S, Torkildsen Ø, Myhr K-M et al (2011) Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS One 6:e26262

    Article  PubMed  CAS  Google Scholar 

  28. Eyles DW, Smith S, Kinobe R et al (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29:21–30

    Article  PubMed  CAS  Google Scholar 

  29. Garcion E, Wion-Barbot N, Montero-Menei CN et al (2002) New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 13:100–105

    Article  PubMed  CAS  Google Scholar 

  30. Wion D, MacGrogan D, Neveu I et al (1991) 1,25-Dihydroxyvitamin D3 is a potent inducer of nerve growth factor synthesis. J Neurosci Res 28:110–114

    Article  PubMed  CAS  Google Scholar 

  31. Musiol IM, Feldman D (1997) 1,25-dihydroxyvitamin D3 induction of nerve growth factor in L929 mouse fibroblasts: effect of vitamin D receptor regulation and potency of vitamin D3 analogs. Endocrinology 138:12–18

    Article  PubMed  CAS  Google Scholar 

  32. Neveu I, Naveilhan P, Baudet C et al (1994) 1,25-dihydroxyvitamin D3 regulates NT-3, NT-4 but not BDNF mRNA in astrocytes. Neuroreport 6:124–126

    Article  PubMed  CAS  Google Scholar 

  33. Sanchez B, Lopez-Martin E, Segura C et al (2002) 1,25-Dihydroxyvitamin D(3) increases striatal GDNF mRNA and protein expression in adult rats. Brain Res Mol Brain Res 108:143–146

    Article  PubMed  CAS  Google Scholar 

  34. Kurtzke JF (1966) An evaluation of the geographic distribution of multiple sclerosis. Acta Neurol Scand 42 (Suppl 19):91–117

    Article  PubMed  Google Scholar 

  35. Hart PH, Gorman S, Finlay-Jones JJ (2011) Modulation of the immune system by UV radiation: more than just the effects of vitamin D? Nat Rev Immunol 11:584-596

    Article  PubMed  CAS  Google Scholar 

  36. van der Mei IAF, Ponsonby A-L, Dwyer T et al (2003) Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study. BMJ 327:316

    Article  Google Scholar 

  37. Tremlett H, van der Mei IAF, Pittas F et al (2008) Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology 31:271–279

    Article  PubMed  Google Scholar 

  38. Islam T, Gauderman WJ, Cozen W, Mack TM (2007) Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology 69:381–388

    Article  PubMed  Google Scholar 

  39. Dalmay F, Bhalla D, Nicoletti A et al (2010) Multiple sclerosis and solar exposure before the age of 15 years: case—control study in Cuba, Martinique and Sicily. Mult Scler 16:899–908

    Article  PubMed  CAS  Google Scholar 

  40. Munger KL, Zhang SM, O’Reilly E et al (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62:60–65

    Article  PubMed  CAS  Google Scholar 

  41. Munger KL, Levin LI, Hollis BW et al (2006) Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis. JAMA 296:2832–2838

    Article  PubMed  CAS  Google Scholar 

  42. Mirzaei F, Michels KB, Munger K et al (2011) Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol 70:30–40

    Article  PubMed  CAS  Google Scholar 

  43. Willer CJ, Dyment DA, Sadovnick AD et al (2005)Timing of birth and risk of multiple sclerosis: population based study. BMJ 330:120–120

    Article  PubMed  Google Scholar 

  44. Sotgiu S, Pugliatti M, Sotgiu MA et al (2005)Seasonal fluctuation of multiple sclerosis births in Sardinia. J Neurol 253:38–44

    Article  PubMed  Google Scholar 

  45. Salzer J, Svenningsson A, Sundström P 2010 () Season of birth and multiple sclerosis in Sweden. Acta Neurol Scand 122:70–73

    Google Scholar 

  46. Jin Y, de Pedro-Cuesta J, Söderström M et al (2000)Seasonal patterns in optic neuritis and multiple sclerosis: a meta-analysis. J Neurol Sci 181:56–64

    Article  PubMed  CAS  Google Scholar 

  47. Handel AE, Disanto G, Jarvis L et al (2011)Seasonality of admissions with multiple sclerosis in Scotland. Eur J Neurol 18:1109–1111

    Article  PubMed  Google Scholar 

  48. Soilu-Hänninen M, Airas L, Mononen I et al (2005) 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler 11:266–271

    Article  PubMed  Google Scholar 

  49. Barnes MS, Bonham MP, Robson PJ et al (2007) Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers. Mult Scler 13:670–672

    Article  PubMed  CAS  Google Scholar 

  50. Holmøy T, Lossius A, Gundersen TE et al (2011) Intrathecal levels of vitamin D and IgG in multiple sclerosis. Acta Neurol Scand. http://onlinelibrary.wiley.com. DOI/10.1111/j.1600-0404.2011.01577.x/abstract (last accessed on 15 March 2012)

  51. Holmøy T, Moen SM, Gundersen TA et al (2009) 25-Hydroxyvitamin D in cerebrospinal fluid during relapse and remission of multiple sclerosis. Mult Scler 15:1280–1285

    Article  PubMed  Google Scholar 

  52. Mowry EM, Krupp LB, Milazzo M et al (2010) Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 67:618–624

    PubMed  CAS  Google Scholar 

  53. Simpson Jr. 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

    PubMed  CAS  Google Scholar 

  54. Embry AF, Snowdon LR, Vieth R (2000) Vitamin D and seasonal fluctuations of gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 48:271–272

    Article  PubMed  CAS  Google Scholar 

  55. Auer DP, Schumann EM, Kümpfel T et al (2000) Seasonal fluctuations of gadolinium-enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol 47:276–277

    Article  PubMed  CAS  Google Scholar 

  56. Goldberg P, Fleming MC, Picard EH (1986) Multiple sclerosis: Decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 21:193–200

    Article  PubMed  CAS  Google Scholar 

  57. Kimball SM, Ursell MR, O’Connor P, Vieth R (2007) Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 86:645–651

    PubMed  CAS  Google Scholar 

  58. Mahon B., Gordon S., Cruz J et al (2003) 1986Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 134:128–32

    Article  PubMed  CAS  Google Scholar 

  59. Burton JM, Kimball S, Vieth R et al (2010) A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis (e–Pub ahead of print)(LOE Classification). Neurology 74:1852–1859

    Article  PubMed  CAS  Google Scholar 

  60. Stein MS, Liu Y, Gray OM et al (2011) A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology 77:1611–1618

    Article  PubMed  CAS  Google Scholar 

  61. Soilu-Hänninen M, Aivo J, Lindström B-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. http://www.ncbi.nlm.nih.gov/pubmed/22362918 (last accessed on 15 March 2012)

  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. Mult Scler. http://www.ncbi.nlm.nih.gov/pubmed/22354743 (last accessed on 15 March 2012)

  63. Wingerchuk D, Lesaux J, Rice G et al (2005) A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing–remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 76:1294–1296

    Article  PubMed  CAS  Google Scholar 

  64. Hathcock JN, Shao A, Vieth R, Heaney R (2007) Risk assessment for vitamin D. Am J Clin Nutr 85:6–18

    PubMed  CAS  Google Scholar 

  65. Jagannath VA, Fedorowicz Z, Asokan GV et al (2010) Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev 12:CD008422

    PubMed  Google Scholar 

  66. Dorr J, Ohlraun S, Skarabis H, Paul F (2012) Efficacy of Vitamin D Supplementation in Multiple Sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial. Trials 13:15

    Article  PubMed  Google Scholar 

  67. Kampman MT, Wilsgaard T, Mellgreen SI (2007) Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J Neurol 254:471–477

    Article  PubMed  CAS  Google Scholar 

  68. Kragt J, van Amerongen B, Killestein J et al (2009) Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult Scler 15:9–15

    Article  PubMed  CAS  Google Scholar 

  69. Holmøy T, Moen SM, Gundersen TA et al (2009) 25-hydroxyvitamin D in cerebrospinal fluid during relapse and remission of multiple sclerosis. Mult Scler 15:1280–1285

    Article  PubMed  Google Scholar 

  70. Lucas RM, Ponsonby AL, Dear K et al (2011) Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 76:540–548

    Article  PubMed  CAS  Google Scholar 

  71. Mosayebi G, Ghazavi A, Ghasami K et al (2011) Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Invest 40:627–639

    Article  PubMed  CAS  Google Scholar 

  72. Runia TF, Hop WC, 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

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt für sich und seine Koautoren an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. NeuroCure Clinical Research Center, Charité – Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, 10117, Berlin, Deutschland

    A. Döring, F. Paul &  J. Dörr

Authors
  1. A. Döring
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Dörr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Dörr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Döring, A., Paul, F. & Dörr, J. Vitamin D und Multiple Sklerose. Nervenarzt 84, 173–189 (2013). https://doi.org/10.1007/s00115-012-3645-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00115-012-3645-z

Schlüsselwörter

Keywords

Search

Navigation