Vitamin D und Multiple Sklerose

Zusammenfassung

Epidemiologische Daten unterstützen einen möglichen Zusammenhang zwischen einem Vitamin-D-Mangel und einem erhöhten Risiko für Multiple Sklerose (MS) und andere Autoimmunerkrankungen. Obwohl kleine klinische Studien Vitamin D als einen wesentlichen Faktor für die Verhinderung von Schüben und Krankheitsprogression bei MS identifiziert haben, fehlen noch Ergebnisse prospektiver, randomisierter, kontrollierter Studien, um diese Effekte zu bestätigen und die optimale therapeutisch wirksame Vitamin-D-Dosis auch unter Berücksichtigung von Sicherheitsaspekten zu identifizieren.

Wir geben einen Überblick über Vitamin D und seinen Metabolismus, Ergebnisse präklinischer In-vitro-und In-vivo-Studien zu immunmodulatorischen Effekten von Vitamin D und berichten über die Ergebnisse erster klinischer Studien zu verlaufsmodifizierenden Effekten von Vitamin D bei Patienten mit MS. Es folgen praktische Empfehlungen zur Handhabung von Vitamin D bei Patienten mit MS bis zum Vorliegen belastbarer klinischer Daten aus prospektiven, randomisierten und kontrollierten Studien.

Summary

Epidemiologic data support an association between vitamin D deficiency and the risk of developing multiple sclerosis and other autoimmune diseases. Although smaller scale studies identified vitamin D to be effective in lowering the risk of relapses and clinical progression in multiple sclerosis, data from prospective randomized controlled clinical trials corroborating the described effects and determining the most efficient dose are currently lacking.

We provide an overview on vitamin D and its metabolism, results from preclinical in vitro and in vivo studies concerning immunomodulatory effects of vitamin D as well as results from first clinical studies regarding disease-modifying effects in patients with multiple sclerosis. Finally, we provide preliminary advice how to handle vitamin D assessment and substitution in patients with multiple sclerosis until above mentioned results from prospective large-scale clinical trials are available.

Schlüsselwörter

Multiple Sklerose - Vitamin D - Immunmodulation

Keywords

Multiple sclerosis - vitamin D - immunomodulation

• Literatur

• 1 Brahic M. Multiple sclerosis and viruses. Ann Neurol 2010; 68: 6-8.
• 2 Goldberg P. et al. Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 1986; 21: 193-200.
• 3 Hutter CD, Laing P. Multiple sclerosis: sunlight, diet, immunology and aetiology. Med Hypotheses 1996; 46: 67-74.
• 4 Leibowitz U. et al. Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation. J Neurol Neurosurg Psychiatry 1966; 29: 60-8.
• 5 Marrie RA. Environmental risk factors in multiple sclerosis aetiology. Lancet Neurol 2004; 03: 709-18.
• 6 Munger KL. et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296: 2832-8.
• 7 Gourraud PA. et al. The genetics of multiple sclerosis: an up-to-date review. Immunol Rev 2012; 248: 87-103.
• 8 Acheson ED. et al. Distribution of multiple sclerosis to latitude, solar radiation, and other variables. Acta Psychiatr Scand Suppl 1960; 35: 132-47.
• 9 Carlyle IP. Multiple sclerosis: a geographical hypothesis. Med Hypotheses 1997; 49: 477-86.
• 10 Hayes CE. et al. Vitamin D and multiple sclerosis. Proc Soc Exp Biol Med 1997; 216: 21-7.
• 11 Kragt J. et al. Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult Scler 2009; 15: 9-15.
• 12 Milo R, Kahana E. Multiple sclerosis: geoepidemiology, genetics and the environment. Autoimmun Rev 2010; 09: A387-A394.
• 13 Munger KL. et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62: 60-5.
• 14 McDowell TY. et al. Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology 2011; 36: 39-45.
• 15 Lucas RM. et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 2011; 76: 540-8.
• 16 Holick MF. Vitamin D. Modern Nutritition in Health and Disease. 10th ed. Philadelphia: Lippincott Wiliams & Wilkins; 2006
• 17 Smolders J. Vitamin D and multiple sclerosis: correlation, causality, and controversy. Autoimmune Dis. 2011: 629538.
• 18 Weinstock-Guttman B. et al. Vitamin D metabolites are associated with clinical and MRI outcomes in multiple sclerosis patients. J Neurol Neurosurg Psychiatry 2011; 82: 189-95.
• 19 Kimball SM. et al. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr 2007; 86: 645-51.
• 20 Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-81.
• 21 Armas LA. et al. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004; 89: 5387-91.
• 22 Holick MF. et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab 2008; 93: 677-81.
• 23 Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr 2006; 84: 694-7.
• 24 Trang HM. et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998; 68: 854-8.
• 25 Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005; 26: 662-87.
• 26 Smolders J. et al. Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol 2008; 194: 7-17.
• 27 Lemire JM, Archer DC. 1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest 1991; 87: 1103-7.
• 28 Chang SH, Chung Y, Dong C. Vitamin D suppresses Th17 cytokine production by inducing C/EBP homologous protein (CHOP) expression. J Biol Chem 2010; 285: 38751-5.
• 29 Mahon BD. et al. Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J Neuroimmunol 2003; 134: 128-32.
• 30 Correale J. et al. Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 2009; 132: 1146-60.
• 31 Mowry EM. et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol 2010; 67: 618-24.
• 32 Simpson S. et al. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 2010; 68: 193-203.
• 33 Smolders J. et al. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS One 2009; 04: e6635.
• 34 Soilu-Hanninen M. et al. 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler 2005; 11: 266-71.
• 35 Smolders J. et al. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 2008; 14: 1220-4.
• 36 van der Mei et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol 2007; 254: 581-90.
• 37 Wingerchuk DM. et al. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2005; 76: 1294-6.
• 38 Burton JM. et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010; 74: 1852-9.
• 39 Smolders J. et al. Efficacy of vitamin D3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci 2011; 311: 44-9.
• 40 Bjelakovic G. et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011: CD007470.
• 41 Cannell JJ. et al. Diagnosis and treatment of vitamin D deficiency. Expert Opin Pharmacother 2008; 09: 107-18.