1. ¹Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam, The Netherlands
2. ²Department of Endocrinology, VU Medical Center, Amsterdam, The Netherlands
3. ³Department of Neurology, VU Medical Center, Amsterdam, The Netherlands
4. ⁴Department of Dental Basic Sciences (ACTA), VU Medical Center, Amsterdam, The Netherlands

Correspondence: BM VanAmerongen, Department of Molecular Cell Biology and Immunology, VU Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: b.m.van.amerongen@inter.nl.net

Guarantor: CD Dijkstra.

Contributors: BV initiated this study together with CD. The paper was written by BV and CD with contribution from PL. CD contributed her expertise on MS, EAE, the immune system and gene polymorphism. PL contributed his expertise on vitamin D deficiency and consequences for bone loss, fractures and therapeutic implications. CP contributed his clinical expertise on patients with MS. All authors read and contributed to the manuscript.

Received 9 June 2003; Revised 23 December 2003; Accepted 10 January 2004; Published online 31 March 2004.

Abstract

MS is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS), with an etiology that is not yet fully understood. The prevalence of MS is highest where environmental supplies of vitamin D are lowest. It is well recognized that the active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH)₂D), is a natural immunoregulator with anti-inflammatory action. The mechanism by which vitamin D nutrition is thought to influence MS involves paracrine or autocrine metabolism of 25OHD by cells expressing the enzyme 1-OHase in peripheral tissues involved in immune and neural function. Administration of the active metabolite 1,25-(OH)₂D in mice and rats with experimental allergic encephalomyelitis (EAE, an animal model of MS) not only prevented, but also reduced disease activity. 1,25-(OH)₂D alters dendritic cell and T-cell function and regulates macrophages in EAE. Interestingly, 1,25-(OH)₂D is thought to be operating on CNS constituent cells as well.

Vitamin D deficiency is caused by insufficient sunlight exposure or low dietary vitamin D₃ intake. Subtle defects in vitamin D metabolism, including genetic polymorphisms related to vitamin D, might possibly be involved as well. Optimal 25OHD serum concentrations, throughout the year, may be beneficial for patients with MS, both to obtain immune-mediated suppression of disease activity, and also to decrease disease-related complications, including increased bone resorption, fractures, and muscle weakness.