Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-27T17:41:56.999Z Has data issue: false hasContentIssue false
  • English
  • Français

Vitamin D: a natural inhibitor of multiple sclerosis

Published online by Cambridge University Press:  28 February 2007

Colleen E. Hayes
Colleen E. Hayes*
Affiliation:
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, USA
*
Corresponding author:Professor C. E. Hayes, fax +1 608 262 3453, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Inheriting genetic risk factors for multiple sclerosis (MS) is not sufficient to cause this demyelinating disease of the central nervous system; exposure to environmental risk factors is also required. MS may be preventable if these unidentified environmental factors can be avoided. MS prevalence increases with decreasing solar radiation, suggesting that sunlight may be protective in MS. Since the vitamin D endocrine system is exquisitely responsive to sunlight, and MS prevalence is highest where environmental supplies of vitamin D are lowest, we have proposed that the hormone, 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), may protect genetically-susceptible individuals from developing MS. Evidence consistent with this hypothesis comes not only from geographic studies, but also genetic and biological studies. Over-representation of the vitamin D receptor gene b allele was found in Japanese MS patients, suggesting it may confer MS susceptibility. Fish oil is an excellent vitamin D source, and diets rich in fish may lower MS prevalence or severity. Vitamin D deficiency afflicts most MS patients, as demonstrated by their low bone mass and high fracture rates. However, the clearest evidence that vitamin D may be a natural inhibitor of MS comes from experiments with experimental autoimmune encephalomyelitis (EAE), a model of MS. Treatment of mice with 1,25-(OH)2D3 completely inhibited EAE induction and progression. The hormone stimulated the synthesis of two anti-encephalitogenic cytokines, interleukin 4 and transforming growth factor β-1, and influenced inflammatory cell trafficking or apoptosis. If vitamin D is a natural inhibitor of MS, providing supplemental vitamin D to individuals who are at risk for MS would be advisable.

Keywords

Vitamin D1,25-DihydroxycholecalciferolMultiple sclerosisExperimental autoimmune encephalomyelitisAutoimmunity
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 59 , Issue 4 , November 2000 , pp. 531 - 535
Copyright
Copyright © The Nutrition Society 2000

References

Acheson, ED, Bachrach, CA & Wright, FM (1960) Some comments on the relationship of the distribution of multiple sclerosis to latitude, solar radiation and other variables. Acta Psychiatrica Neurologica Scandinavica Suppl. 147, 132–147.CrossRefGoogle ScholarPubMed
Anderson, O, Lygner, P-E, Bergström, T, Andersson, M & Vahlne, A (1993) Viral infections trigger multiple sclerosis relapses: A prospective seroepidemiological study. Journal of Neurology 240, 417–422.CrossRefGoogle Scholar
Bates, C, Cartlidge, NEF, French, JM, Jackson, HJ, Nightenhale, S, Shaw, DA, Smith, S, Woo, E, Hawkins, SA, Miller, JH, Belin, J, Conroy, DM, Gill, SK, Sidey, M, Smith, AD, Thompson, RHS, Zilkha, K, Gale, M & Sinclair, HM (1989) A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. Journal of Neurology Neurosurgery and Psychiatry 52, 18–22.CrossRefGoogle ScholarPubMed
Branisteanu, DD, Waer, M, Sobis, H, Marcelis, S, Vandeputte, M & Bouillon, R (1995) Prevention of murine experimental allergic encephalomyelitis: cooperative effects of cyclosporine and 1α,25(OH)2D3. Journal of Neuroimmunology 61, 151–160.CrossRefGoogle Scholar
Cantorna, MT, Hayes, CE & DeLuca, HF (1996) 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proceedings of the National Academy of Sciences USA 93, 7861–7864.CrossRefGoogle Scholar
Cantorna, MT, Humpal-Winter, J & DeLuca, HF (1999) Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice. Journal of Nutrition 129, 1966–1971.CrossRefGoogle Scholar
Cantorna, MT, Woodward, WD, Hayes, CE & DeLuca, HF (1998) 1,25-Dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-β1 and IL-4. Journal of Immunology 160, 5314–5319.CrossRefGoogle Scholar
Chick, H, Dalyell, EJ, Hume, M, Mackay, HMM & Smith, HH (1922) The etiology of rickets in infants: prophylactic and curative observations at the Vienna University Kinderklinik. Lancet i, 7–12.CrossRefGoogle Scholar
Cosman, F, Nieves, J, Komar, L, Ferrer, G, Herbert, J, Formica, C, Shen, V & Lindsay, R (1998) Fracture history and bone loss in patients with MS. Neurology 51, 1161–1165.CrossRefGoogle ScholarPubMed
Davenport, CB (1922) Multiple sclerosis from the standpoint of geographic distribution and race. Archives of Neurology and Psychiatry 8, 51–58.CrossRefGoogle Scholar
Ebers, GC (1998) The pathogenesis of multiple sclerosis. European Journal of Neurology 5, Suppl. 2, S7–S8.Google Scholar
Ebers, GC, Bulman, DE, Sadovnick, AD, Paty, DW, Warren, S, Hader, W, Murray, TJ, Seland, TP, Duquette, P, Gray, T, Nelson, R, Nicolle, M & Brunet, D (1986) A population-based twin study in multiple sclerosis. New England Journal of Medicine 315, 1638–1642.CrossRefGoogle Scholar
Ebers, GC & Dyment, DA (1998) Genetics of multiple sclerosis. Seminars in Neurology 18, 295–299.CrossRefGoogle ScholarPubMed
Ebers, GC & Sadovnick, AD (1994) The role of genetic factors in multiple sclerosis susceptibility. Journal of Neuroimmunology 54, 1–17.CrossRefGoogle ScholarPubMed
EURODIAB Substudy 2 Study Group (1999) Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. Diabetologia 42, 51–54.CrossRefGoogle Scholar
Fukazawa, T, Yabe, I, Kikuchi, S, Sasaki, H, Hamada, T, Miyasaka, K & Tashiro, K (1999) Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese. Journal of Neurological Sciences 166, 47–52.CrossRefGoogle ScholarPubMed
Geiger, R (1965) The Climate Near the Ground, pp. 442–446. Cambridge, MA: Harvard University Press.Google Scholar
Goldberg, P (1974 a) Multiple sclerosis: Vitamin D and calcium as environmental determinants of prevalence (a viewpoint). Part 1: Sunlight, dietary factors and epidemiology. International Journal of Environmental Studies 6, 19–27.CrossRefGoogle Scholar
Goldberg, P (1974 b) Multiple sclerosis: Vitamin D and calcium as environmental determinants of prevalence (a viewpoint). Part 2: Biochemical and Genetic Factors. International Journal of Environmental Studies 6, 121–129.CrossRefGoogle Scholar
Goldberg, P, Fleming, MC & Picard, EM (1986) Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium, and vitamin D. Medical Hypotheses 21, 193–200.CrossRefGoogle ScholarPubMed
Hammond, SR, English, DR & McLeod, JG (2000) The age-range of risk of developing multiple sclerosis. Evidence from a migrant population in Australia. Brain 123, 968–974.Google Scholar
Haussler, MR, Haussler, CA, Jurutka, PW, Thompson, PD, Hsieh, JC, Remus, LS, Selznick, SH & Whitfield, GK (1997) The vitamin D hormone and its nuclear receptor: molecular actions and disease states. Journal of Endocrinology 154, 557–573.Google ScholarPubMed
Hayes, CE, Cantorna, MT & DeLuca, HF (1997) Vitamin D and multiple sclerosis. Proceedings of the Society for Experimental Biology and Medicine 216, 21–27.CrossRefGoogle ScholarPubMed
Hess, AF (1929) Rickets, Osteomalacia and Tetany, pp. 38–61. Philadephia, PA: Lea & Febiger.Google Scholar
Hess, AF & Unger, LF (1921) Cure of infantile rickets by sunlight. Journal of the American Medical Association 39, 77–82.Google Scholar
Holick, MF (1995) Environmental factors that influence the cutaneous production of vitamin D. American Journal of Clinical Nutrition 61, Suppl., 638S–645S.CrossRefGoogle ScholarPubMed
Holick, MF (1998) Vitamin D requirements for humans of all ages: new increased requirements for women and men 50 years and older. Osteoporosis International Suppl. 8, S24–S29.CrossRefGoogle ScholarPubMed
Holick, MF, Schnoes, HK & DeLuca, HF (1971) Identification of 1,25-dihydroxycholecalciferol, a form of vitamin D3 metabolically active in the intestine. Proceedings of the National Academy of Sciences USA 68, 803–804.CrossRefGoogle Scholar
Inobe, JI, Chen, Y & Weiner, HL (1996) In vivo administration of IL-4 induces TGF-beta-producing cells and protects animals from experimental autoimmune encephalomyelitis. Annals of the New York Academy of Sciences 778, 390–392.CrossRefGoogle ScholarPubMed
Johns, LD, Flanders, KC, Ranges, GE & Sriram, S (1991) Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-β1. Journal of Immunology 147, 1792–1796.CrossRefGoogle Scholar
Kurland, LT (1952) The frequency and geographic distribution of multiple sclerosis as indicated by mortality statistics and morbidity surveys in the United States and Canada. American Journal of Hygiene 55, 457–476.Google Scholar
Kurtzke, JF (1967) On the fine structure of the distribution of multiple sclerosis. Acta Neurologica Scandinavica 43, 257–282.CrossRefGoogle ScholarPubMed
Kuruvilla, AP, Shah, R, Hochwald, GM, Liggitt, HD, Palladino, MA & Thorbecke, GJ (1991) Protective effect of transforming growth factor b1 on experimental autoimmune diseases in mice. Proceedings of the National Academy of Sciences USA 88, 2918–2921.CrossRefGoogle Scholar
Lemire, JM & Archer, DC (1991) 1,25-Dihydroxyvitamin D3 suppresses the in vivo induction of murine experimental autoimmune encephalomyelitis. Journal of Clinical Investigation 87, 1103–1107.CrossRefGoogle Scholar
Limburg, CC (1950) Geographic distribution of multiple sclerosis and its estimated prevalence in the US. Proceedings of the Association for Research into Nervous Diseases 28, 15–24.Google Scholar
McDermott, MF, Ramachandran, A, Ogunkolade, BW, Aganna, E, Curtis, D, Boucher, BJ, Snehalatha, C & Hitman, GA (1997) Allelic variation in the vitamin D receptor influences susceptibility to IDDM in Indian Asians. Diabetologia 40, 971–975.CrossRefGoogle ScholarPubMed
Malabanan, A, Veronikis, IE & Holick, MF (1998) Redefining vitamin D insufficiency. Lancet 351, 805–806.CrossRefGoogle ScholarPubMed
Nashold, FE, Miller, DJ & Hayes, CE (2000) 1,25-Dihydroxyvitamin D3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune encephalomyelitis. Journal of Neuroimmunology 103, 171–179.CrossRefGoogle ScholarPubMed
Norman, AW, Myrtle, JF, Midgett, RJ, Nowicki, HG, Williams, V & Popjak, G (1971) 1,25-dihydroxycholecalciferol: identification of the proposed active form of vitamin D3 in the intestine. Science 173, 51–54.CrossRefGoogle Scholar
Noseworthy, JH (1999) Progress in determining the causes and treatment of multiple sclerosis. Nature 399, A40–A47.CrossRefGoogle ScholarPubMed
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, 1687–1692.CrossRefGoogle ScholarPubMed
Olitsky, PK & Yager, RH (1949) Experimental disseminated encephalomyelitis in white mice. Journal of Experimental Medicine 90, 213–223.CrossRefGoogle ScholarPubMed
Panitch, HS (1994) Influence of infection on exacerbations of multiple sclerosis. Annals of Neurology 36, S25–S28.CrossRefGoogle ScholarPubMed
Pratt, RTC, Compston, ND & McAlpine, D (1951) The familial incidence of multiple sclerosis and its significance. Brain 74, 191–232.Google Scholar
Presthus, J (1960) Report on the multiple sclerosis investigations in West Norway. Acta Psychiatrica Neurologica Scandinavica Suppl. 147, 88–92.CrossRefGoogle ScholarPubMed
Racke, MK, Dhib-Jalbut, S, Cannella, B, Albert, PS, Raine, CS & McFarlin, DE (1991) Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-β1. Journal of Immunology 146, 3012–3017.Google Scholar
Sibley, WA, Bamford, CR & Clark, K (1985) Clinical viral infections and multiple sclerosis. Lancet i, 1313–1315.CrossRefGoogle Scholar
Steckley, JL, Dyment, DA, Sadovnick, AD, Risch, N, Hayes, C, Ebers, GC and the Canadian Collaborative Study Group (2000) Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients. Neurology 54, 729–732.Google Scholar
Swank, RL, Lerstad, O, Strøm, A & Backer, J (1952) Multiple sclerosis in rural Norway: Its geographic and occupational incidence in relation to nutrition. New England Journal of Medicine 246, 721.CrossRefGoogle ScholarPubMed
Ulett, G (1948) Geographic distribution of multiple sclerosis. Diseases of the Nervous System 9, 342.Google ScholarPubMed
Vieth, R (1999) Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Clinical Nutrition 69, 842–856.CrossRefGoogle ScholarPubMed
Velluz, L & Amiard, G (1949) Chimie organique-equilibre de reaction entre precalciferol et calciferol (Organic chemistry-balance of reaction between precalciferol and calciferol). Comptes Rendus de l'Academie des Sciences 228, 853–855.Google Scholar
Webb, AR, Kline, L & Holick, MF (1988) Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. Journal of Clinical Endocrinology and Metabolism 67, 373–378.Google Scholar
Westlund, K (1970) Distribution and mortality time trend of multiple sclerosis and some other diseases of Norway. Acta Neurologica Scandinavica 46, 455–483.Google Scholar