The role of vitamin D3 in the pathogenesis of multiple sclerosis Review article
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Published:
Mar 31, 2015
Keywords:
vitamin D3, multiple sclerosis, environmental factors, recommendations
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Abstract
The primary function of vitamin D in the human body is to regulate calcium – phosphate homeostasis and modeling and mineralization of bone tissue. Meanwhile, many studies suggest that it plays an important role not only in skeletal diseases, but also in the prevention of cardiovascular disease, autoimmune diseases and cancer. A positive correlation was also observed between vitamin D deficiency and the prevalence of multiple sclerosis (SM, sclerosis multiplex). However, despite the ongoing research on the pathogenesis of the disease, there was still clear reasons that can cause it. There is only a hypothesis, indicating viral infections, genetic susceptibility or process autoimmune developing in humans exposed to adverse environmental factors among which the most frequently linked to the pathogenesis of SM are bacterial, viral, fungal, geographical location and the deficiency of vitamin D. It is suggested that the increased exposure of the skin to sunlight, vitamin D supplementation routine and well-balanced diet may reduce the risk of developing MS, and modulate the course of the disease and reduce the frequency of relapses in patients with relapsing- remitting form. The aim of the study is to present the current state of knowledge on the potential environmental risk factors that make up the incidence of multiple sclerosis and recommendations of experts on the prevention of vitamin D deficiency.
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References
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2. Prosser E., Jones G.: Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 2004; 29: 664-673.
3. Holick M.F.: Vitamin D: a millennium perspective. J. Cell. Biochem. 2003; 88: 296-307.
4. Chen T.C., Chimeh F., Lu Z. et al.: Factors that infl uence the cutaneous synthesis and dietary sources of vitamin D. Arch. Biochem. Biophys. 2007; 460: 213-217.
5. Holick M.F.: Resurrection of vitamin D deficiency and rickets J. Clin. Invest. 2006; 116: 2062-2072.
6. MacLaughlin J.A., Anderson R.R., Holick M.F.: Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. Science 1982; 216: 1001-1004.
7. Jones G.: Expanding role for vitamin D in chronic kidney disease: importance of blood 25-OH-D levels and extra-renal 1alpha-hydroxylase in the classical and nonclassical actions of 1alpha,25-dihydroxyvitamin D(3). Semin. Dial. 2007; 20: 316-324.
8. DeLuca H.F.: Overview of general physiologic features and functions of vitamin D. Am. J. Clin. Nutr. 2004; 80: 1689S-1696S.
9. Somjen D., Weisman Y., Kohen F. et al.: 25-Hydroxyvitamin D3 -1a hydroxylase is expressed in human vascular smooth muscle cells and is up regulated by parathyroid hormone and estrogenic compounds. Circulation 2005; 111: 1666-1672.
10. Pike J.W.: Vitamin D3 receptors: structure and function in transcription. Ann. Rev. Nutr. 1991; 11: 189-216.
11. Bischoff-Ferrari H.A., Giovannucci E., Willett W.C. et al.: Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am. J. Clin. Nutr. 2006; 84: 18-28.
12. Hathcock J.N., Shao A., Vieth R., Heaney R.: Risk assessment for vitamin D. Am. J. Clin. Nutr. 2007; 85: 6-18.
13. Dawson-Hughes B., Harris S.S., Krall E.A., Dallal G.E.: Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N. Engl. J. Med. 1997; 337: 670-676.
14. Holick M.F.: Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am. J. Clin. Nutr. 2004; 79: 362-371 (errata w: Am. J. Clin. Nutr. 2004; 79: 890).
15. Lips P.: Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr. Rev. 2001; 22: 477-501.
16. Holick M.F., Siris E.S., Binkley N. et al.: Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J. Clin. Endocrinol. Metab. 2005; 90: 3215-3224.
17. Heaney R.P.: Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am. J. Clin. Nutr. 2004; 80 (supl. 6): 1706S-1709S.
18. Holick M.F.: Vitamin D deficiency. N. Engl. J. Med. 2007; 357: 266-281.
19. Karczmarewicz E., Pudłowski P., Łukaszkiewicz J. et al.: Witamina D – standardy diagnostyczne, kliniczna interpretacja oznaczeń. Terapia 2008; 5: 47-53.
20. Lips P.: Relative value of 25(OH)D and 1,25(OH)2D measurements. J. Bone Miner. Res. 2007; 22: 1668-1671.
21. Lips P.: Which circulating level of 25-hydroxyvitamin D is appropriate? J. Steroid Biochem. Mol. Biol. 2004; 89-90: 611-614.
22. Hernán M.A., Olek M.J., Ascherio A.: Geographic variation of MS incidence in two prospective studies of US women. Neurology 1999; 53: 1711-1718.
23. Kampman M.T., Brustad M.: Vitamin D: a candidate for the environmental effect in multiple sclerosis – observations from Norway. Neuroepidemiology 2008; 30: 140-146.
24. Islam T., Gauderman W.J., Cozen W., Mack T.M.: Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology 2007; 69: 381-388.
25. Kampman M.T., Wilsgaard T., Mellgren S.I.: Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J. Neurol. 2007; 254: 471-477.
26. Munger K.L., Zhang S.M., O’Reilly E. et al.: Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62: 60-65.
27. Munger K.L., Levin L.I., Hollis B.W. et al.: Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296: 2832-2838.
28. Soilu-Hänninen M., Airas L., Mononen I. et al.: 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult. Scler. 2005; 11: 266-271.
29. Correale J., Ysrraelit M.C., Gaitán M.I.: Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 2009; 132: 1146-1160.
30. Simpson S. Jr, Taylor B., Blizzard L. et al.: Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann. Neurol. 2010; 68: 193-203.
31. Goldberg P., Fleming M.C., Picard E.H.: Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med. Hypotheses 1986; 21: 193-200.
32. Kimball S.M., Ursell M.R., O’Connor P., Vieth R.: Safety of vitamin D3 in adults with multiple sclerosis. Am. J. Clin. Nutr. 2007; 86: 645-651.
33. Mahon B.D., Gordon S.A., Cruz J. et al.: Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J. Neuroimmunol. 2003; 134: 128-132.
34. Soilu-Hänninen M., Aivo J., Lindström BM. et al.: 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. Psychiatr. 2012; 83: 565-571.
35. Burton J.M., Kimball S., Vieth R., Bar-Or A.: A phase I/II dose escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010; 74: 1852-1859.
36. Kimball S., Vieth R., Dosch H.M. et al.: Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J. Clin. Endocrinol. Metab. 2011; 96: 2826-2834.
37. Mosayebi G., Ghazavi A., Ghasami K. et al.: Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol. Invest. 2011; 40: 627-639.
38. Munger K.L., Ascherio A.: Prevention and treatment of MS: studying the effects of vitamin D. Mult. Scler. 2011; 17: 1405-1411.
39. Armas L.A., Hollis B., Heaney R.P.: Vitamin D2 is much less effective than vitamin D3 in humans. J. Clin. Endocrinol. Metab. 2004; 89: 5387-5391.
40. Kunachowicz H., Nadolna I., Przygoda B. et al.: Tabele składu i wartości odżywczej żywności. Wydawnictwo Lekarskie PZWL, Warszawa 2005.
41. Vitamin and Mineral Requirements in Human Nutrition. WHO and FAO, Rome 2004.
42. Bułhak-Jachymczak B.: Witaminy. W: Normy żywienia człowieka. Podstawy prewencji otyłości i chorób niezakaźnych. Jarosz M., Bułhak-Jachymczak B. (red.). IŻŻ, PZWL, Warszawa 2008: 172-232.
43. Institute of Medicine, Dietary Reference Intakes for Calcium and Vitamin D, Food and Nutrition Board. Nat. Acad. Press, Washington 2010.
44. Misra M., Pacaud D., Petryk A. et al.: Vitamin D deficiency in children and its management: review of current knowledge and recommendation. Pediatrics 2008; 122: 398-417.
2. Prosser E., Jones G.: Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 2004; 29: 664-673.
3. Holick M.F.: Vitamin D: a millennium perspective. J. Cell. Biochem. 2003; 88: 296-307.
4. Chen T.C., Chimeh F., Lu Z. et al.: Factors that infl uence the cutaneous synthesis and dietary sources of vitamin D. Arch. Biochem. Biophys. 2007; 460: 213-217.
5. Holick M.F.: Resurrection of vitamin D deficiency and rickets J. Clin. Invest. 2006; 116: 2062-2072.
6. MacLaughlin J.A., Anderson R.R., Holick M.F.: Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin. Science 1982; 216: 1001-1004.
7. Jones G.: Expanding role for vitamin D in chronic kidney disease: importance of blood 25-OH-D levels and extra-renal 1alpha-hydroxylase in the classical and nonclassical actions of 1alpha,25-dihydroxyvitamin D(3). Semin. Dial. 2007; 20: 316-324.
8. DeLuca H.F.: Overview of general physiologic features and functions of vitamin D. Am. J. Clin. Nutr. 2004; 80: 1689S-1696S.
9. Somjen D., Weisman Y., Kohen F. et al.: 25-Hydroxyvitamin D3 -1a hydroxylase is expressed in human vascular smooth muscle cells and is up regulated by parathyroid hormone and estrogenic compounds. Circulation 2005; 111: 1666-1672.
10. Pike J.W.: Vitamin D3 receptors: structure and function in transcription. Ann. Rev. Nutr. 1991; 11: 189-216.
11. Bischoff-Ferrari H.A., Giovannucci E., Willett W.C. et al.: Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am. J. Clin. Nutr. 2006; 84: 18-28.
12. Hathcock J.N., Shao A., Vieth R., Heaney R.: Risk assessment for vitamin D. Am. J. Clin. Nutr. 2007; 85: 6-18.
13. Dawson-Hughes B., Harris S.S., Krall E.A., Dallal G.E.: Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N. Engl. J. Med. 1997; 337: 670-676.
14. Holick M.F.: Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am. J. Clin. Nutr. 2004; 79: 362-371 (errata w: Am. J. Clin. Nutr. 2004; 79: 890).
15. Lips P.: Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr. Rev. 2001; 22: 477-501.
16. Holick M.F., Siris E.S., Binkley N. et al.: Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J. Clin. Endocrinol. Metab. 2005; 90: 3215-3224.
17. Heaney R.P.: Functional indices of vitamin D status and ramifications of vitamin D deficiency. Am. J. Clin. Nutr. 2004; 80 (supl. 6): 1706S-1709S.
18. Holick M.F.: Vitamin D deficiency. N. Engl. J. Med. 2007; 357: 266-281.
19. Karczmarewicz E., Pudłowski P., Łukaszkiewicz J. et al.: Witamina D – standardy diagnostyczne, kliniczna interpretacja oznaczeń. Terapia 2008; 5: 47-53.
20. Lips P.: Relative value of 25(OH)D and 1,25(OH)2D measurements. J. Bone Miner. Res. 2007; 22: 1668-1671.
21. Lips P.: Which circulating level of 25-hydroxyvitamin D is appropriate? J. Steroid Biochem. Mol. Biol. 2004; 89-90: 611-614.
22. Hernán M.A., Olek M.J., Ascherio A.: Geographic variation of MS incidence in two prospective studies of US women. Neurology 1999; 53: 1711-1718.
23. Kampman M.T., Brustad M.: Vitamin D: a candidate for the environmental effect in multiple sclerosis – observations from Norway. Neuroepidemiology 2008; 30: 140-146.
24. Islam T., Gauderman W.J., Cozen W., Mack T.M.: Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins. Neurology 2007; 69: 381-388.
25. Kampman M.T., Wilsgaard T., Mellgren S.I.: Outdoor activities and diet in childhood and adolescence relate to MS risk above the Arctic Circle. J. Neurol. 2007; 254: 471-477.
26. Munger K.L., Zhang S.M., O’Reilly E. et al.: Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62: 60-65.
27. Munger K.L., Levin L.I., Hollis B.W. et al.: Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296: 2832-2838.
28. Soilu-Hänninen M., Airas L., Mononen I. et al.: 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult. Scler. 2005; 11: 266-271.
29. Correale J., Ysrraelit M.C., Gaitán M.I.: Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 2009; 132: 1146-1160.
30. Simpson S. Jr, Taylor B., Blizzard L. et al.: Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann. Neurol. 2010; 68: 193-203.
31. Goldberg P., Fleming M.C., Picard E.H.: Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med. Hypotheses 1986; 21: 193-200.
32. Kimball S.M., Ursell M.R., O’Connor P., Vieth R.: Safety of vitamin D3 in adults with multiple sclerosis. Am. J. Clin. Nutr. 2007; 86: 645-651.
33. Mahon B.D., Gordon S.A., Cruz J. et al.: Cytokine profile in patients with multiple sclerosis following vitamin D supplementation. J. Neuroimmunol. 2003; 134: 128-132.
34. Soilu-Hänninen M., Aivo J., Lindström BM. et al.: 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. Psychiatr. 2012; 83: 565-571.
35. Burton J.M., Kimball S., Vieth R., Bar-Or A.: A phase I/II dose escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010; 74: 1852-1859.
36. Kimball S., Vieth R., Dosch H.M. et al.: Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J. Clin. Endocrinol. Metab. 2011; 96: 2826-2834.
37. Mosayebi G., Ghazavi A., Ghasami K. et al.: Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol. Invest. 2011; 40: 627-639.
38. Munger K.L., Ascherio A.: Prevention and treatment of MS: studying the effects of vitamin D. Mult. Scler. 2011; 17: 1405-1411.
39. Armas L.A., Hollis B., Heaney R.P.: Vitamin D2 is much less effective than vitamin D3 in humans. J. Clin. Endocrinol. Metab. 2004; 89: 5387-5391.
40. Kunachowicz H., Nadolna I., Przygoda B. et al.: Tabele składu i wartości odżywczej żywności. Wydawnictwo Lekarskie PZWL, Warszawa 2005.
41. Vitamin and Mineral Requirements in Human Nutrition. WHO and FAO, Rome 2004.
42. Bułhak-Jachymczak B.: Witaminy. W: Normy żywienia człowieka. Podstawy prewencji otyłości i chorób niezakaźnych. Jarosz M., Bułhak-Jachymczak B. (red.). IŻŻ, PZWL, Warszawa 2008: 172-232.
43. Institute of Medicine, Dietary Reference Intakes for Calcium and Vitamin D, Food and Nutrition Board. Nat. Acad. Press, Washington 2010.
44. Misra M., Pacaud D., Petryk A. et al.: Vitamin D deficiency in children and its management: review of current knowledge and recommendation. Pediatrics 2008; 122: 398-417.