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Significance of vitamin D for human health


Authors: S. Skácelová
Authors‘ workplace: Revmatologický ústav Praha
Published in: Čes. Revmatol., 18, 2010, No. 1, p. 26-40.
Category: Overview Reports

Overview

Vitamin D is usually perceived as a nutrition component necessary for correct skeletogenesis in the period of growth and for the sustainment of healthy bones in adults. However, it is of much greater significance. The active from of vitamin D, calcitriol, is a product of the metabolism of vitamin D in the organism. As to the structure, metabolism and mechanisms of action, calcitriol is closely related to steroid hormones. An interaction between calcitriol and its receptor takes place in the cell nucleus. Vitamin D receptor is actually a nuclear transcription factor, which is present in virtually every human cell with a nucleus. Following complicated interactions in the cell nucleus with the participation of complexes of coregulatory molecules, the gene transcription of more than 500 target genes is modulated. Calcitriol circulating in the blood stream is produced by the cells of the proximal tubule of the kidney. This secretion is regulated by the serum levels of calcium and phosphate, calcium releasing hormones and mediators, and, most of all, by the serum level of calcitriol alone. Hydroxylases, enzymes necessary for both the synthesis and degradation of calcitriol, can be expressed in a large number of tissues and cells. However, this paracrine/autocrine secretion of calcitriol is subject to other regulatory mechanisms, which explains the pleiotropic effects of vitamin D on the human organism. Lack of vitamin D is linked with higher occurrence of malignant tumours, most of all breast, prostate, and colorectal cancer, with higher occurrence of some cardiovascular risk factors, and increased occurrence of heart failure and sudden cardiac death. Calcitriol has a significant immunomodulatory effect. It plays a protective role in the development of autoimmune diseases such as type I diabetes, multiple sclerosis or idiopathic inflammatory bowel disease. It also plays a dominant role in innate immune reactions. It induces the antimicrobial peptide cathelicidin, which decreases the viability of intracellular pathogens, e.g. Mycobacterium tuberculosis. Calcium-phosphate metabolism and metabolism of the bone and the growth plate are regarded as the typical sphere of action of calcitriol. The right vitamin D saturation is essential for an optimal strength and coordination of muscles. Vitamin D supplementation, which leads to a calcidiol serum level of 75 nmol/l at least, is effective in prevention of fractures.

Key words:
vitamin D, calcitriol, VDR


Sources

1. Holick MF. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging 2007; 24(12):1017–1029.

2. Van Etten E, Stoffels K, Gysemans C, Mathieu C, et al. Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev 2008; 66(suppl 2): S125–S134.

3. Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 2009; 94: 26–34.

4. Barletta F, Dhawan P, Christakos S. Integration of hormone signaling in the regulation of human 25(OH)D3 24-hydroxylase transcription. Am J Physiol Edocrinol Metab 2004; 286: E598–E608.

5. St-Arnaud R, Arabian A, Travers R, et al. Deficient mineralization of intramembranous bone in vitamin D 24-hydroxylase ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25- dihydroxyvitamin D. Endocrinology 2000; 141: 2658-2666.

6. St-Arnaud R. The direct role of vitamin D on bone homeostasis.Arch Biochem Biophys 2008; 473(2): 225–30.

7. Bouillon R, Bischoff-Ferrari H, Willet W. Vitamin D and health: perspectives from mice and man. JBMR 2008; 23(7): 974–979.

8. Köstner K, Denzer N, Müller CS, Klein R, et al. The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the lierature. Anticancer Res 2009; 29(9): 3511–36.

9. Raimondi S, Johansson H, Maisonneuve P, Gandini S. Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk. Carcinogenesis 2009; 30(7): 1170–80.

10. Bouillon R, Carmeliet G, Verlinden L, van Etten E, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocrine Reviews 2008; 29(6): 726–776.

11. Griffin MD, Lutz W, Phan VA, et al. Dendritic cell modulation by 1alpha, 25 dihydroxyvitamin D3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci USA 2001: 98 6800–6805.

12. Mahon BD, Wittke A, Weaver V, et al. The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem 2003;89: 922–932.

13. Bhalla AK, Amento EP, Serog B, et al. 1,25-dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol 1984; 133: 1748–1754.

14. Mattner F, Smiroldo S, Galbiati F, et al. Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3. Eur J Immunol 2000; 30: 498–508.

15. Boonstra A, Barrat FJ, Crain C, Heath VL, et al. 1α,25-dihydroxyvitamin D3 has a direct effect on naive CD4+ T cels to enhance the development of Th2 cells. J Immunol 2001; 167: 4974–4980.

16. Penna G, Adorini L. 1α, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000; 164: 2405–2411.

17. Lemire JM, Archer DC, Beck LO, Spiegelberg HL. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 1995; 125: 1740S–1708S.

18. Chen S, Sims GP, Chen XX, Gu YY, et al. Modulatory effects of 1,25-hydroxyvitamin D3 on human B cell differentiation. J Immunol 2007; 179: 1634–1647.

19. Linker-Isreali M, Elstner E, Klinenberg JR, et al. Vitamin D3 and its synthetic analogs inhibit the spontaneaous in vitro immunoglobulin production by SLE-derived PBMC. Clin Immunol 2001; 99: 82–93.

20. Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes. Diabetologia 2005; 48: 1247–1257.

21. Munger KL, Zhang SM, Oŕeilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 2004; 62: 60–65.

22. Munger KL, Levin LI, Hollis BW, Howard Ns, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 2006; 296: 2832–2838.

23. Hypponen E, Laara E, Reunanen A, Jarvelin MR, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001; 358: 1500–1503

24. Merlino LA, Curtis J, Mikuls TR, et al. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Womenęs Health Study. Arthritis Rheum 2004; 50: 72–77.

25. Cutolo M, Otsa K, Laas K, et al. Circannual vitamin D serum levels and disease activity in rheumatoid arthritis: Northern versus Southern Europe. Clin Exp Rheumatol 2006; 24: 702–704.

26. Alarcon GS, Friedman AW, Straaton KV, et al. Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. Lupus in Minority populations: Nature vs. Nurture. Lupus 1999; 8: 197–209.

27. Kamen DL, Cooper GS, Bouali H, Shaftman SR, et al. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev 2006; 5: 114–117.

28. Cutolo M, Otsa K. Review: Vitamin D, immunity and lupus. Lupus 2008; 17: 6–10.

29. Cantorna MT et, Yu S, Bruce D. The paradoxical effects of vitamin D on type 1 mediated immuity. Mol Aspects Med 2008; 29(6): 369–75.

30. Wah J, Wellek A, Frankenberger M, Unterberger P, et al. Antimicrobial peptides are present in immune and host defense cells of the human respiratory and gastrointestinal tracts. Cell Tissue Res 2006; 324: 449–456.

31. Martineau AR, Wilkinson KA, Newton SM, Floto RA, et al. IFNγ and TNF-independent vitamin D-inducible human suppression of Mycobacteria: the role of cathelicidin LL-37. J Immunol 2007; 178: 7190–7198.

32. Sorensen OE, Follin P, Johnsen AH, Calafat J, et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by exracellular cleavage with proteinase 3. Blood 2001; 97(12): 3951–9.

33. Scott MG, Davidson DJ, Gold MR, Bowdish D, et al. The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 2002; 169: 3883–3891.

34. Davies PDO, Brown RC, Woodhead JS. Serum concentrations of vitamin D metabolites in untreated tuberculosis. Thorax 1985; 40: 187–190.

35. Ustianowski A, Shaffer R, Collin S, Wilkinson RJ, Davidson RN. Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London. J Infect 2005; 50: 432–437.

36. Flynn JL, Chan John. Immunology of tuberculosis. Annu Rev Immunol 2001; 19: 93–129

37. Sorensen OH, Lund B, Saltin B, Lund B, et al. Myopathy in bone loss of aging: improvement by teatment with 1alpha-hydroxycholecalciferol and calcium: Clin Sci (Colch) 1979; 56: 157–161.

38. Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporos Int 2002; 13: 187–194.

39. Dawson-Hughes B. Serum 25-hydroxyvitamin D and functional outcomes in the elderly. Am J Clin Nutr 2008; 88(suppl): 537S-40S.

40. Ward KA, Das G, Berry JL, Roberts SA, et al. Vitamin D status and muscle function in post-menarchal adolescent girls. J Clin Endocrinol Metab 2009; 94: 559–563.

41. Bishoff-Ferrari, et al. Positive association between 25-hydroxyvitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med 2004; 116(9): 634–9.

42. Bishoff-Ferrari, Dawson-Hughes B, Willett WC, et al. Effect of vitamin D on falls: a meta-analysis. JAMA 2004; 291(16): 1999–2006

43. Snijder M, van Dam R, Visser M, et al. Vitamin D and diabetes. Diabetologia 2006; 49: 217–218.

44. Mullin GE, Dobs A. Vitamin D and its role in cancer and immunity: a prescription for sunlight. Nutr Clin Pract 2007; 22: 305–322.

45. Garland CF, Gorham ED, Mohr SB, Grant WB, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem. Mol Biol 2007; 103: 708–711.

46. Giovannucci E. Strengths and limitations of current epidemiologic studies: vitamin D as a modifier of - colon and prostate cancer risk. Nutr Rev 2007:65: S77–S79.

47. Giovannucci E, Liu Y, Rimm EB, Hollis BS, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 2006; 98: 451–459.

48. Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 2007; 49: 1063–1069.

49. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity and blood pressure in the Third national Health and Nutrition Examination Survey. Am J Hypertens 2007; 20: 713–719.

50. Martins D, Wolf M, Opan D, Zadshir A, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States. Arch Intern Med 2007; 167: 1159–1165.

51. Pilz S, März W, Wellnitz B, Seelhorst U, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab 2008; 93: 3927–3935.

52. Dobnig H, Pilz S, Scharnagl H, Renner W, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 2008; 168(12): 1340–1349.

53. Autier P, Gandini S. Vitamin D supplementation and total mortality. Arch Intern Med 2007; 167(16): 1730–1737.

54. Melamed ML Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008; 168(15): 1629–1637.

55. Amling M, Priemel M, Holzmann T, et al. Rescue of the skeletal phenotype of vitamin D receptor ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology 1999; 140: 4982–4987.

56. Christakos S, Dhawan P, Shen Q, Peng X, et al.New insights into the mechanisms involved in the pleiotropic actions of 1,25 dihydroxyvitamin D3. Ann. N.Y. Acad. Sci 2006; 1068: 194–203.

57. Meyer MB, Watanuki M, Kim S, Shevde NK, et al. The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25 dihydroxyvitamin D3 in intestinal cells. Mol Endocrinol 2006; 20(6): 1447–61.

58. Pérez AV, Picotto G, Carpentieri AG, Rivoira MA, et al. Minireview on regulation of intestinal calcium absorption Digestion 2008; 77: 22–34.

59. Li YC, Amling M, Pirro AE, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism,rickets nd osteomalacia, but not alopecia in vitamin D receptor ablated mice. Endocrinology 1998; 139: 4391–4396.

60. Quarles LD. Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 2008; 118: 3820–2828.

61. Brenza HL, DeLuca HF. Regulation of 25-hydroxyvitamin D3 1α-hydroxylase gene expression by parathyroid hormone and 1,25-dihydroxyvitamin D3. Arch Biochem Biophys 2000; 381: 143–152.

62. Shinki T, Ueno Y, DeLuca HF, Suda T. Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D3 1α-hydroxylase normocalcemic rats. Proc Natl Acad Sci USA 1999; 96: 8253–8258.

63. Shimada T, Kakitani M, Yamazaki Y, et al. Targeted ablation of FGF23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 2004; 113: 561–568.

64. Atkins GJ, Anderson PH, Findlay DM, Welldon KJ, et al. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1α,25-dihydroxyvitamin D3. Bone 2007; 40(6): 1517–28.

65. Takasu H. Anti–osteoclastogenic action of active vitamin D. Nutrition Reviews 2008; 66(Suppl.2): S113–S115

66. Yashuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogeneisis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998; 95: 3597–3602.

67. Boonen S, Vanderschueren D, Cheng XG, Vergeke G, et al. Age-related (type II) femoral neck osteoporosis in men: biochemical evidence for both hypovitaminosis D and androgen deficiency-induced bone resorption. J Bone Miner Res 1997; 12: 2119–2126.

68. Chapuy MC, Schott AM, Garnero P, Hans D, et al. Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EPIDO Study Group. J Clin Endocrinol Metab 1996; 81: 1129–1133.

69. Pattanaungkul S, Riggs BL, Yergey AL, Vieira NE, et al. Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D levels in quong versus elderly women: evidence for age-related intestinal resistance to 1,25(OH)2D action. J Clin Endocrinol Metab 2000; 85: 4023–4027.

70. Bishoff-Ferrari HA, Willet WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Jama 2005; 293(18): 2257–2264.

71. Bishoff-Ferrari HA. Prevention of nonvertebral fractures with oral vitamin D and dose-dependency. Arch Intern Med 2009; 160(6): 551–561.

72. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992; 327: 1637–1642.

73. Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitain D3 (cholekalciferol) supplementation on fractures and mortality in men and women living in the community: Randomised double blind controlled trial. BMJ 2003; 326: 469–475.

74. Grant AM, Avenell A, Campbell MK, Mc Donald AM, et al. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly peolpe(Randomised Evaluation of Calcium Or vitamin D, RECORD): A randomised placebo-controlled trial. Lancet 2005; 365: 1621–1628.

75. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, et al. Womenęs Health Initiative Investigators. N Engl J Med 2006; 354: 669–683.

76. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 1996; 124: 400–406.

77. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE. 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.

78. Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, et al. Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence. Calcif Tissue Int 2006; 78: 257–270.

79. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, et al. Estimates of optimal vitamin D status. Osteoporosis Int 2005; 16: 713–716.

80. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequenses for bone loss and fractures and therapeutic implications. Endocr Rev 2001; 22: 477–501.

81. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr Rev. 2008; 66(Suppl 2): S178-181.

82. Glendenning P, Chew GT, Seymour HM, Gillett MJ, et al. Serum 25-hydroxyvitamin D levels in vitamin D-insuffficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone 2009; 45: 870–875.

83. Romagnoli E, Mascia ML, Cipriani C, Fassino V, et al. Short and long-term variations in serum calciotropic hormones after a single very large dose of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) in the elderly. J Clin Endocrinol Metab 2008; 93(8): 3015–3020.

84. Norman AW.From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 2008; 88(suppl): 491S-9S.

85. Bischoff-Ferrari HE, Dietrich T, Orav EJ, et al.Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged ≥ 60 Y. Am J Clin Nutr 2004; 80: 752–8.

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