Vitamin D and Crohn's disease in the adult patient: A review

Journal of Parenteral and Enteral Nutrition

Volumn 38, Issue 4, 2014, Pages 438-458

  Basson, Abigail ^a  

^a UNIVERSITY OF THE WESTERN CAPE   (South Africa)

Author keywords

Autoimmunity; Crohn's disease; disease activity index; Inflammatory bowel disease; vitamin D

Indexed keywords

25 HYDROXYVITAMIN D; POLYPEPTIDE ANTIBIOTIC AGENT; VITAMIN D; VITAMIN D BINDING PROTEIN; VITAMIN D RECEPTOR; IMMUNOLOGIC FACTOR; VITAMIN;

BONE; CIRCULATION; CROHN DISEASE; DENDRITIC CELL; EXCRETION; HUMAN; IMMUNE RESPONSE; IMMUNOREGULATION; NONHUMAN; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; REVIEW; STORAGE; TH1 CELL; TH17 CELL; TH2 CELL; TOXICITY; VITAMIN BLOOD LEVEL; VITAMIN D DEFICIENCY; VITAMIN D METABOLISM; VITAMIN SUPPLEMENTATION; ANIMAL; BLOOD; COMPLICATION; DIET SUPPLEMENTATION;

ANIMALS; CROHN DISEASE; DIETARY SUPPLEMENTS; HUMANS; IMMUNOLOGIC FACTORS; VITAMIN D; VITAMIN D DEFICIENCY; VITAMINS;

EID: 84899559606     PISSN: 01486071     EISSN: 19412444     Source Type: Journal    
DOI: 10.1177/0148607113506013     Document Type: Review

References (278)

1. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012 ; 142: 46-54
2. Loftus EV. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004 ; 126: 1504-1517
3. Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Gastroenterol Hepatol. 2006 ; 37: 390-407 (Pubitemid 44018812)
4. Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011 ; 86: 50-60
5. Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006 ; 92: 4-8 (Pubitemid 43831956)
6. Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it. J Am Acad Dermatol. 2006 ; 54: 301-317 (Pubitemid 43144400)
7. Mezquita Raya P, Munoz Torres M, Lopez Rodriguiz FL, et al. Prevalence of vitamin D deficiency of populations at risk of osteoporosis: impact on bone integrity. Med Clin (Barc). 2002 ; 119: 85-89 (Pubitemid 34874046)
8. Handerslev KV, Jeppersen PB, Sorensen HA, Mortensen PB, Staun M. Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection. Gut. 2003 ; 52: 653-658 (Pubitemid 36528865)
9. Vogelsang H, Ferenci P, Woloszczuk W, et al. Bone disease in vitamin D-deficient patient with Crohn's disease. Dig Dis Sci. 1989 ; 34: 1094-1099 (Pubitemid 19188893)
10. Andreassen H, Rix M, Brot C, Eskildsen P. Regulators of calcium homeostasis and bone mineral density in patients with Crohn's disease. Scand J Gastroenterol. 1998 ; 33: 1087-1093 (Pubitemid 28505654)
11. Driscoll RH, Meredith SC, Sitrin M, Rosenberg IH. Vitamin D deficiency and bone disease in patients with Crohn's disease. Gastroenterology. 1982 ; 83: 1252-1258 (Pubitemid 13235925)
12. Cantorna MT, Mahon BD. D-hormone and the immune system. J Rheumatol. 2005 ; 76: S11 - S20
13. Cantorna MT, Mahon BD. Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood). 2004 ; 229: 1136-1142 (Pubitemid 39602256)
14. Cantorna MT, Zhu Y, Froicu M, Wittke A. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr. 2004 ; 80: S1717 - S1720
15. Garg M, Lubel JS, Sparrow MP, Holt SG, Gibson PR. Review article: vitamin D and inflammatory bowel disease-established concepts and future directions. Aliment Pharmacol Ther. 2012 ; 36: 324-344
16. Lim WC, Hanauer SB, Li YC. Mechanisms of disease: vitamin D and inflammatory bowel disease. Nat Clin Pract Gastroenterol Hepatol. 2005 ; 2: 308-315 (Pubitemid 41102862)
17. Ramagopalan SV, Heger A, Berlanga AJ, et al. A CHIP-seq defined genome-wide map of vitamin D receptor binding: association with disease and evolution. Genome Res. 2010 ; 20: 1352-1360
18. Ulitsky A, Ananthakrishnan AN, Naik A, Skaros S, Zadvornova Y, Binion DG, Issa M. Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. J Parenter Enteral Nutr. 2011 ; 35: 308-316
19. Hassan V, Hassan S, Seyad-Javad P, et al. Association between serum 25(OH) vitamin D concentrations and inflammatory bowel diseases (IBDs) activity. Med J Malaysia. 2013 ; 68: 34-38
20. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011 ; 96: 1911-1930
21. Lai Y, Gallo RL. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defence. Trends Immunol. 2009 ; 30: 131-141
22. VitaminDSociety. Grassroots health brochure. June1, 2011. Available at: http://www.vitamindsociety.org/pdf/ New%20D%20Action%20Call%20to%20action%20and%20FAQ%20sheet%20Jan%2011.pdf. Accessed June 10, 2013.
23. Gallagher ML Krause's Food and Nutrition Therapy. 12 th ed. In: MahanLKEscott-StumpS, eds. Krause's Food and Nutrition Therapy. St. Louis, MO: Saunders Elsevier; 2008:74-78. Mahan LK Escott-Stump S, ed. St. Louis, MO: Saunders Elsevier ; 74-78.
24. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008 ; 88: S582 - S586
25. Holick MF. Vitamin D deficiency. N Engl J Med. 2007 ; 357: 266-281
26. Omdahl JL, Morris HA, May BK. Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Annu Rev Nutr. 2002 ; 22: 139-166 (Pubitemid 35221457)
27. Ardizzone S, Cassinotti A, Bevilacqua M, Clerici M, Porro GB Vitamins and Hormones. Thimann KV, ed. New York: Academic Press ; 367-377.
28. Kamen DL. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. J Mol Med (Berl). 2010 ; 88: 441-450
29. Cross HS. Extrarenal vitamin D hydroxylase expression and activity in normal and malignant cells: modification of expression by epigenetic mechanisms and dietary substances. Nutr Rev. 2007 ; 65: S108 - S112
30. Mawer EB, Backhouse J, Holman CA, Lumb GA, Stanbury SW. The distribution and storage of vitamin D and its metabolites in human tissues. Clin Sci. 1972 ; 43: 413-431
31. Powe CE, Ricciardi C, Berg AH, et al. Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res. 2011 ; 26: 1609-1616
32. The Pharmacology of Vitamin D, Including Fortification Strategies. 2 nd ed.London: Elsevier; 2005. Vieth R, ed. London: Elsevier ; 2005 :
33. Plum LA, DeLuca HF. Vitamin D disease and therapeutic opportunities. Nat Rev Drug Discov. 2010 ; 9: 941-955
34. Zimmerman DR, Reinhardt TA, Kremer R, Beitz DC, Reddy GS, Horst RL. Calcitroic acid is a major catabolic metabolite in the metabolism of 1 alpha-dihydroxyvitamin D(2). Arch Biochem Biophys. 2001 ; 392: 14-22 (Pubitemid 32721609)
35. Chun RF. New perspectives on the vitamin D binding protein. Cell Biochem Funct. 2012 ; 30: 445-456
36. Chishimba L, Thickett DR, Stockely RA, Wood AM. The vitamin D axis in the lung: a key role for vitamin D-binding protein. Thorax. 2010 ; 65: 456-462
37. Chun RF, Lauridsen AL, Suon L, et al. Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab. 2010 ; 95: 3376-3386
38. Rowling MJ, Kemmis CM, Taffany DA, Welsch J. Megalin-mediated protein correlates with 25-hydroxycholecalciferol actions in human mammary cells. J Nutr. 2006 ; 136: 2754-2759 (Pubitemid 44771769)
39. Atkins GJ, Anderson PH, Findlay DM, et al. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1 alpha, 25-dihydroxyvitamin D3. Bone. 2007 ; 40: 1517-1528 (Pubitemid 46756427)
40. Nykjaer A, Dragun D, Walther D, et al. An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999 ; 96: 507-515 (Pubitemid 29106838)
41. Chun RF, Adams JS, Hewison M. Back to the future: a new look at 'old' vitamin D. J Endocrinol. 2008 ; 198: 261-269
42. Arnaud J, Constans J. Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet. 1993 ; 92: 183-288
43. Lauridsen AL, Vestergaard P, Hermann AP, Brot C, Heickendorff L, Mosekilde L, Nexo E. Plasma concentrations of 25-hydroxyvitamin D are related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional study on 595 early postmenopausal women. Calcif Tissue Int. 2005 ; 77: 15-22 (Pubitemid 41504168)
44. Fang Y, van Meurs JB, Arp P, van Leeuwen JPT, Hofman A, Pols H, Uitterlinden AG. Vitamin D binding protein genotype and osteoporosis. Calcif Tissue Int. 2009 ; 85: 85-93
45. Gozdzik A, Zhu J, Wong BY, Fu L, Cole DE, Parra EJ. Association of vitamin D binding protein (VDBP) polymorphisms and serum 25 (OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol. 2011 ; 127: 405-412
46. Engelman CD, Fingerlin TE, Langefeld CD, et al. Genetic and environmental determinants of 25-hydroxyvitamin D and 1,25 hydroxyvitamin D levels in Hispanic and African Americans. J Clin Endocrinol Metab. 2008 ; 93: 3381-3388
47. Chun RF, Peercy BE, Adams JS, Hewison M. Vitamin D binding protein and monocyte response to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: analysis by mathematical modelling. PLoS ONE. 2012 ; 7: e30773
48. Anderson LN, Cotterchio M, Cole DE, Knight JA. Vitamin-D related genetic variants, interactions with vitamin D exposure, and breast cancer risk among Caucasian women in Ontario. Cancer Epidemiol Biomarkers Prev. 2011 ; 20: 1708-1717
49. Abbas S, Linseisen J, Slanger T, et al. The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status. Cancer Epidemiol Biomarkers Prev. 2008 ; 17: 1339-1343
50. Orton SM, Ramagopalan SV, Para AE, et al. Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. J Neurol Sci. 2011 ; 305: 116-120
51. Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis. 2007 ; 66: 1137-1142 (Pubitemid 47309727)
52. Jones G, Strugnell SA, DeLuca HF. Current understanding of the molecular actions of vitamin D. Physiol Rec. 1998 ; 78: 1193-1231 (Pubitemid 28491953)
53. Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology. 2006 ; 147: 5542-5548 (Pubitemid 44833469)
54. Boland RL. VDR activation of intracellular signalling pathways in skeletal muscle. Mol Cell Endocrinol. 2011 ; 347: 11-16
55. Sone T, Marx SJ, Liberman UA, Pike JW. A unique point mutation in the human vitamin D receptor chromosomal gene confers hereditary resistance to 1,25-dihydroxyvitamin D3. Mol Endocrinol. 1990 ; 4: 623-631
56. Valdvielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006 ; 371: 1-12 (Pubitemid 44162891)
57. Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, Kumar R. Dendritic cell modulation by 1alpha,25 dihydroxyvitamin D3 and its analogs: a vitamin D receptor-dependant pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci USA. 2001 ; 98: 6800-6805 (Pubitemid 32538297)
58. Berer A, Stockl J, Majdic O, et al. 1,25-Dihydroxyvitamin D(3) inhibits dendritic cell differentiation and maturation in vitro. Exp Hematol. 2000 ; 28: 575-583 (Pubitemid 30254459)
59. Belsey R, Clark MB, Bernat M, et al. The physiologic significance of plasma transport of vitamin D and metabolites. Am J Med. 1974 ; 57: 50-56
60. Haddad JG, Chuy KJ. Competitive protein binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol Metab. 1971 ; 33: 992-995
61. Chen TC, Turner AK, Holick MF. Methods for the determination of the circulating concentration of 25-hydroxyvitamin D. J Nutr Biochem. 1990 ; 1: 315-319 (Pubitemid 20246336)
62. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006 ; 116: 2062-2072 (Pubitemid 44162310)
63. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006 ; 81: 353-373 (Pubitemid 43334631)
64. Bouillon R Endocrinology. DeGroot LJ Jameson JL, ed. Philadelphia: WB Saunders ; 1009-1028.
65. Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status (editorial). Osteoporosis Int. 2005 ; 16: 713-716 (Pubitemid 40933586)
66. Holick MF. Vitamin D status: measurement, interpretation and clinical application. Ann Epidemiol. 2009 ; 19: 73-78
67. Brown EM, Gamba G, Riccardl D, Lombardi M, Butters, Klfor O. 1 cloning and characterization of an extracellular Ca2+ sensing receptor from bovine parathyroid. Nature. 1993 ; 366: 575-580 (Pubitemid 24035999)
68. Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet. 1998 ; 351: 805-806 (Pubitemid 28112350)
69. Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, Nickelsen T. A global study of vitamin D status and parathyroid function in postmenapausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab. 2001 ; 86: 1212-1221 (Pubitemid 32323007)
70. Bischoff-Ferrari HA, Giovannucci E, Willet WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 ; 84: 18-28 (Pubitemid 44699167)
71. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003 ; 22: 142-146 (Pubitemid 36417827)
72. Chapuy MC, Prexiosi P, Maamer M, et al. Prevalence of vitamin D insufficiency in adult normal population. Osteoporosis Int. 1997 ; 7: 439-443 (Pubitemid 27443069)
73. Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency among free-living healthy young adults. Am J Med. 2002 ; 112: 659-662 (Pubitemid 34597167)
74. Chapuy MC, Chapuy P, Thomas JL, Hazard MC, Meunier PJ. Biochemical effects of calcium and vitamin D supplementation in elderly, institutionalized, vitamin D-deficient patients. Rev Rhum. 1996 ; 63: 135-140 (Pubitemid 26078662)
75. Ross AC. The. 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr. 2011 ; 14: 938-939
76. Granado-Lorencio F, Rubio E, Navarro-Blanco L, Sacritan-Perez B, Rodriguez-Pena R, Lopez Garcia FJ. Hypercalcemia, hypervitaminosis A and 3-epi-26-OH-D3 levels after consumption of an "over the counter" vitamin D remedy. A case report. Food Chem Toxicol. 2012 ; 50: 2106-2108
77. Engel MA, Neurath MF. New pathophysiological insights and modern treatment of IBD. J Gastroenterol. 2010 ; 45: 571-583
78. Spencer DM, Veldman GM, Banerjee S, Willis J, Levine AD. Distinct inflammatory mechanisms mediate early versus late colitis in mice. Gastroenterology. 2002 ; 122: 94-105 (Pubitemid 34049199)
79. Bamias G, Martin C, Mishina M, Ross WG, Rivera-Nieves R, Marini M, Cominelli F. Proinflammatory effects of Th2 cytokines in murine model of chronic small intestinal inflammation. Gastroenterology. 2005 ; 128: 654-666 (Pubitemid 40585368)
80. Neissner M, Volk BA. Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reverse transcribed polymerase chain reaction (RT-PCR). Clin Exp Immunol. 1995 ; 101: 428-435
81. Aranda R, Sydora BC, McAllister PL, et al. Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+, CD45RB high cells in SCID recipients. J Immunol. 1997 ; 258: 3464-3473 (Pubitemid 127484068)
82. Bregenholt S, Claesson MH. Increased intracellular Th1 cytokine in SCID mice with inflammatory bowel disease. Eur J Immunol. 1998 ; 28: 379-389 (Pubitemid 28048308)
83. Bengmark S. Bioecological control of inflammatory bowel disease. Clin Nutr. 2007 ; 26: 169-181 (Pubitemid 46477826)
84. D'Haens G. Anti-TNF therapy for Crohn's disease. Curr Pharma Design. 2003 ; 9: 289-294 (Pubitemid 36131723)
85. Ferguson LR, Shelling AN, Browning BL, Huebner C, Peterman I. Genes, diet and inflammatory bowel disease. Mutat Res. 2007 ; 622: 70-83 (Pubitemid 47214578)
86. Gitter AH, Bendfeldt K, Schulzke JD, Fromm M. Leaks in the epithelial barrier caused by spontaneous and TNF-alpha induced single-cell apoptosis. Faseb F. 2000 ; 14: 1749-1753
87. Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI. Increased intestinal permeability in patients with Crohn's disease and their relatives. A possible etiologic factor. Ann Intern Med. 1986 ; 105: 883-885 (Pubitemid 17201765)
88. Einstein EM, Williams CB. The T(reg)/Th17 cell balance: a new paradigm for autoimmunity. Pediatr Res. 2009 ; 65: 26R - 31R
89. Harrington LE, Mangan PR, Weaver CT. Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol. 2006 ; 18: 349-356
90. Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007 ; 25: 821-852 (Pubitemid 46697925)
91. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006 ; 24: 179-189 (Pubitemid 43214587)
92. McGeachy MJ, Chen Y, Tato CM, et al. The interleukin 23 receptor is essential for the terminal differentiation of interleukin-17 producing effector T helper cells in vivo. Nat Immunol. 2009 ; 10: 314-324
93. Strober W, Zhang F, Kitani A, Fuss I, Fichtner-Feigl S. Pro-inflammatory cytokines underlying the inflammation of Crohn's disease. Curr Opin Gastroenterol. 2010 ; 26: 310-317
94. McGeachy JM, Bak-Jensen KS, Chen Y, et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol. 2007 ; 8: 1390-1397 (Pubitemid 350138974)
95. Elson CO, Cong Y, Weaver CT, et al. Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology. 2007 ; 132: 2359-2370 (Pubitemid 46890867)
96. Hue S, Ahern P, Buonocore S, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J Exp Med. 2006 ; 203: 2473-2483 (Pubitemid 44664617)
97. Fujino S, Andoh A, Bamba S, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003 ; 52: 65-70 (Pubitemid 36020767)
98. Fuss IJ, Becker C, Yang Z, et al. Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL12 p40 monoclonal antibody. Inflamm Bowel Dis. 2006 ; 12: 9-15 (Pubitemid 43032445)
99. Schmidt C, Giese T, Ludwig B, et al. Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 Crohn's disease but not in ulcerative colitis. Inflamm Bowel Dis. 2005 ; 11: 16-23 (Pubitemid 40340252)
100. Yen D, Cheung J, Scheerens H, et al. Il-23 is essential for T-cell mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest. 2006 ; 116: 1310-1316
101. Dam TN, Moller B, Hindkjaer J, Kragballe K. The vitamin D3 analog calcipotriol suppresses the number and antigen-presenting function of Langerhans cells in normal human skin. J Investig Dermatol Symp Proc. 1996 ; 1: 72-77 (Pubitemid 126759346)
102. Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004 ; 21: 467-476 (Pubitemid 39370503)
103. Evans KN, Bulmer JN, Kilby MD, Hewison M. Vitamin D and placental-decidual function. J Soc Gynecol Investig. 2004 ; 11: 263-271 (Pubitemid 38833606)
104. Fabri M, Stenger S, Shin DM, et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med. 2011 ; 3 (104). 104ra102
105. Mahon BD, Wittke A, Weaver V, Cantorna MT. The targets of vitamin D depend on the differentiation and activation status of CD4-positive T cells. J Cell Biochem. 2003 ; 89: 922-932 (Pubitemid 36927724)
106. Lemire JM, Adams JS. Immunomodulatory role of 1,25-dihydroxyvitamin D3 inhibits the passive transfer of cellular immunity by a myelin basic protein-specific T cell clone. J Bone Miner Res. 1992 ; 7: 171-177
107. Lemire JM, Archer DC. 1,25-Dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Investig. 1991 ; 87: 1101-1107
108. Lemire JM. Immunomodulatory role of 1,25-dihydroxyvitamin D3. J Cell Biochem. 1992 ; 49: 26-31
109. Lemire JM, Archer DC, Beck L, Spiegelberg HL. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr. 1995 ; 125: S1704 - S1708
110. Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys. 2000 ; 374: 334-338 (Pubitemid 30120270)
111. Bhalla AK, Amento EP, Serog B, Glimcher LH. 1,25-dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol. 1984 ; 133: 1748-1754 (Pubitemid 14035260)
112. Zhang Y, Leung DY, Richers BN, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012 ; 188: 2127-2135
113. Palmer MT, Lee YK, Maynard CI, et al. Lineage-specific effects of 1,25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J Biol Chem. 2011 ; 286: 997-1004
114. Jonuleit H, Schmitt E. The regulatory T cell family: distinct subsets and their interrelations. J Immunol. 2003 ; 171: 6323-6327 (Pubitemid 37532056)
115. Veldman C, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys. 2000 ; 374: 334-338 (Pubitemid 30120270)
116. Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol. 2006 ; 92: 60-64 (Pubitemid 43831951)
117. Andreassen H, Rungby J, Dahlerup JF, Mosekilde L. Inflammatory bowel disease and osteoporosis. Scand J Gastroenterol. 1997 ; 32: 1247-1255 (Pubitemid 28023130)
118. Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr. 2000 ; 130: 2648-2652
119. Bemiss CJ, Mahon BD, Henry A, Weaver V, Cantorna MT. Interleukin-2 is one of the targets of 1,25-dihydroxyvitamin D3 in the immune system. Arch Biochem Biophys. 2002 ; 402: 249-254 (Pubitemid 34848643)
120. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10- deficient mice develop chronic enterocolitis. Cell. 1993 ; 75: 263-274 (Pubitemid 23320290)
121. Narula SK, Cutler D, Grint P. 1,25-Dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Investig. 1998 ; 87: 1103-1107
122. Barrat FJ, Cua DJ, Boonstra A, et al. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med. 2002 ; 195: 603-616 (Pubitemid 34461505)
123. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O'Garra A. 1 alpha, 25-dihydroxyvitamin D3 has a direct effect on naïve CD4(+) T cells to enhance the development of Th2 cells. J Immunol. 2001 ; 167: 4974-4980 (Pubitemid 33009728)
124. Cantorna MT, Humpal-Winter J, DeLuca HF. Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice. J Nutr. 1999 ; 129: 1966-1971 (Pubitemid 29506371)
125. Cantorna MT, Humpal-Winter J, DeLuca HF. In vivo up-regulation of interleukin-4 is one mechanism underlying the immunoregulatory effects of 1,25-dihydroxyvitamin D3. Arch Biochem Biophys. 2000 ; 377: 135-138 (Pubitemid 30257297)
126. Chang JH, Cha HR, Lee DS, Seo KY, Kweon MN. 1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H)17 cells to protect against experimental autoimmune encephalomyeclitis. PLoS ONE. 2010 ; 5: e12925
127. Xue ML, Zhu H, Thakur A, Willcox M. 1 alpha,25-Dihydroxyvitamin D3 inhibits pro-inflammatory cytokine and chemokine expression in human corneal epithelial cells colonized with Pseudomonas aeruginosa. Immunol Cell Biol. 2002 ; 80: 340-345 (Pubitemid 34779691)
128. Stockinger B. Th17 cells: an orphan with influence. Immunol Cell Biol. 2007 ; 85: 83-84 (Pubitemid 46398729)
129. Daniel C, Sartory NA, Zhan N, Radeke HH, Stein JM. Immune modulatory treatment of TNBS colitis with calcitriol is associated with a change of a Th1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther. 2007 ;:
130. Liu N, Nguyen L, Chun RF, et al. Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation. Endocrinology. 2008 ; 149: 4799-4808
131. Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007 ; 7: 179-190
132. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007 ; 449: 819-826 (Pubitemid 47598622)
133. Weber G, Heilborn JC, Chamorro Jimenez CI, Hammarsjo A, Torma H, Stahle M. Vitamin D induces the antimicrobial protein hCAP18 in human skin. J Invest Dermatol. 2005 ; 124: 1080-1082 (Pubitemid 40629115)
134. Bals R, Wang X, Zasloff M, Wilson JM. The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA. 1998 ; 95: 9541-9546 (Pubitemid 28506267)
135. Gallo RL, Kim KJ, Bernfiels M, et al. Identification of CRAMP, a cathelin-related antimicrobial peptide expressed in the embryonic and adult mouse. J Biol Chem. 1997 ; 272: 13088-13093 (Pubitemid 27216731)
136. Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25- dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004 ; 173: 2909-2912 (Pubitemid 39141992)
137. Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. Faseb J. 2005 ; 19: 1067-1077 (Pubitemid 40946432)
138. Gombart AF, O'Kelly J, Saito T, Koeffler HP. Regulation of the CAMP gene by 1,25(OH)2D3 in various tissues. J Steroid Biochem Mol Biol. 2007 ; 103: 552-557 (Pubitemid 46420532)
139. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 ; 311: 1770-1773
140. Lehmann B, Rudolph T, Pietzsch J, Meurer M. Conversion of vitamin D3 to 1alpha, 25-dihydroxyvitamin D3 in human skin equivalents. Exp Dermatol. 2000 ; 9: 97-103 (Pubitemid 30192707)
141. Szeles L, Keresztes G, Torocsik D, et al. 1,25-dihydroxyvitamin D3 is an autonomous regulator of the transcriptional changes leading to a tolerogenic dendritic cell phenotype. J Immunol. 2009 ; 182: 2074-2083
142. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci USA. 1996 ; 93: 7861-7864 (Pubitemid 26277129)
143. Brennan A, Katz DR, Nunn JD, et al. Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol. Immunology. 1987 ; 61: 457-461 (Pubitemid 17127352)
144. Yuk JM, Shin DM, Lee HM, et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009 ; 6: 231-243
145. Griffin MD, Lutz WH, Phan VA, Bachman LA, McKean DJ, Kumar R. Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem Biophys Res Commun. 2000 ; 279: 701-708 (Pubitemid 30444768)
146. Penna G, Adorini L. 1 alpha, 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 (Pubitemid 30115468)
147. Piemonti L, Monti P, Sironi M, et al. Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol. 2000 ; 164: 4443-4451 (Pubitemid 30238038)
148. Canning MO, Grotenhuis K, de Wit H, Ruwhof C, Drexhage HA. 1-alpha, 25-dihydroxyvitaimin D3 (1,25(OH)(2)(D3)) hampers the maturation of fully active immature dendritic cells from monocytes. Eur J Endocrinol. 2001 ; 145: 351-357 (Pubitemid 32825669)
149. Ascherio A, Munger KL, Simon KC. Vitamin D and multiple sclerosis. Lancet Neurol. 2010 ; 9: 599-612
150. Palmer MT, Weaver CT. Linking vitamin D deficiency to inflammatory bowel disease. Inflamm Bowel Dis. 2013 ; 0: 1-12
151. Cario E. Heads up! How the intestinal epithelium safeguards mucosal barrier immunity through the inflammasome and beyond. Curr Opin Gastroenterol. 2010 ; 26: 583-590
152. Henderson P, van Limbergen JE, Schwarze J, Wilson DC. Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease. Inflamm Bowel Dis. 2011 ; 17: 382-395
153. Schulzke JD, Ploeger S, Amasheh M, et al. Epithelial tight junctions in intestinal inflammation. Ann NY Acad Sci. 2009 ; 1165: 294-300
154. Duchmann R, Kaiser I, Hermann E, et al. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease. Clin Exp Immunol. 1995 ; 102: 448-455 (Pubitemid 26013210)
155. Scharl M, Paul G, Weber A, et al. Protection of epithelial barrier function by the Crohn's disease associated gene protein tyrosine phosphatase n2. Gastroenterology. 2009 ; 137: 2030-2040e5
156. Waterman M, Xu W, Stempak JM, et al. Distinct and overlapping genetic loci in Crohn's disease and ulcerative colitis: correlations with pathogenesis. Inflamm Bowel Dis. 2011 ; 17: 1936-1942
157. Walsh SJ, Rau LM. Autoimmune diseases: a leading cause of death among young and middle-aged women in the United States. Am J Public Health. 2000 ; 90: 1463-1466
158. Greenstein AJ, Janowitz HD, Sachar DB. The extra-intestinal complications of Crohn's disease and ulcerative colitis. A study of 700 patients. Medicine. 1976 ; 55: 401-412
159. Ardizzone S, Puttini PS, Cassinotti A, Porro GB. Extraintestinal manifestations of inflammatory bowel disease. Dig Liver Dis. 2008 ; 40: S253 - S259
160. Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population based study. Am J Gastroenterol. 2001 ; 10: 178-184
161. Williams H, Walker D, Orchard TR. Extraintestinal manifestations of inflammatory bowel disease. Curr Gastroenterol Rep. 2008 ; 10: 597-605
162. Best WR, Becktel JM, Singleton JW, Kern F. Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. Gastroenterology. 1976 ; 70: 439-444
163. Harvey R, Bradshaw J. A simple index of Crohn's disease activity. Lancet. 1980 ; 1: 514
164. Fiocci C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. 1998 ; 115: 182-205
165. Scaldaferri F, Fiocci C. Inflammatory bowel disease: Progress and current concepts of ethiopathogenesis. J Dig Dis. 2007 ; 8: 171-178
166. Mayer L. Evolving paradigms in the pathogenesis of IBD. J Gastroenterol. 2010 ; 45: 9-16
167. Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation I NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 ; 411: 603-606 (Pubitemid 32531409)
168. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2
169. Peltekova VD, Wintle RF, Rubin LA, et al. Functional variants of OCTN cation transporter genes are associated with Crohn's disease. Nat Genet. 2004 ; 36: 471-475 (Pubitemid 38620030)
170. Hampe J, Franke A, Rosenstiel P, et al. A genome-wide association variant for Crohn disease I ATG16L1. Nat Genet. 2007 ; 39: 207-211
171. Rioux JD, Xavier RJ, Taylor KD, et al. Genome-wide association study identifies new susceptibility loci for Crohn's disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 ; 39: 596-604 (Pubitemid 46676115)
172. Deurr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 ; 314: 1461-1463 (Pubitemid 44871953)
173. Binder V. Genetic epidemiology in inflammatory bowel disease. Dig Dis. 1998 ; 16: 351-355 (Pubitemid 128525942)
174. Yang H, Rotter JI Inflammatory Bowel Disease. 4 th ed.Baltimore, MD: Williams & Wilkins. 1995:301-331. Kirsner JB Shorter RG, ed. Baltimore, MD: Williams & Wilkins ; 301-331.
175. Orholm M, Binder V, Sorensen TI, Rasmussen LP, Kvyvik KO. Concordance of inflammatory bowel disease among Danish twins: results of a nationwide study. Scand J Gastroenterol. 2000 ; 101: 993-1002
176. Tysk C, Lindberg D, Jarnerot G, Floderus-Myrhed B. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins: a study of heritability and the influence of smoking. Gut. 1988 ; 29: 990-996
177. Thompson NP, Driscoll R, Pounder RE, Wakefield AJ. Genetics versus environment in inflammatory bowel disease: results of a British twin study. BMJ. 1996 ; 312: 95-96 (Pubitemid 26015449)
178. Halfvarson J, Bodin L, Tysk C, Lindberg E, Garnerot G. Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance in clinical characteristics. Gastroenterology. 2003 ; 124: 1767-1773 (Pubitemid 36666773)
179. Cosnes J, Beaugerie L, Carbonnel F, Gendre JP. Smoking cessation and the course of Crohn's disease: an intervention study. Gastroenterology. 2001 ; 120: 1093-1099 (Pubitemid 32246663)
180. Logan RF, Edmond M, Somerville KW, Langman MJ. Smoking and ulcerative colitis. Br Med J (Clin Res Ed). 1984 ; 288: 751-753 (Pubitemid 14117953)
181. Mahid SS, Minor KS, Soto RE, Hornung CA, Galandiuk S. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clinic Proc. 2006 ; 81: 1462-1471 (Pubitemid 44687433)
182. Duggan AE, Usmani I, Neal KR, Logan RF. Appendectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case control study. Gut. 1998 ; 43: 494-498 (Pubitemid 28462034)
183. Cornish JA, Tan E, Simillis C, Clark SK, Teare J, Tekkis PP. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am J Gastroenterol. 2008 ; 103: 2394-2400
184. Klement E, Cohen RV, Boxman J, Joseph A, Reif S. Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. Am J Clin Nutr. 2004 ; 80: 1342-1352
185. Card T, Logan RFA, Rodrigues LC. Antibiotic use and the development of Crohn's disease. Gut. 2004 ; 53: 246-250 (Pubitemid 38125513)
186. Chapman-Kiddell CA, Davies PS, Gillen L, Radford-Smith GL. Role of diet in the development of inflammatory bowel disease. Inflamm Bowel Dis. 2010 ; 16: 137-151
187. Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol. 2011 ; 106: 563-573
188. Farrokyar F, Swarbrick ET, Irvine EJ. A critical review of epidemiological studies in inflammatory bowel disease. Scand J Gastroenterol. 2001 ; 36: 2-15 (Pubitemid 32147176)
189. Tsironi E, Feakins RM, Roberts CSJ, Rampton DS. Incidence of inflammatory bowel disease is rising and abdominal tuberculosis is falling in Bangladesh in East London, United Kingdom. Am J Gastroenterol. 2004 ; 99: 1749-1755 (Pubitemid 39237504)
190. Bernstein CN, Shanahan F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases. Gut. 2008 ; 57: 1185-1191
191. Mikhailov TA, Furner SE. Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children. World J Gastroenterol. 2009 ; 15: 270-279
192. Wilson J, Hair C, Knight R, et al. High incidence of inflammatory bowel disease in Australia: a prospective population-based Australian incidence study. Inflamm Bowel Dis. 2010 ; 16: 1550-1556
193. Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011 ; 140: 1785-1794
194. Baumgart DC, Bernstein CN, Abbas Z, et al. Around the world: comparing the epidemiology, diagnosis and treatment: proceedings of the World Digestive Health Day. 2010 - inflammatory bowel disease task force meeting. Inflam Bowel Dis. 2011 ; 17: 639-644
195. Gearry RB, Richardson A, Frampton CM, et al. High incidence of Crohn's disease in Canterbury, New Zealand: results of an epidemiologic study. Inflamm Bowel Dis. 2006 ; 12: 936-943 (Pubitemid 44498282)
196. Shivananda S, Lennard-Jones J, Logan R, et al. Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD). Gut. 1996 ; 39: 690-697 (Pubitemid 26426470)
197. Khalili H, Huang ES, Ananthakrishnan AN, et al. Geographical variation and incidence of inflammatory bowel disease among US women. Gut. 2012 ; 12: 1686-1692
198. Nerich V, Jantchou P, Boutron-Ruault MC, et al. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther. 2011 ; 33: 940-945
199. Carr I, Mayberry JF. The effects of migration on ulcerative colitis: a three-year prospective study among Europeans and first- and second-generation South Asians in Leicester (1991-1994). Am J Gastroenterol. 1999 ; 94: 2918-2922 (Pubitemid 29482758)
200. Moum B, Aadland E, Ekbom A, Vatn MH. Seasonal variations in the onset of ulcerative colitis. Gut. 1996 ; 38: 376-378 (Pubitemid 26074317)
201. Zeng L, Anderson FH. Seasonal change in the exacerbations of Crohn's disease. Scand J Gastroenterol. 1996 ; 31: 79-82 (Pubitemid 26018609)
202. Lamb EJ, Wong T, Smith DJ, et al. Metabolic bone disease is present at diagnosis in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2002 ; 16: 1895-1902 (Pubitemid 35253005)
203. Ananthakrishnan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, Richter JM, Fuchs CS, Chan AT. Higher predicted vitamin D status is associated with reduced risk of Crohn's disease. Gastroenterology. 2012 ; 142: 482-489
204. Cantorna MT. Micronutrients and the immune system. Mechanisms underlying the effect of vitamin D on the immune system. Proc Nutr Soc. 2010 ; 69: 286-289
205. Leslie WD, Miller N, Rogala L, Bernstein CN. Vitamin D status and bone mineral density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Am J Gastroenterol. 2008 ; 103: 1451-1459 (Pubitemid 351813899)
206. Silvennoinen J. Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease. J Intern Med. 1996 ; 239: 131-137 (Pubitemid 26043148)
207. Tajika M, Matsura A, Nakamura T, et al. Risk factors for vitamin D deficiency in patients with Crohn's disease. J Gastroenterol. 2004 ; 39: 527-533 (Pubitemid 38996894)
208. McCarthy D, Duggan P, O'Brien M, et al. Seasonality of vitamin D status and bone turnover in patients with Crohn's disease. Aliment Pharmacol Ther. 2005 ; 21: 1073-1083 (Pubitemid 40646532)
209. Siffledeen JS, Siminoski K, Steinhart H, Greenberg G, Fedorak RN. The frequency of vitamin D deficiency in adults with Crohn's disease. Can J Gastroenterol. 2003 ; 17: 473-478 (Pubitemid 37321992)
210. Levin AD, Wadhera V, Leach ST, et al. Vitamin D deficiency in children with inflammatory bowel disease. Dig Dis Sci. 2011 ; 56: 830-836
211. Jahnsen J, Falch JA, Mowinckel P, Aadland E. Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Scand J Gastroenterol. 2002 ; 37: 192-199 (Pubitemid 34102257)
212. Vogelsang H, Ferenci P, Resch H, Kiss A, Gangl A. Prevention of bone mineral loss in patients with Crohn's disease by long-term oral vitamin D supplementation. Eur J Gastroenterol Hepatol. 1995 ; 7: 609-614
213. Bischoff SC, Herrmann A, Goke M, Manns A, ZurMuhlen V, Bragant G. Altered bone metabolism in inflammatory bowel disease. Am J Gastroenterol. 1997 ; 92: 1157-1163 (Pubitemid 27304813)
214. Leichtmann GA, Bengoa JM, Bolt MJ, Sitrin MD. Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection. Am J Clin Nutr. 1991 ; 51: 548-552 (Pubitemid 21898967)
215. Sentonago TA, Semaeco EJ, Stettler N, Piccoli A, Stallings VA, Zemel BS. Vitamin D status in children, adolescents, and young adults with Crohn's disease. Am J Clin Nutr. 2002 ; 76: 1107-1181
216. Zhou C, Assem M, Tay JC, et al. Steroid and xenobiotic receptor and vitamin D receptor crosstalk mediates CYP24 expression and drug-induced osteomalacia. J Clin Invest. 2006 ; 116: 1703-1712
217. Gilman J, Shanahan F, Cashman KD. Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use. Eur J Clin Nutr. 2006 ; 60: 889-896 (Pubitemid 43997702)
218. Gilman J, Shanahan F, Cashman K. Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease. Aliment Pharmacol Ther. 2006 ; 23: 1107-1116
219. Chatu S, Chhaya V, Holmes R, et al. Factors associated with vitamin D deficiency in a multicultural inflammatory bowel disease cohort. Frontline Gastroenterol. 2013 ; 4: 51-56
220. Farraye FA, Nimitphong H, Stucci A, et al. Use of a novel vitamin D bioavailability test demonstrates that vitamin D absorption is decreased in patients with quiescent Crohn's disease. Inflamm Bowel Dis. 2011 ; 17: 2116-2121
221. Basson A. Nutrition management in the adult patient with Crohn's disease. S Afr J Clin Nutr. 2012 ; 25: 164-172
222. Blain A, Cattan S, Beaugerie L, Carbonnel F, Gendre JP, Cosnes J. Crohn's disease clinical course and severity in obese patients. Clin Nutr. 2002 ; 21: 51-57
223. Hass DJ, Brensinger CM, Lewis JD, Lichtenstein GR. The impact of increased body mass index on the clinical course of Crohn's disease. Clin Gastroenterol Hepatol. 2006 ; 4: 482-488
224. Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH. Low circulating vitamin D in obesity. Calcif Tissue Int. 1988 ; 43: 199-201
225. Parikh SJ, Edelman M, Uwaifo GI, et al. The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab. 2004 ; 89: 1196-1199 (Pubitemid 38368412)
226. Holick MF, Matsuoka LY, Wortsman J. Age, vitamin D, and solar ultraviolet (letter). Lancet. 1989 ; 2: 1104-1105 (Pubitemid 19264108)
227. Maclaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest. 1985 ; 76: 1536-1538 (Pubitemid 16193572)
228. Berry D, Hypponen E. Determinants of vitamin D status: focus on genetic variations. Curr Opin Nephrol Hypertens. 2011 ; 20: 331-336
229. Wang TJ, Zhang F, Richards JB, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010 ; 376: 180-188
230. Meyer JE, Smedshaug GB, Kvaavik E, Falch JA, Tverdal A, Pedersen JL. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res. 2002 ; 17: 709-715 (Pubitemid 34246647)
231. Larsen ER, Mosekilde I, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res. 2004 ; 19: 370-378 (Pubitemid 38787391)
232. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr. 2003 ; 77: 204-210 (Pubitemid 36015393)
233. Tilg H, Moschen AR, Kaser A, Pines A, Dotan I. Gut, inflammation and osteoporosis: basic and clinical concepts. Gut. 2008 ; 57: 684-694 (Pubitemid 351579985)
234. Bhottoa HP, Bettembuk P, Ganacharya S, Balogh A. Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women. Osteoporos Int. 2004 ; 15: 447-451 (Pubitemid 38843172)
235. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Positive association between 25-hydrozy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med. 2004 ; 116: 634-639 (Pubitemid 38490539)
236. Mezquita-Raya P, Munoz-Torres M, Luna JD, et al. Relation between vitamin D insufficiency, bone density, and bone metabolism in healthy postmenapausal women. J Bone Miner Res. 2001 ; 16: 1408-1415 (Pubitemid 32675192)
237. Serhan E, Holland MR. Relationship of hypovitaminosis D and secondary hyperparathyroidism with bone mineral density among UK resident Indo-Asians. Ann Rheum Dis. 2002 ; 61: 456-458 (Pubitemid 34496827)
238. Abitol V, Roux C, Guillemant S, et al. Bone assessment in patients with ileal pouch-anal anastomosis for inflammatory bowel disease. Br J Surg. 1997 ; 84: 1551-1554 (Pubitemid 27485530)
239. Ardizzone S, Bollani S, Betticia P, Bevilacqua M, Molteni P, Bianchi Porro G. Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis. J Intern Med. 2000 ; 247: 63-70 (Pubitemid 30073165)
240. Hessov I, Mosekilde L, Melsen F, et al. Osteopenia with normal vitamin D metabolites after a small-bowel resection for Crohn's disease. Scand J Gastroenterol. 1984 ; 19: 691-696 (Pubitemid 14054288)
241. Bartram SA, Peaston RT, Rawlings DJ, Francis RM, Thompson NP. A randomized controlled trial of calcium with vitamin D, alone or in combination with intravenous pamidronate, for the treatment of low bone mineral density associated with Crohn's disease. Aliment Pharmacol Ther. 2003 ; 18: 121-127
242. Siffledeen JS, Fedorak RN, Siminoski K, et al. Randomized trial of etidronate plus calcium and vitamin D for treatment of low bone mineral density in Crohn's disease. Clin Gastroenterol Hepatol. 2005 ; 3: 122-132 (Pubitemid 40220307)
243. von Tirpitz C, Klaus J, Steinkamp M, et al. Therapy of osteoporosis in patients with Crohn's disease: a randomized study comparing sodium fluoride and ibandronate. Aliment Pharmacol Ther. 2003 ; 17: 807-816 (Pubitemid 36418878)
244. Abitbol V, Mary JY, Roux C, et al. Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride. Aliment Pharmacol Ther. 2002 ; 16: 919-927 (Pubitemid 34461761)
245. Harries AD, Brown R, Heatley RV, Williams LA, Woodhead S, Rhodes J. Vitamin D status in Crohn's disease: association with nutrition and disease activity. Gut. 1985 ; 26: 1187-1203
246. Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25(OH) vitamin D level in Crohn's disease: association with sun exposure and disease activity. Indian J Med Res. 2009 ; 130: 133-137
247. Jorgensen SP, Hvas CL, Agnholt J, Christensen LA, Heickendorff L, Dahlerup JF. Active Crohn's disease is associated with low vitamin D levels. J Crohn's Colitis. 2013 ; 7: e407 - e413
248. Irvine EJ, Zhou Q, Thompson AK. The short inflammatory bowel disease questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol. 1996 ; 91: 1571-1578 (Pubitemid 26269173)
249. Ananthakrishnan AN, Cagan A, Gainer VS, et al. Normalization of plasma 25-hydroxyvitamin D is associated with reduced risk of surgery in Crohn's disease. Inflamm Bowel Dis. 2013 ; 0: 1-7
250. Charlson ME, Pompi P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987 ; 40: 373-383 (Pubitemid 17055592)
251. Ross AC, Manson JE, Abrams SA, et al. The. 2011 dietary reference intakes for calcium and vitamin D: what dietetics professionals need to know. J Am Diet Assoc. 2011 ; 111: 524-527
252. Ross AC, Manson JE, Abrams SA, et al. The. 2011 dietary reference intakes for calcium and vitamin D: what clinicians need to know. J Clin Endocrinol Metab. 2011 ; 96: 53-58
253. Binkley N, Krueger D, Cowgill CS, et al. Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab. 2004 ; 89: 3152-3157 (Pubitemid 38951877)
254. Mithal A, Wahl A, Bonhour JP, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporosis Int. 2009 ; 20: 1807-1820
255. Pekkarinen T, Valimaki VV, Aarum S, et al. The same annual dose of 292,000IU of vitamin D (cholecalciferol) on either daily or four monthly basis for elderly women: 1-year comparative study of the effects on serum 25(OH)D concentrations and renal function. Clin Endocrinol (Oxf). 2010 ; 72: 455-461
256. Van der Wielen RP, Lowik MRH, van den berg H, et al. Serum vitamin D concentrations among elderly people in Europe. Lancet. 1995 ; 346: 207-210
257. El-Hajj Fuleihan G, Nabulsi M, Choucair M, et al. Hypovitaminosis D in healthy schoolchildren. Pediatrics. 2001 ; 107: e51 - e53
258. El-Hajj Fuleihan G, Deeb M. Hypovitaminosis in a sunny country. N Engl J Med. 1999 ; 340: 1840-1841
259. Gannage-Yared MH, Chemali R, Yaacoub N, Helaby G. Hypvitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res. 2000 ; 15: 1856-1862 (Pubitemid 30666240)
260. El Sonbaty MR, AbdulGhaffer NU. Vitamin D deficiency in veiled Kuwaiti women. Eur J Clin Nutr. 1996 ; 50: 315-318
261. Holick MF, Maclaughlin JA, Doppelt SH. Regulation of cutaneous previtamin D3 photosynthesis in man-skin pigment is not an essential regulator. Science. 1981 ; 211: 590-593 (Pubitemid 11188172)
262. Clemens TL, Adams JS, Henderson SL, Holick MF. Increased skin pigmentation reduces the capacity of skin to synthesize vitamin D3. Lancet. 1982 ; 1: 74-76 (Pubitemid 12248649)
263. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998 ; 338: 777-783 (Pubitemid 28135983)
264. Puri S, Marwaha RK, Agarwal N, et al. Vitamin D status of apparently healthy schoolgirls from two different socioeconomic strata in Delhi: relation to nutrition and lifestyle. Br J Nutr. 2008 ; 99: 876-882 (Pubitemid 351351644)
265. Harinarayan CV, Ramalakshmi T, Prasad UV, et al. High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr. 2007 ; 85: 1062-1067 (Pubitemid 46557922)
266. Agarwal KS, Mughal MZ, Upadhyay P, Berry JL, Mawer EB, Puliyel JM. The impact of atmosphere pollution on vitamin D status of infants and toddlers in Delhi India. Arch Dis Child. 2002 ; 87: 111-113 (Pubitemid 34828014)
267. Jorgensen SP, Agnholt J, Glerup H, et al. Clinical trial: vitamin D3 treatment in Crohn's disease- a randomized double-blind placebo controlled study. Aliment Pharmacol Ther. 2010 ; 32: 377-383
268. Boothe DL, Lakehomer H, Jacob V, Scherl E, Bosworth B High Dose Vitamin D Improves Clinical Activity in Crohn's Disease. Washington DC: American College of Gastroenterology ; 2011 :
269. Yang L, Weaver V, Smith JP, Bingaman S, Hartman TJ, Cantorna MT. Therapeutic effect of vitamin D supplementation in a pilot study of Crohn's patients. Clin Translat Gastroenterol. 2013 ; 4: e33
270. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998 ; 68: 854-858 (Pubitemid 28471068)
271. Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is effective as vitamin D3 in maintaining circulation concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008 ; 93: 677-681 (Pubitemid 351398538)
272. Binkley N, Gemar D, Engelke J, et al. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600IU daily or 50,000IU monthly in older adults. J Clin Endocrinol Metab. 2011 ; 96: 981-988
273. Miheller P, Muzes G, Hritz I, et al. Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on bone pathophysiology and disease activity in Crohn's disease. Inflamm Bowel Dis. 2009 ; 15: 1656-1662
274. Hackman KL, Gagnon C, Briscoe RK, Lam S, Anpalahan M, Ebeling PR. Efficacy and safety of oral continuous low-dose versus short-term high-dose vitamin D: a prospective randomized trial conducted in a clinical setting. Med J Aust. 2010 ; 192: 686-689
275. US Department of Agriculture. Dietary reference intakes: recommended intakes for individuals. 2010. Available at: http://fnic.nal.usda.gov/dietary- guidance/dietary-reference-intakes/dri-tables. Accessed June 2013.
276. Ross CA, Taylor, Yaktine AL, Del Calle HB DRIs for Calcium and Vitamin D. Washington, DC: National Academies Press ; 2001 :
277. Pramyothin P, Holick MF. Vitamin D supplementation: guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol. 2012 ; 28: 139-150
278. Zhou S, LeBoff MS, Glowacki J. Vitamin D metabolism and action in human bone marrow stromal cells. Endocrinology. 2010 ; 151: 14-22