Role of Vitamin D in inflammatory bowel disease

Nutrition in Clinical Practice

Volumn 32, Issue 3, 2017, Pages 337-345

  Limketkai, Berkeley N ^a,b   Mullin, Gerard E ^b   Limsui, David ^a   Parian, Alyssa M ^b  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cholecalciferol; Crohn's disease; Ergocalciferol; Inflammatory bowel diseases; Ulcerative colitis; Vitamin D; Vitamin D deficiency

Indexed keywords

C REACTIVE PROTEIN; CALCITRIOL; CATHELICIDIN; COLECALCIFEROL; DIHYDROTACHYSTEROL; ERGOCALCIFEROL; LUMISTEROL; PATTERN RECOGNITION RECEPTOR; RETINOID X RECEPTOR; TOLL LIKE RECEPTOR 4; VITAMIN D;

CALCIUM HOMEOSTASIS; CLINICAL OUTCOME; CROHN DISEASE; DISEASE ACTIVITY; DISEASE SEVERITY; ENVIRONMENTAL FACTOR; GENETIC RISK; HUMAN; HYPERCALCEMIA; IMMUNE SYSTEM; INFLAMMATORY BOWEL DISEASE; INTESTINE FLORA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK FACTOR; SYSTEMATIC REVIEW (TOPIC); ULCERATIVE COLITIS; VITAMIN D DEFICIENCY; VITAMIN D RESPONSIVE ELEMENT; BLOOD; DRUG EFFECTS; TREATMENT OUTCOME;

HUMANS; IMMUNE SYSTEM; INFLAMMATORY BOWEL DISEASES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TREATMENT OUTCOME; VITAMIN D; VITAMIN D DEFICIENCY;

EID: 85021762921     PISSN: 08845336     EISSN: 19412452     Source Type: Journal    
DOI: 10.1177/0884533616674492     Document Type: Review

References (123)

1. Orholm M, Munkholm P, Langholz E, Nielsen OH, Sorensen TI, Binder V. Familial occurrence of inflammatory bowel disease. N Engl J Med. 1991;324(2):84-88
2. Tysk C, Lindberg E, 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(7):990-996
3. Halfvarson J, Bresso F, D'Amato M, Jarnerot G, Pettersson S, Tysk C. CARD15/NOD2 polymorphisms do not explain concordance of Crohn's disease in Swedish monozygotic twins. Dig Liver Dis. 2005;37(10):768-772
4. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411(6837):599-603
5. Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001;411(6837):603-606
6. Rioux JD, Xavier RJ, Taylor KD, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007;39(5):596-604
7. McCarroll SA, Huett A, Kuballa P, et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet. 2008;40(9):1107-1112
8. Gradel KO, Nielsen HL, Schonheyder HC, Ejlertsen T, Kristensen B, Nielsen H. Increased short-and long-term risk of inflammatory bowel disease after salmonella or campylobacter gastroenteritis. Gastroenterology. 2009;137(2):495-501
9. Garcia Rodriguez LA, Ruigomez A, Panes J. Acute gastroenteritis is followed by an increased risk of inflammatory bowel disease. Gastroenterology. 2006;130(6):1588-1594
10. Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. Am J Gastroenterol. 2010;105(12):2687-2692
11. 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(4):563-573
12. Nerich V, Monnet E, Etienne A, et al. Geographical variations of inflammatory bowel disease in France: a study based on national health insurance data. Inflamm Bowel Dis. 2006;12(3):218-226
13. 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(5):690-697
14. Khalili H, Huang ES, Ananthakrishnan AN, et al. Geographical variation and incidence of inflammatory bowel disease among US women. Gut. 2012;61(12):1686-1692
15. Copping AM. Origin of Vitamin D in cod-liver oil: Vitamin D content of zooplankton. Biochem J. 1934;28(4):1516-1520
16. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281
17. Holick MF, MacLaughlin JA, Clark MB, et al. Photosynthesis of preVitamin D3 in human skin and the physiologic consequences. Science. 1980;210(4466):203-205
18. Tian XQ, Chen TC, Matsuoka LY, Wortsman J, Holick MF. Kinetic and thermodynamic studies of the conversion of preVitamin D3 to Vitamin D3 in human skin. J Biol Chem. 1993;268(20):14888-14892
19. Holick MF, MacLaughlin JA, Doppelt SH. Regulation of cutaneous preVitamin D3 photosynthesis in man: skin pigment is not an essential regulator. Science. 1981;211(4482):590-593
20. Webb AR, DeCosta BR, Holick MF. Sunlight regulates the cutaneous production of Vitamin D3 by causing its photodegradation. J Clin Endocrinol Metab. 1989;68(5):882-887
21. Bikle DD, Siiteri PK, Ryzen E, Haddad JG. Serum protein binding of 1,25-dihydroxyVitamin D: a reevaluation by direct measurement of free metabolite levels. J Clin Endocrinol Metab. 1985;61(5):969-975
22. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyVitamin D in serum and its regulation by albumin and the Vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954-959
23. Ponchon G, DeLuca HF. The role of the liver in the metabolism of Vitamin D. J Clin Invest. 1969;48(7):1273-1279
24. Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal Vitamin D 25-hydroxilase. J Biol Chem. 2003;278(39):38084-38093
25. Fraser DR, Kodicek E. Unique biosynthesis by kidney of a biological active Vitamin D metabolite. Nature. 1970;228(5273):764-766
26. Haussler MR, Norman AW. Chromosomal receptor for a Vitamin D metabolite. Proc Natl Acad Sci U S A. 1969;62(1):155-162
27. Carlberg C, Bendik I, Wyss A, et al. Two nuclear signalling pathways for Vitamin D. Nature. 1993;361(6413):657-660
28. Nishikawa J, Kitaura M, Matsumoto M, Imagawa M, Nishihara T. Difference and similarity of DNA sequence recognized by VDR homodimer and VDR/RXR heterodimer. Nucleic Acids Res. 1994;22(15):2902-2907
29. Sone T, Kerner S, Pike JW. Vitamin D receptor interaction with specific DNA: association as a 1,25-dihydroxyVitamin D3-modulated heterodimer. J Biol Chem. 1991;266(34):23296-23305
30. Morrison NA, Shine J, Fragonas JC, Verkest V, McMenemy ML, Eisman JA. 1,25-dihydroxyVitamin D-responsive element and glucocorticoid repression in the osteocalcin gene. Science. 1989;246(4934):1158-1161
31. Mesbah M, Nemere I, Papagerakis P, et al. Expression of a 1,25-dihydroxyVitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization. J Bone Miner Res. 2002;17(9):1588-1596
32. Nemere I, Garbi N, Hammerling G, Hintze KJ. Role of the 1,25D(3)-MARRS receptor in the 1,25(OH)(2)D(3)-stimulated uptake of calcium and phosphate in intestinal cells. Steroids. 2012;77(10): 897-902
33. Abe E, Miyaura C, Sakagami H, et al. Differentiation of mouse myeloid leukemia cells induced by 1 alpha, 25-dihydroxyVitamin D3. Proc Natl Acad Sci U S A. 1981;78(8):4990-4994
34. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyVitamin D3 receptors in human leukocytes. Science. 1983;221(4616):1181-1183
35. Kizaki M, Norman AW, Bishop JE, Lin CW, Karmakar A, Koeffler HP. 1,25-DihydroxyVitamin D3 receptor RNA: expression in hematopoietic cells. Blood. 1991;77(6):1238-1247
36. Baeke F, Korf H, Overbergh L, et al. Human T lymphocytes are direct targets of 1,25-dihydroxyVitamin D3 in the immune system. J Steroid Biochem Mol Biol. 2010;121(1-2):221-227
37. Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1,25-dihydroxyVitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab. 1983;57(6):1308-1310
38. Reichel H, Koeffler HP, Norman A. Synthesis in vitro of 1,25-dihydroxyVitamin D3 and 24,25-dihydroxyVitamin D3 by interferon-gamma-stimulated Wnormal human bone marrow and alveolar macrophages. J Biol Chem. 1987;262(23):10931-10937
39. Fritsche J, Mondal K, Ehrnsperger A, Andreesen R, Kreutz M. Regulation of 25-hydroxyVitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyVitamin D3 by human dendritic cells. Blood. 2003;102(9):3314-3316
40. Chen S, Sims GP, Chen XX, Gu YY, Lipsky PE. Modulatory effects of 1,25-dihydroxyVitamin D3 on human B cell differentiation. J Immunol. 2007;179(3):1634-1647
41. Stoffels K, Overbergh L, Giulietti A, Verlinden L, Bouillon R, Mathieu C. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J Bone Miner Res. 2006;21(1):37-47
42. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a Vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770-1773
43. Sadeghi K, Wessner B, Laggner U, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogenassociated molecular patterns. Eur J Immunol. 2006;36(2):361-370
44. Kreutz M, Andreesen R, Krause SW, Szabo A, Ritz E, Reichel H. 1,25-dihydroxyVitamin D3 production and Vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages. Blood. 1993;82(4):1300-1307
45. Tsoukas CD, Provvedini DM, Manolagas SC. 1,25-dihydroxyVitamin D3: a novel immunoregulatory hormone. Science. 1984;224(4656): 1438-1440
46. Manolagas SC, Provvedini DM, Murray EJ, Tsoukas CD, Deftos LJ. The antiproliferative effect of calcitriol on human peripheral blood mononuclear cells. J Clin Endocrinol Metab. 1986;63(2):394-400
47. 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(9):4443-4451
48. 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-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci U S A. 2001;98(12):6800-6805
49. 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(5):2405-2411
50. Adorini L, Penna G, Giarratana N, et al. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J Steroid Biochem Mol Biol. 2004;89-90(1-5):437-441
51. Gregori S, Giarratana N, Smiroldo S, Uskokovic M, Adorini L. A 1alpha,25-dihydroxyVitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes. 2002;51(5):1367-1374
52. Jeffery LE, Burke F, Mura M, et al. 1,25-DihydroxyVitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol. 2009;183(9):5458-5467
53. 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(5):603-616
54. Ghoreishi M, Bach P, Obst J, Komba M, Fleet JC, Dutz JP. Expansion of antigen-specific regulatory T cells with the topical vitamin d analog calcipotriol. J Immunol. 2009;182(10):6071-6078
55. Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther. 2008;324(1):23-33
56. 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(5):922-932
57. 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 encephalomyelitis. PLoS One. 2010;5(9):e12925
58. Palmer MT, Lee YK, Maynard CL, et al. Lineage-specific effects of 1,25-dihydroxyVitamin D(3) on the development of effector CD4 T cells. J Biol Chem. 2011;286(2):997-1004
59. Alroy I, Towers TL, Freedman LP. Transcriptional repression of the interleukin-2 gene by Vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. Mol Cell Biol. 1995;15(10):5789-5799
60. Bhalla AK, Amento EP, Krane SM. Differential effects of 1,25-dihydroxyVitamin D3 on human lymphocytes and monocyte/macrophages: inhibition of interleukin-2 and augmentation of interleukin-1 production. Cell Immunol. 1986;98(2):311-322
61. D'Ambrosio D, Cippitelli M, Cocciolo MG, et al. Inhibition of IL-12 production by 1,25-dihydroxyVitamin D3: involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest. 1998;101(1):252-262
62. Schauber J, Dorschner RA, Coda AB, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a Vitamin D-dependent mechanism. J Clin Invest. 2007;117(3):803-811
63. 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(5):2909-2912
64. 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(9):1067-1077
65. Froicu M, Zhu Y, Cantorna MT. Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice. Immunology. 2006;117(3):310-318
66. Mullin GE, Maycon ZR, Braun-Elwert L, et al. Inflammatory bowel disease mucosal biopsies have specialized lymphokine mRNA profiles. Inflamm Bowel Dis. 1996;2(1):16-26
67. Mullin GE, Lazenby AJ, Harris ML, Bayless TM, James SP. Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn's disease but not ulcerative colitis. Gastroenterology. 1992;102(5):1620-1627
68. Mullin GE, Vezza FR, Sampat A, et al. Abnormal IL-10 mRNA production in the intestinal mucosal lesions of inflammatory bowel disease. Gastroenterology. 1993;104:A751
69. Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT. A crucial role for the Vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol. 2003;17(12):2386-2392
70. Yu S, Bruce D, Froicu M, Weaver V, Cantorna MT. Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of Vitamin D receptor KO mice. Proc Natl Acad Sci U S A. 2008;105(52):20834-20839
71. 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(11):2648-2652
72. Zhu Y, Mahon BD, Froicu M, Cantorna MT. Calcium and 1 alpha,25-dihydroxyVitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease. Eur J Immunol. 2005;35(1):217-224
73. Laverny G, Penna G, Vetrano S, et al. Efficacy of a potent and safe Vitamin D receptor agonist for the treatment of inflammatory bowel disease. Immunol Lett. 2010;131(1):49-58
74. Daniel C, Radeke HH, Sartory NA, et al. The new low calcemic Vitamin D analog 22-ene-25-oxa-Vitamin D prominently ameliorates T helper cell type 1-mediated colitis in mice. J Pharmacol Exp Ther. 2006;319(2):622-631
75. Nerich V, Monnet E, Weill A, et al. Fine-scale geographic variations of inflammatory bowel disease in France: correlation with socioeconomic and house equipment variables. Inflamm Bowel Dis. 2010;16(5):813-821
76. 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(8):940-945
77. Jantchou P, Clavel-Chapelon F, Racine A, Kvaskoff M, Carbonnel F, Boutron-Ruault MC. High residential sun exposure is associated with a low risk of incident Crohn's disease in the prospective E3N cohort. Inflamm Bowel Dis. 2014;20(1):75-81
78. Armitage EL, Aldhous MC, Anderson N, et al. Incidence of juvenileonset Crohn's disease in Scotland: association with northern latitude and affluence. Gastroenterology. 2004;127(4):1051-1057
79. Ananthakrishnan AN, Khalili H, Higuchi LM, et al. Higher predicted Vitamin D status is associated with reduced risk of Crohn's disease. Gastroenterology. 2012;142(3):482-489
80. Sonnenberg A, Jacobsen SJ, Wasserman IH. Periodicity of hospital admissions for inflammatory bowel disease. Am J Gastroenterol. 1994;89(6):847-851
81. Aratari A, Papi C, Galletti B, et al. Seasonal variations in onset of symptoms in Crohn's disease. Dig Liver Dis. 2006;38(5):319-323
82. Lewis JD, Aberra FN, Lichtenstein GR, Bilker WB, Brensinger C, Strom BL. Seasonal variation in flares of inflammatory bowel disease. Gastroenterology. 2004;126(3):665-673
83. Tysk C, Jarnerot G. Seasonal variation in exacerbations of ulcerative colitis. Scand J Gastroenterol. 1993;28(1):95-96
84. Limketkai BN, Bayless TM, Brant SR, Hutfless SM. Lower regional and temporal ultraviolet exposure is associated with increased rates and severity of inflammatory bowel disease hospitalisation. Aliment Pharmacol Ther. 2014;40(5):508-517
85. Ananthakrishnan AN, Cagan A, Gainer VS, et al. Normalization of plasma 25-hydroxy Vitamin D is associated with reduced risk of surgery in Crohn's disease. Inflamm Bowel Dis. 2013;19(9):1921-1927
86. Ulitsky A, Ananthakrishnan AN, Naik A, et al. Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr. 2011;35(3): 308-316
87. Blanck S, Aberra F. Vitamin d deficiency is associated with ulcerative colitis disease activity. Dig Dis Sci. 2013;58(6):1698-1702
88. Benchimol EI, Ward LM, Gallagher JC, et al. Effect of calcium and Vitamin D supplementation on bone mineral density in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;45(5):538-545
89. 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(2): 122-132
90. 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 Transl Gastroenterol. 2013;4:e33
91. 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(3):377-383
92. Miheller P, Muzes G, Hritz I, et al. Comparison of the effects of 1,25 dihydroxyVitamin D and 25 hydroxyVitamin D on bone pathology and disease activity in Crohn's disease patients. Inflamm Bowel Dis. 2009;15(11):1656-1662
93. Zator ZA, Cantu SM, Konijeti GG, et al. Pretreatment 25-hydroxyVitamin D levels and durability of anti-tumor necrosis factor-alpha therapy in inflammatory bowel diseases. JPEN J Parenter Enteral Nutr. 2014;38(3):385-391
94. Santos-Antunes J, Nunes AC, Lopes S, Macedo G. The relevance of Vitamin D and antinuclear antibodies in patients with inflammatory bowel disease under anti-TNF treatment: a prospective study. Inflamm Bowel Dis. 2016;22(5):1101-1106
95. Rosen CJ. Clinical practice: Vitamin D insufficiency. N Engl J Med. 2011;364(3):248-254
96. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014;2(1):76-89
97. Farraye FA, Nimitphong H, Stucchi 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(10):2116-2121
98. Tajika M, Matsuura A, Nakamura T, et al. Risk factors for Vitamin D deficiency in patients with Crohn's disease. J Gastroenterol. 2004;39(6):527-533
99. 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;54(3): 548-552
100. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Calcium and Vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1996;125(12):961-968
101. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med. 1990;112(5):352-364
102. De Sevaux RG, Hoitsma AJ, Corstens FH, Wetzels JF. Treatment with Vitamin D and calcium reduces bone loss after renal transplantation: a randomized study. J Am Soc Nephrol. 2002;13(6):1608-1614
103. Compston JE, Horton LW. Oral 25-hydroxyvitain D3 in treatment of osteomalacia associated with ileal resection and cholestyramine therapy. Gastroenterology. 1978;74(5, pt 1):900-902
104. Krejs GJ, Nicar MJ, Zerwekh JE, Norman DA, Kane MG, Pak CY. Effect of 1,25-dihydroxyVitamin D3 on calcium and magnesium absorption in the healthy human jejunum and ileum. Am J Med. 1983;75(6): 973-976
105. Hlavaty T, Krajcovicova A, Koller T, et al. Higher Vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases. World J Gastroenterol. 2014;20(42): 15787-15796
106. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than Vitamin D3 in humans. J Clin Endocrinol Metab. 2004;89(11): 5387-5391
107. Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D(3) is more potent than Vitamin D(2) in humans. J Clin Endocrinol Metab. 2011;96(3):E447-E452
108. Pappa HM, Mitchell PD, Jiang H, et al. Treatment of Vitamin D insufficiency in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing three regimens. J Clin Endocrinol Metab. 2012;97(6):2134-2142
109. Vogelsang H, Schofl R, Tillinger W, Ferenci P, Gangl A. 25-HydroxyVitamin D absorption in patients with Crohn's disease and with pancreatic insufficiency. Wien Klin Wochenschr. 1997;109(17):678-682
110. Ross AC. The 2011 report on dietary reference intakes for calcium and Vitamin D. Public Health Nutr. 2011;14(5):938-939
111. 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(7):1911-1930
112. 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(4):324-344
113. Holick MF. Sunlight "D"ilemma: risk of skin cancer or bone disease and muscle weakness. Lancet. 2001;357(9249):4-6
114. Bischoff-Ferrari HA, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett WC. Benefit-risk assessment of Vitamin D supplementation. Osteoporos Int. 2010;21(7):1121-1132
115. Leventis P, Kiely PD. The tolerability and biochemical effects of highdose bolus Vitamin D2 and D3 supplementation in patients with Vitamin D insufficiency. Scand J Rheumatol. 2009;38(2):149-153
116. Bacon CJ, Gamble GD, Horne AM, Scott MA, Reid IR. High-dose oral Vitamin D3 supplementation in the elderly. Osteoporos Int. 2009;20(8):1407-1415
117. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for Vitamin D. Am J Clin Nutr. 2007;85(1):6-18
118. Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007;22(suppl 2):V64-V68
119. Jones G. Pharmacokinetics of Vitamin D toxicity. Am J Clin Nutr. 2008;88(2):582S-586S
120. Braam LA, Hoeks AP, Brouns F, Hamulyak K, Gerichhausen MJ, Vermeer C. Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost. 2004;91(2):373-380
121. Yang B, Campbell PT, Gapstur SM, et al. Calcium intake and mortality from all causes, cancer, and cardiovascular disease: the Cancer Prevention Study II Nutrition Cohort. Am J Clin Nutr. 2016;103(3):886-894
122. Pappa HM, Mitchell PD, Jiang H, et al. Maintenance of optimal Vitamin D status in children and adolescents with inflammatory bowel disease: a randomized clinical trial comparing two regimens. J Clin Endocrinol Metab. 2014;99(9):3408-3417
123. Raftery T, Martineau AR, Greiller CL, et al. Effects of Vitamin D supplementation on intestinal permeability, cathelicidin and disease markers in Crohn's disease: results from a randomised doubleblind placebo-controlled study. United European Gastroenterol J. 2015;3(3):294-302