Vitamin D improves inflammatory bowel disease outcomes: Basic science and clinical review

World Journal of Gastroenterology

Volumn 20, Issue 17, 2014, Pages 4934-4947

  Reich, Krista M ^a   Fedorak, Richard N ^a   Madsen, Karen ^a   Kroeker, Karen I ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Cytokines; Immune response; Inflammation; Inflammatory bowel disease; Supplementation; Vitamin D

Indexed keywords

ALFACALCIDOL; ANGIOGENIN; CALCITRIOL; COLECALCIFEROL; ERGOCALCIFEROL; LEXACALCITOL; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; UNCLASSIFIED DRUG; VITAMIN D; VITAMIN D RECEPTOR; ZK 156979; ANTIINFLAMMATORY AGENT; GASTROINTESTINAL AGENT;

ANTIBACTERIAL ACTIVITY; ANTIINFLAMMATORY ACTIVITY; CELLULAR IMMUNITY; COLITIS; CROHN DISEASE; CYTOKINE PRODUCTION; DENDRITIC CELL; DIGESTIVE SYSTEM INFLAMMATION; DISEASE ACTIVITY; DISEASE MODEL; ETHNICITY; GENETIC SUSCEPTIBILITY; GEOGRAPHIC DISTRIBUTION; HELPER CELL; HUMAN; IMMUNOMODULATION; INFLAMMATORY BOWEL DISEASE; LYMPHOCYTE DIFFERENTIATION; META ANALYSIS (TOPIC); MULTICENTER STUDY (TOPIC); NONHUMAN; RANDOMIZED CONTROLLED TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; REVIEW; RISK FACTOR; SYSTEMATIC REVIEW (TOPIC); TH1 TH2 BALANCE; VITAMIN D DEFICIENCY; VITAMIN D METABOLISM; VITAMIN SUPPLEMENTATION; ANIMAL; BLOOD; COMPLICATION; DIET SUPPLEMENTATION; IMMUNOLOGY; INFLAMMATORY BOWEL DISEASES; TREATMENT OUTCOME;

ANIMALS; ANTI-INFLAMMATORY AGENTS; DIETARY SUPPLEMENTS; DISEASE MODELS, ANIMAL; GASTROINTESTINAL AGENTS; HUMANS; INFLAMMATORY BOWEL DISEASES; TREATMENT OUTCOME; VITAMIN D; VITAMIN D DEFICIENCY;

EID: 84899856731     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i17.4934     Document Type: Review

References (78)

1. Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004; 53 Suppl 5: V1-16 [PMID: 15306569 DOI: 10.1136/gut.2004.043372]
2. Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology 2011; 140: 1785-1794 [PMID: 21530745 DOI: 10.1053/j.gastro.2011.01.055]
3. 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 [PMID: 22686333 DOI: 10.1111/ j.1365-2036.2012.05181.x]
4. Javorsky BR, Maybee N, Padia SH, Dalkin AC. Vitamin D deficiency in gastrointestinal disease. Pract Gastroenterol 2006; 29: 52-72
5. Miznerova E, Hlavaty T, Koller T, Toth J, Holociova K, Huorka M, Killinger Z, Payer J. The prevalence and risk factors for osteoporosis in patients with inflammatory bowel disease. Bratisl Lek Listy 2013; 114: 439-445 [PMID: 23944617 DOI: 10.4149/BLL_2013_092]
6. Raman M, Milestone AN, Walters JR, Hart AL, Ghosh S. Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer. Therap Adv Gastroenterol 2011; 4: 49-62 [PMID: 21317994 DOI: 10.1177/1756283X10377820]
7. Lips P. Vitamin D physiology. Prog Biophys Mol Biol 2006; 92: 4-8 [PMID: 16563471 DOI: 10.1016/j.pbiomolbio.2006.02. 016]
8. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266-281 [PMID: 17634462 DOI: 10.1056/NEJMra070553]
9. Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ. Vitamin D: metabolism. Endocrinol Metab Clin North Am 2010; 39: 243-253, table of contents [PMID: 20511049 DOI: 10.1016/j.ecl.2010.02.002]
10. Christakos S, Dhawan P, Liu Y, Peng X, Porta A. New insights into the mechanisms of vitamin D action. J Cell Biochem 2003; 88: 695-705 [PMID: 12577303 DOI: 10.1002/ jcb.10423]
11. Pike JW, Meyer MB. The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D3. Rheum Dis Clin North Am 2012; 38: 13-27 [PMID: 22525840 DOI: 10.1016/j.rdc.2012.03.004]
12. Yasmin R, Williams RM, Xu M, Noy N. Nuclear import of the retinoid X receptor, the vitamin D receptor, and their mutual heterodimer. J Biol Chem 2005; 280: 40152-40160 [PMID: 16204233 DOI: 10.1074/jbc.M507708200]
13. Hewison M. Vitamin D and immune function: an overview. Proc Nutr Soc 2012; 71: 50-61 [PMID: 21849106 DOI: 10.1017/ S0029665111001650]
14. 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: 3314-3316 [PMID: 12855575 DOI: 10.1182/blood-2002-11-3521]
15. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311: 1770-1773 [PMID: 16497887 DOI: 10.1126/science.1123933]
16. Guillot X, Prati C, Saidenberg-Kermanac'h N, Semerano L, Falgarone G, Boissier MC, Wendling D. Inflammation and vitamin D. Watson RR, editor. Handbook of vitamin D in human health: Prevention, treatment and toxicity. The Netherlands: Wageningen Academic Publishers, 2013: 372-390
17. Mora JR, Iwata M, von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 2008; 8: 685-698 [PMID: 19172691 DOI: 10.1038/nri2378]
18. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O' Garra A. 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 2001; 167: 4974-4980 [PMID: 11673504]
19. Barrat FJ, Cua DJ, Boonstra A, Richards DF, Crain C, Savelkoul HF, de Waal-Malefyt R, Coffman RL, Hawrylowicz CM, O'Garra A. 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 [PMID: 11877483 DOI: 10.1084/jem.20011629]
20. 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 [PMID: 10679076]
21. Canning MO, Grotenhuis K, de Wit H, Ruwhof C, Drexhage HA. 1-alpha,25-Dihydroxyvitamin D3 (1,25(OH)(2)D(3) hampers the maturation of fully active immature dendritic cells from monocytes. Eur J Endocrinol 2001; 145: 351-357 [PMID: 11517017 DOI: 10.1530/eje.0.1450351]
22. 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 [PMID: 15985530 DOI: 10.1096/fj.04-3284com]
23. Wang TT, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-Mendoza LE, Dionne S, Servant MJ, Bitton A, Seidman EG, Mader S, Behr MA, White JH. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/ CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem 2010; 285: 2227-2231 [PMID: 19948723 DOI: 10.1074/jbc.C109.071225]
24. Chen Y, Liu W, Sun T, Huang Y, Wang Y, Deb DK, Yoon D, Kong J, Thadhani R, Li YC. 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages. J Immunol 2013; 190: 3687-3695 [PMID: 23436936 DOI: 10.4049/jimmunol. 1203273]
25. Eleftheriadis T, Antoniadi G, Liakopoulos V, Kartsios C, Stefanidis I, Galaktidou G. Paricalcitol reduces basal and lipopolysaccharide-induced (LPS) TNF-alpha and IL-8 production by human peripheral blood mononuclear cells. Int Urol Nephrol 2010; 42: 181-185 [PMID: 19259778 DOI: 10.1007/s11255-009-9541-1]
26. Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 2012; 188: 2127-2135 [PMID: 22301548 DOI: 10.4049/jimmunol.1102412]
27. Müller K, Haahr PM, Diamant M, Rieneck K, Kharazmi A, Bendtzen K. 1,25-Dihydroxyvitamin D3 inhibits cytokine production by human blood monocytes at the post-transcriptional level. Cytokine 1992; 4: 506-512 [PMID: 1337987 DOI: 10.1016/1043-4666(92)90012-G]
28. Stio M, Treves C, Martinesi M, Bonanomi AG. Biochemical effects of KH 1060 and anti-TNF monoclonal antibody on human peripheral blood mononuclear cells. Int Immunopharmacol 2005; 5: 649-659 [PMID: 15710334 DOI: 10.1016/ j.intimp.2004.11.002]
29. Khoo AL, Chai LY, Koenen HJ, Sweep FC, Joosten I, Netea MG, van der Ven AJ. Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals. Clin Exp Immunol 2011; 164: 72-79 [PMID: 21323660 DOI: 10.1111/j.1365-2249.2010.04315.x]
30. Bruewer M, Luegering A, Kucharzik T, Parkos CA, Madara JL, Hopkins AM, Nusrat A. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J Immunol 2003; 171: 6164-6172 [PMID: 14634132]
31. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med 2000; 51: 289-298 [PMID: 10774465 DOI: 10.1146/annurev. med.51.1.289]
32. 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: 217-224 [PMID: 15593122 DOI: 10.1002/eji.200425491]
33. Bartels LE, Jørgensen SP, Agnholt J, Kelsen J, Hvas CL, Dahlerup JF. 1,25-dihydroxyvitamin D3 and dexamethasone increase interleukin-10 production in CD4+ T cells from patients with Crohn's disease. Int Immunopharmacol 2007; 7: 1755-1764 [PMID: 17996686 DOI: 10.1016/j.intimp.2007.09.016]
34. Stio M, Treves C, Martinesi M, d'Albasio G, Bagnoli S, Bonanomi AG. Effect of anti-TNF therapy and vitamin D derivatives on the proliferation of peripheral blood mononuclear cells in Crohn's disease. Dig Dis Sci 2004; 49: 328-335 [PMID: 15104379 DOI: 10.1023/B:DDAS.0000017460.90887.1 1]
35. Wu S, Sun J. Vitamin D, vitamin D receptor, and macroautophagy in inflammation and infection. Discov Med 2011; 11: 325-335 [PMID: 21524386]
36. Bartels LE, Jørgensen SP, Bendix M, Hvas CL, Agnholt J, Agger R, Dahlerup JF. 25-Hydroxy vitamin D3 modulates dendritic cell phenotype and function in Crohn's disease. Inflammopharmacology 2013; 21: 177-186 [PMID: 23341164 DOI: 10.1007/s10787-012-0168-y]
37. Bendix-Struve M, Bartels LE, Agnholt J, Dige A, Jørgensen SP, Dahlerup JF. Vitamin D3 treatment of Crohn's disease patients increases stimulated T cell IL-6 production and proliferation. Aliment Pharmacol Ther 2010; 32: 1364-1372 [PMID: 21050239 DOI: 10.1111/j.1365-2036.2010.04463.x]
38. Froicu M, Cantorna MT. Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury. BMC Immunol 2007; 8: 5 [PMID: 17397543 DOI: 10.1186/1471-2172-8-5]
39. Wu S, Liao AP, Xia Y, Li YC, Li JD, Sartor RB, Sun J. Vitamin D receptor negatively regulates bacterial-stimulated NF-kappaB activity in intestine. Am J Pathol 2010; 177: 686-697 [PMID: 20566739 DOI: 10.2353/ajpath.2010.090998]
40. Bruce D, Cantorna MT. Intrinsic requirement for the vitamin D receptor in the development of CD8α-expressing T cells. J Immunol 2011; 186: 2819-2825 [PMID: 21270396 DOI: 10.4049/jimmunol.1003444]
41. Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, Bissonnette M, Li YC. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008; 294: G208-G216 [PMID: 17962355 DOI: 10.1152/ajpgi.00398.2007]
42. Palmer MT, Weaver CT. Linking vitamin d deficiency to inflammatory bowel disease. Inflamm Bowel Dis 2013; 19: 2245-2256 [PMID: 23591600 DOI: 10.1097/MIB.0b013e31828a3b6f]
43. Bruce D, Yu S, Ooi JH, Cantorna MT. Converging pathways lead to overproduction of IL-17 in the absence of vitamin D signaling. Int Immunol 2011; 23: 519-528 [PMID: 21697289 DOI: 10.1093/intimm/dxr045]
44. Ryz NR, Patterson SJ, Zhang Y, Ma C, Huang T, Bhinder G, Wu X, Chan J, Glesby A, Sham HP, Dutz JP, Levings MK, Jacobson K, Vallance BA. Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses. Am J Physiol Gastrointest Liver Physiol 2012; 303: G1299-G1311 [PMID: 23019194 DOI: 10.1152/ajpgi.00320.2012]
45. Froicu M, Zhu Y, Cantorna MT. Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice. Immunology 2006; 117: 310-318 [PMID: 16476050 DOI: 10.1111/j.1365-2567.2005.02290.x]
46. 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 [PMID: 11053501]
47. 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: 23-33 [PMID: 17911375 DOI: 10.1124/jpet.107.127209]
48. Daniel C, Radeke HH, Sartory NA, Zahn N, Zuegel U, Steinmeyer A, Stein J. 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: 622-631 [PMID: 16914561 DOI: 10.1124/ jpet.106.107599]
49. Lagishetty V, Misharin AV, Liu NQ, Lisse TS, Chun RF, Ouyang Y, McLachlan SM, Adams JS, Hewison M. Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis. Endocrinology 2010; 151: 2423-2432 [PMID: 20392825 DOI: 10.1210/en.2010-0089]
50. Liu N, Nguyen L, Chun RF, Lagishetty V, Ren S, Wu S, Hollis B, DeLuca HF, Adams JS, Hewison M. Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation. Endocrinology 2008; 149: 4799-4808 [PMID: 18535110 DOI: 10.1210/en.2008-0060]
51. Nerich V, Jantchou P, Boutron-Ruault MC, Monnet E, Weill A, Vanbockstael V, Auleley GR, Balaire C, Dubost P, Rican S, Allemand H, Carbonnel F. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther 2011; 33: 940-945 [PMID: 21332762 DOI: 10.1111/j.1365-2036.2011.04601. x]
52. Khalili H, Huang ES, Ananthakrishnan AN, Higuchi L, Richter JM, Fuchs CS, Chan AT. Geographical variation and incidence of inflammatory bowel disease among US women. Gut 2012; 61: 1686-1692 [PMID: 22241842 DOI: 10.1136/ gutjnl-2011-301574]
53. Suibhne TN, Cox G, Healy M, O'Morain C, O'Sullivan M. Vitamin D deficiency in Crohn's disease: prevalence, risk factors and supplement use in an outpatient setting. J Crohns Colitis 2012; 6: 182-188 [PMID: 22325172 DOI: 10.1016/ j.crohns.2011.08.002]
54. 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 [PMID: 12945007]
55. Tajika M, Matsuura A, Nakamura T, Suzuki T, Sawaki A, Kato T, Hara K, Ookubo K, Yamao K, Kato M, Muto Y. Risk factors for vitamin D deficiency in patients with Crohn's disease. J Gastroenterol 2004; 39: 527-533 [PMID: 15235869 DOI: 10.1007/s00535-003-1338-x]
56. Sentongo TA, Semaeo EJ, Stettler N, Piccoli DA, Stallings VA, Zemel BS. Vitamin D status in children, adolescents, and young adults with Crohn disease. Am J Clin Nutr 2002; 76: 1077-1081 [PMID: 12399281]
57. 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. JPEN J Parenter Enteral Nutr 2011; 35: 308-316 [PMID: 21527593 DOI: 10.1177/0148607110381267]
58. Chatu S, Chhaya V, Holmes R, Neild P, Kang J, Pollok RC, Poullis A. Factors associated with vitamin D deficiency in a multicultural inflammatory bowel disease cohort. Frontline Gastroenterol 2013; 4: 51-56 [DOI: 10.1136/flgastro-2012-100231]
59. 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 [PMID: 22155183 DOI: 10.1053/j.gastro.2011.11.040]
60. Holick MF. Vitamin D and health: evolution, biologic functions, and recommended dietary intakes for vitamin D. Clin Rev Bone Miner Metab 2009; 8: 2-19 [DOI: 10.1007/s12018-009-9026-x]
61. Fu YT, Chatur N, Cheong-Lee C, Salh B. Hypovitaminosis D in adults with inflammatory bowel disease: potential role of ethnicity. Dig Dis Sci 2012; 57: 2144-2148 [PMID: 22451117 DOI: 10.1007/s10620-012-2130-7]
62. 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: 1197-1203 [PMID: 3877663 DOI: 10.1136/gut.26.11.1197]
63. Eloranta JJ, Wenger C, Mwinyi J, Hiller C, Gubler C, Vavricka SR, Fried M, Kullak-Ublick GA. Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease. Pharmacogenet Genomics 2011; 21: 559-564 [PMID: 21832969 DOI: 10.1097/FPC.0b013e328348f70c]
64. Xue LN, Xu KQ, Zhang W, Wang Q, Wu J, Wang XY. Associations between vitamin D receptor polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis. Inflamm Bowel Dis 2013; 19: 54-60 [PMID: 22467262 DOI: 10.1002/ibd.22966]
65. Jørgensen SP, Hvas CL, Agnholt J, Christensen LA, Heickendorff L, Dahlerup JF. Active Crohn's disease is associated with low vitamin D levels. J Crohns Colitis 2013; 7: e407-e413 [PMID: 23403039 DOI: 10.1016/j.crohns.2013.01.012]
66. Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25 (OH) vitamin D level in Crohn's disease: association with sun exposure & amp; disease activity. Indian J Med Res 2009; 130: 133-137 [PMID: 19797809]
67. Blanck S, Aberra F. Vitamin d deficiency is associated with ulcerative colitis disease activity. Dig Dis Sci 2013; 58: 1698-1702 [PMID: 23334382 DOI: 10.1007/s10620-012-2531-7]
68. Boyd CA, Limdi JK. Vitamin D deficiency and disease outcomes in South Asian patients with IBD. Dig Dis Sci 2013; 58: 2124-2125 [PMID: 23606110 DOI: 10.1007/s10620-013-2654-5]
69. Hassan V, Hassan S, Seyed-Javad P, Ahmad K, Asieh H, Maryam S, Farid F, Siavash A. Association between Serum 25 (OH) Vitamin D Concentrations and Inflammatory Bowel Diseases (IBDs) Activity. Med J Malaysia 2013; 68: 34-38 [PMID: 23466764]
70. Farraye FA, Nimitphong H, Stucchi A, Dendrinos K, Boulanger AB, Vijjeswarapu A, Tanennbaum A, Biancuzzo R, Chen TC, Holick MF. 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 [PMID: 21910173 DOI: 10.1002/ibd.21595]
71. Abreu MT, Kantorovich V, Vasiliauskas EA, Gruntmanis U, Matuk R, Daigle K, Chen S, Zehnder D, Lin YC, Yang H, Hewison M, Adams JS. Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Gut 2004; 53: 1129-1136 [PMID: 15247180 DOI: 10.1136/gut.2003.036657]
72. Ananthakrishnan AN, Cagan A, Gainer VS, Cai T, Cheng SC, Savova G, Chen P, Szolovits P, Xia Z, De Jager PL, Shaw SY, Churchill S, Karlson EW, Kohane I, Plenge RM, Murphy SN, Liao KP. Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn's disease. Inflamm Bowel Dis 2013; 19: 1921-1927 [PMID: 23751398 DOI: 10.1097/MIB.0b013e3182902ad9]
73. Zator ZA, Cantu SM, Konijeti GG, Nguyen DD, Sauk J, Yajnik V, Ananthakrishnan AN. Pretreatment 25-Hydroxyvitamin D Levels and Durability of Anti-Tumor Necrosis Factor-α Therapy in Inflammatory Bowel Diseases. JPEN J Parenter Enteral Nutr 2014; 38: 385-391 [PMID: 24088707 DOI: 10.1177/ 0148607113504002]
74. Jørgensen SP, Agnholt J, Glerup H, Lyhne S, Villadsen GE, Hvas CL, Bartels LE, Kelsen J, Christensen LA, Dahlerup JF. Clinical trial: vitamin D3 treatment in Crohn's disease-a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther 2010; 32: 377-383 [PMID: 20491740 DOI: 10.1111/j.1365-2036.2010.04355.x]
75. Nicholson I, Dalzell AM, El-Matary W. Vitamin D as a therapy for colitis: a systematic review. J Crohns Colitis 2012; 6: 405-411 [PMID: 22398085 DOI: 10.1016/j.crohns.2012.01.007]
76. Miheller P, Muzes G, Hritz I, Lakatos G, Pregun I, Lakatos PL, Herszényi L, Tulassay Z. 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: 1656-1662 [PMID: 19408329 DOI: 10.1002/ibd.20947]
77. 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 [PMID: 23594800 DOI: 10.1038/ctg.2013.1]
78. Pappa HM, Mitchell PD, Jiang H, Kassiff S, Filip-Dhima R, DiFabio D, Quinn N, Lawton RC, Varvaris M, Van Straaten S, Gordon CM. 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: 2134-2142 [PMID: 22456619 DOI: 10.1210/jc.2011-3182]