Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2015, Article ID 470805, 16 pages
http://dx.doi.org/10.1155/2015/470805
Review Article

Vitamin D and Inflammatory Bowel Disease

1Internal Medicine, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
2Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy
3Clinical Unit for Chronic Bowel Disorders, IBD-UNIT, Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy

Received 27 November 2014; Revised 2 February 2015; Accepted 13 February 2015

Academic Editor: K. Šebeková

Copyright © 2015 Marco Ardesia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. Jones, S. A. Strugnell, and H. F. DeLuca, “Current understanding of the molecular actions of vitamin D,” Physiological Reviews, vol. 78, no. 4, pp. 1193–1231, 1998. View at Google Scholar · View at Scopus
  2. N. Narula and J. K. Marshall, “Management of inflammatory bowel disease with vitamin D: beyond bone health,” Journal of Crohn's & Colitis, vol. 6, no. 4, pp. 397–404, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. M. F. Holick, T. C. Chen, Z. Lu, and E. Sauter, “Vitamin D and skin physiology: a D-lightful story,” Journal of Bone and Mineral Research, vol. 22, no. 2, pp. V28–V33, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. F. Baeke, E. V. Etten, C. Gysemans, L. Overbergh, and C. Mathieu, “Vitamin D signaling in immune-mediated disorders: evolving insights and therapeutic opportunities,” Molecular Aspects of Medicine, vol. 29, no. 6, pp. 376–387, 2008. View at Publisher · View at Google Scholar · View at Scopus
  5. J. W. Pike and M. B. Meyer, “The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D3,” Rheumatic Disease Clinics of North America, vol. 38, no. 1, pp. 13–27, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Raman, A. N. Milestone, J. R. F. Walters, A. L. Har, and S. Ghosh, “Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer,” Therapeutic Advances in Gastroenterology, vol. 4, no. 1, pp. 49–62, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. R. F. Chun, P. T. Liu, R. L. Modlin, J. S. Adams, and M. Hewison, “Impact of vitamin D on immune function: lessons learned from genome-wide analysis,” Frontiers in Physiology, vol. 5, article 151, 15 pages, 2014. View at Publisher · View at Google Scholar
  8. J. Sun, “Vitamin D and mucosal immune function,” Current Opinion in Gastroenterology, vol. 26, no. 6, pp. 591–595, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Chen, D. Bruce, and M. T. Cantorna, “Vitamin D receptor expression controls proliferation of naïve CD8+ T cells and development of CD8 mediated gastrointestinal inflammation,” BMC Immunology, vol. 15, no. 6, pp. 1–11, 2014. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Kühne, A. Schutkowski, S. Weinholz et al., “Vitamin D receptor regulates intestinal proteins involved in cell proliferation, migration and stress response,” Lipids in Health and Disease, vol. 13, article 51, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. E. van Etten and C. Mathieu, “Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 97, no. 1-2, pp. 93–101, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. J. Tang, R. Zhou, D. Luger et al., “Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th17 effector response,” Journal of Immunology, vol. 182, no. 8, pp. 4624–4632, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. L. E. Jeffery, F. Burke, M. Mura 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,” Journal of Immunology, vol. 183, no. 9, pp. 5458–5467, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. M. R. Haussler, C. A. Haussler, G. K. Whitfield et al., “The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the ‘Fountain of Youth’ to mediate healthful aging,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 121, no. 1-2, pp. 88–97, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. J. N. Artaza, F. Sirad, M. G. Ferrini, and K. C. Norris, “1,25(OH)2 vitamin D3 inhibits cell proliferation by promoting cell cycle arrest without inducing apoptosis and modifies cell morphology of mesenchymal multipotent cells,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 119, no. 1-2, pp. 73–83, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. M. G. Bischof, K. Redlich, C. Schiller et al., “Growth inhibitory effects on human colon adenocarcinoma-derived Caco-2 cells and calcemic potential of 1α,25- dihydroxyvitamin D3 analogs: structure-function relationships,” Journal of Pharmacology and Experimental Therapeutics, vol. 275, no. 3, pp. 1254–1260, 1995. View at Google Scholar · View at Scopus
  17. H. S. Cross, M. Pavelka, J. Slavik, and M. Peterlik, “Growth control of human colon cancer cells by vitamin D and calcium in vitro,” Journal of the National Cancer Institute, vol. 84, no. 17, pp. 1355–1362, 1992. View at Publisher · View at Google Scholar · View at Scopus
  18. J. P. Hugot, M. Chamaillard, H. Zouali et al., “Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease,” Nature, vol. 411, no. 6837, pp. 599–603, 2001. View at Publisher · View at Google Scholar
  19. N. Inohara, Y. Ogura, A. Fontalba et al., “Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease,” The Journal of Biological Chemistry, vol. 278, no. 8, pp. 5509–5512, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. T. T. Wang, B. Dabbas, D. Laperriere et al., “Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease,” The Journal of Biological Chemistry, vol. 285, no. 4, pp. 2227–2231, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Wu, Y. G. Zhang, R. Lu et al., “Intestinal epithelial vitamin D receptor deletion leads to defective autophagy in colitis,” Gut, 2014. View at Publisher · View at Google Scholar
  22. M. Verway, M. A. Behr, and J. H. White, “Vitamin D, NOD2, autophagy and Crohn's disease,” Expert Review of Clinical Immunology, vol. 6, no. 4, pp. 505–508, 2010. View at Publisher · View at Google Scholar · View at Scopus
  23. J. D. Simmons, C. Mullighan, K. I. Welsh, and D. P. Jewell, “Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility,” Gut, vol. 47, no. 2, pp. 211–214, 2000. View at Publisher · View at Google Scholar · View at Scopus
  24. K. Martin, M. Radlmayr, R. Borchers, M. Heinzlmann, and C. Folwaczny, “Candidate genes colocalized to linkage regions in inflammatory bowel disease,” Digestion, vol. 66, no. 2, pp. 121–126, 2002. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Köstner, N. Denzer, C. S. L. Müller, R. Klein, W. Tilgen, and J. Reichrath, “The relevance of Vitamin D Receptor (VDR) gene polymorphisms for cancer: a review of the literature,” Anticancer Research, vol. 29, no. 9, pp. 3511–3536, 2009. View at Google Scholar · View at Scopus
  26. Y. Xu, B. He, Y. Pan et al., “Systematic review and meta-analysis on vitamin D receptor polymorphisms and cancer risk,” Tumour Biology, vol. 35, no. 5, pp. 4153–4169, 2014. View at Publisher · View at Google Scholar
  27. K. Tizaoui, A. Berraies, B. Hamdi, W. Kaabachi, K. Hamzaoui, and A. Hamzaoui, “Association of vitamin d receptor gene polymorphisms with asthma risk: systematic review and updated meta-analysis of case-control studies,” Lung, vol. 192, no. 6, pp. 955–965, 2014. View at Publisher · View at Google Scholar
  28. D. Santoro, D. Caccamo, G. Gagliostro et al., “Vitamin D metabolism and activity as well as genetic variants of the vitamin D receptor (VDR) in chronic kidney disease patients,” Journal of Nephrology, vol. 26, no. 4, pp. 636–644, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. D. J. Hughes, R. McManus, P. Neary, C. O'Morain, and M. O'Sullivan, “Common variation in the vitamin D receptor gene and risk of inflammatory bowel disease in an Irish case-control study,” European Journal of Gastroenterology & Hepatology, vol. 23, no. 9, pp. 807–812, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. W. Pluskiewicz, J. Zdrzałek, and D. Karasek, “Spine bone mineral density and VDR polymorphism in subjects with ulcerative colitis,” Journal of Bone and Mineral Metabolism, vol. 27, no. 5, pp. 567–573, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. F. H. Pei, Y. J. Wang, S. L. Gao et al., “Vitamin D receptor gene polymorphism and ulcerative colitis susceptibility in Han Chinese,” Journal of Digestive Diseases, vol. 12, no. 2, pp. 90–98, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. S. L. Xia, L. Q. Yu, H. Chen et al., “Association of vitamin D receptor gene polymorphisms with the susceptibility to ulcerative colitis in patients from Southeast China,” Journal of Receptors and Signal Transduction, 2014. View at Publisher · View at Google Scholar
  33. Y. Y. Luo, X. L. Shu, H. Zhao, J. D. Yu, M. Ma, and J. Chen, “Association between vitamin D receptor gene polymorphisms and pediatric Crohn's disease in China: A study based on gene sequencing,” Zhongguo Dang Dai Er Ke Za Zhi, vol. 15, no. 11, pp. 1006–1008, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. C. L. Noble, J. McCullough, W. Ho et al., “Low body mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease,” Alimentary Pharmacology & Therapeutics, vol. 27, no. 7, pp. 588–596, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. R. W. Bentley, D. Keown, T. R. Merriman et al., “Vitamin D receptor gene polymorphism associated with inflammatory bowel disease in New Zealand males,” Alimentary Pharmacology and Therapeutics, vol. 33, no. 7, pp. 855–856, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. R. Dresner-Pollak, Z. Ackerman, R. Eliakim, A. Karban, Y. Chowers, and H. H. Fidder, “The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients,” Genetic Testing, vol. 8, no. 4, pp. 417–420, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. N. Naderi, A. Farnood, M. Habibi et al., “Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease,” Journal of Gastroenterology and Hepatology, vol. 23, no. 12, pp. 1816–1822, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. L.-N. Xue, K.-Q. Xu, W. Zhang, Q. Wang, J. Wu, and X.-Y. Wang, “Associations between vitamin D receptor polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis,” Inflammatory Bowel Diseases, vol. 19, no. 1, pp. 54–60, 2013. View at Publisher · View at Google Scholar · View at Scopus
  39. L. Wang, Z. T. Wang, J. J. Hu, R. Fan, J. Zhou, and J. Zhong, “Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis,” Genetics and Molecular Research, vol. 13, no. 2, pp. 2598–2610, 2014. View at Publisher · View at Google Scholar · View at Scopus
  40. A. Y. O. M. Carvalho, K. S. Bishop, D. Y. Han et al., “The role of vitamin D level and related single nucleotide polymorphisms in Crohn's disease,” Nutrients, vol. 5, no. 10, pp. 3898–3909, 2013. View at Publisher · View at Google Scholar · View at Scopus
  41. G. Jones and G. Stewart, “Association of PHF11 polymorphisms with asthma and allergy,” Thorax, vol. 65, no. 7, pp. 659–660, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. J. J. Eloranta, C. Wenger, J. Mwinyi et al., “Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease,” Pharmacogenetics and Genomics, vol. 21, no. 9, pp. 559–564, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Sonnenberg, H. Ehms, G. E. Sonnenberg, and G. Strohmeyer, “25-Hydroxycholecalciferol serum levels in patients with Crohn's disease,” Acta Hepato-Gastroenterologica, vol. 24, no. 4, pp. 293–295, 1977. View at Google Scholar · View at Scopus
  44. T. Nic Suibhne, G. Cox, M. Healy, C. O'Morain, and M. O'Sullivan, “Vitamin D deficiency in Crohn's disease: prevalence, risk factors and supplement use in an outpatient setting,” Journal of Crohn's & Colitis, vol. 6, no. 2, pp. 182–188, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Ardizzone, S. Bollani, P. Bettica, M. Bevilacqua, P. Molteni, and G. B. Porro, “Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis,” Journal of Internal Medicine, vol. 247, no. 1, pp. 63–70, 2000. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Tajika, A. Matsuura, T. Nakamura et al., “Risk factors for vitamin D deficiency in patients with Crohn's disease,” Journal of Gastroenterology, vol. 39, no. 6, pp. 527–533, 2004. View at Google Scholar · View at Scopus
  47. M. T. Abreu, Y. Kantorovich, E. A. Vasiliauskas et al., “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, vol. 53, no. 8, pp. 1129–1136, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. J. R. de Bruyn, R. van Heeckeren, C. Y. Ponsioen et al., “Vitamin D deficiency in Crohn's disease and healthy controls: a prospective case-control study in the Netherlands,” Journal of Crohn's and Colitis, vol. 8, no. 10, pp. 1267–1273, 2014. View at Publisher · View at Google Scholar · View at Scopus
  49. L. E. Veit, L. Maranda, J. Fong, and B. U. Nwosu, “The vitamin D status in inflammatory bowel disease,” PLoS ONE, vol. 9, no. 7, Article ID e101583, 2014. View at Publisher · View at Google Scholar
  50. A. D. Harries, R. Brown, R. V. Heatley, L. A. Williams, S. Woodhead, and J. Rhodes, “Vitamin D status in Crohn's disease: association with nutrition and disease activity,” Gut, vol. 26, no. 11, pp. 1197–1203, 1985. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Rudnicki, A. Frølich, and I. Transbøl, “Inappropriate hypercalcitriolemia in ileum-resected patients with Crohn's disease,” Mineral and Electrolyte Metabolism, vol. 18, no. 1, pp. 52–55, 1992. View at Google Scholar · View at Scopus
  52. A. J. Joseph, B. George, A. B. Pulimood, M. S. Seshadri, and A. Chacko, “25 (OH) vitamin D level in Crohn's disease: association with sun exposure & disease activity,” Indian Journal of Medical Research, vol. 130, no. 2, pp. 133–137, 2009. View at Google Scholar · View at Scopus
  53. D. McCarthy, P. Duggan, M. O'Brien et al., “Seasonality of vitamin D status and bone turnover in patients with Crohn's disease,” Alimentary Pharmacology & Therapeutics, vol. 21, no. 9, pp. 1073–1083, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. W. El-Matary, S. Sikora, and D. Spady, “Bone mineral density, vitamin D, and disease activity in children newly diagnosed with inflammatory bowel disease,” Digestive Diseases and Sciences, vol. 56, no. 3, pp. 825–829, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Silvennoinen, “Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease,” Journal of Internal Medicine, vol. 239, no. 2, pp. 131–137, 1996. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Gilman, F. Shanahan, and K. D. Cashman, “Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn's disease and ulcerative colitis,” Alimentary Pharmacology & Therapeutics, vol. 23, no. 7, pp. 1007–1016, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. H. N. de Souza, F. L. Lora, C. A. M. Kulak, N. C. P. Mañas, H. M. B. Amarante, and V. Z. C. Borba, “Low levels of 25-hydroxyvitamin D (25OHD) in patients with inflammatory bowel disease and its correlation with bone mineral density,” Arquivos Brasileiros de Endocrinologia e Metabologia, vol. 52, no. 4, pp. 684–691, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. W. D. Leslie, N. Miller, L. Rogala, and C. N. Bernstein, “Vitamin D status and bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study,” American Journal of Gastroenterology, vol. 103, no. 6, pp. 1451–1459, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Ulitsky, A. N. Ananthakrishnan, A. Naik et al., “Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life,” Journal of Parenteral and Enteral Nutrition, vol. 35, no. 3, pp. 308–316, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. V. Hassan, S. Hassan, P. Seyed-Javad et al., “Association between serum 25 (OH) vitamin D concentrations and inflammatory bowel diseases (IBDS) activity,” Medical Journal of Malaysia, vol. 68, no. 1, pp. 34–38, 2013. View at Google Scholar · View at Scopus
  61. R. H. Alkhouri, H. Hashmi, R. D. Baker, D. Gelfond, and S. S. Baker, “Vitamin and mineral status in patients with inflammatory bowel disease,” Journal of Pediatric Gastroenterology and Nutrition, vol. 56, no. 1, pp. 89–92, 2013. View at Publisher · View at Google Scholar · View at Scopus
  62. H. M. Pappa, C. M. Gordon, T. M. Saslowsky et al., “Vitamin D status in children and young adults with inflammatory bowel disease,” Pediatrics, vol. 118, no. 5, pp. 1950–1961, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. J. Jahnsen, J. A. Falch, P. Mowinckel, and E. Aadland, “Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease,” Scandinavian Journal of Gastroenterology, vol. 37, no. 2, pp. 192–199, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Kuwabara, K. Tanaka, N. Tsugawa et al., “High prevalence of vitamin K and D deficiency and decreased BMD in inflammatory bowel disease,” Osteoporosis International, vol. 20, no. 6, pp. 935–942, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. Y. Ezzat and K. Hamdy, “The frequency of low bone mineral density and its associated risk factors in patients with inflammatory bowel diseases,” International Journal of Rheumatic Diseases, vol. 13, no. 3, pp. 259–265, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Atia, R. Murthy, B. A. Bailey et al., “Vitamin D Status in Veterans with inflammatory bowel disease: relationship to Health care costs and services,” Military Medicine, vol. 176, no. 6, pp. 711–714, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. I. Hessov, L. Mosekilde, F. Melsen et al., “Osteopenia with normal vitamin D metabolites after small-bowel resection for Crohn's disease,” Scandinavian Journal of Gastroenterology, vol. 19, no. 5, pp. 691–696, 1984. View at Google Scholar · View at Scopus
  68. S. Nakajima, H. Iijima, S. Egawa et al., “Association of vitamin K deficiency with bone metabolism and clinical disease activity in inflammatory bowel disease,” Nutrition, vol. 27, no. 10, pp. 1023–1028, 2011. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Laakso, H. Valta, M. Verkasalo, S. Toiviainen-Salo, H. Viljakainen, and O. Mäkitie, “Impaired bone health in inflammatory bowel disease: a case-control study in 80 pediatric patients,” Calcified Tissue International, vol. 91, no. 2, pp. 121–130, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. R. H. Driscoll Jr., S. C. Meredith, M. Sitrin, and I. H. Rosenberg, “Vitamin D deficiency and bone disease in patients with Crohn's disease,” Gastroenterology, vol. 83, no. 6, pp. 1252–1258, 1982. View at Google Scholar · View at Scopus
  71. H. Vogelsang, R. Schöfl, W. Tillinger, P. Ferenci, and A. Gangl, “25-Hydroxyvitamin D absorption in patients with Crohn's disease and with pancreatic insufficiency,” Wiener Klinische Wochenschrift, vol. 109, no. 17, pp. 678–682, 1997. View at Google Scholar · View at Scopus
  72. E. J. Schoon, M. C. A. Müller, C. Vermeer, L. J. Schurgers, R.-J. M. Brummer, and R. W. Stockbrügger, “Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?” Gut, vol. 48, no. 4, pp. 473–477, 2001. View at Publisher · View at Google Scholar · View at Scopus
  73. K. V. Haderslev, P. B. Jeppesen, H. A. Sorensen, P. B. Mortensen, and M. Staun, “Vitamin D status and measurements of markers of bone metabolism in patients with small intestinal resection,” Gut, vol. 52, no. 5, pp. 653–658, 2003. View at Publisher · View at Google Scholar · View at Scopus
  74. J. Gilman, F. Shanahan, and K. D. Cashman, “Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use,” European Journal of Clinical Nutrition, vol. 60, no. 7, pp. 889–896, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. A. D. Levin, V. Wadhera, S. T. Leach et al., “Vitamin D deficiency in children with inflammatory bowel disease,” Digestive Diseases and Sciences, vol. 56, no. 3, pp. 830–836, 2011. View at Publisher · View at Google Scholar · View at Scopus
  76. G. P. Kini, B. Young, P. Herbison, and M. Schultz, “Does seasonal level of serum 25-OH vitamin D correlate with the activity of Crohn's disease?” New Zealand Medical Journal, vol. 127, no. 1394, pp. 51–59, 2014. View at Google Scholar
  77. F. A. Farraye, H. Nimitphong, A. Stucchi et al., “Use of a novel vitamin D bioavailability test demonstrates that vitamin D absorption is decreased in patients with quiescent Crohn's disease,” Inflammatory Bowel Diseases, vol. 17, no. 10, pp. 2116–2121, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. T. A. Sentongo, E. J. Semaeo, N. Stettler, D. A. Piccoli, V. A. Stallings, and B. S. Zemel, “Vitamin D status in children, adolescents, and young adults with Crohn disease,” The American Journal of Clinical Nutrition, vol. 76, no. 5, pp. 1077–1081, 2002. View at Google Scholar · View at Scopus
  79. J. S. Siffledeen, K. Siminoski, H. Steinhart, G. Greenberg, and R. N. Fedorak, “The frequency of vitamin D deficiency in adults with Crohn's disease,” Canadian Journal of Gastroenterology, vol. 17, no. 8, pp. 473–478, 2003. View at Google Scholar · View at Scopus
  80. H. M. Pappa, E. J. Langereis, R. J. Grand, and C. M. Gordon, “Prevalence and risk factors for hypovitaminosis D in young patients with inflammatory bowel disease,” Journal of Pediatric Gastroenterology and Nutrition, vol. 53, no. 4, pp. 361–364, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. A. N. Ananthakrishnan, A. Cagan, V. S. Gainer et al., “Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn's disease,” Inflammatory Bowel Diseases, vol. 19, no. 9, pp. 1921–1927, 2013. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Hlavaty, A. Krajcovicova, T. Koller et al., “Higher vitamin D serum concentration increases health related quality of life in patients with inflammatory bowel diseases,” World Journal of Gastroenterology, vol. 20, no. 42, pp. 15787–15796, 2014. View at Publisher · View at Google Scholar
  83. L. Peyrin-Biroulet, A. Oussalah, and M.-A. Bigard, “Crohn's disease: the hot hypothesis,” Medical Hypotheses, vol. 73, no. 1, pp. 94–96, 2009. View at Publisher · View at Google Scholar · View at Scopus
  84. J. R. de Bruyn, R. van Heeckeren, C. Y. Ponsioen et al., “Vitamin D deficiency in Crohn's disease and healthy controls: a prospective case-control study in the Netherlands,” Journal of Crohn's & Colitis, vol. 8, no. 10, pp. 1267–1273, 2014. View at Publisher · View at Google Scholar
  85. V. Nerich, P. Jantchou, M.-C. Boutron-Ruault et al., “Low exposure to sunlight is a risk factor for Crohn's disease,” Alimentary Pharmacology and Therapeutics, vol. 33, no. 8, pp. 940–945, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. P. Jantchou, F. Clavel-Chapelon, A. Racine, M. Kvaskoff, F. Carbonnel, and M.-C. Boutron-Ruault, “High residential sun exposure is associated with a low risk of incident Crohn's disease in the prospective E3N cohort,” Inflammatory Bowel Diseases, vol. 20, no. 1, pp. 75–81, 2014. View at Publisher · View at Google Scholar · View at Scopus
  87. B. N. Limketkai, T. M. Bayless, S. R. Brant, and S. M. Hutfless, “Lower regional and temporal ultraviolet exposure is associated with increased rates and severity of inflammatory bowel disease hospitalisation,” Alimentary Pharmacology & Therapeutics, vol. 40, no. 5, pp. 508–517, 2014. View at Publisher · View at Google Scholar
  88. S. M. Govani, P. D. R. Higgins, R. W. Stidham, S. J. Montain, and A. K. Waljee, “Increased ultraviolet light exposure is associated with reduced risk of inpatient surgery among patients with Crohn's disease,” Journal of Crohn's and Colitis, vol. 9, no. 1, pp. 77–81, 2015. View at Publisher · View at Google Scholar
  89. A. N. Ananthakrishnan, H. Khalili, L. M. Higuchi et al., “Higher predicted vitamin D status is associated with reduced risk of crohn's disease,” Gastroenterology, vol. 142, no. 3, pp. 482–489, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. M. Garg, O. Rosella, J. S. Lubel, and P. R. Gibson, “Association of circulating vitamin D concentrations with intestinal but not systemic inflammation in inflammatory bowel disease,” Inflammatory Bowel Diseases, vol. 19, no. 12, pp. 2634–2643, 2013. View at Publisher · View at Google Scholar · View at Scopus
  91. A. N. Ananthakrishnan, A. Cagan, V. S. Gainer et al., “Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases,” Alimentary Pharmacology and Therapeutics, vol. 39, no. 10, pp. 1136–1142, 2014. View at Publisher · View at Google Scholar · View at Scopus
  92. Z. A. Zator, S. M. Cantu, G. G. Konijeti et al., “Pretreatment 25-hydroxyvitamin D levels and durability of anti–tumor necrosis factor-α therapy in inflammatory bowel diseases,” Journal of Parenteral and Enteral Nutrition, vol. 38, no. 3, pp. 385–391, 2014. View at Publisher · View at Google Scholar
  93. M. Ham, M. S. Longhi, C. Lahiff, A. Cheifetz, S. Robson, and A. C. Moss, “Vitamin D levels in adults with Crohn's disease are responsive to disease activity and treatment,” Inflammatory Bowel Diseases, vol. 20, no. 5, pp. 856–860, 2014. View at Publisher · View at Google Scholar
  94. D. Reid, B. J. Toole, S. Knox et al., “The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty,” The American Journal of Clinical Nutrition, vol. 93, no. 5, pp. 1006–1011, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. J. L. Waldron, H. L. Ashby, M. P. Cornes et al., “Vitamin D: a negative acute phase reactant,” Journal of Clinical Pathology, vol. 66, no. 7, pp. 620–622, 2013. View at Publisher · View at Google Scholar · View at Scopus
  96. M. T. Cantorna, C. Munsick, C. Bemiss, and B. D. Mahon, “1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease,” Journal of Nutrition, vol. 130, no. 11, pp. 2648–2652, 2000. View at Google Scholar · View at Scopus
  97. C. Daniel, H. H. Radeke, N. A. Sartory 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,” Journal of Pharmacology and Experimental Therapeutics, vol. 319, no. 2, pp. 622–631, 2006. View at Publisher · View at Google Scholar · View at Scopus
  98. G. Laverny, G. Penna, S. Vetrano et al., “Efficacy of a potent and safe vitamin D receptor agonist for the treatment of inflammatory bowel disease,” Immunology Letters, vol. 131, no. 1, pp. 49–58, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. L. Verlinden, C. Leyssens, I. Beullens et al., “The vitamin D analog TX527 ameliorates disease symptoms in a chemically induced model of inflammatory bowel disease,” The Journal of Steroid Biochemistry and Molecular Biology, vol. 136, no. 1, pp. 107–111, 2013. View at Publisher · View at Google Scholar · View at Scopus
  100. J. H. Ooi, Y. Li, C. J. Rogers, and M. T. Cantorna, “Vitamin D regulates the gut microbiome and protects mice from dextran sodium sulfate-induced coliti,” Journal of Nutrition, vol. 143, no. 10, pp. 1679–1686, 2013. View at Publisher · View at Google Scholar · View at Scopus
  101. A. Assa, L. Vong, L. J. Pinnell et al., “Vitamin D deficiency predisposes to adherent-invasive Escherichia coli-induced barrier dysfunction and experimental colonic injury,” Inflammatory Bowel Diseases, vol. 21, no. 2, pp. 297–306, 2015. View at Publisher · View at Google Scholar
  102. Q. Tao, B. Wang, Y. Zheng, X. Jiang, Z. Pan, and J. Ren, “Vitamin D prevents the intestinal fibrosis via induction of vitamin D receptor and inhibition of transforming growth factor-beta1/smad3 pathway,” Digestive Diseases and Sciences, 2014. View at Publisher · View at Google Scholar
  103. S. Ardizzone, A. Cassinotti, D. Trabattoni et al., “Immunomodulatory effects of 1,25-dihydroxyvitamin D3 on Th1/Th2 cytokines in inflammatory bowel disease: an in vitro study,” International Journal of Immunopathology and Pharmacology, vol. 22, no. 1, pp. 63–71, 2009. View at Google Scholar · View at Scopus
  104. M. Bendix-Struve, L. E. Bartels, J. Agnholt, A. Dige, S. P. Jørgensen, and J. F. Dahlerup, “Vitamin D3 treatment of Crohns disease patients increases stimulated T cell IL-6 production and proliferation,” Alimentary Pharmacology & Therapeutics, vol. 32, no. 11-12, pp. 1364–1372, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. M. Stio, M. Martinesi, S. Bruni et al., “The Vitamin D analogue TX 527 blocks NF-kappaB activation in peripheral blood mononuclear cells of patients with Crohn's disease,” Journal of Steroid Biochemistry and Molecular Biology, vol. 103, no. 1, pp. 51–60, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. L. E. Bartels, M. Bendix, C. L. Hvas et al., “Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell maturation and cytokine production in Crohn's disease patients,” Inflammopharmacology, vol. 22, no. 2, pp. 95–103, 2014. View at Publisher · View at Google Scholar
  107. P. Miheller, G. Muzes, I. Hritz 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,” Inflammatory Bowel Diseases, vol. 15, no. 11, pp. 1656–1662, 2009. View at Publisher · View at Google Scholar · View at Scopus
  108. S. P. Jørgensen, J. Agnholt, H. Glerup et al., “Clinical trial: vitamin D3 treatment in Crohn's disease—a randomized double-blind placebo-controlled study,” Alimentary Pharmacology and Therapeutics, vol. 32, no. 3, pp. 377–383, 2010. View at Publisher · View at Google Scholar · View at Scopus
  109. L. Yang, V. Weaver, J. P. Smith, S. Bingaman, T. J. Hartman, and M. T. Cantorna, “Therapeutic effect of vitamin D supplementation in a pilot study of Crohn's patients,” Clinical and Translational Gastroenterology, vol. 4, article e33, 2013. View at Publisher · View at Google Scholar · View at Scopus