Skip to main content

Advertisement

SpringerLink
Log in

Vitamin D and the Pathogenesis of Inflammatory Bowel Disease

  • Nutrition and Obesity (S McClave, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Vitamin D has traditionally been known for its role in bone metabolism, but emerging evidence has suggested a broader role for vitamin D in immune regulation. Vitamin D deficiency has been associated with the pathogenesis of diverse autoimmune disorders and has similarly been implicated as a contributor to inflammatory bowel disease. In this review, we discuss animal, in vitro, genetic, and epidemiologic studies that have linked vitamin D deficiency with inflammatory bowel disease pathogenesis or severity. Nonetheless, we present the caveat in interpreting these studies in the context of reverse causation: Does vitamin D deficiency lead to gastrointestinal disease, or does gastrointestinal disease (with related changes in dietary choices, intestinal absorption, nutritional status, lifestyle) lead to vitamin D deficiency?

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012;491:119–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.

    Article  CAS  PubMed  Google Scholar 

  3. Holick MF, MacLaughlin JA, Clark MB, Holick SA, Potts Jr JT, Anderson RR, et al. Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science. 1980;210:203–5.

    Article  CAS  PubMed  Google Scholar 

  4. 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;268:14888–92.

    CAS  PubMed  Google Scholar 

  5. 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;63:954–9.

    Article  CAS  PubMed  Google Scholar 

  6. Ponchon G, DeLuca HF. The role of the liver in the metabolism of vitamin D. J Clin Invest. 1969;48:1273–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fraser DR, Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970;228:764–6.

    Article  CAS  PubMed  Google Scholar 

  8. Haussler MR, Norman AW. Chromosomal receptor for a vitamin D metabolite. Proc Natl Acad Sci U S A. 1969;62:155–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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;22:2902–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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;266:23296–305.

    CAS  PubMed  Google Scholar 

  11. 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;246:1158–61.

    Article  CAS  PubMed  Google Scholar 

  12. Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T, et al. Differentiation of mouse myeloid leukemia cells induced by 1 alpha, 25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1981;78:4990–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-Dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983;221:1181–3.

    Article  CAS  PubMed  Google Scholar 

  14. 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;57:1308–10.

    Article  CAS  PubMed  Google Scholar 

  15. Kizaki M, Norman AW, Bishop JE, Lin CW, Karmakar A, Koeffler HP. 1,25-Dihydroxyvitamin D3 receptor RNA: expression in hematopoietic cells. Blood. 1991;77:1238–47.

    CAS  PubMed  Google Scholar 

  16. Reichel H, Koeffler HP, Norman AW. Synthesis in vitro of 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 by interferon-gamma-stimulated normal human bone marrow and alveolar macrophages. J Biol Chem. 1987;262:10931–7.

    CAS  PubMed  Google Scholar 

  17. 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;102:3314–6.

    Article  CAS  PubMed  Google Scholar 

  18. Abu-Amer Y, Bar-Shavit Z. Impaired bone marrow-derived macrophage differentiation in vitamin D deficiency. Cell Immunol. 1993;151:356–68.

    Article  CAS  PubMed  Google Scholar 

  19. 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;82:1300–7.

    CAS  PubMed  Google Scholar 

  20. Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 2006;36:361–70.

    Article  CAS  PubMed  Google Scholar 

  21. Tsoukas CD, Provvedini DM, Manolagas SC. 1,25-Dihydroxyvitamin D3: a novel immunoregulatory hormone. Science. 1984;224:1438–40.

    Article  CAS  PubMed  Google Scholar 

  22. 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;179:1634–47.

    Article  CAS  PubMed  Google Scholar 

  23. 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;63:394–400.

    Article  CAS  PubMed  Google Scholar 

  24. 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;98:6800–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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;164:2405–11.

    Article  CAS  PubMed  Google Scholar 

  26. Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, Hewison 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;183:5458–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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;182:6071–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 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.

    Article  CAS  PubMed  Google Scholar 

  29. Palmer MT, Lee YK, Maynard CL, Oliver JR, Bikle DD, Jetten AM, 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.

    Article  CAS  PubMed  Google Scholar 

  30. 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;15:5789–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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;98:311–22.

    Article  CAS  PubMed  Google Scholar 

  32. D’Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, 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;101:252–62.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Towers TL, Freedman LP. Granulocyte-macrophage colony-stimulating factor gene transcription is directly repressed by the vitamin D3 receptor. Implications for allosteric influences on nuclear receptor structure and function by a DNA element. J Biol Chem. 1998;273:10338–48.

    Article  CAS  PubMed  Google Scholar 

  34. Lemire JM, Archer DC. 1,25-Dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest. 1991;87:1103–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 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 U S A. 1996;93:7861–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. DeLuca HF, Plum LA. Vitamin D deficiency diminishes the severity and delays onset of experimental autoimmune encephalomyelitis. Arch Biochem Biophys. 2011;513:140–3.

    Article  CAS  PubMed  Google Scholar 

  37. Yang S, Smith C, Prahl JM, Luo X, DeLuca HF. Vitamin D deficiency suppresses cell-mediated immunity in vivo. Arch Biochem Biophys. 1993;303:98–106.

    Article  CAS  PubMed  Google Scholar 

  38. Munger KL, Zhang SM, O’Reilly E, Hernan MA, Olek MJ, Willett WC, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62:60–5.

    Article  CAS  PubMed  Google Scholar 

  39. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–8.

    Article  CAS  PubMed  Google Scholar 

  40. Fukazawa T, Yabe I, Kikuchi S, Sasaki H, Hamada T, Miyasaka K, et al. Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese. J Neurol Sci. 1999;166:47–52.

    Article  CAS  PubMed  Google Scholar 

  41. Niino M, Fukazawa T, Yabe I, Kikuchi S, Sasaki H, Tashiro K. Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles. J Neurol Sci. 2000;177:65–71.

    Article  CAS  PubMed  Google Scholar 

  42. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum. 2004;50:72–7.

    Article  CAS  PubMed  Google Scholar 

  43. Cantorna MT, Hayes CE, DeLuca HF. 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr. 1998;128:68–72.

    CAS  PubMed  Google Scholar 

  44. O’Regan S, Chesney RW, Hamstra A, Eisman JA, O’Gorman AM, Deluca HF. Reduced serum 1,25-(OH)2 vitamin D3 levels in prednisone-treated adolescents with systemic lupus erythematosus. Acta Paediatr Scand. 1979;68:109–11.

    Article  PubMed  Google Scholar 

  45. Monticielo OA, Teixeira TD, Chies JA, Brenol JC, Xavier RM. Vitamin D and polymorphisms of VDR gene in patients with systemic lupus erythematosus. Clin Rheumatol. 2012;31(10):1411–21.

    Article  PubMed  Google Scholar 

  46. Amital H, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis. 2010;69:1155–7.

    Article  CAS  PubMed  Google Scholar 

  47. 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;51:1367–74.

    Article  CAS  PubMed  Google Scholar 

  48. Mathieu C, Waer M, Laureys J, Rutgeerts O, Bouillon R. Prevention of autoimmune diabetes in NOD mice by 1,25 dihydroxyvitamin D3. Diabetologia. 1994;37:552–8.

    Article  CAS  PubMed  Google Scholar 

  49. Zella JB, McCary LC, DeLuca HF. Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. Arch Biochem Biophys. 2003;417:77–80.

    Article  CAS  PubMed  Google Scholar 

  50. Poon AH, Laprise C, Lemire M, Montpetit A, Sinnett D, Schurr E, et al. Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Am J Respir Crit Care Med. 2004;170:967–73.

    Article  PubMed  Google Scholar 

  51. Raby BA, Lazarus R, Silverman EK, Lake S, Lange C, Wjst M, et al. Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. Am J Respir Crit Care Med. 2004;170:1057–65.

    Article  PubMed  Google Scholar 

  52. Bosse Y, Lemire M, Poon AH, Daley D, He JQ, Sandford A, et al. Asthma and genes encoding components of the vitamin D pathway. Respir Res. 2009;10:98.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr. 2000;130:2648–52.

    CAS  PubMed  Google Scholar 

  54. 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;35:217–24.

    Article  CAS  PubMed  Google Scholar 

  55. Daniel C, Radeke HH, Sartory NA, Zahn N, Zuegel U, Steinmeyer A, 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;319:622–31.

    Article  CAS  PubMed  Google Scholar 

  56. Laverny G, Penna G, Vetrano S, Correale C, Nebuloni M, Danese S, et al. Efficacy of a potent and safe vitamin D receptor agonist for the treatment of inflammatory bowel disease. Immunol Lett. 2010;131:49–58.

    Article  CAS  PubMed  Google Scholar 

  57. 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;17:2386–92.

    Article  CAS  PubMed  Google Scholar 

  58. Froicu M, Zhu Y, Cantorna MT. Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice. Immunology. 2006;117:310–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. 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;105:20834–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Simmons JD, Mullighan C, Welsh KI, Jewell DP. Vitamin D receptor gene polymorphism: association with Crohn’s disease susceptibility. Gut. 2000;47:211–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Naderi N, Farnood A, Habibi M, Derakhshan F, Balaii H, Motahari Z, et al. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol. 2008;23:1816–22.

    Article  CAS  PubMed  Google Scholar 

  62. Dresner-Pollak R, Ackerman Z, Eliakim R, Karban A, Chowers Y, Fidder HH. The BsmI vitamin D receptor gene polymorphism is associated with ulcerative colitis in Jewish Ashkenazi patients. Genet Test. 2004;8:417–20.

    Article  CAS  PubMed  Google Scholar 

  63. Hughes DJ, McManus R, Neary P, O’Morain C, O’Sullivan M. Common variation in the vitamin D receptor gene and risk of inflammatory bowel disease in an Irish case-control study. Eur J Gastroenterol Hepatol. 2011;23:807–12.

    Article  CAS  PubMed  Google Scholar 

  64. Eloranta JJ, Wenger C, Mwinyi J, Hiller C, Gubler C, Vavricka SR, et al. Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease. Pharmacogenet Genomics. 2011;21:559–64.

    Article  CAS  PubMed  Google Scholar 

  65. Wang TT, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-Mendoza LE, et al. 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;285:2227–31.

    Article  CAS  PubMed  Google Scholar 

  66. Armitage EL, Aldhous MC, Anderson N, Drummond HE, Riemersma RA, Ghosh S, et al. Incidence of juvenile-onset Crohn’s disease in Scotland: association with northern latitude and affluence. Gastroenterology. 2004;127:1051–7.

    Article  PubMed  Google Scholar 

  67. Wolters FL, Joling C, Russel MG, Sijbrandij J, De Bruin M, Odes S, et al. Treatment inferred disease severity in Crohn’s disease: evidence for a European gradient of disease course. Scand J Gastroenterol. 2007;42:333–44.

    Article  PubMed  Google Scholar 

  68. Nerich V, Monnet E, Etienne A, Louafi S, Ramee C, Rican S, et al. Geographical variations of inflammatory bowel disease in France: a study based on national health insurance data. Inflamm Bowel Dis. 2006;12:218–26.

    Article  PubMed  Google Scholar 

  69. Nerich V, Jantchou P, Boutron-Ruault MC, Monnet E, Weill A, Vanbockstael V, et al. Low exposure to sunlight is a risk factor for Crohn’s disease. Aliment Pharmacol Ther. 2011;33:940–5.

    Article  CAS  PubMed  Google Scholar 

  70. Joseph AJ, George B, Pulimood AB, Seshadri MS, Chacko A. 25 (OH) vitamin D level in Crohn’s disease: association with sun exposure & disease activity. Indian J Med Res. 2009;130:133–7.

    CAS  PubMed  Google Scholar 

  71. Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, 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;39:690–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Nerich V, Monnet E, Weill A, Vallier N, Vanbockstael V, Auleley GR, et al. Fine-scale geographic variations of inflammatory bowel disease in France: correlation with socioeconomic and house equipment variables. Inflamm Bowel Dis. 2010;16:813–21.

    Article  PubMed  Google Scholar 

  73. Khalili H, Huang ES, Ananthakrishnan AN, Higuchi L, Richter JM, Fuchs CS, et al. Geographical variation and incidence of inflammatory bowel disease among US women. Gut. 2012;61:1686–92.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Sonnenberg A, Genta RM. Geographic distributions of microscopic colitis and inflammatory bowel disease in the United States. Inflamm Bowel Dis. 2012;18:2288–93.

    Article  PubMed  Google Scholar 

  75. Ananthakrishnan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, et al. Higher predicted vitamin D status is associated with reduced risk of Crohn’s disease. Gastroenterology. 2012;142:482–9. Large and long-term prospective study that associated vitamin D status with risk of Crohn’s disease.

    Article  CAS  PubMed  Google Scholar 

  76. Ulitsky A, Ananthakrishnan AN, Naik A, Skaros S, Zadvornova Y, Binion DG, 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;35:308–16.

    Article  CAS  PubMed  Google Scholar 

  77. Blanck S, Aberra F. Vitamin d deficiency is associated with ulcerative colitis disease activity. Dig Dis Sci. 2013;58:1698–702.

    Article  CAS  PubMed  Google Scholar 

  78. Zator ZA, Cantu SM, Konijeti GG, Nguyen DD, Sauk J, Yajnik V, 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;38:385–91.

  79. 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):508–17.

    CAS  PubMed  Google Scholar 

  80. Ananthakrishnan AN, Cagan A, Gainer VS, Cai T, Cheng SC, Savova G, et al. Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn’s disease. Inflamm Bowel Dis. 2013;19:1921–7. Large retrospective study that demonstrated effects of vitamin D repletion on risk of hospitalizations and surgery.

    PubMed  PubMed Central  Google Scholar 

  81. Jorgensen SP, Agnholt J, Glerup H, Lyhne S, Villadsen GE, Hvas CL, et al. Clinical trial: vitamin D3 treatment in Crohn’s disease—a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther. 2010;32:377–83. Randomized trial that assessed effects of vitamin D supplementation on disease activity in Crohn’s disease.

    Article  CAS  PubMed  Google Scholar 

  82. Miheller P, Muzes G, Hritz I, Lakatos G, Pregun I, Lakatos PL, 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;15:1656–62.

    Article  PubMed  Google Scholar 

  83. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pappa HM, Langereis EJ, Grand RJ, Gordon CM. Prevalence and risk factors for hypovitaminosis D in young patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2011;53:361–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 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;37:192–9.

    Article  CAS  PubMed  Google Scholar 

  86. 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;17:473–8.

    Article  PubMed  Google Scholar 

  87. Sinnott BP, Licata AA. Assessment of bone and mineral metabolism in inflammatory bowel disease: case series and review. Endocr Pract. 2006;12:622–9.

    Article  PubMed  Google Scholar 

  88. Tajika M, Matsuura A, Nakamura T, Suzuki T, Sawaki A, Kato T, et al. Risk factors for vitamin D deficiency in patients with Crohn’s disease. J Gastroenterol. 2004;39:527–33.

    Article  CAS  PubMed  Google Scholar 

  89. McCarthy D, Duggan P, O’Brien M, Kiely M, McCarthy J, Shanahan F, et al. Seasonality of vitamin D status and bone turnover in patients with Crohn’s disease. Aliment Pharmacol Ther. 2005;21:1073–83.

    Article  CAS  PubMed  Google Scholar 

  90. Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF. Vitamin D absorption in healthy subjects and in patients with intestinal malabsorption syndromes. Am J Clin Nutr. 1985;42:644–9.

    CAS  PubMed  Google Scholar 

  91. Farraye FA, Nimitphong H, Stucchi A, Dendrinos K, Boulanger AB, Vijjeswarapu 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;17:2116–21.

    Article  CAS  PubMed  Google Scholar 

  92. Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and adolescents before the diagnosis of Crohn’s disease. Gastroenterology. 1988;95:1523–7.

    Article  CAS  PubMed  Google Scholar 

  93. Thjodleifsson B, Sigthorsson G, Cariglia N, Reynisdottir I, Gudbjartsson DF, Kristjansson K, et al. Subclinical intestinal inflammation: an inherited abnormality in Crohn’s disease relatives? Gastroenterology. 2003;124:1728–37.

    Article  PubMed  Google Scholar 

  94. Pham M, Leach ST, Lemberg DA, Day AS. Subclinical intestinal inflammation in siblings of children with Crohn’s disease. Dig Dis Sci. 2010;55:3502–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 300 Pasteur Drive, Alway M211, Stanford, CA, 94305, USA

    Berkeley N. Limketkai

  2. Division of Gastroenterology and Hepatology, University of Missouri School of Medicine, Columbia, MO, USA

    Matthew L. Bechtold

  3. Division of Gastroenterology, University of California, Irvine, CA, USA

    Douglas L. Nguyen

Authors
  1. Berkeley N. Limketkai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew L. Bechtold
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Douglas L. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Berkeley N. Limketkai.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Nutrition and Obesity

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Limketkai, B.N., Bechtold, M.L. & Nguyen, D.L. Vitamin D and the Pathogenesis of Inflammatory Bowel Disease. Curr Gastroenterol Rep 18, 52 (2016). https://doi.org/10.1007/s11894-016-0526-9

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-016-0526-9

Keywords

Search

Navigation