Vitamin D Supplementation as Non-toxic Immunomodulation in Children With Crohn's Disease

Summary

IBD is caused by an abnormal immune response to the gut bacteria in people who are genetically predisposed. There has been a huge increase in the number of people diagnosed with IBD since World War II, likely due to changes in our environment. It is possible that the abundance of vitamin D in the body may be one of those environmental factors that the investigators can control to make patients with IBD better. Vitamin D acts on cells of the immune system and causes many effects, including the production of a "natural antibiotic" called cathelicidin. The investigators know that when people are supplemented with vitamin D, levels of cathelicidin produced by these immune cells increase. By supplementing children with Crohn's disease with vitamin D, the investigators may be able to alter their immune system "naturally," making their disease better. A consensus of vitamin D experts believes that vitamin D levels need to reach a level of 40-70 ng/mL in the blood in order to have effects on the immune system. Raising vitamin D levels to this range is one of the goals in the current study.

Timeline

Start

2010-01

Primary completion

2017-05

Completion

2017-05

Publications

• Background Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr Opin Gastroenterol. 2008 Mar;24(2):176-83. doi: 10.1097/MOG.0b013e3282f4d2f3.
• Background Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008 Dec;29(6):361-8. doi: 10.1016/j.mam.2008.08.008. Epub 2008 Sep 2.
• Background 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 Oct;42(4):644-9. doi: 10.1093/ajcn/42.4.644.
• Background 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 Sep 19;109(17):678-82.
• Background 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 Sep;54(3):548-52. doi: 10.1093/ajcn/54.3.548.
• Background 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 Oct;149(10):4799-808. doi: 10.1210/en.2008-0060. Epub 2008 Jun 5.
• Background Schauber J, Rieger D, Weiler F, Wehkamp J, Eck M, Fellermann K, Scheppach W, Gallo RL, Stange EF. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol. 2006 Jun;18(6):615-21. doi: 10.1097/00042737-200606000-00007.
• Background Tai EK, Wu WK, Wong HP, Lam EK, Yu L, Cho CH. A new role for cathelicidin in ulcerative colitis in mice. Exp Biol Med (Maywood). 2007 Jun;232(6):799-808.
• Background Martineau AR, Wilkinson KA, Newton SM, Floto RA, Norman AW, Skolimowska K, Davidson RN, Sorensen OE, Kampmann B, Griffiths CJ, Wilkinson RJ. IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007 Jun 1;178(11):7190-8. doi: 10.4049/jimmunol.178.11.7190.
• Background 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 Dec;17(12):2386-92. doi: 10.1210/me.2003-0281. Epub 2003 Sep 18.
• Background Simmons JD, Mullighan C, Welsh KI, Jewell DP. Vitamin D receptor gene polymorphism: association with Crohn's disease susceptibility. Gut. 2000 Aug;47(2):211-4. doi: 10.1136/gut.47.2.211.
• Background Heaney RP. Lessons for nutritional science from vitamin D. Am J Clin Nutr. 1999 May;69(5):825-6. doi: 10.1093/ajcn/69.5.825. No abstract available.
• Background Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. doi: 10.1093/ajcn/69.5.842.
• Background Maalouf J, Nabulsi M, Vieth R, Kimball S, El-Rassi R, Mahfoud Z, El-Hajj Fuleihan G. Short- and long-term safety of weekly high-dose vitamin D3 supplementation in school children. J Clin Endocrinol Metab. 2008 Jul;93(7):2693-701. doi: 10.1210/jc.2007-2530. Epub 2008 Apr 29.
• Background Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, Hewison M. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009 Apr 1;182(7):4289-95. doi: 10.4049/jimmunol.0803736.
• Background Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007 Dec;22 Suppl 2:V64-8. doi: 10.1359/jbmr.07s221.

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