: Inflammatory bowel disease is associated with industrialization, and its incidence has increased markedly over time. The prospect of reversing these trends motivates the search for the agent(s) involved. Modernity entails several physical and behavioral modifications that compromise both the photosynthesis of cholecalciferol in the skin and of its bioavailability. Although deficiency in this "vitamin" has therefore emerged as a leading candidate, and despite the publication of a randomized control trial that showed a trend toward statistically significant benefit in Crohn's disease, its causal agency has yet to be demonstrated by an adequately powered study. We discuss the strengths and weaknesses of the case being made by epidemiologists, geneticists, clinicians, and basic researchers, and consolidate their findings into a model that provides mechanistic plausibility to the claim. Specifically, converging data sets suggest that local activation of vitamin D coordinates the activity of the innate and adaptive arms of immunity, and of the intestinal epithelium, in a manner that promotes barrier integrity, facilitates the clearance of translocated flora, and diverts CD4 T cell development away from inflammatory phenotypes. Because smoking is an important risk-altering exposure, we also discuss its newly established melanizing effect and other emerging evidence linking tobacco use to immune function through vitamin D pathways.
[Show abstract][Hide abstract] ABSTRACT: Vitamin D has received a lot of attention recently as a result of a meteoric rise in the number of publications showing that vitamin D plays a crucial role in a plethora of physiological functions and associating vitamin D deficiency with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, some cancers, type 2 diabetes mellitus, infectious diseases and cardiovascular disease. The recent data on vitamin D from experimental, ecological, case-control, retrospective and prospective observational studies, as well as smaller intervention studies, are significant and confirm the sunshine vitamin's essential role in a variety of physiological and preventative functions. The results of these studies justify the recommendation to improve the general vitamin D status in children and adults by means of a healthy approach to sunlight exposure, consumption of foods containing vitamin D and supplementation with vitamin D preparations. In general, closer attention should therefore be paid to vitamin D deficiency in medical and pharmaceutical practice than has been the case hitherto.
[Show abstract][Hide abstract] ABSTRACT: Crohn's disease (CD) is characterized as a chronic immune-mediated inflammatory disorder of the gastrointestinal tract. Current consensus surrounding the cause of the disease suggests a complex interplay between genetic susceptibility, the intestinal microbiome and environmental factors, leading to the aberrant Th1 and Th17 immune cell mediated response. Vitamin D deficiency is common in CD patients, and long-standing deficiency has been associated with reduced bone mineral density (BMD). Accumulating evidence now suggests that in addition to maintaining skeletal integrity, vitamin D also plays an integral role in regulating the general immune response, a function employed via its genomic actions on the vitamin D receptor (VDR). The VDR is expressed in all immune cells and both directly and indirectly targeted by the bioactive form of vitamin D, 1,25-Dihydroxyvitamin D (1,25[OH]2D). Impaired regulation or deficiency of the vitamin has been linked to the promotion of self-reactive T cell development, loss of immune tolerance to self-structures, and experimental colitis in animal models, whereas the subsequent administration of the vitamin in these models resulted in the improvement of immune-mediated symptoms. In addition, low vitamin D has been associated with disease activity in CD patients, and supplementation appears to be beneficial in improving clinical scores and reducing inflammation. Therefore, the primary aims of this article were to review the molecular evidence supporting the immunoregulatory roles of vitamin D and its supplementation in the CD patient, based on existing literature. The physiological processes, accepted serum concentration values, and its well-recognized role in bone health were also summarized.
Journal of Parenteral and Enteral Nutrition 10/2013; 38(4). DOI:10.1177/0148607113506013 · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The north–south geographical gradient of inflammatory bowel disease (IBD) prevalence, its epidemiology, the genetic association of vitamin D receptor polymorphisms, and results in animal models suggest that vitamin D plays an important role in the pathogenesis of IBD.
The purpose of this review was to critically appraise the effectiveness and safety of vitamin D therapy in patients with IBD.
MEDLINE, Scopus and Google Scholar were searched from inception to May 20, 2014 using the terms ‘Crohn’s disease’, ‘ulcerative colitis’ and ‘vitamin D’. Results: Vitamin D deficiency is common in patients with IBD. Limited clinical data suggest an association between low vitamin D concentration and increased disease activity in both ulcerative colitis (UC) and Crohn’s disease (CD). To date, only two small open label trials and one randomized controlled trial have shown a positive effect of vitamin D supplementation on disease activity in patients with CD; no effect has been shown for UC. An optimal vitamin D supplementation protocol for patients with IBD remains undetermined, but targeting serum 25-hydroxy vitamin D [25(OH)D] levels between 30 and 50 ng/mL appears safe and may have benefits for IBD disease activity. Depending on baseline vitamin D serum concentration, ileal involvement in CD, body mass index, and perhaps smoking status, daily vitamin D doses between 1800–10,000 international units/day are probably necessary.
Increasing preclinical and clinical evidence suggests a role for vitamin D deficiency in the development and severity of IBD. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation.
Journal of Crohn s and Colitis 01/2014; 9(2):198-209. DOI:10.1093/ecco-jcc/jju004 · 6.23 Impact Factor
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