Review Article: Vitamin D and Inflammatory Bowel Disease

Established Concepts and Future Directions

M. Garg; J. S. Lubel; M. P. Sparrow; S. G. Holt; P. R. Gibson

Disclosures

Aliment Pharmacol Ther. 2012;36(4):324-344. 

In This Article

Nonclassical Actions of Vitamin D

A series of discoveries charting the anatomical distribution of vitamin D axis components have led to a paradigm shift from a purely endocrine action to intra-organ autocrine, paracrine and intracrine roles. First, the VDR has been isolated in tissues other than the intestinal epithelium, distal renal tubules and osteocytes, including the adrenals, parathyroids, heart, placenta, pituitary gland, ovary, testis, mammary glands, skin, hepatocytes, biliary epithelial cells, promyelocytes, thymus, lymphocytes and colon.[71,73–77] Second, 1α-hydroxylase is also expressed in the colon, skin, lymph nodes, pancreas, adrenal medulla, brain and monocytes and macrophages, demonstrating the capacity for local production of 1,25(OH)2D.[78,79] Third, though DBP is predominantly produced in the liver, mRNA for DBP gene transcripts have been noted in rat kidney, testis, abdominal fat, yolk sac, duodenum and ileum.[80] In fact, some authors have estimated that only about 5% of serum 25(OH)D is involved in the endocrine vitamin D system, with about 85% involved in autocrine and paracrine functions in local target tissues.[81]

Recent research has analysed effects of the vitamin D axis on cardiovascular disease, renal disease, glucose control, infection cancer, asthma and chronic obstructive pulmonary disease, cognitive and psychiatric disease, and autoimmune diseases including multiple sclerosis and IBD. To date, clinical data suggesting an inverse correlation between vitamin D levels and the incidence or risk of these conditions have been largely observational, and hence limited by multiple confounding factors.[5,82] In vitro and animal in vivo data support a beneficial role for vitamin D supplementation or VDR agonism in cardiac hypertrophy, atherosclerosis,[83] hypertension, diabetic nephropathy,[84–86] colon,[87–89] breast[90,91] and prostate cancer,[92–97] asthma and chronic obstructive pulmonary disease.[98–101] There are, however, very few prospective RCTs in humans demonstrating this benefit. The best evidence to date has been in pulmonary tuberculosis and diabetic nephropathy. An RCT demonstrated the superiority of high-dose vitamin D3 supplementation in combination with antituberculous therapy over no supplementation for treatment of pulmonary tuberculosis,[102] and a recent multi-national trial demonstrated that the addition of the VDR agonist, paricalcitol, to inhibition of angiotensin-converting enzyme further reduced albuminuria in patients with diabetic nephropathy.[103] Detailed reviews on the involvement of the vitamin D axis in various organ systems are presented elsewhere.[16,82,83,87,104–111]

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