Current evidence for vitamin D in intestinal function and disease

Abstract

Vitamin D activity is associated with the modulation of a wide variety of biological systems, in addition to its roles in calcium homeostatic mechanisms. While vitamin D is well known to promote gastrointestinal calcium absorption, vitamin D also plays a role in attenuating and/or preventing the progression of several gastrointestinal diseases including Crohn’s disease, ulcerative colitis, and colorectal cancer, and may also play a role in chemotherapy-induced intestinal mucositis. The pro-differentiation, immunomodulatory, and anti-inflammatory effects of vitamin D, which has been reported in numerous circumstances, are key potential mechanisms of action in the prevention of gastrointestinal disorders. While the debate of the effectiveness of vitamin D to treat bone pathologies continues, the clinical importance of vitamin D therapy to prevent gastrointestinal disorders should be investigated given current evidence, using both nutritional and pharmaceutical intervention approaches.

Impact statement: The non-skeletal functions of vitamin D play an important role in health and disease. The anti-inflammatory properties and maintenance of intestinal function fulfilled by vitamin D impact other systems in the body though downstream processing. This review provides insight into the mechanisms underpinning the potential benefits of vitamin D in both maintaining intestinal homeostasis and associated diseased states.

Keywords: Intestine; cancer; colon; inflammation; medicine/oncology; mucositis.

Figure 1.

Role of vitamin D in transcellular Ca²⁺ transport. Ca²⁺ absorption occurs through 1,25(OH)₂D-inducible TRPV6, followed by cytosolic transfer of Ca²⁺ to the basolateral membrane by calcium binding protein, 1,25(OH)₂D-inducible calbindin-D9k (CaBP-9k). Cytosolic calcium is then extruded at the basolateral membrane against a concentration gradient by the intestinal plasma membrane ATPase (PMCA1b). (A color version of this figure is available in the online journal.)

Figure 2.

In normal cells (right), one way 1,25(OH)₂D inhibits β-catenin/TCF transcriptional activity is by stimulating VDR/β-catenin binding, and inhibiting binding of β-catenin to TCF. In CRC cells (left), when APC, AXIN, or β-catenin genes undergo mutation, and 1,25(OH)₂D is reduced, β-catenin accumulates in the nucleus, where it can bind to TCF, upregulating target gene transcription. (A color version of this figure is available in the online journal.)

Figure 3.

1,25(OH)₂D binds to VDR, stimulating production of MKP-1, inhibiting pro-inflammatory cytokines. 1,25(OH)₂D also stimulates production of IκB, inhibiting NFκB, also inhibiting production of pro-inflammatory cytokines. (A color version of this figure is available in the online journal.)