Managing vitamin D deficiency in inflammatory bowel disease

Abstract

Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is generally cumbersome for patients and is a massive health-economic burden. In recent years, the immunomodulating effects of vitamin D have gained a huge interest in its possible pathogenic influence on the pathophysiology of IBD. Vitamin D deficiency is frequent among patients with IBD. Several clinical studies have pointed to a critical role for vitamin D in ameliorating disease outcomes. Although causation versus correlation unfortunately remains an overwhelming issue in the illusive chicken versus egg debate regarding vitamin D and IBD, here we summarise the latest knowledge of the immunological effects of vitamin D in IBD and recommend from available evidence that physicians regularly monitor serum 25(OH)D levels in patients with IBD. Moreover, we propose an algorithm for optimising vitamin D status in patients with IBD in clinical practice. Awaiting well-powered controlled clinical trials, we consider vitamin D supplementation to be an affordable and widely accessible therapeutic strategy to ameliorate IBD clinical outcomes.

Keywords: biologics; clinical control; inflammatory bowel disease; therapy; vitamin D.

Figure 1

Epithelial mechanisms of vitamin D: (1) increased VDR activity is shown to repress NF-κB-dependent epithelial apoptosis pathways in experimental colitis. (2) Claudin-2 (CL-2), a paracellular cation channel involved in barrier formation, seems to be affected by vitamin D, although the precise mechanism needs to be further revealed. An increased expression of CL-2 is observed in the inflamed intestine, which in turn is downregulated by treatment with 1,25(OH)₂D. Low s-1,25(OH)₂D in patients with IBD is associated with decreased expression of zonula occludens 1 (a tight junction protein) and E-cadherin (an adherins junction component). Moreover, caco-2, a colorectal cancer cell line, upregulate tight junction proteins on 1,25(OH)₂D stimulation. (3) Treatment with bacterial product butyrate in human colonic cell lines increase VDR expression significantly. (4) Secretion of cathilicidin-related antimicrobial peptide (cAMP) and other AMPs, such as α-defensins from ileal Paneth cells and β-defensins from colonocytes, are seemingly key factors in regulation of the microbiota. VDR is known to increase AMP expression as well as to negate a pathogen-induced inhibition of cAMP expression. Absence of VDR does also affect lysosomal function and autophagy in the gut epithelium, thus signifying a role of VDR in microbial regulation. (5) VDR plays a role in the antigen presenting function in dendritic cells and thereby in the modulation of their immunological response. VDR activation leads to decreased IL-10/IL-12 ratios, thus favouring maturation of regulatory T cells and thereby decreasing the proinflammatory response. IBD, inflammatory bowel disease; IL, interleukin.

Figure 2

Approach to 25(OH)D supplementation in patients with IBD. Determining adequate daily dose as (target s-25(OH)D level – current s-25(OH)D level) µg. If target level is not reached within 3 months, administration as weekly bolus should be tried. If current level continues