Vitamin D as a novel therapy in inflammatory bowel disease: new hope or false dawn?

Abstract

There is increasing scientific interest in the field of vitamin D research, moving the focus beyond bone health to other disease processes. Low circulating vitamin D levels have been reported as a risk factor for several pathophysiologically divergent diseases, including cancers, diabetes, CVD, multiple sclerosis and inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease (IBD). But, therein, remains the challenge: can any single nutrient contribute to multiple complex disease mechanisms and, ultimately, have therapeutic potential? The aim of this review is to critically evaluate several strands of scientific evidence surrounding vitamin D and inflammation, primarily focusing on IBD. Epidemiological studies suggest an increased incidence of IBD and rheumatoid arthritis in countries of more northern latitudes, mirroring sunlight patterns. A considerable body of evidence supports the anti-inflammatory effects of vitamin D, at least in animal models of IBD. Although it is accepted that suboptimal vitamin D status is common in IBD, some studies suggest that this associates with more severe disease. With regard to treatment, the data are only beginning to emerge from randomised controlled trials to suggest that people with IBD may remain in remission longer when treated with oral vitamin D. In conclusion, several strands of evidence suggest that vitamin D may modify the immune response in IBD. There is a continued need for large well-designed clinical trials and mechanistic studies to determine if, and how, this emerging promise translates into tangible clinical benefits for people with chronic debilitating diseases such as IBD.

Alert for bone alterations and low serum concentrations of vitamin D in patients with intestinal inflammatory disease

“…In addition to the benefit in bone integrity, an improvement in the immune response is expected and, although not yet fully proven, aid in the prevention of colorectal cancer, a complication that can occur in patients with IBD. 17,18 We conclude that our patients with IBD had a high prevalence of bone alterations, found to a greater extent in those with Crohn's disease. Additionally, we observed that serum levels of vitamin D were below the recommended levels in all groups studied.…”

The role of nuclear receptors in regulation of Th17/Treg biology and its implications for diseases

“…94 Because the oral administration of vitamin D3 to patients with Crohn's disease was found to ameliorate disease severity, 95 vitamin D may be an important regimen for autoimmune diseases. 96 Finally, LXR is another important nuclear receptor, and it consists of two subtypes, LXR-a and LXR-b. LXR is a crucial sensor of cholesterol in cells and regulates its metabolism through transcriptional regulation.…”

Is vitamin D supplementation a viable treatment for Crohn’s disease?

“…[19] Vitamin D as therapy -possible biological mechanisms in CD There is plausible evidence from animal models that vitamin D reduces intestinal inflammation, [20,21] supresses tumor necrosis factor-alpha and interferon gamma (IFNγ) and induces IL-10. [20] Consistent with this, increased IL-10 and reduced IFNγ (for review, see [3,4]) has been documented in human CD; however, others [10] failed to detect changes in cytokine profiles in response to vitamin D treatment. Recently, direct effects of vitamin D action on the intestinal barrier and junctional proteins have been reported primarily in animal models [22] although preliminary work in human CD [10] may support this hypothesis.…”

“…Vitamin D deficiency may be a risk factor for developing CD Epidemiological studies, [2] (see [3,4] for review) show a higher incidence of CD in countries of more northern latitudes, mirroring sunlight patterns and likely vitamin D status. This finding is paralleled in other autoimmune diseases and cancer.…”

“…[3,4] Studies differ considerably in terms of design, patient cohorts and the variables used to capture disease activity, and a consistent core outcomes set is lacking across studies. For example, results vary depending on whether the Crohn's disease activity index (CDAI), Harvey Bradshaw Index, C-reactive protein (CRP) or other severity markers were applied, although the association between 25OHD and intestinal inflammation as measured by fecal calprotectin [7,8] whether or not interventions to raise 25OHD levels would modify disease activity or relapse rates in these cohorts.…”