Review Article

Vitamin D and Inflammatory Bowel Diseases

V. P. Mouli; A. N. Ananthakrishnan

Disclosures

Aliment Pharmacol Ther. 2014;39(2):125-136. 

In This Article

Discussion

Limitations

Despite emerging promising data, there exist several limitations in the literature regarding the role of vitamin D in IBD pathogenesis. First, while consistently supported by experimental animal models, the association between low pre-diagnosis vitamin D and increased risk of CD has been examined in a single prospective cohort study that used a regression model to predict an individual's vitamin D status. Ongoing analysis of pre-diagnosis banked specimens from ongoing prospective cohorts as well as additional high-risk IBD cohorts will provide a more definitive answer to this hypothesis as randomised controlled trials of vitamin D in prevention of IBD are unlikely to be feasible, given relatively low incidence of disease in the general population, and need for large numbers of participants and long follow-up. The association between low vitamin D and increased disease activity, particularly in CD, is also supported primarily by observational data. While initial studies were cross-sectional and unable to differentiate effect of vitamin D on disease activity from that of disease course on vitamin D levels, more recent analyses of large cohorts have been able to prospectively demonstrate an association between low vitamin D levels and increased risk for surgery and hospitalisations, particularly in CD.[13] However, only one randomised controlled trial has examined the role of vitamin D in preventing relapse, but was also limited by small numbers.[12] Effect of vitamin D supplementation in ameliorating disease activity in CD has been examined only in two open-label pilot studies, and no studies have evaluated this in UC. Consequently, there is an urgent need for high-quality randomised intervention trials of vitamin D supplementation in both CD and UC with disease activity as a treatment end point.[80,81]

Clinical Practice

Patients with IBD are at risk of developing vitamin D deficiency. The Endocrine Clinical Practice Guidelines Committee recommends screening of patients with IBD as well as patients who are on corticosteroids for vitamin D status.[16] While there is lack of professional guidelines regarding subsequent assessments of vitamin D status, we adopt the following in our practice. If the baseline vitamin D status is normal, it may be logical to consider rechecking the status annually or biennially if there is active disease, if there is documented metabolic bone disease or if there is continued use of systemic corticosteroids. The Institute of Medicine and the Endocrine Practice Guidelines Committee recommend a dietary intake of 400 IU of vitamin D per day for infants, 600 IU of vitamin D per day for children beyond 1 year of age and adults and 800 IU of vitamin D per day for the elderly aged above 70 years.[82] However, to consistently raise the level of 25(OH)D to more than 30 ng/mL, especially in patients who are at risk for vitamin D deficiency, the Endocrine Practice Guidelines Committee recommended that a maintenance dose of at least 1000 IU per day would be required.[16] To treat documented vitamin D deficiency, it is recommended to use either vitamin D2 or vitamin D3 in a dosage of 2000 IU per day for 6 weeks, or 50 000 IU once a week for 6 weeks in case of children and vitamin D2 or vitamin D3 6000 IU per day for 8 weeks, or 50 000 IU once a week for 8 weeks for adults to achieve serum 25(OH)D levels of more than 30 ng/mL. The optimal therapeutic regimen in IBD patients was examined in a single clinical trial by Pappa et al. in which 71 patients with IBD aged 5–21 years with vitamin D deficiency were randomised to one of the following three regimens for 6 weeks: 2000 IU daily of vitamin D2; 2000 IU daily of vitamin D3; or 50 000 IU weekly of vitamin D2.[83] It was found that the 6-week regimens of 50 000 IU of vitamin D2 per week and 2000 IU of vitamin D3 daily were superior to vitamin D2 2000 IU daily. Whereas the regimen of 50 000 IU per week of vitamin D2 improved the serum 25(OH)D levels to more than 32 ng/mL in 75% of patients, only 38% of patients who received 2000 IU of vitamin D3 daily and 25% of patients who received 2000 IU of vitamin D2 daily achieved serum 25(OH)D levels of more 32 ng/mL after 6 weeks of therapy. All the three regimens were found to be safe and well tolerated.

Future Directions

Several unanswered question remain regarding the role of vitamin D in IBD (Table 4). Further investigation is needed to understand the effects of dietary intake of vitamin D and vitamin D supplementation in relation to polymorphisms of DBP or VDR to identify if there are subgroups who may derive greater benefit from prophylaxis or who would require greater doses for treatment. With recent evidence pointing towards vitamin D deficiency as associated with IBD risk, confirmation of such findings in other cohorts would establish the vitamin D as one of the links in the gene-environment-gut microbiome-immune system interactions necessary for the development of IBD. It also merits investigation whether vitamin D deficiency leads causally to increased disease severity or is merely a consequence of severe disease. Furthermore, it needs to be identified if there are high-risk groups of patients who may need to be screened for vitamin D deficiency and preemptively treated to prevent the onset of IBD. Further high-quality studies are needed to evaluate if correction of vitamin D deficiency or if vitamin D supplementation can prevent disease relapses, whether it can be used to induce remission in active disease, and whether it has a role in prevention of long-term disease-related complications like colorectal cancer as has been identified in non-IBD patients. Continued and fertile interactions between biochemists, nutritional epidemiologists, laboratory scientists and clinical researchers will help address many of these unanswered questions, improve our understanding of the role of the complex panoply of functions of vitamin D, and its application into clinical practice.

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