Vitamin D supplementation may lead to significant improvements in ulcerative colitis (UC), based on a placebo-controlled trial involving 60 patients with active disease.
Those who achieved vitamin D levels greater than 40 ng/mL were most likely to benefit, reported lead author Rizwan Ahamed Z, MD, of the Postgraduate Institute of Medical Education and Research in Chandigarh, India, and colleagues. They noted that the findings contribute much-needed clinical data to a largely theoretical subject area.
“[T]he discovery of vitamin D receptors on lymphocytes, monocytes, and dendritic cells initiated various studies which have highlighted the role of vitamin D in regulating gut mucosal immunity and gut barrier,” the investigators wrote in Journal of Clinical Gastroenterology. “In experimental interleukin (IL)-10 knockout mice models, vitamin D deficiency was found to result in severe colitis, progressive wasting, and high mortality. However, vitamin D supplementation not only prevented but also ameliorated symptoms of colitis in the mice model.”
Human studies have revealed similar associations between vitamin D supplementation and inflammatory bowel disease, such as a study by Jørgensen and colleagues that found a lower risk of relapse in Crohn’s disease, and another by Sharifi and colleagues that showed injectable vitamin D could reduce erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients with UC. Still, the investigators suggested that more clinical data are needed, particularly for outcomes after vitamin D therapy. In addition to providing such data, the present trial was also the first of its kind to test oral nano vitamin D3, which may have better bioavailability than conventional supplements.
The investigators initially recruited 110 patients with active UC who had an ulcerative colitis disease activity index (UCDAI) of at least 3. After screening, 50 patients were excluded because they had vitamin D levels greater than 40 ng/mL, were already taking a vitamin D supplement, had severe UC requiring hospitalization, or exhibited severe systemic illness. The remaining 60 patients were randomized in a 1:1 ratio to receive either 60,000 IU nano vitamin D3 once daily for 8 days, or placebo. Disease parameters, which were measured at baseline and then again at 4 weeks, included UCDAI, ESR, CRP, and fecal calprotectin. The primary outcome was response, defined as a UCDAI reduction of at least 3 points. Secondary outcome measures included stool frequency, stool consistency, and remission (UCDAI less than 3); in addition, the investigators evaluated histologic, endoscopic, fecal, and serum inflammatory markers.
The majority of patients in the study were men (60%), with a mean age of 36 years. Most patients had moderate UC (73.3%), while smaller proportions had severe (18%) or mild (8%) disease. All patients were taking a 5-aminosalicylic acid oral compound and some (16.6%) were also taking azathioprine. At baseline, the mean vitamin D level was 14 ng/mL. Most patients (70%) were diagnosed with vitamin D deficiency, based on measurements below 20 ng/mL. The remaining patients were diagnosed with insufficiency (13%; 20-30 ng/mL) or suboptimal levels (17%; 30-40 ng/mL).
From baseline to 4-week follow-up, median vitamin D level in the supplement group increased from 15.4 to 40.83 ng/mL, compared with a much smaller increase in the placebo group, from 13.45 to 18.85 ng/mL. Compared with the placebo group, significantly more patients given nano vitamin D3 achieved a UCDAI 3-point reduction (53% vs 13%; P = .001); this translated to a Pearson correlation coefficient (rho) of –0.713, between vitamin D level and UCDAI. Similar, albeit less strong, inverse relationships were detected between vitamin D level and CRP (rho = −0.603) and calprotectin (rho = −0.368).
Benefits observed in the supplement group also extended to stool frequency, stool consistency, and histologic measures. Those who achieved a vitamin D level greater than 40 ng/mL were 4 times more likely to have a UCDAI 3-point reduction than those who did not meet the same criteria (80% vs 20%; P = .038). Independent predictors of response included baseline histologic activity (odds ratio, 1.92), and to a greater extent, vitamin D supplementation (OR, 9.17). No patients achieved remission, which the investigators attributed to the relatively short study duration.
Minor, self-limiting side effects occurred in 13.3% and 10% of patients given the vitamin D supplement and placebo, respectively.
“[T]he present study showed significant improvement in all inflammatory parameters of the disease including clinical, endoscopic, histopathologic, and serum and fecal markers of inflammation, all of which paralleled each other in showing [the benefit of] oral nano vitamin D supplementation,” the investigators concluded. They advised that larger, longer-term studies are needed before the findings can be generalized to all patients with active UC.
The investigators disclosed no external funding or conflicts of interest.
SOURCE: Ahamed R et al. J Clin Gastroenterol. 2019 Jul 24. doi: 10.1097/MCG.0000000000001233.