Low vitamin D levels increase UC relapse risk

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Lower levels of vitamin D in the blood increase the risk of clinical relapse in patients with ulcerative colitis (UC), found a study led by researchers at Beth Israel Deaconess Medical Centre (BIDMC).

Lower vitamin D levels have been associated with active disease in patients with UC, but it has been unknown whether they increase disease relapses. “Prior studies in patients with Crohn’s disease and ulcerative colitis had linked low vitamin D levels to disease flare-ups,” said senior author Dr Alan Moss, a gastroenterologist at the Digestive Disease Centre at BIDMC and associate professor of medicine at Harvard Medical School.

“However, it has been unclear if the flare-up was lowering vitamin D levels, or if low vitamin D levels were causing the flare-up. We thought that if we looked at vitamin D levels when the disease was inactive and then followed patients moving forward, the impact of baseline vitamin D levels on future events may be clearer.”

Moss and colleagues collected vitamin D serum levels through a physician-blinded prospective study of 70 patients with UC in clinical remission who were followed up after a surveillance colonoscopy at BIDMC. The study measured vitamin D levels in blood samples and levels of inflammation through blood tests and biopsies. The researchers then followed the patients for 12 months and compared the data from participating patients who remained well and the others who experienced relapses. The investigators found the mean baseline vitamin D level to be lower in patients who later relapsed than those who did not.

“Patients who had higher vitamin D levels when their disease was in remission were less likely to experience a relapse in the future,” said Dr John Gubatan, a physician at BIDMC and first author of the study. “This suggests that higher vitamin D levels may play some role in preventing the UC relapse.” The threshold level of blood vitamin D that was protective was greater than 35ng/ml, which is within the range recommended by the National Institutes of Health for a healthy individual.

Ongoing work by Gubatan and Moss is now examining the link between vitamin D and a protein called cathelicidin in the cells lining the colon. The link may have beneficial effects on microbial composition, an important component of a healthy colon. Building on this research, investigators are trying to unravel how vitamin D may protect cells in the colon and the microbial composition of the bacteria, fungi, protozoa and viruses that live on and inside the human body, Moss noted.

Abstract
Background & Aims: Vitamin D levels have been associated with disease activity in patients with ulcerative colitis (UC), but it is unclear whether they affect the risk of disease relapse. We sought to determine the association between baseline vitamin D levels during a period of clinical remission and risk of subsequent UC relapse.
Methods: We performed a physician-blinded prospective study of 70 patients with UC in clinical remission followed up after a surveillance colonoscopy at a tertiary academic medical center. Serum samples were collected at the time of colonoscopy and baseline endoscopic and histologic activity were determined. Levels of 25-hydroxy-vitamin D were measured using an enzyme-linked immunosorbent assay. The primary outcome was rate of clinical relapse, determined over 12 months.
Results: The mean baseline vitamin D level was lower among patients with relapse (29.5 ng/mL) than without (50.3 ng/mL) (P = .001). Remission vitamin D level (≤35 ng/mL) was associated with a risk of clinical relapse (odds ratio, 1.25; 95% confidence interval [CI], 1.01–1.56; P = .044) over 12 months, independent of endoscopic or histologic grade at enrollment. A receiver operating characteristic curve of vitamin D levels for the outcome of relapse had an area under the curve of 0.72; and a serum level of 35 ng/mL or less had a sensitivity of 70% (95% CI, 46%–88%) and a specificity of 74% (95% CI 57%–83%) for predicting risk of clinical relapse.
Conclusions: Serum levels of vitamin D of 35 ng/mL or less during periods of clinical remission increase the risk of UC relapse. Clinical trials to obtain vitamin D levels higher than this threshold should be considered.

Authors
John Gubatan, Shuji Mitsuhashi, Talia Zenlea, Laura Rosenberg, Simon Robson, Alan C Moss

Beth Israel Deaconess Medical Centre material
Clinical Gastroenterology and Hepatology abstract


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