ORLANDO – Vitamin D may protect patients with inflammatory bowel disease from more serious disease flare-ups, investigators reported at the annual Digestive Disease Week.
Among 3,217 patients followed for a median of 8 years, those with Crohn’s disease who had the lowest levels of plasma 25-hydroxyvitamin D had a nearly twofold risk for surgery and double the risk for hospitalization related to IBD, compared with patients who had higher vitamin D levels.
A similar relationship was seen between vitamin D levels and risk of surgery and hospitalization among patients with ulcerative colitis (UC), reported Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston.
Dr. Ashwin Ananthakrishnan
Tellingly, patients with Crohn’s disease (CD) who had initially low vitamin D levels that normalized during the study had significant reductions in their risk of surgery and hospitalization compared with patients whose vitamin D levels did not improve over time. In addition, patients with both CD and UC who normalized their vitamin D status during the study had significantly lower levels of the inflammatory marker C-reactive protein, the investigators found.
"There’s considerable evidence that supports a role for vitamin D in inflammatory bowel diseases," Dr. Ananthakrishnan said.
He noted that high vitamin D levels were associated with a reduced risk for CD in a prior study performed by his group (Gastroenterology 2012;142:482-9), and a second study showed that polymorphisms in the vitamin D receptor were associated with a risk of both CD and UC (Gut 2000;47:211-4).
Although vitamin D levels have been weakly associated with IBD exacerbations in retrospective studies, stronger evidence for the potential anti-inflammatory role of vitamin D has been hard to come by, partly because of researchers’ inability to determine vitamin D status before clinical outcomes such as surgery or hospitalization, Dr. Ananthakrishnan said.
He and colleagues prospectively followed all members of an IBD cohort treated at Massachusetts General Hospital and Brigham and Women’s Hospital, Boston, who had a least one measured plasma 25(OH)D level before a first IBD-related surgery and/or hospitalization (the primary outcome; median C-reactive protein was a secondary outcome).
The researchers found that 16% of all patients had disease-related surgery, and 40% were hospitalized during the follow-up period.
A third of all patients (32%) were considered to be vitamin D deficient, defined as having a plasma 25(OH)D level below 20 ng/mL, and 28% were deemed to be vitamin D insufficient (20-30 ng/mL). The remaining 40% had sufficient vitamin D levels of 30 ng/mL and higher.
When the investigators controlled for age, sex, race, Charlson score (non-IBD comorbidity), disease-related complications, medication, vitamin D supplementation, and season of 25(OH)D measurement, analysis showed that patients with CD who had plasma vitamin D levels below 20 ng/mL had odds ratios of 1.76 for surgery and 2.07 for IBD-related hospitalization.
Similarly, for patients with UC and low vitamin D levels, the odds ratios for surgery and hospitalization were 1.70 and 2.26, respectively.
Overall, 76% of patients in the study with CD who had initial vitamin D levels below 30 ng/mL had subsequent normalization of their D values, as did 80% of those with ulcerative colitis.
In adjusted analysis, patients with CD had a nearly 50% reduction in the risk of surgery (odds ratio, 0.56) and a nearly 25% reduction in the risk of hospitalization (OR, 0.78), compared with patients whose vitamin D levels never corrected to the normal range. Patients with UC also had reductions in risk for both surgery and hospitalization, but these reductions were not significant.
In addition, patients with CD and UC who had vitamin D that normalized over the course of the study had significantly lower C-reactive protein levels than did those who remained vitamin D deficient (–5. 2 mg/L, P = .002).
The study was supported by grants and awards from the American Gastroenterological Association, the IBD Working Group, the Broad Foundation, and the National Institutes of Health. Dr. Ananthakrishnan reported having no financial disclosures.