Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza and Upper Respiratory Infection in Patients With Inflammatory Bowel Disease

Randomized, placebo-controlled trial in adults with stable inflammatory bowel disease, including ulcerative colitis and Crohn's disease, recruited from multiple hospitals affiliated with Jikei University School of Medicine in Tokyo and Chiba, Japan. Enrollment occurred from August to October 2014, with follow-up from October 1, 2014 to March 31, 2015; active-arm reporting lists the vitamin D group as the intervention arm.

Oral vitamin D3, 500 IU per day, given as 2 capsules daily for 6 months during winter and early spring, compared with placebo.

Vitamin D supplementation lowered upper respiratory infection incidence but did not reduce influenza in patients with inflammatory bowel disease. In the vitamin D group, URTI occurred in 19 of 115 participants (16.5%) versus 30 of 108 (27.8%) with placebo, RR 0.59, 95% CI 0.35-0.98, P = 0.042. Benefit was greater in participants with baseline 25-hydroxyvitamin D <20 ng/mL, where URTI occurred in 5 of 40 (12.5%) versus 13 of 37 (35.1%), RR 0.36, 95% CI 0.14-0.90, P = 0.019. No serious adverse events were reported, but the intervention was associated with worsening of the Lichtiger clinical activity index in ulcerative colitis.

The trial was relatively small and conducted at a limited number of hospitals in Japan, which may restrict generalizability. Follow-up covered only one winter-to-early-spring season, influenza events were not reduced, and subgroup findings by baseline vitamin D status were exploratory. The report also raised a safety/tolerability concern in ulcerative colitis because the Lichtiger clinical activity index worsened.