Downloaded from http://journals.lww.com/jcge by BhDMf5ePHKbH4TTImqenVI2V1DuJ82ZX0Lr/ajvcsivSdiUbgYuUBpJGUhtS8Btwy0rHP2YdVwY= on 01/13/2020 Oral Nano Vitamin D Supplementation Reduces Disease Activity in Ulcerative Colitis A Double-Blind Randomized Parallel Group Placebo-controlled Trial Rizwan Ahamed Z, MD, DM,* Usha Dutta, MD, DM, MSc,* Vishal Sharma, MD, DM,* Kaushal Kishor Prasad, MD,* Priyanka Popli, MSc,* Dimple Kalsi, MSc,* Chetana Vaishnavi, MSc, PhD,* Sunil Arora, MSc, PhD,*† and Rakesh Kochhar, MD, DM* Introduction: Vitamin D possesses anti-inflammatory properties and could be beneficial in ulcerative colitis (UC). Methods: We studied the effect of oral nano vitamin D 3 supple- mentation on disease activity in active UC [ulcerative colitis dis- ease activity index (UCDAI) ≥ 3]. Patients with active UC and vitamin D <40 ng/mL were randomized to receive either oral nano vitamin D (60,000 IU/d×8 d) or placebo. They were evaluated for disease activity (UCDAI scores, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin) at baseline and reas- sessed at 4 weeks. The response was defined as a 3-point reduction in UCDAI score at 4 weeks and reduction in inflammatory markers. Results: The median vitamin D levels increased from 15.4 to 40.83 mg/dL in vitamin D group (P ≤ 0.001) and marginally from 13.45 to 18.85 mg/dL (P = 0.027) in controls. The 3-point reduction in UCDAI was seen more often in vitamin D group as compared with the control (53% vs. 13%; P = 0.001). Increase in vitamin D levels correlated with reduction in UCDAI score (P ≤ 0.001; ρ = -0.713), C-reactive protein (P ≤ 0.001; ρ = -0.603), and calpro- tectin (P = 0.004; ρ = -0.368). Patients who achieved target vitamin D of > 40 ng/mL (n = 17) more often had a 3-point reduction in UCDAI (80% vs. 20%; P ≤ 0.001) and reduction in grade of severity from 60% to 35% (P = 0.038). Vitamin D administration (odds ratio, 9.17; 95% confidence interval, 2.02-41.67) and baseline his- tologic activity (odds ratio, 1.92; 95% confidence intervals, 1.2-3.08) independently predicted response. Conclusions: Oral nano vitamin D supplementation in active UC is associated with a reduction in disease activity and severity grade and is seen more often in those who achieved a target vitamin D level of 40 ng/mL. Key Words: ulcerative colitis, nano vitamin D, calprotectin, disease activity (J Clin Gastroenterol 2019;53:e409–e415) V itamin D plays a primary role in calcium, phosphorus, and bone metabolism. 1 However, the 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. 2–5 Ulcerative colitis (UC) is characterized by an inappropriate and exaggerated mucosal immune response to gastrointestinal antigens in genetically susceptible individuals. 6 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. 7–9 Vitamin D supple- mentation may have a therapeutic role in reducing disease activity and inflammation. 9,10 Patients with UC have a diminished oral intake of vitamin D–rich food because of dietary restrictions, dimin- ished outdoor activities resulting in lower sunlight exposure, and high gastrointestinal losses of vitamin D–binding pro- tein because of chronic mucosal illness. 10–12 They are thus at high risk for vitamin D deficiency, which is likely to further perpetuate the illness. 7–9 Among patients with Crohn’s dis- ease, supplementation among those in remission was found to reduce the risk of relapse. 5,6 Among patients with UC, a single intramuscular dose of 300,000 IU resulted in a reduction in C-reactive protein (CRP) and erythrocyte sed- imentation rate (ESR) and increased cathelicidin gene expression, which has an immunoregulatory role. However, data in patients with IUC with regards to clinical response to vitamin D supplementation and its relation to the post- treatment vitamin D status is limited. Recently, oral nano preparation of vitamin D in solution form has been avail- able which is claimed to have better bioavailability than oral sachet preparation. We planned a double-blind randomized placebo-controlled trial of oral nano vitamin D adminis- tered daily for 8 days in patients with active UC to assess its role in eliciting a clinical response as well as in reducing serological, fecal, and histologic markers of inflammation. METHODS Study Setting and Study Design The study was a single-center double-blind randomized parallel placebo-controlled trial with concealed allocation done at a single center in North India from November 2016 to May 2017. The patients were followed up for 4 weeks after intervention. The study conforms to the ethical Received for publication July 30, 2018; accepted May 5, 2019. From the *Department of Gastroenterology; and †Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. The authors declare that they have nothing to disclose. Address correspondence to: Usha Dutta, MD, DM, MSc, Department of Gastroenterology, PGIMER, Sector-12, Chandigarh 160012, India (e-mail: ushadutta@gmail.com). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.jcge. com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MCG.0000000000001233 ORIGINAL ARTICLE J Clin Gastroenterol  Volume 53, Number 10, November/December 2019 www.jcge.com | e409 Copyright r 2019 Wolters Kluwer Health, Inc. All rights reserved.