Systematic Review With Meta-analysis

Association of Vitamin D Status With Clinical Outcomes in Adult Patients With Inflammatory Bowel Disease

John Gubatan; Naomi D. Chou; Ole Haagen Nielsen; Alan C. Moss


Aliment Pharmacol Ther. 2019;50(11):1146-1158. 

In This Article

Abstract and Introduction


Background: Vitamin D deficiency is highly prevalent among patients with IBD, however, data on its association with clinical outcomes are conflicting.

Aim: To perform a systematic review and meta-analysis to explore the association of low vitamin D status with clinical outcomes in patients with IBD.

Methods: We searched PubMed, Embase, Scopus and Web of Science from inception to February 2018 for observational studies evaluating the association of low 25(OH)D status on IBD disease activity, mucosal inflammation, clinical relapse and quality of life. Odds ratios (ORs) were pooled and analysed using a random effects model.

Results: Twenty-seven studies were eligible for inclusion comprising 8316 IBD patients (3115 ulcerative colitis, 5201 Crohn's disease). Among IBD patients, low 25(OH)D status was associated with increased odds of disease activity (OR 1.53, 95% CI 1.32–1.77, I 2 = 0%), mucosal inflammation (OR 1.25, 95% CI 1.06–1.47, I 2 = 0%), low quality of life (QOL) scores (OR 1.30, 95% CI 1.06–1.60, I 2 = 0%) and future clinical relapse (OR 1.23, 95% CI 1.03–1.47, I 2 = 0%). In subgroup analysis, low vitamin D status was associated with Crohn's disease activity (OR 1.66, 95% CI 1.36–2.03, I 2 = 0%), mucosal inflammation (OR 1.39, 95% CI 1.03–1.85, I 2 = 0%), clinical relapse (OR 1.35, 95% CI 1.14–1.59, I 2 = 0%), and low QOL scores (OR 1.25, 95% CI 1.04–1.50, I 2 = 0%) and ulcerative colitis disease activity (OR 1.47, 95% CI 1.03–2.09, I 2 = 0%) and clinical relapse (OR 1.20, 95% 1.01–1.43, I 2 = 0%).

Conclusions: Low 25(OH)D status is a biomarker for disease activity and predictor of poor clinical outcomes in IBD patients.


Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic, inflammatory disorder of the gastrointestinal tract. The incidence and prevalence of IBD is increasing worldwide[1] and is associated with significant healthcare utilisation in the United States.[2] Although the exact aetiology of IBD remains unclear, IBD is speculated to arise from a complex interaction between genetic susceptibility, derangements in immune homeostasis, inappropriate responses to gut microflora and various environmental triggers.[3–7] Increasing evidence has proposed that vitamin D plays a protective role in the pathogenesis of inflammatory bowel disease.[8,9] Vitamin D has been shown to maintain gut epithelial barrier integrity against inflammatory and pathogenic stimuli.[10,11] Previous studies have demonstrated that vitamin D has anti-inflammatory effects on immune responses[12–15] and plays a role in regulating the gut microbiome.[16–18]

Vitamin D deficiency is highly prevalent among patients with inflammatory bowel disease. In one systematic review and meta-analysis[19] comprising of over 900 IBD patients, vitamin D deficiency (defined as serum 25(OH)D levels ≤25 ng/mL) was prevalent in 38.1% of patients with Crohn's disease and 31.6% in patients with ulcerative colitis. The same study demonstrated that IBD patients also had increased odds of lower vitamin D levels compared to matched controls. Due to the potential mechanistic link between vitamin D and colitis and the high prevalence of vitamin D deficiency in IBD patients, many groups have sought to examine the impact of vitamin D levels on IBD clinical outcomes,[20–46] often with conflicting results. Many of these previous studies were limited by their small sample size and inability to detect differences in clinical outcomes between low and high vitamin D groups. Differences in definitions of low vitamin D status, heterogeneity in disease characteristics among IBD cohorts and outcomes and measures evaluated have resulted in conflicting results between vitamin D and IBD clinical outcomes. There remains an unmet need for an understanding of vitamin D thresholds for beneficial outcomes in IBD, particularly in light of controversies over the impact of vitamin D thresholds on bone health in the general population. Given the conflicting results from previous studies and need for clarification, we performed a systematic review and meta-analysis to explore the association of low vitamin D status on IBD clinical outcomes (disease activity, mucosal inflammation, clinical relapse and quality of life).