Association of Vitamin D Level With Clinical Status in Inflammatory Bowel Disease

A 5-Year Longitudinal Study

Toufic A Kabbani, MD, MPH; Ioannis E. Koutroubakis, MD, PhD; Robert E. Schoen, MD, MPH; Claudia Ramos-Rivers, MD; Nilesh Shah, PhD; Jason Swoger, MD, MPH; Miguel Regueiro, MD; Arthur Barrie, MD, PhD; Marc Schwartz, MD; Jana G. Hashash, MD; Leonard Baidoo, MD; Michael A. Dunn, MD; David G. Binion, MD


Am J Gastroenterol. 2016;111(5):712-719. 

In This Article

Abstract and Introduction


Objectives: Emerging data suggest that vitamin D has a significant role in inflammatory bowel disease (IBD). Prospective data evaluating the association of vitamin D serum status and disease course are lacking. We sought to determine the relationship between vitamin D status and clinical course of IBD over a multiyear time period.

Methods: IBD patients with up to 5-year follow-up from a longitudinal IBD natural history registry were included. Patients were categorized according to their mean serum 25-OH vitamin D level. IBD clinical status was approximated with patterns of medication use, health-care utilization, biochemical markers of inflammation (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), pain and clinical disease activity scores, and health-related quality of life.

Results: A total of 965 IBD patients (61.9% Crohn's disease, 38.1% ulcerative colitis) formed the study population (mean age 44 years, 52.3% female). Among them, 29.9% had low mean vitamin D levels. Over the 5-year study period, subjects with low mean vitamin D required significantly more steroids, biologics, narcotics, computed tomography scans, emergency department visits, hospital admissions, and surgery compared with subjects with normal mean vitamin D levels (P<0.05). Moreover, subjects with low vitamin D levels had worse pain, disease activity scores, and quality of life (P<0.05). Finally, subjects who received vitamin D supplements had a significant reduction in their health-care utilization.

Conclusions: Low vitamin D levels are common in IBD patients and are associated with higher morbidity and disease severity, signifying the potential importance of vitamin D monitoring and treatment.


Inflammatory bowel diseases (IBDs) including ulcerative colitis (UC) and Crohn's disease (CD) are characterized by chronic inflammation involving the gastrointestinal tract.[1] Although the pathogenesis of IBD is not fully understood, immune dysregulation has a pivotal role.[1] Over the past decade, animal and human literature has emerged to support a role of vitamin D in regulating the innate and adaptive immune systems.[2–8] In addition to its established role in calcium homeostasis,[9] vitamin D directly acts on CD4+ cells, favoring the maturation of T2 helper lymphocyte (Th2) over T1 helper lymphocyte (Th1/Th17) cells[10] and increasing the production of anti-inflammatory cytokines such as interleukin-4 (IL-4), IL-5, and IL-13. Simultaneously, vitamin D acts on dendritic cells, leading to decreased production and differentiation of Th1 cells.[10] Consequently, the release of proinflammatory cytokines such as interferon-γ, IL-2, and tumor necrosis factor-α is significantly reduced.[10,11] Another important mechanism by which human monocytes eliminate pathogens is autophagy. This occurs through the action of anti-bacterial proteins released locally by vitamin D.[11]

Several epidemiological studies have consistently shown higher prevalence of vitamin D deficiency in patients with IBD[10] and a significant inverse association between vitamin D status and the development of IBD.[11] The incidence and prevalence of IBD follow a "North-to-South gradient", with highest incidence and prevalence in colder climates and lowest risks in subjects living closest to the equator.[11] This suggests a protective role of vitamin D against inflammation and IBD and is supported by data from the Nurses Health Study that demonstrate lower incidence of IBD in subjects with high baseline 25-OH vitamin D plasma levels.[11]

Despite these advances, there are no long-term prospective studies evaluating the association of vitamin D status with clinical course in IBD. The aim of this study was to determine the relationship between mean vitamin D status over a multiyear time period and the clinical course in a large cohort of IBD patients who were followed prospectively in a tertiary referral IBD center.