The nondietary determinants of vitamin D status in pediatric inflammatory bowel disease

Highlights

• We conducted a case–control study of patients with inflammatory bowel disease (IBD) and normal controls.

• There was a higher prevalence of vitamin D deficiency in the IBD group compared with controls.

• Intestinal inflammation was the key determinant of vitamin D in the IBD group.

• Seasons and skin pigmentation were also determinants of vitamin D in the IBD group.

• Adiposity and hepatic inflammation were non-determinants of vitamin D in the IBD group.

Abstract

Objectives

The aim of this study was to investigate the relationships between 25-hydroxy vitamin D (25[OH]D) and markers of vitamin D status in inflammatory bowel disease (IBD).

Methods

We conducted a retrospective case–control study of 59 pediatric patients with IBD (age 16.4 ± 2.2 y) and 116 controls (age 14.6 ± 4.4 y), to investigate the association between 25(OH)D and albuminemia for protein-losing enteropathy (PLE) and hepatic dysfunction; alanine transaminase (ALT) for hepatic inflammation; erythrocyte sedimentation rate (ESR) for intestinal inflammation; body mass index (BMI) for adiposity; seasons and skin pigmentation for insolation. Vitamin D deficiency was defined as 25(OH)D < 50 nmol/L; abnormal liver enzyme by ALT >40 U/L; overweight status by BMI of ≥85th but <95th percentile, and obesity by BMI ≥95th percentile. Seasons were categorized as summer, winter, spring, and fall.

Results

Patients with IBD had a higher prevalence of vitamin D deficiency (42.4% versus 26.7%; P = 0.04), elevated ALT (16.9% versus 2.6%; P < 0.001), and lower albumin (41.1 ± 4.8 versus 45.1 ± 3.8; P < 0.001) than controls. In both the IBD cohort and controls, 25(OH)D was highest in summer and lowest in winter, and significantly higher in white than in non-white patients. ESR varied significantly with 25(OH)D (R² = 0.24; β = –0.32; P = 0.010), and only patients with IBD with elevated ESR had lower 25(OH)D than controls (49.5 ± 25.2 versus 65.3 ± 28.0 nmol/L; P = 0.045).

Conclusion

Intestinal inflammation, not the loss of albumin-bound vitamin D in the gut, is the primary intestinal determinant of vitamin D status in IBD. The extraintestinal determinants are seasons and skin pigmentation, but not adiposity and hepatic inflammation.

Introduction

The mechanism of vitamin D deficiency in inflammatory bowel disease (IBD) is not clear. Uncontrolled studies examining the determinants of vitamin D status in IBD identified serum albumin concentration as both a surrogate marker of protein-losing enteropathy (PLE) [1] and a stronger predictor of vitamin D status in IBD than body mass index (BMI) z-score, season, skin pigmentation, and erythrocyte sedimentation rate (ESR) [2]. This has led to the hypothesis that hypoalbuminemia (from PLE), not malabsorption, is the primary mechanism for hypovitaminosis D in IBD [2], [3]. This hypovitaminosis D is believed to result from the loss of vitamin D bound to vitamin D–binding protein into the gut lumen.

However, because hepatic inflammation can also result in hypoalbuminemia, a comprehensive examination of the relationship between hypoalbuminemia and vitamin D status in IBD necessitates an evaluation of hepatic inflammation. Furthermore, a crucial step in vitamin D metabolism, the hydroxylation of vitamin D at the 25 position to form 25-hydroxy vitamin D (25[OH]D), occurs in the liver [4] and pathologic states that impair this hydroxylation step may also result in vitamin D deficiency. Additionally, hepatobiliary disorders are common in IBD [5]; and some of the medications employed in the management of IBD are hepatotoxic and could result in hepatic dysfunction.

Additionally, the role of intestinal inflammation on vitamin D status in IBD has not been fully examined. Traditionally, ESR serves as a marker of the degree of intestinal inflammation in IBD [1], but its relationship with 25(OH)D has not been adequately evaluated [1], [2].

Similarly, although adiposity is associated with vitamin D deficiency in healthy individuals [6], [7], this association is unclear in IBD. This is crucial because, despite the strong association between IBD and growth retardation, obesity and overweight have been reported in IBD [8] at rates of 20% and 30%, respectively [9].

Finally, the role of insolation, the exposure of the skin to solar radiation, as assessed by season and skin pigmentation has not been fully investigated in IBD [10], [11]. Whereas one study reported that darkly pigmented individuals with IBD had lower vitamin D concentration than a light-pigmented cohort [10], another study found no difference in 25(OH)D between black children with IBD and their black controls [11]. Two uncontrolled studies [12], [13] investigating the effect of seasons on vitamin D status in IBD reported lower serum 25(OH)D concentration in winter than in summer.

The aim of this study was to investigate the relationships between 25(OH)D and markers of non-dietary determinants of vitamin D status in IBD using a case–control study design. Its hypothesis is that intestinal inflammation, not protein-losing enteropathy, is the principal determinant of vitamin D status in IBD.