Measuring Vitamin D Status in Chronic Inflammatory Disorders: How does Chronic Inflammation Affect the Reliability of Vitamin D Metabolites in Patients with IBD?

Aysegül Aksan,Katharina Boettger,Franz-Paul Armbruster,Jürgen Stein,Yurani Caicedo-Zea,Claudia Schumann,Ina Diehl,Dilem Tugal,Nathalena Hein

doi:10.3390/jcm9020547

Abstract

Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.

Highlights

For more than a century, vitamin D has primarily been known for its favorable effects on calcium and bone metabolism [1]
Mounting evidence suggests that vitamin D may play an important pathophysiological role in the conditions associated with immune system dysfunction such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus and inflammatory bowel disease (IBD) [10,11]
Many patients were on tumor necrosis factor alpha (TNF-α) inhibitor therapy (83/188, 44.1%), while 12.8% of the patients were on antibiotics

Summary

Introduction

For more than a century, vitamin D has primarily been known for its favorable effects on calcium and bone metabolism [1]. In the early 1980s, the vitamin D receptor (VDR) was detected in over 30 different types of human tissue such as peripheral blood monocytes and leukocytes, antigen-presenting cells and activated CD4+ and CD8+ T cells [2,3,4]. Vitamin D serves to inhibit the demarcation of monocytes to dendritic cells, reducing the availability of antigen-presenting cells for T cell activation [6,7,8]. Vitamin D has been characterized as a natural immune modulator [9]. Mounting evidence suggests that vitamin D may play an important pathophysiological role in the conditions associated with immune system dysfunction such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus and inflammatory bowel disease (IBD) [10,11]

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