Introduction
Vitamin D levels are associated with important clinical parameters and outcomes in patients with IBD. However, the complex interplay of inflammation with vitamin D (vitD) and its metabolites poses a vicious circle in which cause and effect are unclear. We previously showed that all vitD metabolites, including 1,25OH2D, 24,25OH2D, free and bioavailable 25OHD and VDBP, but not total 25OHD, were influenced by at least one inflammatory marker.
Aims & Methods
In this study, we aimed to assess effects of vitD supplementation on serum levels of vitD metabolites and VDBP in patients with IBD with and without inflammation. A comparative, cross-sectional retrospective study was conducted using medical records and routine samples of IBD patients and controls. Blood count, serum albumin, transferrin, ESR, hsCRP and faecal calprotectin (FC) concentrations were analysed. Inflammatory disease activity was defined as hsCRP ≥5mg/dL and/or FC ≥250μg/g. Serum total 25OHD and 24,25OH2D levels were measured using ImmuTube® VitD duo LC-MS/MS (Immundiagnostik AG, Bensheim, Germany). Concentrations of 1,25OH2D and VDBP were detected with direct competitive ELISA using the IDK® human VDBP immunoassay kit (Immundiagnostik AG). Free and bioavailable 25OHD were calculated according to Bikle et al. Subjects were treated with 20,000 IU cholecalciferol p.o. in different frequencies based on severity of vitD insufficiency/deficiency: Patients with 25OHD levels of 21-29ng/mL 1x/wk for 2 weeks; those with 25OHD levels 11-20ng/mL 2x/wk for 2 weeks; those with 25OHD levels ≤10ng/mL 3x/wk for 1 week and 2x/wk for 2 weeks. In each case, therapy was followed by 2 therapy-free weeks. Statistical data were collected in Microsoft Excel 2016 and analyzed with IBM SPSS Statistics 25, p<0.05 was taken to be statistically significant.
Results
Overall, 265 subjects were included, 68 in the control group (27m/41f; age range 18-65y; mean age (±SD) 42.9±15.6y) and 197 patients with IBD (96m/101f; 18-65y; 42.3±13.0y; 115 Crohn’s disease, 82 ulcerative colitis). Inflammatory disease activity was seen in 96/197 (49%). No significant difference was found for season of blood sampling (with vs. without inflammation: p=0.468, IBD pats vs. controls: p=0.613; chi-square test for all results). As expected, vitD supplementation resulted in a significantly increased serum 25OHD, 24,25OH2D, free 25OHD and bioavailable 25OHD. Interestingly, vitD supplementation did not affect levels of VDBP or 1,25OH2D. After correlation coefficients were calculated, neither specific correlation nor statistical significance was observed between vitD parameters and ESR or FC. Also, no correlation was seen between hsCRP and serum 25OHD, 1,25OH2D, and 24,25OH2D regardless of vitD supplementation. However, for both supplemented (r=0.481, p<0.001) and non-supplemented groups (r=0.421, p<0.001), a significant moderate positive correlation was found for VDBP with hsCRP. Serum free 25OHD (r=-0.496, p<0.001; r=-0.450, p<0.001 respectively in supplemented and non-supplemented groups) and bioavailable 25OHD (r=-0.532, p<0.001; r=-0.497, p <0.001, respectively) showed a significant moderate negative correlation with hsCRP in both groups.
Conclusion
The vitD parameters VDBP, free vitD and 25OHD were primarily influenced by the presence of inflammation. The significant increase in VDBP observed in the presence of inflammation was uninfluenced by vitD supplementation. Since hsCRP and VDBP positively correlated, VDBP may have potential as a biomarker for inflammatory processes.
Disclosure
Julia Stötzel and Lea Tessmer have nothing to disclose.
Aysegül Aksan is an employee of Immundiagnostik AG, Bensheim, Germany.
Oliver Schröder: Lecturing fees: Abbvie, Falk, Janssen, Takeda, Norgine and Pfizer. Congress expenses: Falk, Pfizer.
Jürgen Stein: Consulting: Abbvie, Bristol Myers Squibb, Dr Schär, Falk, Ferring, Fresenius Kabi, Immundiagnostik, Janssen, Medice, MSD, Pfizer, Pharmacosmos, Shire, Takeda, Thermofisher, Vifor. Board member: Abbvie, Bristol Myers Squibb, Dr Schär, Ferring, Fresenius Kabi, Immundiagnostik, Janssen, MSD, NPS, Pharmacosmos, Takeda, Vifor and Shield. Lecturing fees: Vifor Pharma