[Effects of oral vitamin D supplementation in Crohn's disease patients: Modulation of clinical active/remission phases by pro-inflammatory cytokines profile and oxidative stress].

The 25-hydroxyvitamin D (25OHD) deficiency in Crohn's disease (CD) is associated with the immune system dysfunction and redox status alteration. These two events affect intestinal mucosal function through macrophages cells infiltration and to lead a pro-inflammatory cytokines storm and ROS (reactive oxygen species) overproduction. The objective of this study was to investigate the immunomodulatory and antioxidant effects of vitamin D supplementation (DS) in clinical active phase. A cohort of 262 CD patients and vitamin D deficient (< 50 nmol/L or < 20 ng/mL) was randomized into 2 groups according to the DS doses at 200,000 IU/month (D group) versus 6,000 IU/day (D group). Serum 25OHD levels were assessed before and after 6 and 12 months of DS. The clinical active phase was characterized by the CDAI score (Crohn's Disease Activity Index) and the fecal calprotectin assay. The 25OHD profile was analyzed by LC-MS/MS. The pro-inflammatory cytokines (TNFα, IL-6, IL-12, IL-17, IL-23) were assessed by ELISA tests. The serum trace elements (Se, Mn, Cu, Zn) was determined by mass spectrometry. The antioxidant status (TAS, SOD, GPx, GSH) was evaluated by Randox kits. The results showed that the serum 25OHD concentrations became normal (> 75 nmol/L or > 30 ng/mL) in the 2 groups. Our data showed that vitamin D supplementation allowed the clinical remission phase. The DS3 decreased serum levels of CRPus, TNFα, IL-17 and IL-23. The DS3 modulates the trace elements ratio and increased the SOD and GPx activities. The DS3 corrects the denutrition state. The vitamin D supplementation benefits are more significant in D group (continuous 6,000 IU/day) than in D group (intermittent 200,000 IU/month). Our study suggests that the serum 25OHD profile can be considered a reliable biomarker in the bioclinic CD evolution to prevent the active phase, to extend the remission phase and to avoid the surgical bowel resection.