No impact of vitamin D on the CYP3A biomarker 4?-hydroxycholesterol in patients with abnormal glucose regulation.

ABSTRACT: PURPOSE:To investigate the effect of vitamin D3 on hepatic Cytochrome P450 enzyme (CYP) 3A4 in patients with abnormal glucose regulation using the endogenous marker 4?-hydroxycholesterol (4?-OHC):cholesterol ratio. METHODS:The present study took advantage of a trial primarily aiming to investigate the effect of vitamin D3 on beta cell function and insulin sensitivity in patients with abnormal glucose regulation. 44 subjects were randomized to receive vitamin D3, 30000 IU given orally once weekly or placebo for 8 weeks. The two sample t-test was used to test the means of the intra-individual differences of 4?-OHC:cholesterol ratio between the two groups. RESULTS:Mean (SD) 4?-OHC in the whole group of patients before and after the intervention was 26 (11) ng/ml and 26 (12). Mean (SD) 4?-OHC:cholesterol ratio in the whole group of patients before and after the intervention was 0.12 (0.046) and 0.13 (0.047). In the Vitamin D group mean (SD) serum 25-OH-vitamin D3 increased from 46 (16) to 85nM (13) during the corresponding time period. To investigate the impact of vitamin D3 on hepatic CYP3A4 we calculated the mean intra-individual differences in 4?-OHC:cholesterol ratio (delta 4?-OHC:cholesterol ratio) before versus after the intervention in the two treatment groups. The difference (95% CI) between delta 4?-OHC:cholesterol ratio in the control group and intervention group was -0.0010 (-0.0093, 0.0072), a difference being not statistically significant (p = 0.80). CONCLUSIONS:We provide further evidence that vitamin D3 may not substantially affect hepatic CYP3A4. This does not exclude the possibility of an impact of intestinal first-pass metabolism of orally administered drugs which should be investigated. TRIAL REGISTRATION:ClinicalTrials.gov NCT01497132.

SUBMITTER: Mannheimer B 

PROVIDER: S-EPMC4383380 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature