title: No impact of vitamin D on the CYP3A biomarker 4β-hydroxycholesterol in patients with abnormal glucose regulation.
abstract: OBJECTIVE
  To investigate the effect of vitamin D3 on hepatic Cytochrome P450 enzyme (CYP) 3A4 in patients with abnormal glucose regulation using the endogenous marker 4β-hydroxycholesterol (4β-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 4β-OHC:cholesterol ratio between the two groups.
  
  
  RESULTS
  Mean (SD) 4β-OHC in the whole group of patients before and after the intervention was 26 (11) ng/ml and 26 (12). Mean (SD) 4β-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 4β-OHC:cholesterol ratio (delta 4β-OHC:cholesterol ratio) before versus after the intervention in the two treatment groups. The difference (95% CI) between delta 4β-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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01497132.
authors.affiliation: Karolinska Institutet, Department of Clinical Science and Education at Södersjukhuset, SE 118 82, Stockholm, Sweden.
authors.forename: Buster
authors.initials: B
authors.lastname: Mannheimer
authors.affiliation: Karolinska Institutet, Department of Molecular Medicine and Surgery, D2:04, SE 171 76, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Wagner
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes at Karolinska Institutet, Karolinska University Hospital, D2:04, SE 171 76, Stockholm, Sweden.
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Östenson
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Chemistry at Karolinska Institutet, Karolinska University Hospital, C1.74, Huddinge, SE-141 86, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Diczfalusy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006888:Hydroxycholesterols; D014807:Vitamin D; C099828:cholest-5-ene-3,4-diol; D002784:Cholesterol; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
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