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

Mannheimer B, Wagner H, Östenson CG, Diczfalusy U - PLoS ONE (2015)

Bottom Line: 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.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).This does not exclude the possibility of an impact of intestinal first-pass metabolism of orally administered drugs which should be investigated.

View Article: PubMed Central - PubMed

Affiliation: Karolinska Institutet, Department of Clinical Science and Education at Södersjukhuset, SE 118 82, Stockholm, Sweden.

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 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.

Trial registration: ClinicalTrials.gov NCT01497132.

No MeSH data available.


Related in: MedlinePlus

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pone.0121984.g001: Patient flow chart.

Mentions: The individuals were recruited from February 29, 2012 to March 15, 2013 and subsequently followed up from March 2, 2012 to May 29, 2013. Forty-four patients were included, 22 patients in the control group and 22 patients in the Vitamin D group. The baseline characteristics of the groups were similar (Table 1). One 67 year old female in Vitamin D group was excluded after randomization due to the initiation of oral corticosteroids due to relapse in her chronic inflammatory bowel disease. Thus 22 patients in the control and 21 in the Vitamin D group were further analysed (Fig 1).


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

Mannheimer B, Wagner H, Östenson CG, Diczfalusy U - PLoS ONE (2015)

Patient flow chart.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383380&req=5

pone.0121984.g001: Patient flow chart.
Mentions: The individuals were recruited from February 29, 2012 to March 15, 2013 and subsequently followed up from March 2, 2012 to May 29, 2013. Forty-four patients were included, 22 patients in the control group and 22 patients in the Vitamin D group. The baseline characteristics of the groups were similar (Table 1). One 67 year old female in Vitamin D group was excluded after randomization due to the initiation of oral corticosteroids due to relapse in her chronic inflammatory bowel disease. Thus 22 patients in the control and 21 in the Vitamin D group were further analysed (Fig 1).

Bottom Line: 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.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).This does not exclude the possibility of an impact of intestinal first-pass metabolism of orally administered drugs which should be investigated.

View Article: PubMed Central - PubMed

Affiliation: Karolinska Institutet, Department of Clinical Science and Education at Södersjukhuset, SE 118 82, Stockholm, Sweden.

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 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.

Trial registration: ClinicalTrials.gov NCT01497132.

No MeSH data available.


Related in: MedlinePlus