Serum levels of 25-hydroxyvitamin D and the CYP3A biomarker 4β-hydroxycholesterol in a high-dose vitamin D supplementation study

Drug Metab Dispos. 2013 Apr;41(4):704-8. doi: 10.1124/dmd.113.051136. Epub 2013 Feb 5.

Abstract

The primary aim was to study the relationship between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol, which is an endogenous biomarker of the drug-metabolizing CYP3A enzymes. In addition, the relationship between this biomarker and inflammation, measured as C-reactive protein (CRP), was investigated. Serum samples were used from a recently performed clinical trial in patients with antibody deficiency or increased susceptibility to respiratory tract infections that were randomized to either placebo or high-dose (4000 IU/day) vitamin D for 12 months. One hundred sixteen patients were included in the final analyses, and serum samples collected 6 months after study start were analyzed. At this time point, 25-hydroxyvitamin D levels were found to range between 10 and 284 nM. Individual levels of 25-hydroxyvitamin D as well as CRP were compared with 4β-hydroxycholesterol levels. In addition, all participants were genotyped for two polymorphisms (Taq1 and Foq1) in the vitamin D receptor gene. There was no significant correlation between individual serum levels of 25-hydroxyvitamin D and 4β-hydroxycholesterol. However, a moderate, but statistically significant, negative correlation between CRP and 4β-hydroxycholesterol levels was observed. This study in patients with highly variable serum levels of 25-hydroxyvitamin D could not reveal any relationship between vitamin D and 4β-hydroxycholesterol, an endogenous biomarker of CYP3A activity. However, the negative correlation between CRP and 4β-hydroxycholesterol supports earlier experimental results that inflammation may suppress hepatic CYP3A activity, a finding of potentially high clinical relevance that warrants further exploration.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Pharmacological / blood
  • C-Reactive Protein / metabolism
  • Female
  • Genotype
  • Humans
  • Hydroxycholesterols / blood*
  • Immunologic Deficiency Syndromes / blood
  • Immunologic Deficiency Syndromes / drug therapy
  • Immunologic Deficiency Syndromes / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, Calcitriol / genetics
  • Respiratory Tract Infections / blood
  • Respiratory Tract Infections / drug therapy
  • Respiratory Tract Infections / genetics
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / therapeutic use*

Substances

  • Biomarkers, Pharmacological
  • Hydroxycholesterols
  • Receptors, Calcitriol
  • Vitamin D
  • cholest-5-ene-3,4-diol
  • C-Reactive Protein
  • 25-hydroxyvitamin D