title: Serum levels of 25-hydroxyvitamin D and the CYP3A biomarker 4β-hydroxycholesterol in a high-dose vitamin D supplementation study.
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.
authors: Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology, Stockholm, Sweden. linda.bjorkhem-bergman@karolinska.se
authors: Linda
authors: L
authors: Björkhem-Bergman
authors: Hanna
authors: H
authors: Nylén
authors: Anna-Carin
authors: AC
authors: Norlin
authors: Jonatan D
authors: JD
authors: Lindh
authors: Lena
authors: L
authors: Ekström
authors: Erik
authors: E
authors: Eliasson
authors: Peter
authors: P
authors: Bergman
authors: Ulf
authors: U
authors: Diczfalusy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054316:Biomarkers, Pharmacological / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D012141:Respiratory Tract Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*
chemical_list: D054316:Biomarkers, Pharmacological; D006888:Hydroxycholesterols; D018167:Receptors, Calcitriol; D014807:Vitamin D; C099828:cholest-5-ene-3,4-diol; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D