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Serum Levels of 25-Hydroxyvitamin D and the CYP3A Biomarker 4β-Hydroxycholesterol in a High-Dose Vitamin D Supplementation Study

Linda Björkhem-Bergman, Hanna Nylén, Anna-Carin Norlin, Jonatan D. Lindh, Lena Ekström, Erik Eliasson, Peter Bergman and Ulf Diczfalusy
Drug Metabolism and Disposition April 2013, 41 (4) 704-708; DOI: https://doi.org/10.1124/dmd.113.051136
Linda Björkhem-Bergman
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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Hanna Nylén
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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Anna-Carin Norlin
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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Jonatan D. Lindh
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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Lena Ekström
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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Erik Eliasson
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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Peter Bergman
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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Ulf Diczfalusy
Karolinska Institutet, Department of Laboratory Medicine, Divisions of Clinical Pharmacology (L.B.B., J.D.L., L.E., E.E.), Clinical Chemistry (H.N., U.D.), Clinical Immunology (A.C.N.), and Clinical Microbiology (P.B.), and Department of Medicine, Center for Infectious Medicine (P.B.), Karolinska University Hospital Huddinge, Stockholm, Sweden
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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.

Footnotes

  • Financial support was provided through the regional agreement on training and clinical research (ALF) between Karolinska Institutet and Stockholm County Council. In addition, the study was supported by grants from Swedish Research Council; Strategic Research Foundation (SSF); Swedish Heart and Lung Foundation; Karolinska Institutet; Magnus Bergwall and Åke Wiberg Foundations. L.B.B., P.B., and J.D.L. are holding Post Doc positions financed by Karolinska Institutet and Stockholm County Council (KI/SLL).

  • dx.doi.org/10.1124/dmd.113.051136.

  • Received January 21, 2013.
  • Accepted February 5, 2013.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 41 (4)
Drug Metabolism and Disposition
Vol. 41, Issue 4
1 Apr 2013
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Rapid CommunicationShort Communication

Vitamin D and the CYP3A Biomarker 4β-Hydroxycholesterol

Linda Björkhem-Bergman, Hanna Nylén, Anna-Carin Norlin, Jonatan D. Lindh, Lena Ekström, Erik Eliasson, Peter Bergman and Ulf Diczfalusy
Drug Metabolism and Disposition April 1, 2013, 41 (4) 704-708; DOI: https://doi.org/10.1124/dmd.113.051136

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Rapid CommunicationShort Communication

Vitamin D and the CYP3A Biomarker 4β-Hydroxycholesterol

Linda Björkhem-Bergman, Hanna Nylén, Anna-Carin Norlin, Jonatan D. Lindh, Lena Ekström, Erik Eliasson, Peter Bergman and Ulf Diczfalusy
Drug Metabolism and Disposition April 1, 2013, 41 (4) 704-708; DOI: https://doi.org/10.1124/dmd.113.051136
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