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Effect of pravastatin on plasma sterols and oxysterols in men

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Abstract

Objectives

The HMG-CoA reductase inhibitors, or statins, are well established in the prevention and treatment of coronary artery disease, mainly by lowering low-density lipoprotein (LDL) cholesterol levels. These compounds are structurally similar, but differ in their lipophilicity. Several studies have indicated a link between cholesterol and Alzheimer’s disease (AD), and there is also epidemiological evidence that statin treatment may decrease the prevalence of dementias. In the present study we wanted to investigate whether pravastatin treatment affects brain cholesterol metabolism.

Methods

A post hoc analysis was performed with plasma material from a clinical trial where 51 healthy men (35±4 years) were randomly assigned to receive either pravastatin (40 mg/day) or placebo for 6 months. Cholesterol, its precursor lathosterol, its brain-specific metabolite 24(S)-hydroxycholesterol (24S-OH-chol) and 27-hydroxycholesterol (27-OH-chol) were determined in plasma samples before and after treatment by using gas-liquid chromatography (GC)-flame ionization detection (GC-FID) and GC mass spectrometry (GC-MS).

Results

Besides reducing total cholesterol (−20%, P<0.001) and LDL cholesterol (LDL-C; −33%, P<0.001) concentrations, pravastatin treatment resulted in a decrease of the ratio of lathosterol to cholesterol, a surrogate marker of endogenous cholesterol synthesis, by 20% (P<0.05). Absolute concentrations of 24S-OH-chol were not altered, but its ratio to cholesterol slightly increased by 15% (P<0.05). 27-OH-chol concentrations as well as its ratio to cholesterol were both significantly altered due to pravastatin treatment (−7% and +14%, P<0.05 for both, respectively).

Conclusions

The treatment with pravastatin 40 mg once a day for 6 months does not affect brain cholesterol metabolism as judged by plasma concentrations of 24(S)-hydroxycholesterol.

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Acknowledgements

We thank Silvia Friedrichs and Ms. Marita Koli for their skilful technical assistance. This study was financially supported by the Tampere University Hospital Medical Fund. The procedures in this study complied with the current laws of the country in which they were performed (Finland).

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany

    Karin M. Thelen, Dieter Lütjohann & Klaus von Bergmann

  2. Department of Medicine, University of Turku, Turku, Finland

    Risto Vesalainen

  3. Turku-PET Centre, University of Turku, Turku, Finland

    Tuula Janatuinen & Juhani Knuuti

  4. Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, University Hospital of Tampere and Medical School at the University of Tampere, Tampere, Finland

    Terho Lehtimäki

  5. Department of Neurology, Erasme Hospital, Free University of Brussels, Brussels, Belgium

    Reijo Laaksonen

  6. Drug Discovery and Technology Development Center, University of Helsinki, Helsinki, Finland

    Reijo Laaksonen

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  1. Karin M. Thelen
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Correspondence to Dieter Lütjohann.

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Thelen, K.M., Lütjohann, D., Vesalainen, R. et al. Effect of pravastatin on plasma sterols and oxysterols in men. Eur J Clin Pharmacol 62, 9–14 (2006). https://doi.org/10.1007/s00228-005-0068-9

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  • DOI: https://doi.org/10.1007/s00228-005-0068-9

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