Effect of pravastatin on plasma sterols and oxysterols in men.
OBJECTIVE
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.
Thelen
Karin M
KM
Department of Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany, and Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, University Hospital of Tampere, Finland.
Lütjohann
Dieter
D
Vesalainen
Risto
R
Janatuinen
Tuula
T
Knuuti
Juhani
J
von Bergmann
Klaus
K
Lehtimäki
Terho
T
Laaksonen
Reijo
R
D000328:Adult; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D017035:Pravastatin / Q000494:pharmacology*; D013261:Sterols / Q000097:blood*
D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013261:Sterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; C001521:lathosterol; D002784:Cholesterol; D017035:Pravastatin