1994
DOI: 10.1002/hep.1840190413
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Short-term effects of simvastatin on bile acid synthesis and bile lipid secretion in human subjects

Abstract: To test whether de novo synthesis of cholesterol is a limiting factor for bile acid synthesis, we studied the acute effect of simvastatin, an inhibitor of HMG-coenzyme A reductase (the limiting step of cholesterol synthesis) on bile acid synthesis and biliary lipid secretion in subjects with interrupted enterohepatic circulation. In these conditions bile acid synthesis is derepressed and is assumed to equal biliary bile acid secretion. Five cholecystectomized patients fitted with T-tubes were studied. All subj… Show more

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Cited by 26 publications
(12 citation statements)
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“…In this study the acute reduction in serum LDL concentration was accompanied by decreased bile acid and phospholipid secretion, and by unchanged cholesterol secretion. Unchanged HDL cholesterol and decreased serum LDL concentrations have also been reported by Loria and colleagues,2 to be accompanied by unchanged cholesterol and decreased bile acid secretion in bile during acute simvastatin administration in cholecystectomised patients. Furthermore, increased biliary cholesterol secretion has been observed by Kozarsky and colleagues34 using a murine model with an overexpressed HDL receptor enhancing hepatic uptake of this lipoprotein.…”
Section: Discussionsupporting
confidence: 60%
See 1 more Smart Citation
“…In this study the acute reduction in serum LDL concentration was accompanied by decreased bile acid and phospholipid secretion, and by unchanged cholesterol secretion. Unchanged HDL cholesterol and decreased serum LDL concentrations have also been reported by Loria and colleagues,2 to be accompanied by unchanged cholesterol and decreased bile acid secretion in bile during acute simvastatin administration in cholecystectomised patients. Furthermore, increased biliary cholesterol secretion has been observed by Kozarsky and colleagues34 using a murine model with an overexpressed HDL receptor enhancing hepatic uptake of this lipoprotein.…”
Section: Discussionsupporting
confidence: 60%
“…In addition to their effect on serum lipids, statins have also been reported to influence biliary lipid composition, but the evidence for this phenomenon is conflicting 2-13. Thus acute administration of simvastatin to cholecystectomised normolipaemic patients has been reported by Loria and colleagues2 to reduce hepatic bile acid secretion with no effect on cholesterol secretion. An opposite effect has been reported by Mazzella and colleagues3 during short term administration of simvastatin to hypercholesterolaemic patients.…”
mentioning
confidence: 87%
“…On the other hand, when statin treatment was superimposed to a chronic stimulation of bile acid synthesis with resin treatment, a reduction in cholesterol 7α-hydroxylation rates in vivo was disclosed, as measured by isotope release [ 156 ]. Similar data were also obtained in bile fistula patients [ 160 ].…”
Section: Regulation Of Bile Acid Synthesis In Different Situationssupporting
confidence: 86%
“…Expression levels of LDL receptors are increased by a compensatory mechanism, leading to increased hepatic LDL uptake and decreased plasma cholesterol . Statins decrease biliary cholesterol output by reducing availability of biliary cholesterol in both healthy individuals and hypercholesterolaemic patients . Statins have also beneficial effects on the vascular wall by stabilizing the atherosclerotic plaques, ameliorating impaired endothelial function, and reducing vascular inflammation .…”
Section: Introductionmentioning
confidence: 99%