Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects.

Duane, William

doi:10.1172/jci116666

Cited by 40 publications

(25 citation statements)

References 42 publications

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“…In small-scale cholesterol balance studies, Miettinen et al (7)(8)(9) have documented that statins markedly lower cholesterol synthesis and bile acid production, but also significantly increase fractional intestinal cholesterol absorption. Duane (10) reported similar observations. Miettinen, Strandberg, and Gylling (11) have also reported in a subset of CHD patients participating in the Scandinavian Simvastatin Survival Study (4S) that those in the highest quartile of the cholestanol/C ratio (indicative of high cholesterol absorption), while on simvastatin had no reduction in CHD events as compared with the placebo-treated group, with the converse also being the case.…”

supporting

confidence: 54%

Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers

Himbergen

Matthan

Resteghini

et al. 2009

Journal of Lipid Research

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We measured plasma markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, and cholestanol) in order to compare the effects of maximal doses of rosuvastatin with atorvastatin and investigate the basis for the significant individual variation in lipid lowering response to statin therapy. Measurements were performed in participants (n 5 135) at baseline and after 6 weeks on either rosuvastatin (40 mg/day) or atorvastatin (80 mg/day) therapy. Plasma sterols were measured using gas-liquid chromatography. Rosuvastatin and atorvastatin significantly (P , 0.001) altered plasma total cholesterol (C) levels by 240%, and the ratios of lathosterol/C by 264% and 268%, and campesterol/C by 152% and 172%, respectively, with significant differences (P , 0.001) between the treatment groups for the latter parameter. When using absolute values of these markers, subjects with the greatest reductions in both synthesis (lathosterol) and absorption (campesterol) had significantly greater reductions in total C than subjects in whom the converse was true (246% versus 234%, P 5 0.001), with similar effects for LDL-C. Rosuvastatin and atorvastatin decreased markers of cholesterol synthesis and increased markers of fractional cholesterol absorption, with rosuvastatin having significantly less effect on the latter parameter than atorvastatin. In addition, alterations in absolute values of plasma sterols correlated with the cholesterol lowering response.-van Himbergen, T.

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supporting

confidence: 54%

Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers

Himbergen

Matthan

Resteghini

et al. 2009

Journal of Lipid Research

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“…We and others have documented that alterations in specifi c plasma markers of cholesterol absorption, namely, campesterol and ␤ -sitosterol, can affect LDL-C lowering response to statins (17)(18)(19)(20). Moreover, it has been reported that a subset of patients placed on simvastatin in the Scandinavian Simvastatin Survival Study showed no benefi t from therapy compared with placebo if they had elevated baseline levels of markers of cholesterol absorption, including cholestanol ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly

Polisecki

Peter

Simon³

et al. 2010

Journal of Lipid Research

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“…Direct measurement of the latter has failed to show consistent effects of other statins. 7,13,14 However, a decrease in biliary cholesterol secretion could also lead to an increase in cholesterol absorption, as shown in mice 15 and in dietary studies in humans. 16 Low cholesterol absorption efficiency in obesity may be because of an increased biliary cholesterol pool that competes with dietary cholesterol and noncholesterol sterols for intestinal absorption.…”

Section: Discussionmentioning

confidence: 99%

Effect of a statin on hepatic apolipoprotein B-100 secretion and plasma campesterol levels in the metabolic syndrome

et al. 2003

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OBJECTIVE:We aimed to study the effect of atorvastatin, a statin, on cholesterol synthesis and absorption and VLDL-apoB metabolism in obese men with the metabolic syndrome. METHODS: A total of 25 dyslipidaemic obese men were randomized to atorvastatin (n ¼ 13) (40 mg/day) or matching placebo (n ¼ 12) for 6 weeks. Hepatic secretion and fractional catabolic rate (FCR) of VLDL-apoB was measured using an intravenous bolus of d 3 -leucine before and after treatment. ApoB isotopic enrichment was measured using GCMS and multicompartmental modelling. Plasma lathosterol: cholesterol and campesterol:cholesterol ratios were determined to assess cholesterol synthesis and cholesterol absorption, respectively. RESULTS: Compared with placebo, atorvastatin significantly decreased (Po0.05) total cholesterol, triglyceride, LDL-cholesterol and VLDL-apoB. Plasma lathosterol:cholesterol ratio decreased from 26.472.4 to 8.870.8, while the campesterol:cholesterol ratio increased from 26.574.4 to 38.675.8 (Po0.01). Atorvastatin also increased VLDL-apoB FCR from 3.8270.33 to 6.3070.75 pools/day (Po0.01), but did not significantly alter VLDL-apoB secretion (12.871.7 to 13.872.0 mg/kg/day). CONCLUSIONS: In obesity, atorvastatin inhibits cholesterogenesis but increases intestinal cholesterol absorption. The increased cholesterol absorption may counteract the inhibitory effect on hepatic VLDL-apoB secretion, but it does not apparently influence enhanced catabolism of VLDL-apoB.

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Effects of lovastatin and dietary cholesterol on sterol homeostasis in healthy human subjects.

Cited by 40 publications

References 42 publications

Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers

Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers

Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly

Effect of a statin on hepatic apolipoprotein B-100 secretion and plasma campesterol levels in the metabolic syndrome

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