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

We measured biliary and fecal sterol outputs in 12 human sub-jects on a metabolic ward in four randomly allocated, 6-7 wk periods: (a) lovastatin (40 mg b.i.d.) + low cholesterol diet (mean 246 mg/d), (b) lovastatin + high cholesterol diet (mean 1,071 mg/d), (c) low cholesterol diet alone, (d) high choles-terol diet alone. In addition to lowering serum LDL cholesterol, lovastatin significantly lowered biliary secretion of cholesterol, fecal output of endogenous neutral sterols, cholesterol balance, and systemic cholesterol input (the sum of cholesterol synthe-sis and absorbed dietary cholesterol). The high cholesterol diet significantly lowered cholesterol balance, but significantly in-creased systemic cholesterol input and fecal output of acidic sterols. There was no significant interaction between lovastatin and dietary cholesterol for any parameter measured. Judging from these data, the primary action of lovastatin is to lower cholesterol synthesis and systemic cholesterol input, the main compensatory response being reduced biliary cholesterol secre-tion. Conversely, increased dietary cholesterol appears to in-crease systemic cholesterol input, the major compensatory re-sponse being increased bile acid synthesis. There appears to be no interaction between these two perturbations of systemic cho-lesterol input. (J. Clin. Invest. 1993. 92:911-918.) Key words: cholesterol * bile acids and salts * hydroxymethylglutaryl CoA reductases * atherosclerosis * cholelithiasi