EFFECTS OF LOVASTATIN AND DIETARY-CHOLESTEROL ON STEROL HOMEOSTASIS IN HEALTHY-HUMAN SUBJECTS

We measured biliary and fecal sterol outputs in 12 human subjects on a metabolic ward in four randomly allocated, 6-7 wk periods: (a) lovast atin (40 mg b.i.d.) + low cholesterol diet (mean 246 mg/d), (b) lovast atin + high cholesterol diet (mean 1,071 mg/d), (c) low cholesterol di et alone, (d) high cholesterol diet alone. In addition to lowering ser um LDL cholesterol, lovastatin significantly lowered biliary secretion of cholesterol, fecal output of endogenous neutral sterols, cholester ol balance, and systemic cholesterol input (the sum of cholesterol syn thesis and absorbed dietary cholesterol). The high cholesterol diet si gnificantly lowered cholesterol balance, but significantly increased s ystemic cholesterol input and fecal output of acidic sterols. There wa s no significant interaction between lovastatin and dietary cholestero l for any parameter measured. Judging from these data, the primary act ion of lovastatin is to lower cholesterol synthesis and systemic chole sterol input, the main compensatory response being reduced biliary cho lesterol secretion. Conversely, increased dietary cholesterol appears to increase systemic cholesterol input, the major compensatory respons e being increased bile acid synthesis. There appears to be no interact ion between these two perturbations of systemic cholesterol input.