Changes in cholesterol synthesis and excretion when cholesterol intake is increased.

The metabolic responses to increased amounts of dietary cholesterol include, in man, a reduction in the synthesis and an increase in the re-excretion of cholesterol. The effectiveness of these compensating mechanisms in preventing increases in the plasma cholesterol concentration was studied in nine subjects. Cholesterol absorption, the excretion of bile acids, the excretion of endogenous neutral steroids, and the cholesterol balance (synthesis) were measured twice during intakes of cholesterol of about 250 and 750 mg/day. The serum of the compensating mechanisms (reduction in synthesis and increase in excretion of cholesterol) almost equalled the increase in absorbed cholesterol when the intake was raised by 500 mg (mean change in compensation, 226 mg/day; mean changes in absorption, 230 mg/day). In three subjects in whom re-excretion of cholesterol was predominant and compensated for absorbed cholesterol, the plasma cholesterol levels rose substantially. In five others, in whom the predominant change was reduction in cholesterol synthesis, the rise in plasma cholesterol levels was not significant. At moderate intakes of cholesterol both compensating mechanisms prevented retention of dietary cholesterol in the body, though a rise in the plasma cholesterol level was prevented only when cholesterol synthesis was suppressed.