Long term steroid metabolism balance studies in subjects on cholesterol-free and cholesterol-rich diets: comparison between normal and hypercholesterolemic individuals

Abstract

Regulation of cholesterol metabolism was investigated in eight hypercholesterolemic and five normal individuals by combined intravenous pulse-labeling with radioactive cholesterol and fecal steroids balance techniques. Mean serum cholesterol concentrations ranged from 168 to 717 mg/dl. Experiments were scheduled in the following sequence: a cholesterol-free diet period lasting 4-6 weeks (PI); cholesterol intake of 1350 mg/day lasting 9-10 weeks (PII); and a cholesterol-free diet for 2 weeks (PIII). It was observed that body cholesterol synthesis in PI and absorption of dietary cholesterol in PII were completely independent of the serum cholesterol levels and varied widely among the subjects. During the cholesterol intake period, seven individuals maintained a negative fecal steroid balance, whereas six others accumulated cholesterol in the body (positive balance) irrespective of cholesterol concentration. A strong positive correlation was found between dietary cholesterol absorption and cholesterol balance in PII and reflected two events: 1) decreased synthesis as the major mechanism to prevent body storage of cholesterol, whereas the increase of fecal bile acids and endogenous neutral steroids excretion played a secondary role; 2) increasing amounts of cholesterol accumulated in the body proportionally to the amount absorbed, whenever the latter surpassed the ability of the compensatory mechanisms. These compensatory mechanisms seem to have been equally efficient in both normal and hypercholesterolemic subjects. Changes in serum cholesterol subsequent to cholesterol feeding were also unrelated to the amount absorbed and to the steroid balance in PII.