A B S T R A C T The metabolism of P-sitosterol was compared to that of cholesterol in 12 patients. Sterol balance methods were supplemented by radiosterol studies, with the following results. (a) Plasma concentrations of P-sitosterol ranged from 0.30 to 1.02 mg/100 ml plasma in patients on intakes of 6-sitosterol typical of the American diet. Plasma levels were raised little when intakes were increased greatly, and on fixed intakes they were constant from week to week. On diets devoid of plant sterols, the plasma and feces rapidly became free of p-sitosterol. (b) The percentage of esterified P-sitosterol in the plasma was the same as for cholesterol. However, the rate of esterification of P-sitosterol was slower than that for cholesterol. (c) Specific activitytime curves after simultaneous pulse labeling with #-sitosterol-3H and cholesterol-"C conformed to twopool models. The two exponential half-lives of f-sitosterol were much shorter than for cholesterol, and pool sizes were much smaller. Values of turnover for ,8-sitosterol obtained by the sterol balance method agreed closely with those derived by use of the two-pool model. There was no endogenous synthesis of P-sitosterol in the patients studied; hence, daily turnover of P-sitosterol equaled its daily absorption. Absorption of P-sitosterol was 5% (or less) of daily intake, while cholesterol absorption ranged from 45 to 54% of intake. (d) About 20% of the absorbed f-sitosterol was converted to cholic and chenodeoxycholic acids. The remainder was excreted in bile as free sterol; this excretion was more rapid than that of cholesterol. (e) The employment of i3-sitosterol as an internal standard to correct for losses of cholesterol in sterol balance studies is further validated by the results presented here.

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Studies were carried out to examine the effects of dietary fat and cholesterol on cholesterol homeostasis in man. 75 12-wk studies were carried out during intake of 35% of calories as either saturated or polyunsaturated fat, first low and then high in dietary cholesterol. Dietary fat and cholesterol intakes, plasma lipid and lipoprotein levels, cholesterol absorption and sterol synthesis in isolated blood mononuclear leukocytes were measured during each diet period. In 69% of the studies the subjects compensated for the increased cholesterol intake by decreasing cholesterol fractional absorption and/or endogenous cholesterol synthesis. When an increase in plasma cholesterol levels was observed there was a failure to suppress endogenous cholesterol synthesis. Plasma cholesterol levels were more sensitive to dietary fat quality than to cholesterol quantity.The results demonstrate that the responses to dietary cholesterol and fat are highly individualized and that most individuals have effective feedback control mechanisms.

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