Hypocholesterolemic agents and mobilization of tissue cholesterol in man

Plasma cholesterol was pulse-labelled with [4- 14C]cholesterol in 11 hyperlipemic subjects on cholesterol balance studies. When the decline in the specific activity of plasma cholesterol became exponential, various parameters of cholesterol metabolism were measured during steady state conditions of the control period. The subjects were then given clofibrate, nicotinic acid, or plant sterols and the changes in these parameters were noted. There was a prompt decline in the plasma cholesterol concentration and a marked upswing in the specific activity slope; the latter could only occur by the entry of cholesterol from the tissues. The amounts of tissue cholesterol entering plasma were estimated (a) from the increases in the fecal excretion of endogenous cholesterol and its metabolites, and (b) from the increases in the secretion of endogenous cholesterol into the lumen of the gastrointestinal tract. Both estimates were in good agreement. The increases in plasma cholesterol specific activity had excellent correlations with the amounts of cholesterol mobilized from the tissues. These parameters in turn correlated well with fall in plasma cholesterol concentration suggesting that the mobilization was secondary to the acute reduction in the plasma cholesterol cencentrations and was not caused directly by the drugs.