The long term effects of dietary cholesterol upon the plasma lipids, lipoproteins, cholesterol absorption, and the sterol balance in man: the demonstration of feedback inhibition of cholesterol biosynthesis and increased bile acid excretion

In order to study the metabolic responses of humans consuming a diet moderately high in cholesterol content, we carried out a long-term sterol balance study, up to 25 weeks in duration. Two subjects, one normocholesterolemic and one hypercholesterolemic, were given, in sequence, a very low cholesterol diet and then a diet containing 1000 mg cholesterol per day. The plasma lipids, lipoproteins, cholesterol absorption and synthesis, and fecal steroid excretion were then measured during the different dietary periods (10-14 weeks of a very low cholesterol diet and 11 weeks of a moderately high cholesterol diet). During the high cholestrol dietary period, the plasma cholesterol level increased from 280 to 427 mg/dl for Subject 1 and from 123 to 166 mg/dl for Subject 2. The low density lipoprotein (LDL) cholesterol increased from 215 to 318 mg/dl and from 76 to 112 mg/dl. The high density lipoprotein (HDL) cholesterol also increased. Of the possible compensatory mechanisms against cholesterol overloading from the diet, two mechanisms were partially effective: cholesterol biosynthesis decreased (feedback inhibition) and bile acid excretion increased. Cholesterol absorption remained unchanged after the high cholesterol diet and was not a compensatory mechanism despite earlier assumptions that it might be. In spite of these compensatory mechanisms, the cholesterol feeding led to a 44% increase in the plasma cholesterol levels of these subjects. The predominant component of the plasma cholesterol increase was in the cholesterol transported by LDL and with presumably greater atherogenicity as a result. In the hypercholesterolemic subject, the LDL/HDL ratio increased and there was a net storage of cholesterol in the body. Storage of cholesterol did not occur in the normal subject.