Sterol balance in hyperlipidemic patients after dietary exchange of carbohydrate for fat

Dextrose was exchanged isocalorically for polyunsaturated fat in the liquid formula diets of 10 hyperlipidemic patients maintained under metabolic steady state conditions. Carbohydrate caused an increase of plasma triglycerides in all 10; plasma cholesterol rose in 7, and 6 of these 7 failed to show any increase in total fecal excretion of cholesterol. In contrast, fecal steroid excretion increased significantly in the three patients who maintained an unchanged or lower plasma cholesterol on the high-carbohydrate diet. Squalene, an obligatory precursor in the biosynthesis of cholesterol, rose in the plasma during carbohydrate feeding in 6 out of 6 patients studied. After a single intravenous infusion of radioactive cholesterol, plasma and feces were analyzed for specific activity over at least a four-month period. Plasma and fecal neutral sterol specific activity were essentially equivalent at all times in all patients, regardless of feeding regimen. On institution of carbohydrate feeding, the slope of cholesterol specific activity flattened for those seven patients who had a rise in plasma cholesterol concentration. There was no change in slope for the two patients with fixed plasma cholesterol levels nor for the one patient with a decreased plasma cholesterol on the high-carbohydrate diet. These experiments demonstrate a divergent response between plasma cholesterol concentration and cholesterol excretion. To establish causal relationship between the two (i.e., plasma cholesterol increases because excretion does not increase) will require further research. The flattening of specific activity die-away curves with rising cholesterol concentrations is best explained by mobilization of slowly turning-over tissue cholesterol into plasma. A subsequent decrease in cholesterol synthesis would also add to the slower decline of plasma cholesterol specific activity.