The hypocholesterolaemic effects of sitostanol in the guinea pig are in part related to changes in hepatic lipids and lipoprotein composition

To evaluate some of the mechanisms involved in the plasma cholesterol lower ing of sitostanol (SI), male Hartley guinea pigs were fed diets containing cholesterol (0.25 g/100 g) and four doses of SI: either 0 (control), 0.75, 1.5 or 2.25 g/100 g. In addition a negative control (-C) group with dietary cholesterol (0.04 g/100 g) was included. Corn oil was used as the source o f fat and the contribution of fat energy was 35 %. Plasma total cholesterol was 43, 49 and 53 % (P < 0.0001) lower after SI intake compared to the con trol. Plasma LDL concentrations were 47, 53 and 61 % lower with increasing doses of SI. In addition, intake of SI resulted in 26-42 % lower hepatic to tal cholesterol. Hepatic esterified cholesterol and triacylglycerols were 3 2-60 % and 55-61 % lower after SI intake. SI intake resulted in favourable plasma and hepatic cholesterol concentrations similar to those in guinea pi gs fed low levels of dietary cholesterol (-C). The LDL obtained from the co ntrol group had a higher number of molecules of free and esterified cholest erol than the SI groups. SI intake resulted in 69-71 % higher cholesterol e xcretion compared to the control. SI treatment enhanced the total faecal ne utral sterol excretion by 54-58 % compared to control and by 70-76 % compar ed to the (-C) group. These results suggest that SI might have its hypochol esterolaemic effect by reducing cholesterol absorption, which results in lo wer concentration of cholesterol in liver. This reduction in hepatic choles terol might possibly alter hepatic cholesterol metabolism and affect lipopr otein concentration and composition.