Dietary silostanol reciprocally influences cholesterol absorption and biosynthesis in hamsters and rabbits

The aim of this study was to examine the efficacy of variable dietary sitostanol (SI) concentrations on cholesterol absorption, synthesis and excretion rates in two animal models. Hamsters and rabbits were fed semi-purified diets supplemented with cholesterol and 1% (w/w) phytosterols containing either 0.007, 0.17, 0.8 or 1% (w/w) SI. The control (0% (w/w) SI) groups consumed the same diets but no phytosterols were added. The dual-isotope plasma ratio of [C-13]- and [O-18]cholesterol and deuterium incorporation methods were applied to measure simultaneously cholesterol absorption and fractional synthesis, respectively. Plasma total cholesterol levels were lower in rabbits and hamsters fed 0.8 and 1% (w/w) SI, respectively, as compared to their controls. Percent cholesterol absorption was lower (P = 0.03) in hamsters fed 1% (w/w) SI (42.5 +/- 13.3%) than control (65.1 +/- 13.4%). Moreover, cholesterol excretion in the feces was 77 and 57% higher (P = 0.017) in the 1% (w/w) SI- relative to control- and 0.17% (w/w) SI-fed groups, respectively. In rabbits, cholesterol excretion was 64% higher (P = 0.018) in 0.8% (w/w) SI- compared with control-fed groups. Fractional synthesis rate was higher (P = 0.033) in hamsters fed 1% (w/w) SI (0.116 +/- 0.054 pool day(-1)) as compared to control(0.053 +/- 0.034 pool day(-1)). However, cholesterol synthesis rates did not vary among groups fed variable concentrations of SI. In rabbits, percent cholesterol absorption and its fractional synthesis rate varied but did not reach significance. Fractional synthesis rate in hamsters was correlated (r = -0.32, P = 0.03) with percent cholesterol absorption. In conclusion, dietary SI exhibited a dose-dependent action in inhibiting cholesterol absorption while increasing cholesterol excretion and upregulating cholesterogenesis in hamsters resulting in lower circulating lipid levels. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.