4-Desmethylsterols and -stanols reduce plasma total cholesterol (TC) and LDL cholesterol by inhibition of intestinal cholesterol absorption, while the cholesterol-lowering potential of 4,4′-dimethylsterols is less well defined. The present study aimed to compare the effects of 4-desmethylsterols, -stanols, and 4,4′-dimethylsterols on plasma and hepatic cholesterol, sterol excretion and bile acid metabolism. Male golden Syrian hamsters were fed diets containing 13 g/100 g fat, 0·08 g/100 g cholesterol and 0 (control), 0·24 or 0·48 % (w/w) esterified 4-desmethylsterols (sterols) and esterified hydrogenated 4-desmethylsterols (stanols) from common vegetable oils or esterified 4,4′-dimethylsterols from rice bran oil for 5 weeks. Sterol and stanol esters at the dose of 0·24 % were equally effective and significantly (P<0·05) lowered TC by 15 %, while 0·24 % 4,4-dimethylsterols reduced TC by 10 %. Liver total and esterified cholesterol concentrations were significantly (P<0·05) lowered by 40, 22, 43 and 31 % in hamsters fed 0·48 % sterols, 0·24 % stanols, 0·48 % stanols or 0·48 % dimethylsterols, respectively. Daily faecal bile acid excretion and hepatic cholesterol 7α-hydroxylase activity were not altered, indicating that sterols, stanols and dimethylsterols had no effect on the intestinal re-absorption of bile acids or on hepatic bile acid synthesis. Daily excretion of cholesterol was significantly higher in hamsters fed esterified sterols and stanols, but was only slightly increased in those fed dimethylsterols. The results indicate that esterified sterols and stanols were equally effective in lowering plasma TC and LDL cholesterol, while dimethylsterol esters caused a weaker cholesterol-lowering effect. Sterols and stanols achieve their cholesterol-lowering effect by stimulating faecal cholesterol excretion through inhibiting intestinal cholesterol absorption, but do not affect bile acid excretion. Other mechanisms need to be considered to explain the effect on plasma and hepatic cholesterol of dimethylsterols.
Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone disease
