Molecular insights into the mechanisms underlying the cholesterol-lowering effects of phytosterols.
Dietary phytosterols, which comprise plant sterols and stanols, reduce plasma low-density lipoprotein- cholesterol (LDL-C) levels when given at 2 g/day. Since this dose has not been reported to cause health- related side effects in long-term human studies, food products containing these plant compounds are used as potential therapeutic dietary options to reduce LDL-C and cardiovascular disease risk. Several mechanisms have been proposed to explain the cholesterol-lowering action of phytosterols. They may compete with dietary and biliary cholesterol for micellar solubilization in the intestinal lumen, impairing intestinal cholesterol absorption. Recent evidence indicates that phytosterols may also regulate other pathways. Impaired intestinal cholesterol absorption is usually associated with reduced cholesterol transport to the liver, which may reduce the incorporation of cholesterol into very-low-density lipoprotein (VLDL) particles, thereby lowering the rate of VLDL assembly and secretion. Impaired liver VLDL production may reduce the rate of LDL production. On the other hand, significant evidence supports a role for plant sterols in the transintestinal cholesterol excretion (TICE) pathway, although the exact mechanisms by which they promote the flow of cholesterol from blood to enterocytes and intestinal lumen remains unknown. Dietary phytosterols may also alter the conversion of bile acids into secondary bile acids, and may lower the bile acid hydrophobic/hydrophilic ratio, thereby reducing intestinal cholesterol absorption. This article reviews the progress to date in research on the molecular mechanisms underlying the cholesterol-lowering effects of phytosterols.