Sitosterol reduces micellar cholesterol solubility in model bile

Plant sterol consumption can significantly reduce plasma low-density lipoprotein cholesterol concentration, a major risk factor for atherosclerotic disease. It is generally assumed that plant sterols function by displacing cholesterol from intestinal micelles, thus reducing cholesterol absorption. Direct evidence for this mechanism, however, is limited. This study tested the hypothesis that sitosterol, the most common dietary plant sterol, reduces micellar cholesterol solubilization using an in vitro model bile system. Model bile solutions were prepared by sonicating a mixture of bile salts (52.5 mmol/L), phosphatidylcholine (15.0 mmol/L), and cholesterol (3.0 mmol/L) in saline with variable amounts of sitosterol (0.0, 3.0, and 6.0 mmol/L). Micelles were separated and analyzed using Superose 6 (Amersham Pharmacia Biotech, Piscataway, NJ) gel filtration. The addition of 3.0 mmol/L sitosterol to model bile (ie, an equimolar amount relative to cholesterol) significantly reduced cholesterol solubilization in micelles, as indicated by the cholesterol-phosphatidylcholine molar ratio, which decreased from 0.131 ± 0.010 (0.0 mmol/L sitosterol) to 0.043 ± 0.009 (3.0 mmol/L sitosterol). Increasing the sitosterol concentration to 6.0 mmol/L caused no further reductions in cholesterol solubility. Thus, our in vitro findings support the belief that displacement of cholesterol from micelles is a primary mechanism by which sitosterol and other plant sterols decrease cholesterol absorption in vivo.