Sitostanol administered in lecithin micelles potently reduces cholesterol absorption in humans.

BACKGROUND: Phytosterol feeding in human clinical trials has had generally small and inconsistent effects on serum cholesterol concentrations, raising doubts about the importance of phytosterols in natural diets and supplements. OBJECTIVE: The hypothesis tested was that the low intestinal bioavailability of purified phytosterols can be increased by formulation with lecithin. DESIGN: The ability of sitostanol to reduce cholesterol absorption was measured directly by including hexadeuterated cholesterol tracer in a standard test breakfast and measuring plasma tracer concentration 4 and 5 d later by gas chromatography-negative ion mass spectrometry. The tracer amount after a test meal containing sitostanol was compared with that after an identical meal containing placebo. Each subject served as his or her own control and the order of testing was random. Sitostanol was formulated either as a powder or as a sonicated micellar solution with lecithin. A total of 38 single-meal tests were performed in 6 healthy subjects. RESULTS: Sitostanol powder (1 g) reduced cholesterol absorption by only 11.3 +/- 7.4% (P = 0.2), confirming in vitro data showing poor solubility of sitostanol powder in artificial bile. In contrast, sitostanol in lecithin micelles reduced cholesterol absorption by 36.7 +/- 4.2% (P = 0.003) at a dose of 700 mg and by 34.4 +/- 5.8% (P = 0.01) at a dose of 300 mg. CONCLUSIONS: Sitostanol reduced cholesterol absorption at doses lower than reported previously, but only if presented in lecithin micelles. Properly formulated sitostanol as well as naturally occurring complexes of phytosterol and phospholipid might be therapeutically useful for cholesterol lowering.