Plant stanol fatty acid esters inhibit cholesterol absorption and hepatic hydroxymethyl glutaryl coenzyme A reductase activity to reduce plasma levels in rabbits

The aim of this study was to study the inhibitory effect of dietary stanols (campestanol and sitostanol) fatty acid esters ISE) on intestinal choleste rol absorption. New Zealand white rabbits were fed regular chow alone or en riched with 0.2% cholesterol, 0.33% SE + cholesterol, 0.66% SE + cholestero l, 1.2% SE + cholesterol, 2.4% SE + cholesterol, and 1.2% SE alone. After 2 weeks, plasma cholesterol levels increased 3.6 times in the cholesterol gr oup and did not decrease after addition of 0.33% or 0.66% SE to the cholest erol-enriched diets. However, after addition of 1.2% SE to the cholesterol diet, plasma cholesterol concentration decreased 50% (P <.001), but it did not decrease further after doubling of SE to 2.4%. Percent cholesterol abso rption measured by the plasma dual-isotope ratio method was 73.0% +/- 8.1% in the cholesterol group, which was similar to untreated baseline control. The percent absorption of cholesterol did not decrease significantly after addition of 0.33% or 0.66% SE to the cholesterol diet but decreased 43.8% ( P <.001) in the 1.2% SE + cholesterol group, a finding similar to those in rabbits fed 1.2% SE alone. Increasing SE to 2.4% in the cholesterol diet di d not further decrease absorption. Hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase activity reflecting cholesterol synthesis and low-den sity lipoprotein receptor-mediated binding unexpectedly decreased 67% (P <. 01) and 57% (P <.05) in rabbits fed 1.2% SE alone. Increasing dietary SE in take to 1.2% reduced cholesterol absorption and plasma levels. Dietary SE i ntake below 1.2% was ineffective and above 2.4% did not further decrease pe rcent absorption or plasma cholesterol levels. These results support the hy pothesis that dietary SEs competitively displace cholesterol from intestina l micelles to reduce cholesterol absorption and decrease plasma cholesterol levels. Copyright (C) 2001 by W.B. Saunders Company.