Use of plasma markers as indices of sterol metabolism

Abstract

Plasma markers of sterol metabolism provide a means of assessing the synthesis of cholesterol and bile acids and the absorption of cholesterol and plant sterols. Synthetic markers are products of the rate-limiting enzymes HMG CoA reductase and cholesterol 7α-hydroxylase, whereas absorptive markers are usually exogenous, exemplified by plant sterols. Markers of cholesterol synthesis include plasma levels of mevalonic acid (MVA) and lathosterol. We have measured both in order to investigate pathophysiological influences on cholesterol synthesis and to monitor the effects of lipid-lowering interventions, such as LDL apheresis and statins. Plasma levels of plant sterols provide a surrogate marker of cholesterol absorption but also reflect other influences including the plant sterol content of the diet and therapeutic interventions, such as plant stanols, statins and ezetimibe. Plasma levels of 7α-hydroxycholestenone, the product once removed of cholesterol 7α-hydroxylase, reflect rates of bile acid synthesis. We have used this marker to monitor the effects of statin therapy on the latter and of feeding plant sterols and stanols.