Effect of Statins on Noncholesterol Sterol Levels: Implications for Use of Plant Stanols and Sterols

Normal serum contains small amounts of noncholesterol sterols, including those reflecting cholesterol absorption and those that are markers of cholesterol synthesis. Absorption marker sterols include serum plant sterols, whereas cholesterol precursor sterols correlate with whole-body synthesis of cholesterol. Thus, serum noncholesterol sterols, and especially their ratios to cholesterol, can be used to evaluate the major features of cholesterol metabolism (ie, synthesis and absorption). Statin treatment reduces serum cholesterol precursors but increases serum plant sterols severalfold, especially in subjects with high-absorption marker sterol levels indicative of efficient cholesterol and sterol absorption in general. Statin therapy is most effective in subjects with high serum cholesterol precursor levels. In subjects with high-absorption sterol markers, dietary cholesterol absorption inhibition (eg, with plant stanol and sterol ester margarine) needs to be combined with a statin to achieve effective serum cholesterol reduction. However, whereas dietary plant stanol esters reduce statin-induced elevations of serum plant sterol levels, serum plant sterol levels remain elevated during dietary plant sterol ester consumption. The clinical implication of high serum plant sterol levels is under active investigation.