Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment

Abstract

Background  Serum contains noncholesterol sterols, which are reliable markers of cholesterol metabolism, but their presence and importance in different lipoproteins have been insufficiently studied.

Materials and methods  Serum and lipoprotein cholesterol precursors squalene, cholestenol, desmosterol and lathosterol (markers of cholesterol synthesis) and cholestanol and plant sterols (markers of cholesterol absorption), and absorption efficacy and absolute synthesis of cholesterol were studied at baseline and during 6-month atorvastatin (80 mg day⁻¹) treatment by the sterol balance technique in men with type 2 diabetes.

Results  At baseline, approximately 14% of serum squalene was transported by VLDL, 12% by IDL, 40% by LDL and 30% by HDL. The respective values for the noncholesterol sterols were approximately 8, 4, 61 and 26%. The squalene to cholesterol ratios were highest in VLDL and IDL, those of cholestenol, desmosterol and absorption marker sterols were gradually higher, and that of lathosterol lower from VLDL to HDL. Atorvastatin reduced LDL cholesterol by approximately 50%, decreased the absolute cholesterol synthesis and turnover by approximately 40%, but increased significantly the fractional and mass absorption of cholesterol. In accordance with the fecal data, the ratios of the precursor sterols to cholesterol were reduced (−50%), but those of squalene (+48%) and the absorption sterols increased (e.g. 2·6-fold for sitosterol) similarly in each lipoprotein, but progressively from VLDL to HDL.

Conclusions  Effective lowering of LDL cholesterol by large dose of statin is associated with decreased synthesis and turnover of cholesterol and increased fractional and mass absorption of cholesterol. These changes are detectable by noncholesterol sterols in serum and in different lipoprotein fractions.