Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment.
BACKGROUND
Serum contains noncholesterol sterols, which are reliable markers of cholesterol metabolism, but their presence and importance in different lipoproteins have been insufficiently studied.


METHODS
Serum and lipoprotein cholesterol precursors squalene, cholestanol, 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 cholestanol, 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.
Miettinen
T A
TA
University of Helsinki, Helsinki, Finland. tatu.a.miettinen@helsinki.fi
Gylling
H
H
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D005243:Feces / Q000737:chemistry; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D007408:Intestinal Absorption; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood; D011758:Pyrroles / Q000627:therapeutic use*; D013185:Squalene / Q000097:blood
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D008055:Lipids; D008074:Lipoproteins; D010840:Phytosterols; D011758:Pyrroles; D013185:Squalene; D002784:Cholesterol; D000069059:Atorvastatin