Postprandial vitamin A and squalene clearances and cholesterol synthesis off and on lovastatin treatment in type III hyperlipoproteinemia.
Postprandial fat clearance and absorption, fecal elimination and synthesis of cholesterol, bile acid synthesis, and cholesterol precursors and plant sterols in serum were studied in five patients with type III dyslipoproteinemia off and on lovastatin. The basal values were related to those in nontreated normolipidemic control subjects with apolipoprotein E3/3 phenotype (apo E3 controls, n = 16). On regular home diets, cholesterol precursor concentrations and cholesterol precursor/cholesterol ratios were high in the type III group. However, cholesterol absorption efficiency, bile acid and cholesterol synthesis measured with sterol balance technique and the precursor sterol/plant sterol ratios in serum were similar to the control values, suggesting that cholesterol absorption and metabolism was normal in these subjects. Lovastatin normalized the increased lipoprotein concentrations and reduced biliary cholesterol secretion, absolute absorption of cholesterol, precursor sterol/cholesterol and precursor sterol/plant sterol ratios in serum, fecal neutral and total sterol outputs and cholesterol synthesis. Lovastatin had no effect on cholesterol absorption efficiency or bile acid synthesis. Despite normalization of the triglyceride-rich lipoprotein levels by lovastatin, the postprandial vitamin A and squalene peak concentrations and the areas under the curves remained above the control ranges. The findings show that in type III hyperlipidemia, the precursor sterol/cholesterol ratios do not predict cholesterol synthesis. The latter, bile acid synthesis, precursor sterol/plant sterol ratios in serum, and cholesterol absorption are normal under basal conditions. The normalization of increased lipids by lovastatin is mainly due to reduced synthesis and absolute absorption of cholesterol, while the retarded postprandial fat clearance was not normalized by the drug.
Gylling
H
H
Department of Medicine, University of Helsinki, Finland.
Relas
H
H
Miettinen
T A
TA
D000328:Adult; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D002791:Cholesterol, Dietary; D015331:Cohort Studies; D004041:Dietary Fats; D004435:Eating; D005260:Female; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood*; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010641:Phenotype; D012016:Reference Values; D013185:Squalene / Q000097:blood*; D013261:Sterols / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000097:blood*
D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008074:Lipoproteins; D013261:Sterols; D014280:Triglycerides; D014801:Vitamin A; D013185:Squalene; D002784:Cholesterol; D008148:Lovastatin