title: Limits for the use of (18O)cholesterol and (18O)sitosterol in studies of cholesterol metabolism in humans.
abstract: The present study was undertaken in order to determine whether 18O-labeled sterols could be used in place of 14C-sterols in clinical studies of cholesterol metabolism. (3 beta-18OH)Cholesterol and (3 beta-18OH)sitosterol were simply and inexpensively synthesized and precisely and accurately quantified by gas chromatography/mass spectrometry. 18O-Sterols added to fecal homogenate and saponified were completely recovered. However, in a series of validation studies in humans, the fecal recoveries of orally administered (18O)cholesterol and (18O)sitosterol were significantly lower than the recoveries of 14C-sterols given simultaneously. We found that the losses were largely limited to the coprostanol and ethylcoprostanol fecal metabolites. In vitro fecal incubations of 18O-sterols and unlabeled water or of unlabeled sterols with H2(18)O indicated that the losses occurred during fecal bacterial metabolism and were likely due to 3 beta-oxygen exchange with the oxygen of water, possibly via a 3-ketosteroid intermediate. These data indicate that (18O)cholesterol and (18O)sitosterol are invalid tracers for the measurement of human cholesterol metabolism by methods based on fecal sterol recovery.
authors.affiliation: Rockefeller University, New York, New York 10021.
authors.forename: L C
authors.initials: LC
authors.lastname: Hudgins
authors.forename: T S
authors.initials: TS
authors.lastname: Parker
authors.forename: D J
authors.initials: DJ
authors.lastname: McNamara
authors.forename: F A
authors.initials: FA
authors.lastname: Bencsath
authors.forename: F H
authors.initials: FH
authors.lastname: Field
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D005243:Feces / Q000032:analysis*; D005260:Female; D008297:Male; D010103:Oxygen Isotopes; D012855:Sitosterols / Q000378:metabolism*
chemical_list: D010103:Oxygen Isotopes; D012855:Sitosterols; D002784:Cholesterol