Limits for the use of (18O)cholesterol and (18O)sitosterol in studies of cholesterol metabolism in humans.
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.
Hudgins
L C
LC
Rockefeller University, New York, New York 10021.
Parker
T S
TS
McNamara
D J
DJ
Bencsath
F A
FA
Field
F H
FH
D002784:Cholesterol / Q000378:metabolism*; D005243:Feces / Q000032:analysis*; D005260:Female; D008297:Male; D010103:Oxygen Isotopes; D012855:Sitosterols / Q000378:metabolism*
D010103:Oxygen Isotopes; D012855:Sitosterols; D002784:Cholesterol