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Journal of Lipid Research, Vol 36, 1763-1773, Copyright © 1995 by Lipid Research, Inc.
D Lutjohann, I Bjorkhem, UF Beil and K von Bergmann
Absorption of dietary cholesterol, campesterol, and sitosterol, cholesterol
balance, and fecal excretion of plant sterols were determined in three
unrelated patients with phytosterolemia and three healthy volunteers during
constant intake of cholesterol and plant sterols using accurate gas-liquid
chromatography-mass spectrometry techniques. Each subject received a
mixture of [26,26,26,27,27,27- 2H6]cholesterol, [6,7,7-2H3]sitostanol, and
[6,7,7-2H3]campesterol together with two non-absorbable markers,
[5,6,22,23-2H4]sitostanol and chromic oxide. Feces were collected from days
5 to 7 and absorption of different sterols was calculated from the
intestinal disappearance of the different sterols relative to
[5,6,22,23-2H4]sitostanol and chromic oxide. The results obtained by the
two markers were not different and the absorption of cholesterol averaged
53 +/- 4% for the patients (mean +/- SD) and 43 +/- 3% for the volunteers.
Campesterol absorption averaged 24 +/- 4% in patients and 16 +/- 3% in
healthy volunteers, whereas sitosterol absorption averaged 16 +/- 1% and 5
+/- 1%, respectively. Cholesterol synthesis expressed by body weight varied
considerably in the two groups but appeared to be about 5 times lower in
patients than in controls. Administration of a high dose of sitostanol (0.5
g t.i.d.) to two patients was followed by a reduction in cholesterol
absorption by 24% and 44%, an increase in fecal output of cholesterol and
steroids derived from cholesterol and plant steroids, and a marked
reduction of serum cholesterol, campesterol, and sitosterol. Under the
conditions used, inhibition of cholesterol absorption by sitostanol was not
followed by a significant rise in cholesterol synthesis. The time of
observation was, however, too short to allow final conclusion on this. The
results show that the absolute difference in absorption rate of different
sterols between the patients and healthy volunteers was about the same. As
a consequence, increasing hydrophobicity causes a relative decrease of
absorption rates. Thus, patients with phytosterolemia seem to have a
generally increased absorption of sterols rather than a loss of a specific
discriminatory mechanism, and oral administration of sitostanol seems to be
an interesting new approach for treatment of phytosterolemia.
ARTICLES
Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment
Department of Clinical Pharmacology, University of Bonn, Germany.
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