Feedback regulation of bile acid synthesis measured by stable isotope kinetics in humans.
OBJECTIVE
To investigate the effect of a low dose of exogenous bile acids and a non-absorbable antibiotic on bile acid kinetics in healthy human subjects.


METHODS
Pool size, synthesis rate and fractional turnover rate of the three main bile acids were determined simultaneously with stable isotope labelled bile acids in volunteers before and during intake of 500 mg cholic acid (n = 6), chenodeoxycholic acid (n = 6) or deoxycholic acid (n = 5) per day for 4 weeks or 1 g of paromomycin (n = 6) per day for 2 weeks.


RESULTS
Administration of cholic acid nearly doubled the input and pool of deoxycholic acid; chenodeoxycholic acid synthesis was inhibited by 38% and pool size was reduced by 50%. Deoxycholic acid administration resulted in a suppression of both cholic acid and chenodeoxycholic acid synthesis by 53%; the corresponding pool sizes were reduced by 64% and 57%, respectively. The degree of suppression of chenodeoxycholic acid synthesis correlated significantly (P < 0.001) with the relative change of deoxycholic acid input and pool size. Oral chenodeoxycholic acid resulted in an inhibition of cholic acid synthesis (65%) and deoxycholic acid input (67%). The effects of the antibiotic were variable.


CONCLUSIONS
The suppressive effect of cholic acid may be mediated by deoxycholic acid, which is nearly as effective as chenodeoxycholate.
Department of Internal Medicine, Medical University of Lübeck, Germany.
G
G
Tauber
K
K
Empen
J
J
Scheibner
M
M
Fuchs
E F
EF
Stange
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D002635:Chenodeoxycholic Acid / Q000097:blood / Q000494:pharmacology; D002793:Cholic Acids / Q000097:blood / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000097:blood / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D010303:Paromomycin / Q000494:pharmacology; D012044:Regression Analysis; D018709:Statistics, Nonparametric
D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D002793:Cholic Acids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D010303:Paromomycin