Does ursodeoxycholic acid change the proliferation of the colorectal mucosa?. A randomized, placebo-controlled study.
BACKGROUND
In animal models ursodeoxycholic acid (UDCA) showed a chemoprotective effect against colon cancer. To explain this, a reduced proliferation of the colorectal mucosal proliferation was suggested. We, therefore, examined the influence of UDCA on the proliferation of normal colorectal mucosa in humans.


METHODS
Following endoscopic polypectomy, 20 patients with colorectal adenomas were randomized to receive either UDCA (750 mg/day, n = 10, group A) or placebo (n = 10, group B) for 6 months in a double-blinded way. Colorectal biopsies were sampled before and at the end of the medication by total colonoscopy. Colorectal mucosal proliferation was measured by FACScan analysis of propidium iodine labeling. Serum was sampled, and serum bile acids were analyzed by gas chromatography.


RESULTS
The proliferation rates at the end of the study were similar in both groups (median 15.4%; range 12.0-20.9 in group A; median 16.0%, 14.0-20.2 in group B, p = 0.41). Serum lithocholic acid levels at the end of the study were significantly higher in group A (1.3 micromol/l, 0.9-1.8) than in group B (0.7 micromol/l, 0-1.7, p < 0.02), whereas serum deoxycholic acid levels were similar in both groups.


CONCLUSIONS
In this study, UDCA treatment for 6 months does not seem to induce changes in the proliferative behavior of the colorectal mucosa in patients with adenomas. It seems likely that a putative chemopreventive effect of UDCA in humans is not exerted by a reduction of the colorectal proliferation.
Ochsenkühn
Thomas
T
Department of Medicine II, Klinikum Grosshadern, Munich, Germany. ochsenkuehn@med2.med.uni-muenchen.de
Marsteller
Igor
I
Hay
Ulrich
U
Diebold
Joachim
J
Paumgartner
Gustav
G
Göke
Burkhard
B
Sackmann
Michael
M
D000236:Adenoma / Q000503:physiopathology / Q000517:prevention & control*; D000368:Aged; D002455:Cell Division / Q000187:drug effects*; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000503:physiopathology / Q000517:prevention & control*; D004311:Double-Blind Method; D016099:Endoscopy, Gastrointestinal; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012007:Rectum / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D010919:Placebos; D014580:Ursodeoxycholic Acid