Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans.
Qualitative and quantitative changes in intraluminal bile acid composition may alter cholesterol absorption and synthesis and LDL receptor expression. In a randomized crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day ursodeoxycholic acid (UDCA) or no bile acid supplement (control) for 20 days while being fed a controlled diet (AHA Step II). A liquid meal of defined composition was then given and luminal samples collected. Cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods. With UDCA treatment, bile was enriched significantly (P < 0.0001) to 40.6 +/- 2.6% (mean +/- SEM) compared with 2.2 +/- 2.6% for controls. Regardless, plasma total, HDL, and LDL cholesterol were unchanged with UDCA treatment. Intraluminal cholesterol solubilized in the aqueous phase during the entire collection was decreased (P = 0.012) in UDCA-treated subjects (101.0 +/- 7.2 mg/ml/120 min) compared with controls (132.5 +/- 7.2 mg/ml/120 min.). Percent micellar cholesterol was increased in UDCA-treated versus controls after meal ingestion. No changes were found in cholesterol absorption, FSR, or LDL receptor mRNA with UDCA treatment compared with controls. Thus, despite marked enrichment in luminal bile with UDCA and decreased cholesterol solubilization, no differences in cholesterol absorption or metabolism are found when diet and genetic differences in absorption are carefully controlled.
Woollett
Laura A
LA
Division of Pediatric Gastroenterology/Hepatology and Nutrition, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Buckley
Donna D
DD
Yao
Lihang
L
Jones
Peter J H
PJ
Granholm
Norman A
NA
Tolley
Elizabeth A
EA
Heubi
James E
JE
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000378:metabolism*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008823:Micelles; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008823:Micelles; D012333:RNA, Messenger; D011973:Receptors, LDL; D014580:Ursodeoxycholic Acid