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Journal of Lipid Research, Vol. 44, 935-942, May 2003
Copyright © 2003 by Lipid Research, Inc.

Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans

Laura A. Woollett, Donna D. Buckley, Lihang Yao, Peter J. H. Jones^**, Norman A. Granholm, Elizabeth A. Tolley and James E. Heubi^1,*,

^* Division of Pediatric Gastroenterology/Hepatology and Nutrition, Children's Hospital Medical Center, Cincinnati, OH 45229
Department of Pediatrics, Clinical Research Center, Children's Hospital Medical Center, Cincinnati, OH 45229
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267
^** School of Dietetics, Human Nutrition, McGill University, Montreal, Quebec, Canada
University of Tennessee, Memphis, TN 38163

¹ To whom correspondence should be addressed. e-mail: james.heubi{at}chmcc.org

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.

Abbreviations: CRC, Clinical Research Center; FSR, fractional synthetic rate; IRMS, isotope ratio mass spectrometry; RBC, red blood cell; UDCA, ursodeoxycholic acid

Supplementary key words cholesterol synthesis • low density lipoprotein receptor • luminal contents • bile acid

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				L A Woollett, Y Wang, D D Buckley, L Yao, S Chin, N Granholm, P J H Jones, K D R Setchell, P Tso, and J E Heubi Micellar solubilisation of cholesterol is essential for absorption in humans Gut, February 1, 2006; 55(2): 197 - 204. [Abstract] [Full Text] [PDF]