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Effect of replacement therapy with cholylsarcosine on fat malabsorption associated with severe bile acid malabsorption

Studies in dogs with ileal resection

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Abstract

The efficacy of cholylsarcosine, a synthetic deconjugation-resistant and nonsecretory conjugated bile acid analog for the treatment of fat malabsorption caused by severe bile acid malabsorption, was assessed in an animal model. In two dogs, the ileum and ileocecal valve were resected, causing severe diarrhea, steatorrhea, bile acid malabsorption, and progressive weight loss. Cholylsarcosine was administered as the water-soluble sodium salt by mixing with the dog food. Various doses were explored as well as varying intakes of dog food. Fat absorption was assessed by gravimetric measurement of fecal fat; a nonabsorbable recovery marker (polyethylene glycol mol wt 4000) was used to correct for incomplete fecal collections. Cholylsarcosine caused a 5- to 30-fold increase in fat absorption but had no significant effect on weight loss or fecal weight. Duodenal content was collected during digestion of a meal via a surgically placed Thomas cannula; the aspirates were dilute, acidic, and had a low bile acid concentration. The bile acid concentration increased modestly when cholylsarcosine was administered, but remained below the critical micellization concentration. The results indicate that oral administration of cholylsarcosine improved dietary fat absorption in a canine model of severe bile acid malabsorption with associated steatorrhea and bile acid deficiency in the proximal small intestine. Studies with this compound in patients with nutritional problems because of steatorrhea and severe bile acid malabsorption appear warranted.

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Author information

Author notes

  1. Claudio D. Schteingart PhD, Oliver Esch MD & Alan F. Hofmann MD, PhD

    Present address: Division of Gastroenterology, Department of Medicine, University of California at San Diego, 9500 Gilman Drive, 92093, La Jolla, California

  2. Sarah J. Longmire-Cook MD (Brohm Travelling Scholar)

    Present address: Department of Surgery, University of Louisville, Louisville, Kentucky

  3. Jan Lillienau PhD (Visiting postdoctoral fellow)

    Present address: Swedish Medical Research Council, Sweden

  4. Young Soo Kim MD

    Present address: Department of Physiological Chemistry, University of Lund, Box 94, S-221 00, Lund, Sweden

  5. Rudy G. Danzinger MD

    Present address: Department of Internal Medicine, Chung-Ang University Hospital, 100-272, Seoul, Korea

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, University of California at San Diego, 9500 Gilman Drive, 92093, La Jolla, California

    Sarah J. Longmire-Cook MD (Brohm Travelling Scholar),  Jan Lillienau PhD (Visiting postdoctoral fellow),  Young Soo Kim MD & Rudy G. Danzinger MD

Authors
  1. Sarah J. Longmire-Cook MD
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  2. Jan Lillienau PhD
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  6. Oliver Esch MD
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  7. Alan F. Hofmann MD, PhD
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Additional information

This work was supported in part by NIH grants DK21506 and DK32130, as well as grants-in-aid from the Price Fund for Surgical Research, Lithox Systems, Inc., Salem, Massachusetts; Falk Foundation e.V., Freiburg, Germany; Burroughs Wellcome Co., Research Triangle Park, North Carolina.

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Longmire-Cook, S.J., Lillienau, J., Kim, Y.S. et al. Effect of replacement therapy with cholylsarcosine on fat malabsorption associated with severe bile acid malabsorption. Digest Dis Sci 37, 1217–1227 (1992). https://doi.org/10.1007/BF01296563

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  • DOI: https://doi.org/10.1007/BF01296563

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