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Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

Eur J Clin Nutr. 2003 Dec;57(12):1579-85. doi: 10.1038/sj.ejcn.1601727.

Abstract

Objective: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine.

Design: A randomized crossover dietary intervention.

Subjects and interventions: In all, 15 healthy volunteers (age 23+/-1.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time=-24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t=-9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t=-1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t=0, a permeability test was performed.

Results: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio=0.036; 0.014-0.092, P<0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P=0.3).

Conclusion: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders.

Sponsorship: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / antagonists & inhibitors
  • Cross-Over Studies
  • Double-Blind Method
  • Duodenum / drug effects
  • Duodenum / metabolism
  • Gastric Mucosa / metabolism
  • Gastrointestinal Diseases / chemically induced
  • Gastrointestinal Diseases / prevention & control*
  • Humans
  • Indomethacin / adverse effects*
  • Indomethacin / antagonists & inhibitors
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Lactoferrin / administration & dosage*
  • Lactulose / urine
  • Male
  • Permeability / drug effects
  • Recombinant Proteins / administration & dosage
  • Rhamnose / urine
  • Stomach / drug effects
  • Sucrose / urine

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Recombinant Proteins
  • Lactulose
  • Sucrose
  • Lactoferrin
  • Rhamnose
  • Indomethacin