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


METHODS
A randomized crossover dietary intervention.


METHODS
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).


CONCLUSIONS
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.


BACKGROUND
Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.
Troost
F J
FJ
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands. f.troost@hb.unimaas.nl
Saris
W H M
WH
Brummer
R-J M
RJ
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage*; D007792:Lactulose / Q000652:urine; D008297:Male; D010539:Permeability / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012210:Rhamnose / Q000652:urine; D013270:Stomach / Q000187:drug effects; D013395:Sucrose / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011994:Recombinant Proteins; D007792:Lactulose; D013395:Sucrose; D007781:Lactoferrin; D012210:Rhamnose; D007213:Indomethacin