N-Acetyl-l-Glutamine, A Liquid-Stable Source of Glutamine, Partially Prevents Changes in Body Weight and on Intestinal Immunity Induced by Protein Energy Malnutrition in Pigs

  • José M. López-Pedrosa
  • Manuel Manzano
  • Jeffrey H. Baxter
  • Ricardo Rueda
Original Paper


The goal of this study was to evaluate the preventive effect of free glutamine versus N-acetyl-l-glutamine, a liquid-stable source of glutamine, on gut damage induced by protein energy malnutrition in pigs. Healthy pigs (n=6) were fed a liquid formula for 30 days. Three subgroups of malnourished pigs (n=6) received daily 20% of the food intake recorded in control group, supplemented with calcium caseinate, glutamine, or N-acetyl-l-glutamine. Body weight was recorded, and small intestinal samples were evaluated for biochemical and immunologic parameters. Suppression in body weight gain was significantly lower in pigs fed with N-acetyl-l-glutamine than in the rest of malnourished pigs. Total number of lymphocytes, CD21+ B cells and CD4+ T cells in ileal Peyer patches were not significantly different in malnourished pigs fed with N-acetyl-l-glutamine and in healthy pigs. In conclusion, N-acetyl-l-glutamine has a moderate protective effect, partially preventing changes induced by protein energy malnutrition.


Glutamine N-acetyl-l-glutamine Pig Malnutrition Intestinal immunity 



The authors thank María Luisa Jiménez for her technical assistance, the Animal Nutrition Department of CSIC for providing animal facilities and, Mrs. Cristina Cazorla for editorial assistance.


  1. 1.
    Kelly D, Wischmeyer PE (2003) Role of L-glutamine in critical illness: new insights. Curr Opin Clin Nutr Metab Care 6:217–222PubMedCrossRefGoogle Scholar
  2. 2.
    Boelens PG, Nijveldt RJ, Houdijk AP, Meijer S, van Leeuwen PA (2001) Glutamine alimentation in catabolic state. J Nutr 131(9 Suppl):2569S–77SPubMedGoogle Scholar
  3. 3.
    Wilmore DW (2001) The effect of glutamine supplementation in patients following effective surgery and accidental injury. J Nutr 131(9 Suppl):2543S–2549SPubMedGoogle Scholar
  4. 4.
    Newsholme P (2001) Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J Nutr 131(9 Suppl):2515S–2522SPubMedGoogle Scholar
  5. 5.
    Coeffier M, Dechelotte P (2005) The role of glutamine in intensive care unit patients: mechanisms of action and clinical outcome. Nutr Rev 63:65–69PubMedCrossRefGoogle Scholar
  6. 6.
    Ziegler TR, Bazargan N, Leader LM, Martindale RG (2000) Glutamine and the gastrointestinal tract. Curr Opin Clin Nutr Metab Care 3:355–362PubMedCrossRefGoogle Scholar
  7. 7.
    Calder PC, Yaqoob P (1999) Glutamine and the immune system. Amino Acids 17:227–241PubMedCrossRefGoogle Scholar
  8. 8.
    Andrews FJ, Griffiths RD (2002) Glutamine: essential for immune nutrition in the critically ill. Br J Nutr 87(Suppl 1):S3–8PubMedCrossRefGoogle Scholar
  9. 9.
    Wilmore DW, Shabert JK (1998) Role of glutamine in immunologic response. Nutrition 14:618–626PubMedCrossRefGoogle Scholar
  10. 10.
    Melis GC, ter Wengel N, Boelens PG, van Leeuwen PA (2004) Glutamine: recent developments in research on the clinical significance of glutamine. Curr Opin Clin Nutr Metab Care 7:59–70PubMedCrossRefGoogle Scholar
  11. 11.
    Martensson J, Jain A, Meister A (1990) Glutathione is required for intestinal function. Proc Natl Acad Sci 87:1715–1719PubMedCrossRefGoogle Scholar
  12. 12.
    Brunser O, Araya M, Espinosa J (1991) Damage and repair of the small intestinal mucosa in diarrhea and malnutrition. In: Lebenthal E (ed) Textbook of gastroenterology and nutrition in infancy New York: Raven Press; pp 535–544Google Scholar
  13. 13.
    López-Pedrosa JM, Torres MI, Fernández MI, Ríos A, Gil A (1998) Severe malnutrition alters lipid composition and fatty acid profile of small intestine in newborn piglets. J Nutr 128:224–233PubMedGoogle Scholar
  14. 14.
    Furst P, Albers S, Stehle P (1990) Glutamine-containing dipeptides in parenteral nutrition. J Parenter Enteral Nutr 14(4 Suppl):118S–124SCrossRefGoogle Scholar
  15. 15.
    Furst P, Pogan K, Stehle P (1997) Glutamine dipeptides in clinical nutrition. Nutrition 13:731–737PubMedCrossRefGoogle Scholar
  16. 16.
    Furst P (2001) New developments in glutamine delivery. J Nutr 131(9 Suppl):2562S–2568SGoogle Scholar
  17. 17.
    Preiser JC, Peres-Bota D, Eisendrath P, Vincent JL, Van Gossum A (2003) Gut mucosal and plasma concentrations of glutamine: a comparison between two enriched enteral feeding solutions in critically ill patients. Nutr J 2:13PubMedCrossRefGoogle Scholar
  18. 18.
    Snowden MK, Baxter JH, Mamula Bergana M, Reyzer I, Pound V (2002) Stability of N-acetylglutamine and glutamine in aqueous solution and in a liquid nutritional product by an improved HPLC method. J Food Sci 67:384–389CrossRefGoogle Scholar
  19. 19.
    Arnaud A, Ramírez M, Baxter JH, Angulo AJ (2004) Absorption of enterally administered N-acetyl-L-glutamine versus glutamine in pigs. Clin Nutr 23:1303–1312PubMedCrossRefGoogle Scholar
  20. 20.
    Egorova VV, Egorova GG, Lasarenko LV, Timofeeva NM, Sherlakov (2001) Topography of digestive enzymes in the pigs small intestine at the early stages of ontogeny in the norm and pathology. In: Lindberg JE, Ogle B (eds) Digestive Physiology of Pigs New York: CABI Publishing, pp 49–51Google Scholar
  21. 21.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities utilizing the principle of protein-dye binding. Anan Biochem 72: 248–254CrossRefGoogle Scholar
  22. 22.
    Labarca C, Paigen K (1980) A simple, rapid and sensitive DNA assay procedure. Anal Biochem 102:344–354PubMedCrossRefGoogle Scholar
  23. 23.
    Carlberg I, Mannervick B (1985) Glutathione reductase. Methods Enzymol 113:485–495Google Scholar
  24. 24.
    Habig WH, Pabst MJ, Jakoby WB (1984) Glutathione-S-transferases, the first enzymatic step in mercapturie acid formation. J Biol Chem 294:7130–7139Google Scholar
  25. 25.
    Flohé L, Günzler WA (1985) Assays for glutathione peroxidase. Methods Enzymol 105:209–221Google Scholar
  26. 26.
    Anderson ME (1985) Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol 113:548–559PubMedGoogle Scholar
  27. 27.
    Nuñez MC, Bueno JD, Ayudarte MV, Almendros A, Rios A, Suarez MD, Gil A (1996) Dietary restriction induces biochemical and morphometric changes in the small intestine of nursing piglets. J Nutr 126:933–944PubMedGoogle Scholar
  28. 28.
    Gautreaux MD, Deitch EA, Berg RD (1994) T lymphocytes in host defense against bacterial translocation from the gastrointestinal tract. Infect Immun 62:2874–2884PubMedGoogle Scholar
  29. 29.
    Alpers DH (2002) Enteral feeding and gut atrophy. Curr Opin Clin Nutr Metab Care 5:679–683PubMedCrossRefGoogle Scholar
  30. 30.
    Hanna MK, Kudsk KA (2000) Nutritional and pharmacological enhancement of gut-associated lymphoid tissue. Can J Gastroenterol 14(Suppl D):145D–151DPubMedGoogle Scholar
  31. 31.
    Gramlich L, Kichian K, Pinilla J, Rodych NJ, Dhaliwal R, Heyland DK (2004) Does enteral nutrition compared to parenteral nutrition results in better outcomes in critically ill adult patients? A systematic review of the literature. Nutrition 20:843–848PubMedCrossRefGoogle Scholar
  32. 32.
    Neuhäuser-Berthold M, Wirth S, Hellmann U, Bässler KH (1988) Utilization of N-acetyl-L-glutamine during long-term parenteral nutrition in growing rats: significance of glutamine for weight and nitrogen balance. Clin Nutr 7:145–150CrossRefGoogle Scholar
  33. 33.
    Magnusson I, Kihlber R, Alvestrand A, Wernerman J, Ekman L, Wahren J (1989) Utilization of intravenously administered N-acetyl-L-glutamine in humans. Metabolism 38:82–88PubMedCrossRefGoogle Scholar
  34. 34.
    Cotgreave IA, Gerdes RG (1998) Recent trends in glutathione biochemistry-glutathione-protein interactions: a molecular link between oxidative stress and cell proliferation? Biochem Biophys Res Commun 242:1–9PubMedCrossRefGoogle Scholar
  35. 35.
    Aw TY (2003) Cellular redox: a modulator of intestinal epithelial cell proliferation. News Physiol Sci 18:201–203PubMedGoogle Scholar
  36. 36.
    Tsunada S, Iwakiri R, Noda T, Fujimoto K, Fuseler J, Rhoads CA, Aw TY (2003) Chronic exposure to subtoxic levels of peroxidized lipids suppresses mucosal cell turnover in rat small intestine and reversal by glutathione. Dig Dis Sci 48:210–222PubMedCrossRefGoogle Scholar
  37. 37.
    Li J, Kudsk KA, Janu P, Renegar KB (1997) Effect of glutamine-enriched total parenteral nutrition on small intestinal gut-associated lymphoid tissue and upper respiratory tract immunity. Surgery 121:542–549PubMedCrossRefGoogle Scholar
  38. 38.
    Li J, King BK, Janu PG, Renegar KB, Kudsk KA (1998) Glycil-L-glutamine-enriched total parenteral nutrition maintains small intestine gut-associated lymphoid tissue and upper respiratory tract immunity. J Parenter Enteral Nutr 22:31–36CrossRefGoogle Scholar
  39. 39.
    Kudsk KA, Wu Y, Fukatsu K, Zarzaur BL, Johnason CD, Wang R, Hanna MK (2000) Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels. J Parenter Enteral Nutr 24:270–274Google Scholar
  40. 40.
    Manhart N, Vierlinger K, Spittler A, Bergmeister H, Sautner T, Roth E (2001) Oral feeding with glutamine prevents lymphocyte and glutathion depletion of Peyer's patches in endotoxemic mice. Ann Surg 234:92–97PubMedCrossRefGoogle Scholar
  41. 41.
    Lai YN, Yeh SL, Lin MT, Shang HF, Yeh CL, Chen WJ (2004) Glutamine supplementation enhances mucosal immunity in rats with gut-derived sepsis. Nutrition 20:286–291PubMedCrossRefGoogle Scholar
  42. 42.
    Boza JJ, Maire JC, Bovetto L, Ballevre O (2000) Plasma glutamine response to enteral administration of L-glutamine in human volunteers (free glutamine versus protein-bound glutamine). Nutrition 16:1037–1042PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • José M. López-Pedrosa
    • 1
  • Manuel Manzano
    • 1
  • Jeffrey H. Baxter
    • 2
  • Ricardo Rueda
    • 1
  1. 1.Strategic R&DAbbott Nutrition International, Abbott LaboratoriesGranadaSpain
  2. 2.Strategic Research, Ross Products DivisionAbbott LaboratoriesColumbusUSA

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