Effect of the route of nutrition and l-alanyl-l-glutamine supplementation in amino acids’ concentration in trauma patients

  • J. M. Raurich
  • J. A. Llompart-Pou
  • A. García-de-Lorenzo
  • A. Buño Soto
  • P. Marsé
  • G. Frontera
  • J. Pérez-Bárcena
Original Article



Our purpose was to assess the amino acids’ (AAs) profile in trauma patients and to assess the effect of the route of nutrition and the exogenous ALA-GLN dipeptide supplementation on plasma AAs’ concentration.


This is a secondary analysis of a previous randomized controlled trial. On day 1 and day 6 after trauma, plasma concentration of 25 AAs was measured using reverse phase high-performance liquid chromatography. Results were analyzed in relation to the route of nutrition and supplementation of ALA-GLN dipeptide. Differences between plasma AAs’ concentrations at day 1 and day 6 were evaluated using the Student’s t test or Mann–Whitney–Wilcoxon test. One-way ANOVA and the Kruskal–Wallis test were used to compare groups. A two-sided p value less than 0.05 was considered statistically significant.


Ninety-eight patients were analyzed. Mean plasma concentrations at day 1 were close to the lower normal level for most AAs. At day 6 we found an increase in the eight essential AAs’ concentrations and in 9 out of 17 measured non-essential AAs. At day 6 we found no differences in plasma concentrations for the sum of all AAs (p = .72), glutamine (p = .31) and arginine (p = .23) distributed by the route of nutrition. Administration of ALA-GLN dipeptide increased the plasma concentration of alanine (p = .004), glutamine (p < .001) and citrulline (p = .006).


We found an early depletion of plasma AAs’ concentration which partially recovered at day 6, which was unaffected by the route of nutrition. ALA-GLN dipeptide supplementation produced a small increase in plasma levels of glutamine and citrulline.


Amino acids Severe trauma Glutamine Nutrition 


Compliance with ethical standards

Conflict of interest

Llompart-Pou JA, Raurich JM, Buño Soto A, Frontera G, Pérez-Bárcena J declare no conflict of interest. García-de-Lorenzo A and Marsé P declare having received speaking honoraria from Fresenius Kabi.


The study was supported by a grant from the Ministerio de Sanidad y Consumo of Spain.


  1. 1.
    Dolp R, Fekl W, Ahnefeld W. Free amino acids in plasma in the post-traumatic period. Infusionsther Klin Ernahr. 1975;2:321–4.PubMedGoogle Scholar
  2. 2.
    Druml W, Heinzel G, Kleinberger G. Amino acid kinetics in patients with sepsis. Am J Clin Nutr. 2001;73:908–13.PubMedGoogle Scholar
  3. 3.
    Hirose T, Shimizu K, Ogura H, et al. Altered balance of the aminogram in patients with sepsis—the relation to mortality. Clin Nutr. 2014;33:179–82.CrossRefPubMedGoogle Scholar
  4. 4.
    Jeevanandam M, Young DH, Ramias L, Schiller WR. Aminoaciduria of severe trauma. Am J Clin Nutr. 1989;49:814–22.PubMedGoogle Scholar
  5. 5.
    Jimenez Jimenez FJ, Ortiz LC, Morales MS, Barros-Perez M, Munoz GJ, Herruzo AA. Variations in plasma amino acids in septic patients subjected to parenteral nutrition with a high proportion of branched-chain amino acids. Nutrition. 1992;8:237–44.PubMedGoogle Scholar
  6. 6.
    Parent BA, Seaton M, Sood RF, et al. Use of metabolomics to trend recovery and therapy after injury in critically Ill trauma patients. JAMA Surg. 2016;151:e160853.CrossRefPubMedGoogle Scholar
  7. 7.
    Su L, Li H, Xie A, et al. Dynamic changes in amino acid concentration profiles in patients with sepsis. PLoS One. 2015;10:e0121933.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wilmore DW, Goodwin CW, Aulick LH, Powanda MC, Mason AD Jr, Pruitt BA. Jr. Effect of injury and infection on visceral metabolism and circulation. Ann Surg. 1980;192:491–504.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Raurich JM, Ibanez J. Metabolic rate in severe head trauma. JPEN. 1994;18:521–4.CrossRefGoogle Scholar
  10. 10.
    Raubich JM, Ibanez J, Marse P, Velasco J, Bergada J. Energy expenditure in patients with multiple organ failure. Clin Nutr. 1997;16:307–12.CrossRefPubMedGoogle Scholar
  11. 11.
    Heyland DK, Dhaliwal R, Wang M, Day AG. The prevalence of iatrogenic underfeeding in the nutritionally ‘at-risk’ critically ill patient: results of an international, multicenter, prospective study. Clin Nutr. 2015;34:659–66.CrossRefPubMedGoogle Scholar
  12. 12.
    van Barneveld KW, Smeets BJ, Heesakkers FF, et al. Beneficial effects of early enteral nutrition after major rectal surgery: a possible role for conditionally essential amino acids? Results of a randomized clinical trial. Crit Care Med. 2016;44:e353-e361.Google Scholar
  13. 13.
    Vente JP, von Meyenfeldt MF, van Eijk HM, et al. Plasma-amino acid profiles in sepsis and stress. Ann Surg. 1989;209(1):57–62.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Boelens PG, Melis GC, van Leeuwen PA, ten Have GA, Deutz NE. Route of administration (enteral or parenteral) affects the contribution of l-glutamine to de novo l-arginine synthesis in mice: a stable-isotope study. Am J Physiol Endocrinol Metab. 2006;291:E683-E690.CrossRefGoogle Scholar
  15. 15.
    Ligthart-Melis GC, van de Poll MC, Dejong CH, Boelens PG, Deutz NE, van Leeuwen PA. The route of administration (enteral or parenteral) affects the conversion of isotopically labeled l-[2-15N]glutamine into citrulline and arginine in humans. JPEN. 2007;31:343–8.CrossRefGoogle Scholar
  16. 16.
    Cynober LA. Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance. Nutrition. 2002;18:761–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Boelens PG, van Leeuwen PA, Dejong CH, Deutz NE. Intestinal renal metabolism of l-citrulline and l-arginine following enteral or parenteral infusion of l-alanyl-l-[2,15N]glutamine or l-[2,15N]glutamine in mice. Am J Physiol Gastrointest Liver Physiol. 2005;289:G679-G685.Google Scholar
  18. 18.
    Buijs N, Brinkmann SJ, Oosterink JE, et al. Intravenous glutamine supplementation enhances renal de novo arginine synthesis in humans: a stable isotope study. Am J Clin Nutr. 2014;100:1385–91.CrossRefPubMedGoogle Scholar
  19. 19.
    Melis GC, Boelens PG, van der Sijp JR, et al. The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients. Br J Nutr. 2005;94:19–26.CrossRefPubMedGoogle Scholar
  20. 20.
    Murphy C, Newsholme P. Importance of glutamine metabolism in murine macrophages and human monocytes to l-arginine biosynthesis and rates of nitrite or urea production. Clin Sci (Lond). 1998;95:397–407.CrossRefGoogle Scholar
  21. 21.
    Newsholme P. Why is l-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J Nutr. 2001;131:2515S-2522S.Google Scholar
  22. 22.
    Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC. Regulation of T cell receptor CD3zeta chain expression by l-arginine. J Biol Chem. 2002;277:21123–9.CrossRefPubMedGoogle Scholar
  23. 23.
    Andrews PJ, Avenell A, Noble DW, et al. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ. 2011;342:d1542.CrossRefPubMedGoogle Scholar
  24. 24.
    Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013;368:1489–97.CrossRefPubMedGoogle Scholar
  25. 25.
    Perez-Barcena J, Marse P, Zabalegui-Perez A, et al. A randomized trial of intravenous glutamine supplementation in trauma ICU patients. Intensive Care Med. 2014;40:539–47.CrossRefPubMedGoogle Scholar
  26. 26.
    Blesa Malpica AL, Garcia DL, Robles GA. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: update. Consensus SEMICYUC-SENPE: multiple trauma patient. Nutr Hosp. 2011;26(Suppl 2):63–6.PubMedGoogle Scholar
  27. 27.
    Singer P, Berger MM, Van den Berghe G, et al. ESPEN guidelines on parenteral nutrition: intensive care. Clin Nutr. 2009;28:387–400.CrossRefPubMedGoogle Scholar
  28. 28.
    Sharma B, Lawrence DW, Hutchison MG. Branched chain amino acids (BCAAs) and traumatic brain injury: a systematic review. J Head Trauma Rehabil. 2017. doi: 10.1097/HTR.0000000000000280.PubMedGoogle Scholar
  29. 29.
    Fish J, Sporay G, Beyer K, et al. A prospective randomized study of glutamine-enriched parenteral compared with enteral feeding in postoperative patients. Am J Clin Nutr. 1997;65:977–83.PubMedGoogle Scholar
  30. 30.
    Peters JH, Beishuizen A, Keur MB, Dobrowolski L, Wierdsma NJ, van Bodegraven AA. Assessment of small bowel function in critical illness: potential role of citrulline metabolism. J Intensive Care Med. 2011;26:105–10.CrossRefPubMedGoogle Scholar
  31. 31.
    Piton G, Manzon C, Monnet E, et al. Plasma citrulline kinetics and prognostic value in critically ill patients. Intensive Care Med. 2010;36:702–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Bertolo RF, Burrin DG. Comparative aspects of tissue glutamine and proline metabolism. J Nutr. 2008;138(10):2032S-2039S.PubMedGoogle Scholar
  33. 33.
    van de Poll MC, Ligthart-Melis GC, Boelens PG, Deutz NE, van Leeuwen PA, Dejong CH. Intestinal and hepatic metabolism of glutamine and citrulline in humans. J Physiol. 2007;581:819–27.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Chiarla C, Giovannini I, Siegel JH. Plasma arginine correlations in trauma and sepsis. Amino Acids. 2006;30:81–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Kao C, Hsu J, Bandi V, Jahoor F. Alterations in glutamine metabolism and its conversion to citrulline in sepsis. Am J Physiol Endocrinol Metab. 2013;304:E1359-E1364.CrossRefPubMedCentralGoogle Scholar
  36. 36.
    Ochoa JB, Bernard AC, O’Brien WE, et al. Arginase I expression and activity in human mononuclear cells after injury. Ann Surg. 2001;233:393–9.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Vermeulen MA, Brinkmann SJ, Buijs N, et al. Enteral glutamine administration in critically ill nonseptic patients does not trigger arginine synthesis. J Nutr Metab. 2016;2016:1373060.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001;286:944–53.CrossRefPubMedGoogle Scholar
  39. 39.
    Luiking YC, Poeze M, Ramsay G, Deutz NE. Reduced citrulline production in sepsis is related to diminished de novo arginine and nitric oxide production. Am J Clin Nutr. 2009;89:142–52.CrossRefPubMedGoogle Scholar
  40. 40.
    Wierdsma NJ, Peters JH, Weijs PJ, et al. Malabsorption and nutritional balance in the ICU: fecal weight as a biomarker: a prospective observational pilot study. Crit Care. 2011;15:R264.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • J. M. Raurich
    • 1
  • J. A. Llompart-Pou
    • 1
    • 2
  • A. García-de-Lorenzo
    • 3
  • A. Buño Soto
    • 4
  • P. Marsé
    • 1
  • G. Frontera
    • 2
  • J. Pérez-Bárcena
    • 1
    • 2
  1. 1.Servei de Medicina IntensivaHospital Universitari Son EspasesPalma de MallorcaSpain
  2. 2.Instituto de Investigación Sanitaria de Palma (IdISPa)Palma de MallorcaSpain
  3. 3.Servicio de Medicina IntensivaHospital Universitario La Paz/Carlos III, IdiPAZMadridSpain
  4. 4.Laboratory Medicine DepartmentHospital Universitario La Paz/Carlos III, IdiPAZMadridSpain

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