Aktuelle Ernährungsmedizin 2020; 45(01): 40-52
DOI: 10.1055/a-1006-5952
CME-Fortbildung
© Georg Thieme Verlag KG Stuttgart · New York

Glutamin in der Ernährungstherapie – Welche Indikation bleibt?

Glutamin for Nutrition Support – Any Recommendations Left?
Mathias Plauth

Subject Editor: Wissenschaftlich verantwortlich gemäß Zertifizierungsbestimmungen für diesen Beitrag ist Prof. Dr. med. Mathias Plauth, Dessau.
Further Information

Publication History

Publication Date:
19 February 2020 (online)

Die nichtessenzielle Aminosäure Glutamin ist ein unverzichtbares Substrat für alle rasch proliferierenden Zellen und Bestandteil in enteralen Nahrungen, während die konventionellen Aminosäurenlösungen der parenteralen Ernährung aus galenischen Gründen kein Glutamin enthalten. Der anfängliche Enthusiasmus für das Behandlungskonzept einer Glutamin-Supplementierung, insbesondere der parenteralen Ernährung, ist inzwischen einer nüchternen Betrachtung gewichen.

Abstract

Glutamine, a non-essential amino acid, is an indispensable substrate for all rapidly dividing cells. Enteral feeding solutions contain glutamine at approximately 5–6 g per liter while conventional amino acid solutions for parenteral nutrition do not contain any glutamine for pharmaceutical reasons. In critically ill patients, an association between subnormal plasma levels of glutamine and increased morbidity and mortality was noted and led to the concept of glutamine as a conditionally essential amino acid. Accordingly, supplementing glutamine, particularly in total parenteral nutrition, was expected to improve clinical outcome. The initial enthusiasm for this therapeutic concept, however, has waned and given way for a sobering view questioning the concept of glutamine as a conditionally essential amino acid and the resulting indication to supplement. Currently, the supplementation of glutamine can be considered only in critically ill patients without multi-organ failure who need to be managed on total parenteral nutrition exclusively for more than five days.

Kernaussagen
  • Glutamin ist ein unabdingbares Substrat für alle rasch proliferierenden Zellen.

  • Der Körper hat eine große Kapazität zur endogenen Glutaminsynthese.

  • Die Handlungsrelevanz subnormaler Glutaminspiegel bei schwerer Krankheit ist weiterhin unklar.

  • Die Datenlage zur klinischen Wirksamkeit bei operierten Patienten, bei onkologischen Patienten, bei Patienten mit Darmerkrankungen und in der Ernährung von Sportlern erlaubt keine Empfehlung einer Glutaminsupplementierung.

  • Der Einsatz von Glutamin-Dipeptiden kann bei länger als 5 Tage ausschließlich parenteral ernährten kritisch Kranken ohne Mehrorganversagen erwogen werden.

 
  • Literatur

  • 1 Weimann A, Braga M, Carli F. et al. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr 2017; 36: 623-650
  • 2 Elke G, Hartl WH, Kreymann G. et al. Klinische Ernährung in der Intensivmedizin. S2k-Leitlinie (AWMF-Registernummer 073-004) der Deutschen Gesellschaft für Ernährungsmedizin (DGEM) in Zusammenarbeit mit der DIVI, der DGAI, der DGCH, der DGIIN, der DGK, der DGTHG und der DSG. Aktuel Ernahrungsmed 2018; 43: 341-408
  • 3 Singer P, Blaser AR, Berger MM. et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr 2019; 38: 48-79
  • 4 Lamprecht G, Pape U-F, Witte M. et al. und das DGEM Steering Committee. S3-Leitlinie der Deutschen Gesellschaft für Ernährungsmedizin e. V. in Zusammenarbeit mit der AKE, der GESKES und der DGVS Klinische Ernährung in der Gastroenterologie (Teil 3) – Chronisches Darmversagen. Aktuel Ernahrungsmed 2014; 39: e57-e71
  • 5 Bischoff SC, Koletzko B, Lochs H. et al. und das DGEM Steering Committee. S3-Leitlinie der Deutschen Gesellschaft für Ernährungsmedizin (DGEM) in Zusammenarbeit mit GESKES, der AKE und der DGVS. Klinische Ernährung in der Gastroenterologie (Teil 4) – Chronisch-entzündliche Darmerkrankungen. Aktuel Ernahrungsmed 2014; 39: e72-e98
  • 6 Forbes A, Escher J, Hébuterne X. et al. ESPEN guideline: Clinical nutrition in inflammatory bowel disease. Clin Nutr 2017; 36: 321-347
  • 7 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Supportive Therapie bei onkologischen PatientInnen – Langversion 1.1. 2017. AWMF Registernummer: 032/054OL, http://leitlinienprogramm-onkologie.de/Supportive-Therapie.95.0.html (Zugriff am 21.07.2019)
  • 8 Jordan K, Feyer P, Höller U. et al. Clinical practice guideline: Supportive treatments for patients with cancer. Dtsch Arztebl Int 2017; 114: 481-487
  • 9 Cruzat V, Rogero MM, Keane KN. et al. Glutamin: metabolism and immune function, supplementation and clinical translation. Nutrients 2018; 10: 1564
  • 10 van Acker BA, Hulsewe KW, Wagenmakers AJ. et al. Glutamine appearance rate in plasma is not increased after gastrointestinal surgery in humans. J Nutr 2000; 130: 1566-1571
  • 11 Mori M, Rooyackers O, Smedberg M. et al. Endogenous glutamine production in critically ill patients: the effect of exogenous glutamine supplementation. Crit Care 2014; 18: R72
  • 12 Bergström J, Fürst P, Norée LO. et al. Intracelular free amino acid concentration in human muscle tissue. J Appl Physiol 1974; 36: 693-696
  • 13 Stehle P, Fürst P. The occurrence of neurotoxic pyroglutamic acid in parenteral amino acid solutions. Specific determination by means of capillary isotachophoresis. Clin Chim Acta 1987; 169: 323-328
  • 14 Fürst P, Stehle P. Glutaminzufuhr in der parenteralen Ernährungstherapie. Aktuel Ernahrungsmed 1995; 20: 89-97
  • 15 Eagle H, Oyama VI, Levy M. et al. The Growth response of mammalian cells in tissue culture to l-glutamine and l-glutamic acid. J Biol Chem 1956; 218: 607-616
  • 16 Windmueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 1974; 249: 5070-5079
  • 17 Addae SK, Lotspeich WD. Relation between glutamine utilization and production in metabolic acidosis. Am J Physiol 1968; 215: 269-277
  • 18 Hanson PJ, Parsons DS. The utilization of glucose and production of lactate by in vitro preparations of rat small intestine: effects of vascular perfusion. J Physiol 1976; 255: 775-795
  • 19 Heitmann RN, Bergmann AE. Glutamine metabolism, inter-organ transport and glucogenicity in the sheep. Am J Physiol 1978; 234: E197-E203
  • 20 Felig P, Wahren J, Karl I. et al. Glutamine and glutamate metabolism in normal and diabetic subjects. Diabetes 1973; 22: 573-576
  • 21 Felig P, Wahren J, Räf L. Evidence of inter-organ amino acid transport by blood cells in humans. Proc Natl Acad Sci USA 1973; 70: 1775-1779
  • 22 Owen OE, Reichle FA, Mozzoli MA. et al. Hepatic, gut and renal substrate flux rates in patients with hepatic cirrhosis. J Clin Invest 1981; 68: 240-252
  • 23 Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract. J Parent Ent Nutr 1985; 9: 608-617
  • 24 Plauth M, Hartmann F. The role of the small intestine in intermediary metabolism. Metabolism of L-glutamine. Progress Pharmacol Clin Pharmacol 1989; 7: 99-117
  • 25 Windmueller HG, Spaeth AE. Intestinal metabolism of glutamine and glutamate from the lumen as compared to glutamine from blood. Arch Biophys Biochem 1975; 171: 662-672
  • 26 Windmueller HG, Spaeth AE. Identification of ketone bodies and glutamine as the respiratory fuels for postabsorptive rat small intestine. J Biol Chem 1978; 253: 69-76
  • 27 Windmueller HG, Spaeth AE. Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. Quantitative importance of glutamine, glutamate and aspartate. J Biol Chem 1980; 255: 107-112
  • 28 Newsholme EA, Crabtree B, Ardawi MSM. Glutamine metabolism in lymphocytes: Its biochemical physiological and clinical importance. Quart J Exp Physiol 1985; 70: 473-489
  • 29 Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Am J Physiol 1981; 241: E473-E480
  • 30 Van de Poll MCG, Siroen MPC, van Leeuwen PAM. et al. Interorgan amino acid exchange in humans: consequences for arginine and citrulline metabolism. Am J Clin Nutr 2007; 85: 167-172
  • 31 Van de Poll MCG, Ligthart-Melis GC, Boelens PG. et al. Intestinal and hepatic metabolism of glutamine and citrulline in humans. J Physiol 2007; 581: 819-827
  • 32 Ligthart-Melis GC, van de Poll MCG, Boelens PG. et al. Glutamine is an important precursor for de novo synthesis of arginine in humans. Am J Clin Nutr 2008; 87: 1282-1289
  • 33 Kao C, Hsu J, Bandi V. et al. Alterations in glutamine metabolism and its conversion to citrulline in sepsis. Am J Physiol Endocrinol Metab 2013; 304: E1359-E1364
  • 34 Ligthart-Melis GC, van de Poll MC, Dejong CH. et al. The route of administration (enteral or parenteral) affects the conversion of isotopically labeled L-[2-15N]glutamine into citrulline and arginine in humans. J Parenter Enteral Nutr 2007; 31: 343-348
  • 35 Ligthart-Melis GC, van de Poll MCG, Vermeulen MAR. et al. Enteral administration of alanyl-[2-15N]glutamine contributes more to the de novo synthesis of arginine than does intravenous infusion of the dipeptide in humans. Am J Clin Nutr 2009; 90: 95-105
  • 36 Vermeulen MAR, van de Poll MCG, Ligthart-Melis GC. et al. Specific amino acids in the critically ill patient – Exogenous glutamine/arginine: A common denominator?. Crit Care Med 2007; 35 (Suppl. 09) S568-S576
  • 37 Häussinger D, Gerok W, Sies H. Regulation of flux through glutaminase and glutamine synthetase in isolated perfused rat liver. Biochim Biophys Acta 1983; 755: 272-278
  • 38 Phromphetcharat V, Jackson A, Dass PD. et al. Ammonia partitioning between glutamine and urea: interorgan participation in metabolic acidosis. Kidney International 1981; 20: 598-605
  • 39 Häussinger D, Gerok W, Sies H. Hepatic role in pH regulation. Role of the intercellular glutamine cycle. Trends Biochem Sci 1984; 9: 300-302
  • 40 Weber FL, Veach GL. The importance of the small intestine in gut ammonium production in the fasting dog. Gastroenterology 1979; 77: 235-240
  • 41 Plauth M, Roske A-E, Romaniuk P. et al. Post-Feeding Hyperammonemia in Patients with Transjugular Intrahepatic Portosystemic Shunt and Liver Cirrhosis: Role of Small Intestinal Ammonia Release and Route of Nutrient Administration. Gut 2000; 46: 849-855
  • 42 Hayashi M, Ohnishi H, Kawade Y. et al. Augmented utilisation of branched-chain amino acids by skeletal muscle in decompensated cirrhosis in special relation to ammonia detoxification. Gastroenterol Japon 1981; 16: 64-70
  • 43 Plauth M, Egberts E-H, Abele R. et al. Characteristic pattern of free amino acids in plasma and skeletal muscle in stable hepatic cirrhosis. Hepato-Gastroenterol 1990; 37: 135-139
  • 44 Clemmesen JO, Kondrup J, Ott P. Splanchnic and leg exchange of amino acids and ammonia in acute liver failure. Gastroenterology 2000; 118: 1131-1139
  • 45 Kumar A, Davuluri G, Nascimento e Silva R. et al. Ammonia lowering reverses sarcopenia of cirrhosis by restoring skeletal muscle proteostasis. Hepatology 2017; 65: 2045-2058
  • 46 Plauth M, Raible A, Vieillard-Baron D. et al. Is glutamine essential for the maintenance of intestinal function? A study in the isolated perfused rat small intestine. Int J Colorect Dis 1999; 14: 86-94
  • 47 Vinnars E, Bergström J, Fürst P. Influence of postoperative state on the intracellular free amino acids in human muscle tissue. Ann Surg 1975; 182: 665-671
  • 48 Askanazi J, Fürst P, Michelsen CB. et al. Muscle and plasma amino acids after injury: hypocaloric glucose vs. amino acids after injury. Ann Surg 1980; 191: 465-472
  • 49 Fürst P. Peptides in parenteral nutrition. Clin Nutr 1985; 4: S105-S115
  • 50 Stehle P, Zander J, Mertes N. et al. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet 1989; 1: 231-233
  • 51 Hammarqvist F, Wernerman J, Ali R. et al. Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann Surg 1989; 209: 455-461
  • 52 Oudemans-van Straaten HM, Bosman RJ, Treskes M. et al. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 2001; 27: 84-90
  • 53 Rodas PC, Rooyackers O, Hebert C. et al. Glutamine and glutathione at ICU admission in relation to outcome. Clin Sci 2012; 122: 591-597
  • 54 Parry-Billings M, Evans J, Calder PC. et al. Does glutamine contribute to immunosuppression after major burns?. Lancet 1990; 336: 523-525
  • 55 Smedberg M, Wernerman J. Is the glutamine story over?. Crit Care 2016; 20: 361
  • 56 Schulman AS, Willcutts KF, Claridge JA. et al. Does the addition of glutamine to enteral feeds affect patient mortality?. Crit Care Med 2005; 33: 2501-2506
  • 57 Andrews PJD, Avenell A, Noble DW. et al. and the SIGNET Trials Group. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 2011; 342: d1542
  • 58 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: 1489-1497
  • 59 van den Berghe G. Low glutamine levels during critical illness – adaptive or maladaptive?. N Engl J Med 2013; 368: 1549-1550
  • 60 Gianotti L, Braga M, Biffi R. et al. Perioperative intravenous glutamine supplementation in major abdominal surgery for cancer: a randomized multi-center trial. Ann Surg 2009; 250: 684-690
  • 61 Ziegler TR, May AK, Hebbar G. et al. Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial. Ann Surg 2016; 263: 646-655
  • 62 van der Hulst RRW, van Kreel BK, von Meyenfeldt MF. et al. Glutamine and the preservation of gut integrity. Lancet 1993; 341: 1363-1365
  • 63 Tremel H, Kienle B, Weilemann LS. et al. Glutamine dipeptide-supplemented parenteral nutrition maintains intestinal function in the critically ill. Gastroenterol 1994; 107: 1595-1601
  • 64 Bakalar B, Duska F, Pachl J. et al. Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple-trauma patients. Crit Care Med 2006; 34: 381-386
  • 65 Déchelotte P, Hasselmann M, Cynober L. et al. L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med 2006; 34: 598-604
  • 66 Grau T, Bonet A, Minambres E. et al. The effect of L-alanyl-L-glutamine dipeptide supplemented total parenteral nutrition on infectious morbidity and insulin sensitivity in critically ill patients. Crit Care Med 2011; 39: 1263-1268
  • 67 Grintescu IM, Luca Vasiliu I, Cucereanu Badica I. et al. The influence of parenteral glutamine supplementation on glucose homeostasis in critically ill polytrauma patients – A randomized-controlled clinical study. Clin Nutr 2015; 34: 377-382
  • 68 Wischmeyer PE, Lynch J, Liedel J. et al. Glutamine administration reduces Gram-negative bacteremia in severely burned patients: a prospective, randomized, double-blind trial versus isonitrogenous control. Crit Care Med 2001; 29: 2075-2080
  • 69 Fuentes-Orozco C, Anaya-Prado R, Gonzalez-Ojeda A. et al. L-Alanyl-L-glutamine-supplemented parenteral nutrition improves infectious morbidity in secondary peritonitis. Clin Nutr 2004; 23: 13-21
  • 70 Fuentes-Orozco C, Cervantes-Guevara G, Muciño-Hernández I. et al. l-Alanyl-l-Glutamine-supplemented parenteral nutrition decreases infectious morbidity rate in patients with severe acute pancreatitis. J Parenter Enteral Nutr 2008; 32: 403-411
  • 71 Griffiths RD, Jones C, Palmer TEA. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 1997; 13: 295-302
  • 72 Goeters C, Wenn A, Mertes N. et al. Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Crit Care Med 2002; 30: 2032-2037
  • 73 Wernerman J, Kirketeig T, Andersson B. et al. Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients. Acta Anaesthesiol Scand 2011; 55: 812-818
  • 74 Griffiths RD, Andrews F. Glutamine: a life-threatening deficiency in the critically ill?. Intensive Care Med 2001; 27: 12-15
  • 75 Novak F, Heyland DK, Avenell A. et al. Glutamine supplementation in serious illness: a systematic review of the evidence. Crit Care Med 2002; 30: 2022-2029
  • 76 Canadian Critical Care Clinical Practice Guidelines Committee. Nutritional support in mechanically ventilated critically ill adult patients. 2009. update, available via http://www.criticalcarenutrition.com/index.php?option1⁄4com_content&task1⁄4view&id1⁄417&Itemid1⁄440 [accessed September 2009]
  • 77 Singer P, Berger MM, van den Berghe G. et al. ESPEN Guidelines on Parenteral Nutrition: Intensive care. Clin Nutr 2009; 28: 387-400
  • 78 Kreymann G, Adolph M, Druml W. et al. Leitlinie Parenterale Ernährung der DGEM. Intensivmedizin. Aktuel Ernahrungsmed 2007; 32: S89-S92
  • 79 Heyland DK, Elke G, Cook D. et al. Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient: a post hoc analysis of a large-scale randomized trial. J Parenter Enteral Nutr 2015; 39: 401-409
  • 80 Preiser J-C, Wernerman J. REDOXs: Important answers, many more questions raised!. J Paent Ent Nutr 2013; 37: 566-567
  • 81 Wernerman J. Glutamine supplementation to critically ill patients?. Crit Care 2014; 18: 214
  • 82 Bollhalder L, Pfeil AM, Tomonaga Y. et al. A systematic literature review and meta-analysis of randomized clinical trials of parenteral glutamine supplementation. Clin Nutr 2013; 32: 213-223
  • 83 Wischmeyer PE, Dhaliwal R, McCall M. et al. Parenteral glutamine supplementation in critical illness: a systematic review. Crit Care 2014; 18: R76
  • 84 Stehle P, Ellger B, Kojic D. et al. Glutamine dipeptide-supplemented parenteral nutrition improves the clinical outcomes of critically ill patients: A systematic evaluation of randomised controlled trials. Clin Nutr ESPEN 2017; 17: 75-85
  • 85 van Zanten ARH, Elke G. Parenteral glutamine should not be routinely used in adult critically ill patients. Clin Nutr 2017; 36: 1184-1185
  • 86 McRae MP. Therapeutic benefits of glutamine: An umbrella review of meta-analyses. Biomed Rep 2017; 6: 576-584
  • 87 Tao KM, Li XQ, Yang LQ. et al. Glutamine supplementation for critically ill adults. Cochrane Database Syst Rev 2014 Sep 9.9:CD010050. [PubMed: 25199493]
  • 88 van Zanten AR, Dhaliwal R, Garrel D. et al. Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis. Crit Care 2015; 19: 294
  • 89 van Zanten AR, Sztark F, Kaisers UX. et al. High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high protein enteral nutrition and nosocomial infections in the ICU: a randomized clinical trial. JAMA 2014; 312: 514-524
  • 90 Beale RJ, Sherry T, Lei K. et al. Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: outcome of a randomized, controlled, double-blind trial. Crit Care Med 2008; 36: 131-144
  • 91 Beaugerie L, Carbonnel F, Hecketsweiler B. et al. Effects of an isotonic oral rehydration solution, enriched with glutamine, on fluid and sodium absorption in patients with short-bowel syndrome. Aliment Pharmacol Ther 1997; 11: 741-746
  • 92 Scolapio JS. Effect of growth hormone, glutamine, and diet on body composition in short bowel syndrome: A randomized, controlled study. J Parenter Enter Nutr 1999; 23: 309-313
  • 93 Szkudlarek J, Jeppesen P, Mortensen P. Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: A randomised, double blind, crossover, placebo controlled study. Gut 2000; 47: 199-205
  • 94 Scolapio J, McGreevy K, Tennyson G. et al. Effect of glutamine in short-bowel syndrome. Clin Nutr 2001; 20: 319-323
  • 95 van Gossum A, Cabrè E, Hébuterne X. et al. ESPEN Guidelines on Parenteral Nutrition: Gastroenterology. Clin Nutr 2009; 28: 415-427
  • 96 Akobeng AK, Miller V, Stanton J. et al. Double-blind randomized controlled trial of glutamine-enriched polymeric diet in the treatment of active Crohn’s disease. J Pediatr Gastroenterol Nutr 2000; 30: 78-84
  • 97 Den Hond E, Hiele M, Peeters M. et al. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn’s disease. JPEN J Parenter Enteral Nutr 1999; 23: 7-11
  • 98 Benjamin J, Makharia G, Ahuja V. et al. Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn’s disease: A randomized controlled trial. Dig Dis Sci 2012; 57: 1000-1012
  • 99 Ziegler TR, Young LA, Benfell K. et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. Ann Intern Med 1992; 116: 821-828
  • 100 Schloerb P, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study). J Parenter Enteral Nutr 1993; 17: 407-413
  • 101 van Zaanen HCT, van der Lelie H, Timmer JG. et al. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 1994; 74: 2879-2884
  • 102 Pytlík R, Beneš P, Patorková M. et al. Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo-controlled study. Bone Marrow Transplant 2002; 30: 953-961
  • 103 Sayles C, Hickerson SC, Bhat RR. et al. Oral glutamine in preventing treatment-related mucositis in adult patients with cancer: A systematic review. Nutr Clin Pract 2016; 31: 171-179
  • 104 Jebb SA, Osborne RJ, Maughn TS. 5-Fluorouracil and folinic acid-linduced mucositis: no effect of glutamine supplementation. Br J Cancer 1994; 70: 732-735
  • 105 Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998; 83: 1433-1439
  • 106 Anderson PM, Ramsay NK, Shu XO. et al. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant 1998; 22: 339-344
  • 107 Daniele B, Perrone F, Gallo C. et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: A double blind, placebo controlled, randomised trial. Gut 2001; 48: 28-33
  • 108 Bowen JM, Gibson RJ, Coller JK. et al. Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines. Support Care Cancer 2019; Jul 8, [Epub ahead of print] DOI: 10.1007/s00520-019-04892-0.
  • 109 Cruzat VF, Krause M, Newsholme P. Amino acid supplementation and impact on immune function in the context of exercise. J Int Soc Sports Nutr 2014; 11: 61
  • 110 Gleeson M, Nieman DC, Pedersen BK. Exercise, nutrition and immune function. J Sports Sci 2004; 22: 115-125
  • 111 Castell LM, Poortmans JR, Leclercq R. et al. Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation. Eur J Appl Physiol Occup Physiol 1996; 75: 47-53
  • 112 Parry-Billings M, Budgett R, Koutedakis Y. et al. Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system. Med Sci Sports Exerc 1992; 24: 1353-1358
  • 113 Hiscock N, Pedersen BK. Exercise-induced immunodepression – plasma glutamine is not the link. J Appl Physiol 2002; 93: 813-822
  • 114 Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition 1997; 13: 738-742
  • 115 Krzywkowski K, Petersen EW, Ostrowski K. et al. Effect of glutamine supplementation on exercise-induced changes in lymphocyte function. Am J Physiol Cell Physiol 2001; 281: C1259-C1265
  • 116 Gleeson M. Dosing and efficacy of glutamine supplementation in human exercise and sport training. J Nutr 2008; 138: 2045S-2049S
  • 117 Walsh NP, Gleeson M, Pyne DB. et al. Position statement. Part two: maintaining immune health. Exerc Immunol Rev 2011; 17: 64-103