Sobre las propiedades y los usos de la glutamina en la citorreducción tumoral

María Belén Andrade Hernández, Marcela Alejandra Chaug Solórzano, Francisco Xavier Andino Hernández, Dolores Rodríguez Veintimilla

Texto completo:

PDF

Resumen

La glutamina (Gln) participa en numerosas funciones biológicas que recorren desde el mantenimiento de la homeostasis del nitrógeno (N) corporal hasta la inmunocompetencia y la respuesta a la agresión. La Gln ha sido reconocida como el aminoácido condicionalmente esencial más abundante de la economía. Las concentraciones séricas de Gln se depletan rápidamente durante la agresión, la injuria y la sepsis. La célula cancerosa actúa como una trampa de N, y le disputa a la célula sana la disponibilidad y el acceso a nutrientes, la Gln entre ellos. La depleción tisular de Gln pudiera afectar la efectividad de las distintas modalidades de la citorreducción tumoral (CRT). Se ha propuesto la suplementación exógena de Gln para paliar las concentraciones tisulares disminuidas del aminoácido, restablecer las funciones biológicas afectadas, y asegurar la efectividad de los esquemas citorreductores. La suplementación exógena de Gln también podría servir para promover el arraigo y la proliferación de las subpoblaciones leucocitarias de neutrófilos tras el trasplante de médula ósea (TMO). Una tercera aplicación de la suplementación exógena con Gln sería la paliación de la mucositis, la diarrea, y otros efectos colaterales de la CRT. Se podrían beneficiar de la suplementación exógena con Gln aquellos enfermos en los que se anticiparía la interrupción de la CRT debido a la pérdida experimentada de peso, la reducción de la masa magra corporal, y el riesgo incrementado de infección y sepsis. Las indicaciones de la suplementación exógena con Gln deben extenderse a las necesarias consideraciones econométricas sobre la inclusión de esta modalidad de apoyo nutricional en la CRT.

Palabras clave

Glutamina; Citorreducción tumoral; Cáncer; Cirugía; Trasplante de médula ósea; Quimioterapia; Radioterapia

Referencias

Newsholme P, Lima MMR, Procopio J, Pithon-Curi TC, Bazotte RB, Curi R. Glutamine and glutamate as vital metabolites. Braz J Med Biol Res 2003; 36:153-63.

Souba WW, Herskowitz K, Austgen TR, Chen MK, Salloum RM. Glutamine nutrition: Theoretical considerations and therapeutic impact. JPEN J Parenter Enter Nutr 1990;14(5 Suppl):S237-S243.

Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJI, Zandstra DF. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 2001;27:84-90.

Rodas PC, Rooyackers O, Hebert C, Norberg Å, Wernerman J. Glutamine and glutathione at ICU admission in relation to outcome. Clin Sci 2012;122:591-7.

Souba WW, Herskowitz K, Klimberg VS, Salloum RM, Plumley DA, Flynn TC, Copeland 3rd EM. The effects of sepsis and endotoxemia on gut glutamine metabolism. Ann Surg 1990;211:543-7.

Dudrick PS, Souba WW. Amino acids in surgical nutrition: Principles and practice. Surg Clin North Am 1991;71:459-76.

Coster J, McCauley R, Hall J. Glutamine: Metabolism and application in nutrition support. Asia Pac J Clin Nutr 2004;13:25-31.

Mertes N, Schulzki C, Goeters C, Winde G, Benzing S, Kuhn KS; et al. Cost containment through L-alanyl-L-glutamine supplemented total parenteral nutrition after major abdominal surgery: A prospective randomized double-blind controlled study. Clin Nutr 2000;19:395-401.

Dallas MJ, Bowling D, Roig JC, Auestad N, Neu J. Enteral glutamine supplementation for very‐low‐birth‐weight infants decreases hospital costs. JPEN J Parenter Enter Nutr 1998;22:352-6.

Bozzetti, F. Perioperative nutritional management. Proc Nutr Soc 2011;70:305-10 .

de Aguilar-Nascimento JE, Caporossi C, Dock-Nascimento DB, de Arruda IS, Moreno K. Oral glutamine in addition to parenteral nutrition improves mortality and the healing of high-output intestinal fistulas. Nutrición Hospitalaria [España] 2007;22:672-6.

Wishart DS. Metabolomics: The principles and potential applications to transplantation. Am J Transplant 2005;5:2814-20.

Baue AE. Nutrition and metabolism in sepsis and multisystem organ failure. Surg Clin North Am 1991;71:549-65.

Mizock BA. Immunonutrition and critical illness: An update. Nu¬trition 2010;26:701-7.

Klimberg VS, McClellan JL. Glutamine, cancer, and its therapy. Am J Surg 1996;172:418-24.

Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev 2003;29:501-13.

Zaloga GP. Immune-enhancing enteral diets: Where's the beef? Crit Care Med 1998;26:1143-6.

Stroster JA, Uranues S, Latifi R. Nutritional controversies in critical care: Revisiting enteral glutamine during critical illness and injury. Cur Op Crit Care 2015;21:527-30.

Preiser JC, van Zanten AR, Berger MM, Biolo G, Casaer MP, Doig GS; et al. Metabolic and nutritional support of critically ill patients: Consensus and controversies. Crit Care 2015;19:35-42.

Berger MM, Mechanick JI. Continuing controversy in the intensive care unit: Why tight glycemic control, nutrition support, and nutritional pharmacology are each necessary therapeutic considerations. Cur Op Clin Nutr Metab Care 2010;13:167-9.

Santana Porbén S, Barreto Penié J. Metabolismo de los sustratos. En: Nutrición enteral y parenteral [Editores: Arenas Márquez H, Anaya Prado R]. McGraw Hill Interamericana. México: 2007.

Joy KW. Ammonia, glutamine, and asparagine: A carbon-nitrogen interface. Can J Botany 1988;66:2103-9.

Brunengraber H, Roe CR. Anaplerotic molecules: Current and future. J Inherit Metab Dis 2006;29:327-31.

Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J; et al. Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell 2014;56:414-24.

Meister A. Glutamine synthetase of mammals. En: The enzymes. Volume 10. Academic Press. New York: 1974. pp 699-754.

Chang TW, Goldberg AL. The metabolic fates of amino acids and the formation of glutamine in skeletal muscle. J Biol Chem 1978;253:3685-93.

Souba WW, Herskowitz K, Plumley DA. Lung glutamine metabolism. JPEN J Parenter Enter Nutr 1990;14(4 Suppl):S68-S70.

Curthoys NP, Watford M. Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 1995;15:133-59.

Nurjhan N, Bucci A, Perriello G, Stumvoll M, Dailey G, Bier DM; et al. Glutamine: A major gluconeogenic precursor and vehicle for interorgan carbon transport in man. J Clin Invest 1995;95:272-7.

van Acker BA, von Meyenfeldt MF, van der Hulst RR, Hulsewé KW, Wagenmakers AJ, Deutz NE; et al. Glutamine: The pivot of our nitrogen economy? JPEN J Parenter Enter Nutr 1999;23(5 Suppl):S45-S48.

Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev 1990;48:297-309.

Wernerman J, Hammarqvist F, Vinnars E. α-ketoglutarate and postoperative muscle catabolism. The Lancet 1990;335(8691):701-3.

Ashy AA, Ardawi MSM. Glucose, glutamine, and ketone-body metabolism in human enterocytes. Metabolism 1988;37:602-9.

Ardawi MS, Newsholme EA. Fuel utilization in colonocytes of the rat. Biochem J 1985;231:713-20.

Newsholme EA, Carrie AL. Quantitative aspects of glucose and glutamine metabolism by intestinal cells. Gut 1994;35(1 Suppl):S13-S17.

Verhoeven AJ, Iwaarden JF, Joseph SK, Meijer AJ. Control of rat‐liver glutaminase by ammonia and pH. FEBS J 1983;133:241-4.

Newsholme P, Curi R, Curi TP, Murphy CJ, Garcia C, de Melo MP. Glutamine metabolism by lymphocytes, macrophages, and neutrophils: Its importance in health and disease. J Nutr Biochem 1999;10:316-24.

Curi R, Newsholme P, Pithon-Curi TC, Pires de Melo M, Garcia C, Guimarães ARP. Metabolic fate of glutamine in lymphocytes, macrophages and neutrophils. Braz J Med Biol Res 1999;32:15-21.

Sumbilla CM, Zielke CL, Reed WD, Ozand PT, Zielke HR. Comparison of the oxidation of glutamine, glucose, ketone bodies and fatty acids by human diploid fibroblasts. Biochim Biophys Acta 1981;675:301-4.

Darmaun D, Matthews DE, Desjeux JF, Bier DM. Glutamine and glutamate nitrogen exchangeable pools in cultured fibroblasts: A stable isotope study. J Cell Physiol 1988;134:143-8.

Brand K, Fekl W, von Hintzenstern J, Langer K, Luppa P, Schoerner C. Metabolism of glutamine in lymphocytes. Metabolism Clin Exp 1989;38:29-33.

Bellows CF, Jaffe BM. Glutamine is essential for nitric oxide synthesis by murine macrophages. J Surg Res 1999;86:213-9.

Furukawa S, Saito H, Fukatsu K, Hashiguchi Y, Inaba T, Lin MT; et al. Glutamine-enhanced bacterial killing by neutrophils from postoperative patients. Nutrition 1997;13:863-9.

Ruderman NB, Berger M. The formation of glutamine and alanine in skeletal muscle. J Biol Chem 1974;249:5500-6.

Curi R, Lagranha CJ, Doi SQ, Sellitti DF, Procópio J, Pithon‐Curi TC; et al. Molecular mechanisms of glutamine action. J Cell Physiol 2005;204:392-401.

Cynober LA. Plasma amino acid levels with a note on membrane transport: Characteristics, regulation, and metabolic significance. Nutrition 2002;18:761-6.

Bach SJ, Smith M. Glutamine: A nitrogen source in urea synthesis. Biochem J 1956;64:417-25.

Lund P, Wiggins D. The ornithine requirement of urea synthesis. Formation of ornithine from glutamine in hepatocytes. Biochem J 1986;239:773-6.

Wu G, Knabe DA, Flynn NE. Synthesis of citrulline from glutamine in pig enterocytes. Biochem J 1994;299(Pt 1):115-22.

Hankard RG, Haymond MW, Darmaun D. Role of glutamine as a glucose precursor in fasting humans. Diabetes 1997;46:1535-41.

Richterich RW, Goldstein L. Distribution of glutamine metabolizing enzymes and production of urinary ammonia in the mammalian kidney. Am J Physiol 1958;195:316-20.

Fonnum F. Glutamate: A neurotransmitter in mammalian brain. J Neurochem 1984;42:1-11.

Martin DL, Rimvall K. Regulation of γ‐aminobutyric acid synthesis in the brain. J Neurochem 1993;60:395-407.

Watford M. Glutamine metabolism and function in relation to proline synthesis and the safety of glutamine and proline supplementation. J Nutr 2008;138:S2003-S2007.

McCauley R, Kong SE, Hall J. Glutamine and nucleotide metabolism within enterocytes. JPEN J Parenter Enter Nutr 1998;22:105-11.

Cory JG, Cory AH. Critical roles of glutamine as nitrogen donors in purine and pyrimidine nucleotide synthesis: Asparaginase treatment in childhood acute lymphoblastic leukemia. In Vivo [Athens: Greece] 2006;20:587-9.

Krebs HA, Hems R, Tyler B. The regulation of folate and methionine metabolism. Biochem J 1976;158:341-8.

Wischmeyer PE. Glutamine and heat shock protein expression. Nutrition 2002;18:225-8.

Lindquist S, Craig EA. The heat-shock proteins. Annu Rev Genet 1988;22:631-77.

Amores Sánchez MI, Medina MÁ. Glutamine as a precursor of glutathione, and oxidative stress. Mol Genet Metab 1999;67:100-5.

Matés JM, Pérez Gómez C, de Castro IN, Asenjo M, Márquez J. Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death. Int J Biochem Cell Biol 2002;34:439-58.

Bellows CF, Jaffe BM. Glutamine is essential for nitric oxide synthesis by murine macrophages. J Surg Res 1999;86:213-9.

Hibbs Jr JB, Taintor RR, Vavrin Z, Rachlin EM. Nitric oxide: A cytotoxic activated macrophage effector molecule. Biochem Biophys Res Comm 1988;157:87-94.

Taylor L, Curthoys NP. Glutamine metabolism: Role in acid‐base balance. Biochem Mol Biol Edu 2004;32:291-304.

Rao R, Samak G. Role of glutamine in protection of intestinal epithelial tight junctions. J Epithel Biol Pharmacol 2012;5(M7 Suppl 1):47-54.

Forstner JF. Intestinal mucins in health and disease. Digestion 1978;17:234-63.

Li C, Buettger C, Kwagh J, Matter A, Daikhin Y, Nissim IB; et al. A signaling role of glutamine in insulin secretion. J Biol Chem 2004;279:13393-401.

Rohde T, MacLean DA, Klarlund Pedersen B. Glutamine, lymphocyte proliferation and cytokine production. Scand J Immunol 1996;44:648-50.

Yaqoob P, Calder PC. Cytokine production by human peripheral blood mononuclear cells: Differential senstivity to glutamine availability. Cytokine 1998;10:790-4.

Smith RJ, Wilmore DW. Glutamine nutrition and requirements. JPEN J Parenter Enter Nutr 1990;14(Suppl 4): S94-S99.

Hartmann R, Meisel H. Food-derived peptides with biological activity: from research to food applications. Cur Op Biotechnol 2007;18:163-9.

Speck JF. The enzymic synthesis of glutamine. J Biol Chem 1947;168:403-4.

Speck JF. The enzymatic synthesis of glutamine, a reaction utilizing adenosine triphosphate. J Biol Chem 1949;179:1405-26.

Elliott WH. Studies on the enzymic synthesis of glutamine. Biochem J 1951;49:106-12.

Felig P. The glucose-alanine cycle. Metabolism 1973;22:179-207.

Felig P, Pozefsk T, Marlis E, Cahill Jr GF. Alanine: Key role in gluconeo-genesis. Science 1970;167(3920):1003-4.

Felig P, Marliss E, Pozefsky T, Cahill GF. Amino acid metabolism in the regulation of gluconeogenesis in man. Am J Clin Nutr 1970;23:986-92.

Eagle H. Amino acid metabolism in mammalian cell cultures. Science 1959; 130(3373):432-7.

Fürst P, Albers S, Sehle P. Stress-induced intracellular glutamine depletion. Contr Infusion Ther Clin Nutr 1987;17:117-36.

Ziegler TR, Smith RJ, Byrne TA, Wilmore DW. Potential role of glutamine supplementation in nutrition support. Clin Nutr 1993;12(Suppl):S82-S90.

Meacham CE, Morrison SJ. Tumour heterogeneity and cancer cell plasticity. Nature 2013;501(7467):328-37.

Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99.

DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008;7:11-20.

Shaw RJ. Glucose metabolism and cancer. Cur Op Cell Biol 2006;18:598-608.

DeBerardinis RJ, Cheng T. Q's next: The diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene 2010;29:313-24.

Matsuno T. Bioenergetics of tumor cells: Glutamine metabolism in tumor cell mitochondria. Int J Biochem 1987;19: 303-7.

Fenninger LD, Mider GB. Energy and nitrogen metabolism in cancer. En: Advances in cancer research. Volume 2. Academic Press. New York: 1954. pp. 229-253.

Yasutomi M. Advances in rectal cancer surgery in Japan. Dis Colon Rectum 1997;40(10 Suppl):S74-S79.

Kaufmann SH, Earnshaw WC. Induction of apoptosis by cancer chemotherapy. Exp Cell Res 2000;256:42-9.

Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: Current advances and future directions. Int J Medical Sci 2012;9:193-9.

Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335:462-7.

Wanebo HJ, Glicksman AS, Vezeridis MP, Clark J, Tibbetts L, Koness RJ, Levy A. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg 2000;135:81-7.

Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE; et al. Bone-marrow transplantation. N Engl J Med 1975;292(17):895-902.

van Cutsem E, Arends J. The causes and consequences of cancer-associated malnutrition. Eur J Oncol Nurs 2005;9(Suppl):S51-S63.

Harvey KB, Bothe A, Blackburn GL. Nutritional assessment and patient outcome during oncological therapy. Cancer 1979;43(Suppl 5):S2065-S2069.

Tchekmedyian NS. Costs and benefits of nutrition support in cancer. Oncology [Huntington] 1995;9:79-84.

Souba WW. Glutamine and cancer. Ann Surg 1993;218:715-28.

Kuhn KS, Muscaritoli M, Wischmeyer, P, Stehle P. Glutamine as indispensable nutrient in oncology: Experimental and clinical evidence. Eur J Nutr 2010;49:197-210.

Yoshida S, Kaibara A, Ishibashi N, Shirouzu K. Glutamine supplementation in cancer patients. Nutrition 2001;17:766-8.

Bozzetti F, Biganzoli L, Gavazzi C, Cappuzzo F, Carnaghi C, Buzzoni R, Baietta E. Glutamine supplementation in cancer patients receiving chemotherapy: A double-blind randomized study. Nutrition 1997;13:748-51.

Gaurav K, Goel RK, Shukla M, Pandey M. Glutamine: A novel approach to chemotherapy-induced toxicity. Indian J Med Paediatr Oncol 2012;33:13-20.

Schloerb PR, Skikne BS. Oral and parenteral glutamine in bone marrow transplantation: A randomized, double-blind study. JPEN J Parenter Enter Nutr 1999;23:117-22.

Kuskonmaz B, Yalcin S, Kucukbayrak O, Cetin N, Cetin M, Tezcan I, Uckan D. The effect of glutamine supplementation on hematopoietic stem cell transplant outcome in children: A case-control study. Pediatr Transplant 2008;12:47-51.

Fürst P, Pogan K, Stehle P. Glutamine dipeptides in clinical nutrition. Nutrition 1997;13:731-7.

Fürst P. New developments in glutamine delivery. J Nutr 2001;131(9 Suppl):S2562-S2568.

Hübl W, Druml W, Langer K, Lochs H. Influence of molecular structure and plasma hydrolysis on the metabolism of glutamine-containing dipeptides in humans. Metab Clin Exp 1989;38:59-62.

Daly JM, Weintraub FN, Shou J, Rosato EF, Lucia M. Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Ann Surg 1995;221:327-38.

Mekhail TM, Adelstein DJ, Rybicki LA, Larto MA, Saxton JP, Lavertu P. Enteral nutrition during the treatment of head and neck carcinoma. Cancer 2001; 91:1785-90.

Nugent B, Lewis S, O'Sullivan JM. Enteral feeding methods for nutritional management in patients with head and neck cancers being treated with radiotherapy and/or chemotherapy. Cochrane Database Syst Rev 2013(1):CD007904-CD007904.

Noe JE. L-glutamine use in the treatment and prevention of mucositis and cachexia: A naturopathic perspective. Integrat Cancer Ther 2009;8:409-15.

Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr 2001;131(9 Suppl):S2556-S2561.

Gianotti L, Braga M, Nespoli L, Radaelli G, Beneduce A, Di Carlo V. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gastrointestinal cancer. Gastroenterol 2002;122:1763-70.

Senkal M, Zumtobel V, Bauer KH, Marpe B, Wolfram G, Frei A; et al. Outcome and cost-effectiveness of perioperative enteral immunonutrition in patients undergoing elective upper gastrointestinal tract surgery: A prospective randomized study. Arch Surg 1999;134:1309-16.

Fujitani K, Tsujinaka T, Fujita J, Miyashiro I, Imamura H, Kimura Y; et al; for the Osaka Gastrointestinal Cancer Chemotherapy Study Group. Prospective randomized trial of preoperative enteral immunonutrition followed by elective total gastrectomy for gastric cancer. Brit J Surg 2012;99:621-9.

Azman M, Mohd Yunus MR, Sulaiman S; et al. Enteral glutamine supplementation in surgical patients with head and neck malignancy: A randomized controlled trial. Head Neck 2015;37:1799–807.

Stableforth WD, Thomas S, Lewis SJ. A systematic review of the role of immunonutrition in patients undergoing surgery for head and neck cancer. Int J Oral Maxillofac Surg 2009;38:103-10.

Suchner U, Kuhn KS; Fürst P. The scientific basis of immunonutrition. Proc Nutr Soc 2000;59:553-63.

Ren L, Zhu D, Wei Y, Pan X, Liang L, Xu J; et al. Enhanced Recovery After Surgery (ERAS) program attenuates stress and accelerates recovery in patients after radical resection for colorectal cancer: A prospective randomized controlled trial. World J Surg 2012;36:407-14.

Luketich JD, Pennathur A, Awais O, Levy RM, Keeley S, Shende M; et al. Outcomes after minimally invasive esophagectomy: Review of over 1,000 patients. Ann Surg 2012;256:95-103.

Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-9.

Kucuktulu E, Guner A, Kahraman I, Topbas M, Kucuktulu U. The protective effects of glutamine on radiation-induced diarrhea. Support Care Cancer 2013;21:1071-5.

García de Lorenzo A, Zarazaga A, García Luna PP, González Huix F, López Martínez J, Miján A; et al. Clinical evidence for enteral nutritional support with glutamine. Nutrition 2003;19:805-11.

Vidal A, Calleja A, Ballesteros MD, Cano I. Efficacy of glutamine in the prevention of oral mucositis and acute radiation-induced esophagitis: A retrospective study. Nutr Cancer 2013; 65:424-9.

Sayles C, Hickerson SC, Bhat RR, Hall J, Garey KW, Trivedi MV. Oral glutamine in preventing treatment-related mucositis in adult patients with cancer: A systematic review. Nutr Clin Pract 2016;31:171-9.

Leung HWC, Chan ALF. Glutamine in alleviation of radiation-induced severe oral mucositis: A meta-analysis. Nutr Cancer 2016;68:734-42

Jebb SA, Osborne RJ, Maughan TS, Mohideen N, Mack P, Mort D; et al. 5-fluorouracil and folinic acid-induced mucositis: No effect of oral glutamine supplementation. Brit J Cancer 1994;70:732-5.

Anderson PM, Ramsay NKC, Shu XO, Rydholm N, Rogosheske J, Nicklow R; et al. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant 1998;22:339-44.

Coghlin-Dickson TM, Wong RM, Negrin RS, Shizuru JA, Johnston LJ, Hu WW; et al. Effect of oral glutamine supplementation during bone marrow transplantation. JPEN J Parenter Enteral Nutr 2000;24:61-6.

Canovas G, León-Sanz M, Gómez P, Valero MA, Gomis P, La Huerta JJ. Oral glutamine supplements in autologous hematopoietic transplant: Impact on gastrointestinal toxicity and plasma protein levels. Haematologica 2000;85:1229-30.

Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R; et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: A double blind, placebo controlled, randomised trial. Gut 2001;48:28-33.

Aquino VM, Harvey AR, Garvin JH, Godder KT, Nieder ML, Adams RH; et al; for the Pediatric Blood and Marrow Transplant Consortium. A double-blind randomized placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: A Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant 2005;36:611-6.

Kozjek NR, Kompan L, Soeters P, Oblak I, Mastnak DM, Mozina B; et al. Oral glutamine supplementation during preoperative radiochemotherapy in patients with rectal cancer: A randomised double blinded, placebo controlled pilot study. Clin Nutr 2011;30:567-70.

Peterson DE, Jones JB, Petit RG. Randomized, placebo‐controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline‐based chemo-therapy. Cancer 2007;109:322-31.

Topkan E, Parlak C, Topuk S, Pehlivan B. Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer. BMC Cancer 2012;12:502. Disponible en: https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-502. Fecha de última visita: 2 de Marzo del 2017.

Chattopadhyay S, Saha A, Azam M, Mukherjee A, Sur PK. Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: A prospective randomized study. South Asian J Cancer 2014;3:8-12.

Kanyilmaz G, Koc M, Aktan M, Temiz SA, Adli M. The effects of oral glutamine supplementation on clinical and survival outcomes of non-small cell cancer patients treated with chemoradiation therapy. Int J Radiation Oncol Biol Phys 2015;93(3 Suppl):E428. Disponible en: http://www.redjournal.org/article/S0360-3016(15)02370-6/abstract. Fecha de última visita: 3 de Marzo del 2017.

Tsujimoto T, Yamamoto Y, Wasa M, Takenaka Y, Nakahara S, Takagi T; et al. L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer: A double-blind, randomized, placebo-controlled trial. Oncology Reports 2015;33:33-9.

Pattanayak L, Panda N, Dash MK, Mohanty S, Samantaray S. Management of chemoradiation-induced mucositis in head and neck cancers with oral glutamine. J Global Oncol 2016;2:200-6.

Tanaka Y, Takahashi T, Yamaguchi K, Osada S, Shimokawa T, Yoshida K. Elemental diet plus glutamine for the prevention of mucositis in esophageal cancer patients receiving chemotherapy: A feasibility study. Support Care Cancer 2016;24:933-41.

Ogata Y, Ishibashi N, Yamaguchi K, Uchida S, Kamei H, Nakayama G; et al. Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: A prospective pilot study. Support Care Cancer 2016;24:783-9.

Ziegler TR. Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. J Nutr 2001;131(9 Suppl):S2578-S2584.

Albers S, Wernerman J, Stehle P, Vinnars E, Furst P. Availability of amino acids supplied intravenously in healthy man as synthetic dipeptides: Kinetic evaluation of L-alanyl-L-glutamine and glycyl-L-tyrosine. Clin Sci 1988;75: 463-8.

Melis GC, Boelens PG, van der Sijp JR, Popovici T, De Bandt JP, Cynober L, van Leeuwen PA. 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. Brit J Nutr 2005;94:19-26.

Bozzetti F. Rationale and indications for preoperative feeding of malnourished surgical cancer patients. Nutrition 2002;18:953-9.

O'Riordain MG, Fearon KC, Ross JA, Rogers P, Falconer JS, Bartolo DC; et al. Glutamine-supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection. Ann Surg 1994;220:212-21.

Morlion BJ, Stehle P, Wachtler P, Siedhoff HP, Köller M, König W; et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: A randomized, double-blind, controlled study. Ann Surg 1998;227:302-8.

Alivizatos V, Athanasopoulos P, Makris N, Karageorgos N. Early postoperative glutamine-supplemented parenteral nutrition versus enteral immunonutrition in cancer patients undergoing major gastrointestinal surgery. J BUON. 2005;10:119–22.

Jo S, Choi SH, Heo JS; et al. Missing effect of glutamine supplementation on the surgical outcome after pancreatico-duodenectomy for periampullary tumors: A prospective, randomized, double-blind, controlled clinical trial. World J Surg 2006;30:1974-82.

Oguz M, Kerem M, Bedirli A, Mentes BB, Sakrak O, Salman B, Bostanci H. L‐alanin‐l‐glutamine supplementation improves the outcome after colorectal surgery for cancer. Colorectal Dis 2007;9:515-20.

Gianotti L, Braga M, Biffi R, Bozzetti F, Mariani L. Perioperative intravenous glutamine supplementation in major abdominal surgery for cancer: A randomized multicenter trial. Ann Surg 2009;250:684-90.

Marton S, Ghosh S, Papp A, Bogar L, Koszegi T, Juhasz V; et al. Effect of glutamine in patients with esophagus resection. Diseases Esophagus 2010;23:106-11.

Lu CY, Shih YL, Sun LC, Chuang JF, Ma CJ, Chen FM; et al. The inflammatory modulation effect of glutamine-enriched total parenteral nutrition in postoperative gastrointestinal cancer patients. Am Surgeon 2011;77:59-64.

Cui Y, Hu L, Liu YJ, Wu YM, Jing L. Intravenous alanyl-L-glutamine balances glucose-insulin homeostasis and facilitates recovery in patients undergoing colonic resection: A randomised controlled trial. Eur J Anaesthesiol 2014;31:212-8.

Zheng YM, Li F, Zhang MM, Wu XT. Glutamine dipeptide for parenteral nutrition in abdominal surgery: A meta-analysis of randomized controlled trials. World J Gastroenterol 2006;12:7537-44.

Yue C, Tian W, Wang W, Huang Q, Zhao R, Zhao Y; et al. The impact of perioperative glutamine-supplemented parenteral nutrition on outcomes of patients undergoing abdominal surgery: A meta-analysis of randomized clinical trials. Am Surgeon 2013;79:506-13.

Kang K, Shu XL, Zhang YS, Liu XL, Zhao J. Effect of glutamine enriched nutrition support on surgical patients with gastrointestinal tumor: A meta-analysis of randomized controlled trials. Chinese M J 2015;128:245-51.

Bollhalder L, Pfeil AM, Tomonaga Y, Schwenkglenks M. A systematic literature review and meta-analysis of randomized clinical trials of parenteral glutamine supplementation. Clin Nutr 2013;32:213-23.

Sandini M, Nespoli L, Oldani M, Bernasconi DP, Gianotti L. Effect of glutamine dipeptide supplementation on primary outcomes for elective major surgery: Systematic review and meta-analysis. Nutrients 2015;7:481-99.

van Zaanen HC, van der Lelie H, Timmer JG, Fürst P, Sauerwein HP. Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy‐induced toxicity. Cancer 1994;74:2879-84.

Decker-Baumann C, Buhl K, Frohmüller S, Herbay AV, Dueck M, Schlag PM. Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer. Eur J Cancer 1999;35:202-7.

Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM; et al. Oral glutamine to alleviate radiation-induced oral mucositis: A pilot randomized trial. Int J Rad Oncol Biol Phys 2000;46:535-9.

Scheid C, Hermann K, Kremer G, Holsing A, Heck G, Fuchs M; et al. Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. Nutrition 2004;20:249-54.

Cerchietti LCA, Navigante AH, Lutteral MA. Double-blinded, placebo-controlled trial on intravenous l-alanyl-l-glutamine in the incidence of oral mucositis following chemo-radiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys 2006;65:1330-7.

Sornsuvit C, Komindr S, Chuncharunee S; et al. Pilot study: Effects of parenteral glutamine dipeptide supplementation on neutrophil functions and prevention of chemotherapy-induced side-effects in acute myeloid leukaemia patients. J Int Med Res 2008;36:1383-91.

Yildirim ZK, Bidev D, Buyukavci M. Parenteral glutamine supplementation has no effect on chemotherapy-induced toxicity in children with non-Hodgkin Lymphoma. J Pediatric Hematology/ Oncology 2013;35:371-6.

Chang YH, Yu MS, Wu KH, Hsu MC, Chiou YH, Wu HP; et al. Effectiveness of parenteral glutamine on methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. Nutr Cancer 2017;69:746-51.

Wang J, Li Y, Qi Y. Effect of glutamine-enriched nutritional support on intestinal mucosal barrier function, MMP-2, MMP-9 and inmune function in patients with advanced gastric cancer during perioperative chemoterapy. Oncol Lett 2017;14:3606-14.

Gibson RJ, Keefe DM, Lalla RV, Bateman E, Blijlevens N, Fijlstra M; et al. Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Support Care Cancer 2013;21:313-26.

Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A; et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 2011(4):CD000978. Disponible en: https://www.ncbi.nlm.nih.gov/pubmed/21491378. Fecha de última visita: 3 de Marzo del 2017.

Sun J, Wang H, Hu H. Glutamine for chemotherapy induced diarrhea: A meta-analysis. Asia Pac J Clin Nutr 2012;21:380-5.

Jolfaie NR, Mirzaie S, Ghiasvand R, Askari G, Miraghajani M. The effect of glutamine intake on complications of colorectal and colon cancer treatment: A systematic review. J Res Med Sci 2015; 20:910-8.

Ziegler TR. Glutamine supplementation in bone marrow transplantation. Brit J Nutr 2002;87(1 Suppl):S9-S15.

Muscaritoli M, Grieco G, Capria S, Iori AP, Fanelli FR. Nutritional and metabolic support in patients undergoing bone marrow transplantation. Am J Clin Nutr 2002;75:183-90.

Crowther M. A review of the use of glutamine supplementation in the nutritional support of patients undergoing bone-marrow transplantation and traditional cancer therapy [Hot topics in parenteral nutrition]. Proc Nutr Soc 2009;68:269-73.

Ziegler TR, Benfell K, Smith RJ, Young LS, Brown E, Ferrari‐Baliviera E; et al. Safety and metabolic effects of L‐glutamine administration in humans. JPEN J Parenter Enter Nutr 1990; 14(4 Suppl):S137-S146.

Young LS, Bye R, Scheltinga M, Ziegler TR, Jacobs DO, Wilmore DW. Patients receiving glutamine‐supplemented intravenous feedings report an improvement in mood. JPEN J Parenter Enter Nutr 1993;17:422-7.

Scheltinga MR, Young LS, Benfell K, Bye RL, Ziegler TR, Santos AA; et al. Glutamine-enriched intravenous feedings attenuate extracellular fluid expansion after a standard stress. Ann Surg 1991;214:385-93.

Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R; et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation: A randomized, double-blind, controlled study. Ann Int Med 1992;116:821-8.

Schloerb PR, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study). JPEN J Parenter Enter Nutr 1993;17:407-13.

MacBurney M, Young LS, Ziegler TR, Wilmore DW. A cost-evaluation of glutamine-supplemented parenteral nutrition in adult bone marrow transplant patients. J Am Diet Assoc 1994;94:1263-6.

Ziegler TR, Bye RL, Persinger RL, Young LS, Antin JH, Wilmore DW. Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: A pilot study. Am J Med Sci 1998;315:4-10.

Brown SA, Goringe A, Fegan C, Davies SV, Giddings J, Whittaker JA; et al. Parenteral glutamine protects hepatic function during bone marrow transplantation. Bone Marrow Transplant 1998;22:281-4.

Pytlik R, Benes P, Patorkova M. Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: A randomized, double-blind, placebo controlled study. Bone Marrow Transplant 2002;30:953-61.

Piccirillo N, De Matteis S, Laurenti L, Chiusolo P, Sorà F, Pittiruti M; et al. Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: Effects on immune reconstitution and mucositis. Haematologica 2003;88:192-200.

Blijlevens NMA, Donnelly JP, Naber AHJ, Schattenberg AVMB. A randomised, double-blinded, placebo-controlled, pilot study of parenteral glutamine for allogeneic stem cell transplant patients. Support Care Cancer 2005;13:790-6.

Sykorova A, Horacek J, Zak P, Kmonicek M, Bukac J, Maly J. A randomized, double blind comparative study of prophylactic parenteral nutritional support with or without glutamine in autologous stem cell transplantation for hematological malignancies- Three years' follow-up. Neoplasma 2005;52:476-82.

Kuskonmaz B, Yalcin S, Kucukbayrak O, Cetin N, Cetin M, Tezcan I, Uckan D. The effect of glutamine supplementation on hematopoietic stem cell transplant outcome in children: A case-control study. Pediatr Transplant 2008;12:47-51.

da Gama Torres HO, Vilela EG, da Cunha AS, Goulart EM, Souza MH, Aguirre AC et al. Efficacy of glutamine-supplemented parenteral nutrition on short-term survival following allo-SCT: A randomized study. Bone Marrow Transplant 2008;41:1021-7.

Pérez L, Fernández A, Valero MA, Gomis P, León M, Herreros A. Parenteral nutrition supplemented with glutamine in patients undergoing bone marrow transplantation. Nutrición Hospitalaria [España] 2010;25:49-52.

Oliva JG, Pereyra F, Suárez JP, Ríos P, Breña J, Palacio JE. Eficacia de la glutamina parenteral en pacientes sometidos a trasplante autólogo de médula ósea. Nutrición Hospitalaria [España] 2012;27:205-8.

Herrera AD, Alhambra MR, Manzano G, Molina MJ, Calañas A, Bahamondez R; et al. Use of glutamine in total parenteral nutrition of bone marrow transplant patients. Nutrición Hospitalaria [España] 2015;31:1620-4.

Crowther M, Avenell A, Culligan DJ. Systematic review and meta-analyses of studies of glutamine supplementation in haematopoietic stem cell transplantation. Bone Marrow Transplant 2009;44:413-25.

Murray SM, Pindoria S. Nutrition support for bone marrow transplant patients. Cochrane Database Syst Rev 2009(1):CD002920.

Arfons LM, Lazarus HM. Total parenteral nutrition and hematopoietic stem cell transplantation: An expensive placebo? Bone Marrow Transplant 2005;36:281-8.

Heyland DK, Dhaliwal R, Day AG, Muscedere J, Drover J, Suchner U; et al; for the Canadian Critical Care Trials Group. REducing Deaths due to OXidative Stress (The REDOXS© Study): Rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients. Proc Nutr Soc 2006;65;250-63.

Heyland D, Muscedere J, Wischmeyer PE; et al; for the Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013;368(16):1489-97.

van Zanten AR, Sztark F, Kaisers UX, Zielmann S, Felbinger TW, Sablotzki AR; 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;312:514-24.

Heyland DK, Elke G, Cook D, Berger MM, Wischmeyer PE, Albert M; et al; for the Canadian Critical Care Trials Group. Glutamine and antioxidants in the critically ill patient: A post hoc analysis of a large-scale randomized trial. JPEN J Parenter Enter Nutr 2015;39:401-9.

van Zanten AR, Hofman Z, Heyland DK. Consequences of the REDOXS and METAPLUS trials: The end of an era of glutamine and antioxidant supplementation for critically ill patients? JPEN J Parenter Enter Nutr 2015;39:890-2.

McRae MP. Therapeutic benefits of glutamine: An umbrella review of meta-analyses. Biomed Rep 2017;6:576-84.

Wernerman J, Kirketeig T, Andersson B; et al; for the Scandinavian Critical Care Trials Group. Scandinavian Glutamine Trial: A pragmatic multi-centre randomised clinical trial of intensive care unit patients. Acta Anaesthesiol Scand 2011;55:812-8.

Ma CJ, Wang JY. Glutamine-enriched total parenteral nutrition and glutamine supplementation in gastrointestinal cancer patients. En: Diet and Nutrition in Critical Care [Editor: Rajendram R, Preedy VR, Patel VB]. Springer Science + Business Media. New York: 2015. pp 1841-51. Disponible en: https://link.springer.com/referenceworkentry/10.1007%2F978-1-4614-7836-2_60. Fecha de última visita: 3 de Febrero del 2017.

Tydeman Edwards R. Glutamine and its use in selected oncology settings. South Afr J Clin Nutr 2017;30:109-17.

Wischmeyer P. Glutamine supplementation in parenteral nutrition and intensive care unit patients: Are we throwing the baby out with the bathwater? JPEN J Parenter Enter Nutr 2015;39:893-7.

Thompson KL, Elliott L, Fuchs-Tarlovsky V, Levin RM, Voss AC, Piemonte T. Oncology evidence-based nutrition practice guideline for adults. J Acad Nutr Diet 2017;117:297-310.

McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C; et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient. JPEN J Parenter Enter Nutr 2016;40:159-211.

Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F; et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr 2017;36:11-48.

Sociedad Argentina de Terapia Intensiva. Asociación Argentina de Nutrición Enteral y Parenteral. Soporte nutricional en el paciente adulto críticamente enfermo. Un consenso de práctica clínica. RCAN Rev Cubana Aliment Nutr 2016;26(1 Supl 1):S1-S82. Disponible en: http://www.revalnutricion.sld.cu/index.php/rcan/issue/view/4/showToc. Fecha de última visita: 10 de Marzo del 2017.

Critical Care Nutrition. Canadian Clinical Practice Guidelines 2015. Disponible en: http://www.criticalcarenutrition.com/docs/CPGs%202015/Summary%20CPGs%202015%20vs%202013.pdf. Fecha de última visita: 14 de Septiembre del 2016.

Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM; et al; for the Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 2014;120:1453-61.

Sánchez Álvarez C, Zabarte Martínez de Aguirre M, Bordejé Laguna L. Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Gastrointestinal surgery [Chapter 9]. Nutrición Hospitalaria [España] 2011;26(Supl 2): S41-S45.

Planas M, Fernández Ortega JF, Abilés J. Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Oncohematological patient [Chapter 11]. Nutrición Hospitalaria [España] 2011; 26(Supl 2):S50-S53.

Enlaces refback

  • No hay ningún enlace refback.