Abstract
Background
In hypermetabolic situations, glutamine is intensively used by rapidly dividing cells such as enterocytes, lymphocytes, and fibroblasts as nitrogen source and/or alternative energy fuel. It is hypothesized that in cancer patients the increased glutamine demands of the host increase the capacity of endogenous production resulting in a strong glutamine deprivation with detrimental effects on organ functions. In long-term periods of cancer cachexia, an adequate nutrition support including glutamine can essentially contribute to cover glutamine needs and, thus, to spare energy reserves of the host and to retard severe complications such as multi-organ failure. Due to the early in vitro knowledge that cancer cells preferably consume glutamine, oncologists often refuse to supply glutamine to the tumor-bearing host to avoid any potential risk. An objective evaluation whether supplemental glutamine supports tumor growth in vivo is, however, still lacking.
Aim of the study
The present review evaluates in vivo experimental and clinical data with respect to potential effects of glutamine administration in tumor-bearing hosts and draws conclusions for the use of glutamine supplements in clinical oncology.
Methods
Experimental and clinical intervention studies were identified in a systematic review of MEDLINE Database (last entry: June 2008) using key search terms and review articles. These studies were supplemented with reports identified through manual searches and other studies previously known by the authors.
Results
Numerous experimental studies (rat/mouse model) show that oral/enteral or intravenous glutamine supports metabolism of the tumor-bearing host and can ameliorate gastrointestinal toxicity of therapeutical measures. Within the last two decades, 36 (24 oral/enteral, 12 parenteral) clinical studies evaluating the tolerance, safety and effects of glutamine in various patient groups have been published. In the great majority of these clinical studies, glutamine supplementation in cancer patients improves host metabolism and clinical situation without increasing tumor growth. Potential mechanisms of glutamine effects include maintenance of mucosal integrity, improved immune competence, inhibition of cell proliferation, increased apoptosis rate, increased synthesis of glutathione, induction of heat shock protein synthesis, and increased synthesis of glucagons-like peptides.
Conclusions
In various clinical situations, appropriate exogenous glutamine supply is safe and can beneficially contribute to diminish risks of high-dose chemotherapy and radiation. In addition, there is some evidence that adequate glutamine availability can beneficially affect outcome, especially in patients undergoing bone marrow transplantation.
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References
Aledo JC, de Pedro E, Gomez-Fabre PM, Nunez de Castro I, Marquez J (2000) Changes in mRNAs for enzymes of glutamine metabolism in the tumor-bearing mouse. Anticancer Res 20:1463–1466
Anderson PM, Ramsay NK, Shu XO, Rydholm N, Rogosheske J, Nicklow R, Weisdorf DJ, Skubitz KM (1998) Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transpl 22:339–344
Anderson PM, Schroeder G, Skubitz KM (1998) Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 83:1433–1439
Arends J, Bodoky G, Bozzetti F, Fearon K, Muscaritoli M, Selga G, van Bokhorst-De Van Der Schueren MA, von Meyenfeldt M, Zurcher G, Fietkau R, Aulbert E, Frick B, Holm M, Kneba M, Mestrom HJ, Zander A (2006) ESPEN guidelines on enteral nutrition: non-surgical oncology. Clin Nutr 25:245–249
Austgen TR, Dudrick PS, Sitren H, Bland KI, Copeland E, Souba WW (1992) The effects of glutamine-enriched total parenteral nutrition on tumor growth and host tissues. Ann Surg 215:107–113
Barber MD (2002) The pathophysiology and treatment of cancer cachexia. Nutr Clin Pract 17:203–209
Bartlett DL, Charland S, Torosian MH (1995) Effect of glutamine on tumor and host growth. Ann Surg Oncol 2:71–76
Benlloch M, Mena S, Ferrer P, Obrador E, Asensi M, Pellicer JA, Carretero J, Ortega A, Estrela JM (2006) Bcl-2 and Mn-SOD antisense oligodeoxynucleotides and a glutamine-enriched diet facilitate elimination of highly resistant B16 melanoma cells by tumor necrosis factor-alpha and chemotherapy. J Biol Chem 281:69–79
Bobrovnika-Marjon E (2005) Breast cancer cells respond to glutamine deprivation by activation of NF-kappaB: mechanism and implications for breast cancer progression. Thesis, University of New Mexico, pp 1–142
Bode BP, Kaminski DL, Souba WW, Li AP (1995) Glutamine transport in isolated human hepatocytes and transformed liver cells. Hepatology 21:511–520
Bozzetti F, Biganzoli L, Gavazzi C, Cappuzzo F, Carnaghi C, Buzzoni R, Dibartolomeo M, Baietta E (1997) Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition 13:748–751
Brown SA, Goringe A, Fegan C, Davies SV, Giddings J, Whittaker JA, Burnett AK, Poynton CH (1998) Parenteral glutamine protects hepatic function during bone marrow transplantation. Bone Marrow Transpl 22:281–284
Bunpo P, Murray B, Cundiff J, Brizius E, Aldrich CJ, Anthony TG (2008) Alanyl-glutamine consumption modifies the suppressive effect of l-asparaginase on lymphocyte populations in mice. J Nutr 138:338–343
Carretero J, Obrador E, Pellicer JA, Pascual A, Estrela JM (2000) Mitochondrial glutathione depletion by glutamine in growing tumor cells. Free Radic Biol Med 29:913–923
Cerchietti LC, Navigante AH, Lutteral MA, Castro MA, Kirchuk R, Bonomi M, Cabalar ME, Roth B, Negretti G, Sheinker B, Uchima P (2006) Double-blinded, placebo-controlled trial on intravenous l-alanyl-l-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys 65:1330–1337
Chen MK, Espat NJ, Bland KI, Copeland EM III, Souba WW (1993) Influence of progressive tumor growth on glutamine metabolism in skeletal muscle and kidney. Ann Surg 217:655–666
Chen MK, Salloum RM, Austgen TR, Bland JB, Bland KI, Copeland EM III, Souba WW (1991) Tumor regulation of hepatic glutamine metabolism. J Parenteral Enteral Nutr 15:159–164
Choi K, Lee SS, Oh SJ, Lim SY, Lim SY, Jeon WK, Oh TY, Kim JW (2007) The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr 26:57–62
Coghlin Dickson TM, Wong RM, Offrin RS, Shizuru JA, Johnston LJ, Hu WW, Blume KG, Stockerl-Goldstein KE (2000) Effect of oral glutamine supplementation during bone marrow transplantation. J Parenteral Enteral Nutr 4:61–66
Collins CL, Wasa M, Souba WW, Abcouwer SF (1998) Determinants of glutamine dependence and utilization by normal and tumor-derived breast cell lines. J Cell Physiol 176:166–178
da Gama Torres HO, Vilela EG, da Cunha AS, Goulart EMA, Souza MHC, Aguirre ACC, Azevedo WM, Lodi FM, Silva AA, Bittencourt HNS (2008) Efficacy of glutamine-supplemented parenteral nutrition on short term survival following Allo-SCT: a randomized study. Bone Marrow Transpl 41:1021–1027
Daly JM, Hoffman K, Lieberman M, Leon P, Redmond HP, Shou J, Torosian MH (1990) Nutritional support in the cancer patient. J Parenteral Enteral Nutr 14:244S–2448S
Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, Barletta E, Tambaro R, Abbiati R, D’Agostino L (2001) Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut 48:28–33
de Blaauw I, Deutz NE, Van Der Hulst RR, Von Meyenfeldt MF (1997) Glutamine depletion and increased gut permeability in nonanorectic, non-weight-losing tumor-bearing rats. Gastroenterology 112:118–126
de Blaauw I, Deutz NEP, Von Meyenfeldt MF (1997) Metabolic changes in cancer cachexia—first of two parts. Clin Nutr 16:169–176
Decker-Baumann C, Buhl K, Frohmuller S, von Herbay A, Dueck M, Schlag PM (1999) Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer. Eur J Cancer 35:202–207
Diestel CF, Marques RG, Lopes-Paulo F, Paiva D, Horst NL, Caetano CE, Portela MC (2007) Role of l-glutamine and glycine supplementation on irradiated colonic wall. Int J Colorectal Dis 22:1523–1529
Drucker DJ (2006) The biology of incretin hormones. Cell Metab 3:153–165
Eagle H (1935) Nutritional needs of mammalian cells in tissue culture. Science 122:501
El Malt M, Ceelen W, Boterberg T, Claeys G, de Hemptinne B, de Neve W, Pattyn P (2003) Does the addition of glutamine to total parenteral nutrition have beneficial effect on the healing of colon anastomosis and bacterial translocation after preoperative radiotherapy? Am J Clin Oncol 26:e54–e59
Fahr MJ, Kornbluth J, Blossom S, Schaeffer R, Klimberg VS (1994) Harry M. Vars Research Award. Glutamine enhances immunoregulation of tumor growth. J Parenteral Enteral Nutr 18:471–476
Fischer CP, Bode BP, Souba WW (1998) Adaptive alterations in cellular metabolism with malignant transformation. Ann Surg 227:627–634
Fox AD, Kripke SA, De Paula J, Berman JM, Settle RG, Rombeau JL (1988) Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis. J Parenteral Enteral Nutr 12:325–331
Friedman H (1971) l-Asparaginase induced immunosuppression. Inhibition of bone marrow derived antibody precursor cells. Science 174:139–141
Fürst P, Pogan K, Stehle P (1997) Glutamine dipeptides in clinical nutrition. Nutrition 13:731–737
Gieldanowski J (1976) Studies on the immunosuppressive and anti-inflammatory action of l-asparaginase. Arch Immunol Ther Exp 24:243–247
Greenfield JR, Farooqi IS, Keogh JM, Henning E, Habib AM, Blackwood A, Reimann F, Holst JJ, Gribble FM (2008) Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects. Am J Clin Nutr [Epub ahead of print]
Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY (2000) Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys 46:535–559
Ishibashi N, Yoshida S, Kaibara A, Noake T, Kakegawa T (1997) Effect of glutamine supplementation on host protein metabolism during chemotherapy in tumor bearing rats. Nutrition 13:80–81
Jacobson SD, Loprinzi CL, Sloan JA, Wilke JL, Novotny PJ, Okuno SH, Jatoi A, Moynihan TJ (2003) Glutamine does not prevent paclitaxel-associated myalgias and arthralgias. J Support Oncol 1:274–278
Jazieh AR, Younas A, Safa M, Redmond K, Buncher R, Howington J (2007) Phase I clinical trial of concurrent paclitaxel, carboplatin, and external beam chest irradiation with glutamine in patients with locally advanced non-small cell lung cancer. Cancer Invest 25:294–298
Jebb SA, Osborne RJ, Maughan TS, Mohideen N, Mack P, Mort D, Shelley MD, Elia M (1994) 5-Fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation. Br J Cancer 70:732–735
Jiang HP, Liu CA (2006) Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy. Zhonghua Wei Chang Wai Ke Za Zhi 9:59–61
Johnson AT, Kaufmann Y, Luo S, Babb K, Hawk R, Klimberg VS (2003) Gut glutathione metabolism and changes with 7,12-DMBA and glutamine. J Surg Res 115:242–246
Johnson AT, Kaufmann YC, Luo S, Todorova V, Klimberg VS (2003) Effect of glutamine on glutathione, IGF-I, and TGF-beta 1. J Surg Res 111:222–228
Kafkewitz D, Bendich A (1983) Enzyme-induced asparagine and glutamine depletion and immune system function. Am J Clin Nutr 37:1025–1030
Kaibara A, Yoshida S, Yamasaki K, Ishibashi N, Kakegawa T (1994) Effect of glutamine and chemotherapy on host protein metabolism in tumor bearing rats. J Surg Res 57:143–149
Kaufmann Y, Kornbluth J, Feng Z, Fahr M, Schaefer RF, Klimberg VS (2003) Effect of glutamine on the initiation and promotion phases of DMBA-induced mammary tumor development. J Parenteral Enteral Nutr 27:411–418
Kaufmann Y, Luo S, Johnson A, Babb K, Klimberg VS (2003) Timing of oral glutamine on DMBA-induced tumorigenesis. J Surg Res 111:158–165
Klimberg VS, Kornbluth J, Cao Y, Dang A, Blossom S, Schaeffer RF (1996) Glutamine suppresses PGE2 synthesis and breast cancer growth. J Surg Res 63:293–297
Klimberg VS, McClellan JL, Organ CH Jr (1996) Honorary Lectureship. Glutamine, cancer, and its therapy. Am J Surg 172:418–424
Klimberg VS, Nwokedi E, Hutchins LF, Pappas AA, Lang NP, Broadwater JR, Read RC, Westbrook KC (1992) Glutamine facilitates chemotherapy while reducing toxicity. J Parenteral Enteral Nutr 16:83S–87S
Klimberg VS, Pappas AA, Nwokedi E, Jensen JC, Broadwater JR, Lang NP, Westbrook KC (1992) Effect of supplemental dietary glutamine on methotrexate concentrations in tumors. Arch Surg 127:1317–1320
Klimberg VS, Souba WW, Dolson DJ, Salloum RM, Hautamaki RD, Plumley DA, Mendenhall WM, Bova FJ, Khan SR, Hackett RL (1990) Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 66:62–68
Klimberg VS, Souba WW, Salloum RM, Plumley DA, Cohen FS, Dolson DJ, Bland KI, Copeland EM (1990) Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. J Surg Res 48:319–323
Klimberg VS (2005) Is glutamine effective in enhancing host immune response to tumors? J Nutr 135:2920S
Knox WE, Horowitz ML, Friedell GH (1969) The proportionality of w glutaminase content to growth rate and morphology of rat neoplasms. Cancer Res 29:669–680
Koehler JA, Harper W, Barnard M, Yusta B, Drucker DJ (2008) Glucagon-like peptide-2 does not modify the growth or survival of murine or human intestinal tumor cells. Cancer Res 68:7897–7904
Kozelsky TF, Meyers GE, Sloan JA, Shanahan TG, Dick SJ, Moore RL, Engeler GP, Frank AR, McKone TK, Urias RE, Pilepich MV, Novotny PJ, Martenson JA (2003) Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol 21:1669–1674
Kuhn KS, Stehle P, Fürst P (1996) Glutamine content of protein and peptide-based enteral products. J Parenteral Enteral Nutr 20:292–295
Labow BI, Souba WW (2000) Glutamine. World J Surg 24:504–513
Laviano A, Meguid MM (1996) Nutritional issues in cancer management. Nutrition 12:358–371
Laviano A, Renvyle T, Yang ZJ (1996) From laboratory to bedside: new strategies in the treatment of malnutrition in cancer patients. Nutrition 12:112–122
Leitao RF, Ribeiro RA, Lira AM, Silva LR, Bellaguarda EA, Macedo FD, Sousa RB, Brito GA (2008) Glutamine and alanyl-glutamine accelerate the recovery from 5-fluorouracil-induced experimental oral mucositis in hamster. Cancer Chemother Pharmacol 61:215–222
Li Y, Yu Z, Liu F, Tan L, Wu B, Li J (2006) Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori 92:396–401
Liang CM, Lee N, Cattell D, Liang SM (1989) Glutathione regulates interleukin-2 activity on cytotoxic T-cells. J Biol Chem 264:13519–13523
Liu SL, Shi DY, Shen ZH, Wu YD (2000) Effects of glutamine on tumor growth and apoptosis of hepatoma cells. Acta Pharmacol Sin 21:668–672
Marks SL, Cook AK, Reader R, Kass PH, Theon AP, Greve C, Rogers QR (1999) Effects of glutamine supplementation of an amino acid-based purified diet on intestinal mucosal integrity in cats with methotrexate-induced enteritis. Am J Vet Res 60:755–763
Medina MA (2001) Glutamine and cancer. J Nutr 131:2539S–2542S
Obrador E, Carretero J, Esteve JM, Pellicer JA, Pascual A, Petschen I, Estrela JM (2001) Glutamine potentiates TNF-alpha-induced tumor cytotoxicity. Free Radic Biol Med 31:642–650
Oguz M, Kerem M, Bedirli A, Mentes BB, Sakrak O, Salman B, Bostanci H (2007) l-Alanine-l-glutamine supplementation improves the outcome after colorectal surgery for cancer. Colorectal Dis 9:515–520
Okur A, Ezgu FS, Tumer L, Cinasal G, Oguz A, Hasanoglu A, Karadeniz C (2006) Effects of oral glutamine supplementation on children with solid tumors receiving chemotherapy. Pediatr Hematol Oncol 23:277–285
Pan CX, Loehrer P, Seitz D, Helft P, Juliar B, Ansari R, Pletcher W, Vinson J, Cheng L, Sweeney C (2005) A phase II trial of irinotecan, 5-fluorouracil and leucovorin combined with celecoxib and glutamine as first-line therapy for advanced colorectal cancer. Oncology 69:63–70
Peng ZY, Hamiel CR, Banerjee A, Wischmeyer PE, Friese RS, Wischmeyer P (2006) Glutamine attenuation of cell death and inducible nitric oxide synthase expression following inflammatory cytokine-induced injury is dependent on heat shock factor-1 expression. J Parenteral Enteral Nutr 30:400–406
Peterson DE, Jones JB, Petit RG (2007) Randomized, placebo-controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy. Cancer 109:322–331
Piccirillo N, De Matteis S, Laurenti L, Chiusolo P, Sorà F, Pittiruti M, Rutella S, Cicconi S, Fiorini A, D’Onofrio G, Leone G, Sica S (2003) Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis. Haematologica 88:192–200
Prada PO, Hirabara SM, de Souza CT, Schenka AA, Zecchin HG, Vassallo J, Velloso LA, Carneiro E, Carvalheira JB, Curi R, Saad MJ (2007) l-Glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity. Diabetologia 50:1949–1959
Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E, Prochazka B, Kozak T (2002) Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Bone Marrow Transpl 30:953–961
Rossi-Fanelli F, Cascino A, Muscaritoli M (1991) Abnormal substrate metabolism and nutritional strategies in cancer management. J Parenteral Enteral Nutr 15:680–683
Rouse K, Nwokedi E, Woodliff JE, Epstein J, Klimberg VS (1995) Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg 221:420–426
Rubio IT, Cao Y, Hutchins LF, Westbrook KC, Klimberg VS (1998) Effect of glutamine on methotrexate efficacy and toxicity. Ann Surg 227:772–778
Salman B, Oguz M, Akmansu M, Bebitoglu I, Akca G, Sultan N, Emre U, Kerem M, Yilmaz U (2007) Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation. Adv Ther 24:648–661
Sauer LA, Dauchy RT (1983) Ketone body, glucose, lactic acid, and amino acid utilization by tumors in vivo in fasted rats. Cancer Res 43:3497–3503
Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B (2003) Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev 29:501–513
Scheid C, Hermann K, Kremer G, Holsing A, Heck G, Fuchs M, Waldschmidt D, Herrmann HJ, Sohngen D, Diehl V, Schwenk A (2004) Randomized, double-blind, controlled study of glycyl-glutamine-dipeptide in the parenteral nutrition of patients with acute leukemia undergoing intensive chemotherapy. Nutrition 20:249–254
Schloerb PR, Amare M (1993) Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomized, double-blind study). J Parenteral Enteral Nutr 17:407–413
Schloerb PR, Skikne BS (1999) Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study. J Parenteral Enteral Nutr 23:117–122
Shou J, Lieberman MD, Hofmann K, Leon P, Redmond HP, Davies H, Daly JM (1991) Dietary manipulation of methotrexate-induced enterocolitis. J Parenteral Enteral Nutr 15:307–312
Singleton KD, Serkova N, Banerjee A, Meng X, Gamboni-Robertson F, Wischmeyer P (2005) Glutamine attenuates endotoxin-induced lung metabolic dysfunction: potential role of heat shock protein 70. Nutrition 21:214–223
Singleton KD, Serkova N, Beckey VE, Wischmeyer PE (2005) Glutamine attenuates lung injury and improves survival after sepsis: role of enhanced heat shock protein expression. Crit Care Med 33:1206–1213
Singleton KD, Wischmeyer PE (2008) Glutamine induces heat shock protein expression via O-glycosylation and phosphorylation of HSF-1 and Sp1. J Parenteral Enteral Nutr 32:371–376
Singleton KD, Wischmeyer PE (2007) Glutamine’s protection against sepsis and lung injury is dependent on heat shock protein 70 expression. Am J Physiol Regul Integr Comp Physiol 292:R1839–R1845
Skubitz KM, Anderson PM (1996) Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med 127:223–228
Soh H, Wasa M, Wang HS, Fukuzawa M (2005) Glutamine regulates amino acid transport and glutathione levels in a human neuroblastoma cell line. Pediatr Surg Int 21:29–33
Stubblefield MD, Vahdat LT, Balmaceda CM, Troxel AB, Hesdorffer CS, Gooch CL (2005) Glutamine as a neuroprotective agent in high-dose paclitaxel-induced peripheral neuropathy: a clinical and electrophysiologic study. Clin Oncol (R Coll Radiol) 17:271–276
Sykorova A, Horacek J, Zak P, Kmonicek M, Bukac J, Maly J (2005) 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 52:476–482
Tisdale MJ (2001) Cancer anorexia and cachexia. Nutrition 17:438–442
Todorova VK, Harms SA, Kaufmann Y, Luo S, Luo KQ, Babb K, Klimberg VS (2004) Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats. Breast Cancer Res Treat 88:247–256
Todorova VK, Harms SA, Luo S, Kaufmann Y, Babb KB, Klimberg VS (2003) Oral glutamine (AES-14) supplementation inhibits PI-3k/Akt signaling in experimental breast cancer. J Parenteral Enteral Nutr 27:404–410
Todorova VK, Kaufmann Y, Luo S, Klimberg VS (2006) Modulation of p53 and c-myc in DMBA-induced mammary tumors by oral glutamine. Nutr Cancer 54:263–273
Turowski GA, Rashid Z, Hong F, Madri JA, Basson MD (1994) Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines. Cancer Res 54:5974–5980
Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, Garrett T, Savage D, Antman K, Hesdorffer CS, Balmaceda C (2001) Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res 7:1192–1197
van Zaanen HC, van der LH, Timmer JG, Fürst P, Sauerwein HP (1994) Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 74:2879–2884
Wang WS, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Chiou TJ, Liu JH, Yen CC, Chen PM (2007) Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist 12:312–319
Ward E, Picton S, Reid U, Thomas D, Gardener C, Smith M, Henderson M, Holden V, Kinsey S, Lewis I, Allgar V (2003) Oral glutamine in paediatric oncology patients: a dose finding study. Eur J Clin Nutr 57:31–36
Wasa M, Bode BP, Abcouwer SF, Collins CL, Tanabe KK, Souba WW (1996) Glutamine as a regulator of DNA and protein biosynthesis in human solid tumor cell lines. Ann Surg 224:189–197
Wigmore SJ, Barber MD, Ross JA, Tisdale MJ, Fearon KC (2000) Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr Cancer 36:177–184
Wigmore SJ, Fearon KC, Maingay JP, Ross JA (1997) Down-regulation of the acute-phase response in patients with pancreatic cancer cachexia receiving oral eicosapentaenoic acid is mediated via suppression of interleukin-6. Clin Sci 92:215–221
Wischmeyer PE (2003) Clinical applications of l-glutamine: past, present, and future. Nutr Clin Pract 18:377–385
Wischmeyer PE (2001) Glutamine: role in critical illness and ongoing clinical trials. Curr Opin Gastroenterol 24:190–197
Yoshida S, Kaibara A, Ishibashi N, Shirouzu K (2001) Glutamine supplementation in cancer patients. Nutrition 17:766–768
Yoshida S, Kaibara A, Yamasaki K, Ishibashi N, Noake T, Kakegawa T (1995) Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats. J Parenteral Enteral Nutr 19:492–497
Yoshida S, Matsui M, Shirouzu Y, Fujita H, Yamana H, Shirouzu K (1998) Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg 227:485–491
Yu JC, Jiang ZM, Li DM, Yang NF, Bai MX (1996) Alanyl-glutamine preserves hepatic glutathione stores after 5-FU treatment. Clin Nutr 15:261–265
Ziegler TR, Young LS, Benfell K, Scheltinga M, Hortos K, Bye R, Morrow FD, Jacobs DO, Smith RJ, Antin JH (1992) Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med 116:821–828
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Kuhn, K.S., Muscaritoli, M., Wischmeyer, P. et al. Glutamine as indispensable nutrient in oncology: experimental and clinical evidence. Eur J Nutr 49, 197–210 (2010). https://doi.org/10.1007/s00394-009-0082-2
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DOI: https://doi.org/10.1007/s00394-009-0082-2