Department of Nutrition and Food Sciences, IEL-Nutrition Physiology, University of Bonn, Endenicher Allee 11-13, 53115, Bonn, Germany.
Eur J Nutr. 2010 Jun;49(4):197-210. doi: 10.1007/s00394-009-0082-2. Epub 2009 Nov 21.
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.
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.
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.
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.
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.
在代谢亢进的情况下，谷氨酰胺被肠细胞、淋巴细胞和成纤维细胞等快速分裂的细胞用作氮源和/或替代能源燃料。据推测，在癌症患者中，宿主对谷氨酰胺的需求增加会增加内源性产生的能力，从而导致强烈的谷氨酰胺剥夺，对器官功能产生不利影响。在癌症恶病质的长期时期，适当的营养支持，包括谷氨酰胺，可以有效地满足谷氨酰胺的需求，从而节省宿主的能量储备，并延缓多器官衰竭等严重并发症。由于早期的体外知识表明癌细胞更喜欢消耗谷氨酰胺，肿瘤学家通常拒绝向肿瘤宿主提供谷氨酰胺，以避免任何潜在的风险。然而，目前仍然缺乏关于补充谷氨酰胺是否支持体内肿瘤生长的客观评价。
本综述评估了关于谷氨酰胺在肿瘤宿主中的潜在作用的体内实验和临床数据，并为临床肿瘤学中谷氨酰胺补充剂的使用得出结论。
通过系统地检索 MEDLINE 数据库（最后一次检索：2008 年 6 月），使用关键搜索词和综述文章，确定了实验和临床干预研究。这些研究还补充了通过手动搜索和作者先前已知的其他研究确定的报告。
许多实验研究（大鼠/小鼠模型）表明，口服/肠内或静脉内谷氨酰胺支持肿瘤宿主的代谢，并能改善治疗措施的胃肠道毒性。在过去的二十年中，已经发表了 36 项（24 项口服/肠内，12 项静脉内）评估各种患者群体中谷氨酰胺耐受性、安全性和效果的临床研究。在这些临床研究中，绝大多数癌症患者的谷氨酰胺补充改善了宿主的代谢和临床状况，而不会增加肿瘤生长。谷氨酰胺作用的潜在机制包括维持粘膜完整性、提高免疫能力、抑制细胞增殖、增加细胞凋亡率、增加谷胱甘肽合成、诱导热休克蛋白合成和增加胰高血糖素样肽合成。
在各种临床情况下，适当的外源性谷氨酰胺供应是安全的，可以有助于降低大剂量化疗和放疗的风险。此外，有一些证据表明，适当的谷氨酰胺供应可以有益地影响结果，特别是在接受骨髓移植的患者中。
