Glutamine-(dipeptides) -an update
作者：Peter F rst ,MD ,PhD
单位：
关键词：
中国临床营养杂志000135Glutamine- (dipeptides) -an update
Peter F rst,MD,PhD
(University of Hohenheim, Institute of Biological Chemistry & Nutrition, Stuttgart)
A) What should be known about supplemental glutamine-(dipeptides)?
In numerous controlled clinical trials it could be convincingly demonstrated that supplemental glutamine- (dipeptide) nutrtion was associated with improved nitrogen balance and mood; increased protein synthesis and lymphocyte count (total and subpopulation); maintained intestinal function, intracellular mused free glutamine pool, gut permeability and function, reduced 3MeHis excretion, morbidity, length of hospital stay and sepsis frequency. A current European multi center study with ala-gln provides convincing evidence that the clinical use of glutamine dipeptide spares nitrogen and shortens length of hospital stay as compared with the controls. The infusion of the glutamine containing dipeptide solution was free of any side effects, and recovery was normal for each patient. Provision of glutamine- (dipeptide) should be considered as a replacement of a deficiency rather than a supplement. This implies that the beneficial effects observed are due to a correction of disadvantages produced by an inadequacy of conventional nutrition.
, 百拇医药
B)What is new in glutamine (dipeptide) research?
1) It is purposed that tissue glutathione synthesis is a crucial factor in causing reversal of the dinical, biochemieal signs of critical illness, a condition associated with decreased glutathione status. Indeed, the decreased ratio GSH/GSSG suggests oxidative stress in the tissues. In the future, glutamine containing dipeptides will certainly serve as a means to maintain and/or restore tissue glutathione concentrations.
, 百拇医药
2)Modification of the endogenous inflammatory response:
attenuation of the elaboration of pro-inflammatory mediators, upregulation of antiinfiammatory factors, improved immune response. Studies are in progress showing that supplemental glutamine containing dipeptides decrease eytotoxieity and the synthesis of TNFα, and IL8 while they enhance the ability to express the anti-inflammatory IL10. An encouraging perspective is the novel finding that provision of alanyl-glutamine promotes the synthesis of cysteinyl-leukotrienes and that the capacity to generate eysteinylleukotrienes is associated with the outcome, serving as a biomarker for survival. The question might be raisd, whether the combined deficiency of gluathione and glutamine is intrinsically related to the lenkotriene synthesizing capacity of the sick cell. These factors migh
, http://www.100md.com
be mediated through enhanced synthesis of glutathione.
3) Growth faetors-glutamine- (dipeptide) interaction
represents a nwe strategy to enhance the efficacy of glutamine- (dipeptide) nutrition. Growth factors to consider: human growth hormone, insulin-like growth factor Ⅰ and epidermal growth factor
4) A novel method enabling accurate measurements of protein-bound glutamine in protein or peptide-hased enteral diets. The knowledge of glutamine content in various proteins facilitates revision of tissue/organ glutamine kinetics.
, 百拇医药
C)How to use glutamine (dipeptides) in routine elinicial setting?
Major questions: which patients, when to start, how much, how long to administer, which route of administration, how to monitor efficacy?
Outlook
Future implications of glutamine (dipeptide) therapy are full of promise. A consistent observation is that glutamine (dipeptide) -enriched parenteral feeding attenuates the stressinduced expansion of extracellular and total body water membrane function and thereby changing the cellular hydration state. Experimental studies suggest that glutamine availability is an essential factor during conditions associated with glucose intolerance, lunting insulin action on glucose production and enhanced insulin-mediated glucose utilization. A further fascinating approach proposes glutamine (dipeptides) as a suitable cardioprotective and rescue agent. The mechanism through which giutamine exerts its beneficial effects may involve maintenance of myocardial glutamate and thus glutsthione as well as myocardial high energy phosphates and prevention of myocardial lactate accumulation. Supplemental glutsmine (dipeptide) might thus support the heart during reperfusion in patients with acute myocardial infarction and might improve the postoperative ventricular function and the postoperative survival in patients with coronary artery disease., 百拇医药
单位：
关键词：
中国临床营养杂志000135Glutamine- (dipeptides) -an update
Peter F rst,MD,PhD
(University of Hohenheim, Institute of Biological Chemistry & Nutrition, Stuttgart)
A) What should be known about supplemental glutamine-(dipeptides)?
In numerous controlled clinical trials it could be convincingly demonstrated that supplemental glutamine- (dipeptide) nutrtion was associated with improved nitrogen balance and mood; increased protein synthesis and lymphocyte count (total and subpopulation); maintained intestinal function, intracellular mused free glutamine pool, gut permeability and function, reduced 3MeHis excretion, morbidity, length of hospital stay and sepsis frequency. A current European multi center study with ala-gln provides convincing evidence that the clinical use of glutamine dipeptide spares nitrogen and shortens length of hospital stay as compared with the controls. The infusion of the glutamine containing dipeptide solution was free of any side effects, and recovery was normal for each patient. Provision of glutamine- (dipeptide) should be considered as a replacement of a deficiency rather than a supplement. This implies that the beneficial effects observed are due to a correction of disadvantages produced by an inadequacy of conventional nutrition.
, 百拇医药
B)What is new in glutamine (dipeptide) research?
1) It is purposed that tissue glutathione synthesis is a crucial factor in causing reversal of the dinical, biochemieal signs of critical illness, a condition associated with decreased glutathione status. Indeed, the decreased ratio GSH/GSSG suggests oxidative stress in the tissues. In the future, glutamine containing dipeptides will certainly serve as a means to maintain and/or restore tissue glutathione concentrations.
, 百拇医药
2)Modification of the endogenous inflammatory response:
attenuation of the elaboration of pro-inflammatory mediators, upregulation of antiinfiammatory factors, improved immune response. Studies are in progress showing that supplemental glutamine containing dipeptides decrease eytotoxieity and the synthesis of TNFα, and IL8 while they enhance the ability to express the anti-inflammatory IL10. An encouraging perspective is the novel finding that provision of alanyl-glutamine promotes the synthesis of cysteinyl-leukotrienes and that the capacity to generate eysteinylleukotrienes is associated with the outcome, serving as a biomarker for survival. The question might be raisd, whether the combined deficiency of gluathione and glutamine is intrinsically related to the lenkotriene synthesizing capacity of the sick cell. These factors migh
, http://www.100md.com
be mediated through enhanced synthesis of glutathione.
3) Growth faetors-glutamine- (dipeptide) interaction
represents a nwe strategy to enhance the efficacy of glutamine- (dipeptide) nutrition. Growth factors to consider: human growth hormone, insulin-like growth factor Ⅰ and epidermal growth factor
4) A novel method enabling accurate measurements of protein-bound glutamine in protein or peptide-hased enteral diets. The knowledge of glutamine content in various proteins facilitates revision of tissue/organ glutamine kinetics.
, 百拇医药
C)How to use glutamine (dipeptides) in routine elinicial setting?
Major questions: which patients, when to start, how much, how long to administer, which route of administration, how to monitor efficacy?
Outlook
Future implications of glutamine (dipeptide) therapy are full of promise. A consistent observation is that glutamine (dipeptide) -enriched parenteral feeding attenuates the stressinduced expansion of extracellular and total body water membrane function and thereby changing the cellular hydration state. Experimental studies suggest that glutamine availability is an essential factor during conditions associated with glucose intolerance, lunting insulin action on glucose production and enhanced insulin-mediated glucose utilization. A further fascinating approach proposes glutamine (dipeptides) as a suitable cardioprotective and rescue agent. The mechanism through which giutamine exerts its beneficial effects may involve maintenance of myocardial glutamate and thus glutsthione as well as myocardial high energy phosphates and prevention of myocardial lactate accumulation. Supplemental glutsmine (dipeptide) might thus support the heart during reperfusion in patients with acute myocardial infarction and might improve the postoperative ventricular function and the postoperative survival in patients with coronary artery disease., 百拇医药