L-Glutamine

  Effect of physical activity on glutamine metabolism.
Agostini F, Biolo G.
Curr Opin Clin Nutr Metab Care. 2010 Jan;13(1):58-64

 Glutamine is largely synthesized in skeletal muscles and provides fuel to rapidly dividing cells of the immune system and precursors to gluconeogenesis in the liver. Physical exercise is known to affect glutamine synthesis and to modulate glutamine uptake. Overtraining is frequently associated with reduced availability of glutamine and decreased immunocompetence. Inactivity affects glutamine metabolism, but this subject was poorly investigated. Strenuous physical exercise as well as exhaustive training programs lead to glutamine depletion due to lowered synthesis and enhanced uptake by liver and immune cells. Evidence suggests that postexercise glutamine depletion is associated with immunodepression. Counterwise, moderate training leads to improved glutamine availability due to a positive balance between muscle synthesis and peripheral clearance. Physical inactivity, as investigated by experimental bed rest in healthy volunteers, reduced glutamine synthesis and availability. After exercise, a reduced glutamine availability may be considered as a marker of overtraining. An increased glutamine availability may contribute to decreased inflammation and health benefits associated with optimal training. Thus, glutamine supplementation may enhance immunocompetence after strenuous exercise. The potential of glutamine supplementation during physical inactivity needs to be explored. PMID: 19841583

  Glutamine administration in patients undergoing cardiac surgery and the influence on blood glutathione levels.
Engel JM, Mühling J, Kwapisz M, Heidt M.
Acta Anaesthesiol Scand. 2009 Nov;53(10):1317-23

 Cardiac surgery with an extracorporeal circulation cardiopulmonary bypass (CPB) is characterized by an oxidative stress response. Glutathione (GSH) belongs to the major antioxidative defense. In metabolic stress, glutamine (GLN) may be the rate-limiting factor of GSH synthesis. Decreased GLN plasma levels were observed after various critical states. We evaluated, in patients undergoing open heart surgery with CPB, the effects of a peri-operative GLN supplementation on GSH in whole blood and assessed their influence on the Sequential Organ Failure Assessment score and the intensive care unit length of stay. In this prospective, randomized, double-blinded study, we included 60 patients (age older than 70 years, ejection fraction <40% or mitral valve replacement) undergoing an elective cardiac surgery with CPB. We randomly assigned each subject to receive an infusion with either GLN (0.5 g/kg/day, group 1) or an isonitrogeneous, isocaloric, isovolemic amino acids solution (group 2) or saline (group 3). From the first post-operative day GLN plasma levels in group 1 were significantly increased compared with the other groups. With saline GSH the levels decreased significantly post-operatively compared with GLN. We observed a significant correlation between GLN delivery and GSH levels. A peri-operative high-dose GLN infusion increased plasma GLN concentrations and maintained the GSH levels after cardiac surgery with CPB.
PMID: 19681775

  Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation.
Wang J, Chen L, Li P, Li X, Zhou H, Wang F, Li D, Yin Y, Wu G.
J Nutr. 2008 Jun;138(6):1025-32.

 Dietary supplementation of glutamine prevents intestinal dysfunction and atrophy in weanling piglets, but the underlying mechanism(s) are largely unknown. This study was conducted to test the hypothesis that weaning or glutamine may modulate expression of genes that are crucial for intestinal metabolism and function. In Expt. 1, we obtained small intestine from 28-d-old pigs weaned at 21 d of age and from age-matched suckling piglets. In Expt. 2, piglets were weaned at 21 d of age and then had free access to diets supplemented with 1% L-glutamine (wt:wt) or isonitrogenous L-alanine (control). At d 28, we collected small intestine for biochemical and morphological measurements and microarray analysis of gene expression using the Operon Porcine Genome Oligo set. Early weaning resulted in increased (52-346%) expression of genes related to oxidative stress and immune activation but decreased (35-77%) expression of genes related to macronutrient metabolism and cell proliferation in the gut. Dietary glutamine  supplementation increased intestinal expression (120-124%) of genes that are necessary for cell growth and removal of oxidants, while reducing (34-75%) expression of genes that promote oxidative stress and immune activation. Functionally, the glutamine treatment enhanced intestinal oxidative-defense capacity (indicated by a 29% increase in glutathione concentration), prevented jejunal atrophy, and promoted small intestine growth (+12%) and body weight gain (+19%) in weaned piglets. These findings reveal coordinate alterations of gene expression in response to weaning and aid in providing molecular mechanisms for the beneficial effect of dietary glutamine supplementation to improve nutrition status in young mammals. PMID: 18492829

  Enteral glutamine: a novel mediator of PPARgamma in the postischemicgut.
Ban K, Kozar RA.
J Leukoc Biol. 2008 Sep;84(3):595-9

 Early enteral nutrition supplemented with glutamine, arginine, omega-3 fatty acids, and nucleotides has been shown to decrease infection complications in critically injured patients. Concern has been raised, however, that under conditions of hyperinflammation, these diets may be injurious through the induction of inducible NO synthase by enteral arginine. In a rodent model of gut ischemia/reperfusion, inflammation and injury are intensified by enteral arginine and abrogated by glutamine. These findings correlate with the degree of metabolic stress imposed upon the gut by hypoperfusion. Glutamine is metabolized by the gut and therefore, can contribute back energy in the form of ATP, whereas arginine is a nonmetabolizable nutrient, using but not contributing energy. Recent data suggest that one of the molecular mechanisms responsible for the gut-protective effects of enteral glutamine is the activation of peroxisome proliferator-activated receptor gamma. This anti-inflammatory transcription factor belongs to the family of nuclear receptors, plays a key role in adipocyte development and glucose homeostasis, and has been recognized as an endogenous regulator of intestinal inflammation. Preliminary clinical studies support the use of enteral glutamine in patients with gut hypoperfusion. PMID: 18390929

  Enteral glutamine during active shock resuscitation is safe and enhances tolerance of enteral feeding.
McQuiggan M, Kozar R, Sailors RM, Ahn C, McKinley B, Moore F.
JPEN J Parenter Enteral Nutr. 2008 Jan-Feb;32(1):28-35.

 Feeding the hemodynamically unstable patient is increasingly practiced, yet few data exist on its safety. Because enteral glutamine is protective to the gut in experimental models of shock and improves clinical outcomes, it may benefit trauma patients undergoing shock resuscitation and improve tolerance if administered early. This pilot study aimed to evaluate gastrointestinal tolerance and safety of enteral feeding with glutamine, beginning during shock resuscitation in severely injured patients. In a prospective randomized trial, 20 patients were randomly assigned to either an enteral glutamine group (n = 10) or a control group (n = 10). Patients with severe trauma meeting standardized shock resuscitation criteria received enteral glutamine 0.5 g/kg/d during the first 24 hours of resuscitation and 10 days thereafter. Immune-enhancing diet began on postinjury day 1, with a target of 25 kcal/kg/d. Control patients received isonitrogenous whey powder plus immune-enhancing diet. Tolerance (vomiting, nasogastric output, diarrhea, and distention) was assessed throughout the study. Glutamine was well tolerated and no adverse events occurred. Treated patients had significantly fewer instances of high nasogastric output (5 vs 23; p = .010), abdominal distention (3 vs 12; p = .021), and total instances of intolerance (8 vs 42; p = .011). Intensive care unit (ICU) and hospital length of stay were comparable. Control patients required supplemental parenteral nutrition (PN) to meet goals at day 7. Enteral glutamine administered during active shock resuscitation and through the early postinjury period is safe and enhances gastrointestinal tolerance. A large clinical trial is warranted to determine if enteral glutamine administered to the hemodynamically unstable patient can reduce infectious morbidity and mortality. PMID: 18165444

  Regulation of protein metabolism by glutamine: implications for nutrition and health.
Xi P, Jiang Z, Zheng C, Lin Y, Wu G.
Front Biosci. 2011 Jan 1;16:578-97.

 Glutamine is the most abundant free alpha-amino acid in plasma and skeletal muscle. This nutrient plays an important role in regulating gene expression, protein turnover, anti-oxidative function, nutrient metabolism, immunity, and acid-base balance. Interestingly, intracellular and extracellular concentrations of glutamine exhibit marked reductions in response to infection, sepsis, severe burn, cancer, and other pathological factors. This raised an important question of whether glutamine may be a key mediator of muscle loss and negative nitrogen balance in critically ill and injured patients. Therefore, since the initial reports in late 1980s that glutamine could stimulate protein synthesis and inhibit proteolysis in rat skeletal muscle, there has been growing interest in the use of this functional amino acid to improve protein balance under various physiological and disease conditions. Although inconsistent results have appeared in the literature regarding a therapeutic role of glutamine in clinical medicine, a majority of studies indicate that supplementing appropriate doses of glutamine to enteral diets or parenteral solutions is beneficial for improving nitrogen balance in animals or humans with glutamine deficiency. PMID: 21196190

  Glutamine preserves skeletal muscle force during an inflammatory insult.
Meador BM, Huey KA.
Muscle Nerve. 2009 Dec;40(6):1000-7

 The purpose of this study was to test the hypothesis that acute glutamine (GLN)  supplementation can counteract skeletal muscle contractile dysfunction occurring in response to inflammation by elevating muscle heat shock protein (Hsp) expression and reducing inflammatory cytokines. Mice received 5 mg/kg lipopolysaccharide (LPS) concurrently with 1 g/kg GLN or vehicle treatments. Plantarflexor isometric force production was measured at 2 hours post-injection. Blood and gastrocnemius  muscles were collected, and serum and muscle tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and muscleHsp70 and Hsp25 were quantified. Saline/LPS treatment was associated with a 33% reduction in maximal force and elevated serum TNF-alpha and IL-6. GLN completely prevented this force decrement with LPS. GLN was found to reduce muscle Hsp70 and IL-6, but only in the presence of LPS. GLN supplementation provides an effective, novel, clinically applicable means of preserving muscle force during acute inflammation. These data indicate that force preservation is not dependent on reductions in serum cytokines or muscle TNF-alpha, or elevated Hsp levels. PMID: 19705479

  Increased plasma bicarbonate and growth hormone after an oral glutamine load.
Welbourne TC.
Am J Clin Nutr. 1995 May;61(5):1058-61

 An oral glutamine load was administered to nine healthy subjects to determine the effect on plasma glutamine, bicarbonate, and circulating growth hormone concentrations. Two grams glutamine were dissolved in a cola drink and ingested over a 20-min period 45 min after a light breakfast. Forearm venous blood samples were obtained at zero time and at 30-min intervals for 90 min and compared with time controls obtained 1 wk earlier. Eight of nine subjects responded to the oral glutamine load with an increase in plasma glutamine at 30 and 60 min before returning to the control value at 90 min. Ninety minutes after the glutamine administration load both plasma bicarbonate concentration and circulating plasma growth hormone concentration were elevated. These findings demonstrate that a surprisingly small oral glutamine load is capable of elevating alkaline reserves as well as plasma growth hormone. PMID: 7733028