Glutamine-supplemented Total Parenteral Nutrition Research Articles

Glutamine for induction of remission in Crohn's disease.

Crohn's disease is a chronic relapsing condition of the alimentary tract with a high morbidity secondary to bowel inflammation. Glutamine plays a key role in maintaining the integrity of the intestinal mucosa and has been shown to reduce inflammation and disease activity in experimental models of Crohn's disease. To evaluate the efficacy and safety of glutamine supplementation for induction of remission in Crohn's disease. We searched the following databases from inception to November 15, 2015: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialised Register. Study references were also searched for additional trials. There were no language restrictions. Randomised controlled trials (RCTs) that compared glutamine supplementation administered by any route to a placebo, active comparator or no intervention in people with active Crohn's disease were considered for inclusion. Two authors independently extracted data and assessed the methodological quality of the included studies. The Cochrane risk of bias tool was used to assess methodological quality. The primary outcome measure was clinical or endoscopic remission. Secondary outcomes included intestinal permeability, clinical response, quality of life, growth in children and adverse events. Risk ratios and 95% confidence intervals were calculated for dichotomous outcomes. The overall quality of the evidence supporting the primary outcome was evaluated using the GRADE criteria. Two small RCTs (total 42 patients) met the inclusion criteria and were included in the review. One study (18 patients) compared four weeks of treatment with a glutamine-enriched polymeric diet (42% amino acid composition) to a standard polymeric diet (4% amino acid composition) with low glutamine content in paediatric patients (< 18 years of age) with active Crohn's disease. The other study (24 patients) compared glutamine-supplemented total parenteral nutrition to non-supplemented total parenteral nutrition in adult patients (> 18 years of age) with acute exacerbation of inflammatory bowel disease. The paediatric study was rated as low risk of bias. The study in adult patients was rated as unclear risk of bias for blinding and low risk of bias for all other items. It was not possible to pool data for meta-analysis because of significant differences in study populations, nature of interventions, and the way outcomes were assessed. Data from one study showed no statistically significant difference in clinical remission rates at four weeks. Forty-four per cent (4/9) of patients who received a glutamine-enriched polymeric diet achieved remission compared to 56% (5/9) of patients who received a standard low-glutamine polymeric diet (RR 0.80, 95% CI 0.31 to 2.04). A GRADE analysis indicated that the overall quality of evidence for this outcome was low due to serious imprecision (9 events). In both included studies, no statistically significant changes in intestinal permeability were found between patients who received glutamine supplementation and those who did not. Neither study reported on clinical response, quality of life or growth in children. Adverse event data were not well documented. There were no serious adverse events in the paediatric study. The study in adult patients reported three central catheter infections with positive blood cultures in the glutamine group compared to none in the control group (RR 7.00, 95% CI 0.40 to 122.44). Currently there is insufficient evidence to allow firm conclusions regarding the efficacy and safety of glutamine for induction of remission in Crohn's disease. Data from two small studies suggest that glutamine supplementation may not be beneficial in active Crohn's disease but these results need to be interpreted with caution as they are based on small numbers of patients. This review highlights the need for adequately powered randomised controlled trials to investigate the efficacy and safety of glutamine for induction of remission in Crohn's disease.

GlutamineSupplementedParenteralNutritiontoPreventVentilatorAssociated Pneumonia in the Intensive Care Unit

Ventilator-associated pneumonia (VAP) is a form of nosocomial pneumonia that increases patient morbidity and mortality, length of hospital stay, and healthcare costs. Glutamine preserves the intestinal mucosal structure, increases immune function, and reduces harmful changes in gut permeability in patients receiving total parenteral nutrition (TPN). We hypothesized that TPN supplemented by glutamine might prevent the development of VAP in patients on mechanical ventilator support in the intensive care unit (ICU). With the approval of the ethics committee and informed consent from relatives, 60 patients who were followed in the ICU with mechanical ventilator support were included in our study. Patients were divided into three groups. The first group received enteral nutrition (n=20), and the second was prescribed TPN (n=20) while the third group was given glutamine-supplemented TPN (n=20). C-reactive protein (CRP), sedimentation rate, body temperature, development of purulent secretions, increase in the amount of secretions, changes in the characteristics of secretions and an increase in requirement of deep tracheal aspiration were monitored for seven days by daily examination and radiographs. No statistically significant difference was found among groups in terms of development of VAP (p=0.622). Although VAP developed at a lower rate in the glutamine-supplemented TPN group, no statistically significant difference was found among any of the groups. Glutamine-supplemented TPN may have no superiority over unsupplemented enteral and TPN in preventing VAP.

Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome

Glutamine is an important substrate for enterocyte and other rapidly proliferating cells. Low plasma and tissue levels present in glutamine in critically ill patients suggest that demand may exceed endogenous supply. Because commercially available amino acid solutions do not contain glutamine because of its instability in aqueous solution, conventional total parenteral nutrition (TPN) does not prevent stress-induced glutamine depletion. In this study, we administered intravenous glutamine-supplemented TPN to patients with systemic inflammatory response syndrome (SIRS) to investigate the effect of glutamine supplementation on immune states. This study is a prospective, randomized clinical trial. All patients received TPN given continuously for 6 days. Thirty patients with SIRS were allocated to either a glutamine group ( l-glutamine 0.4g/[kg d]) (n = 15) or a control group (n = 15). Blood samples were collected on day 1 and day 6 after admission for C-reactive protein, immunoglobulin (Ig) M, IgG, IgA, C 3, C4, and lymphocyte analysis. The Acute Physiologic and Chronic Health Evaluation II score and the Simplified Acute Physiologic II (SAPS II) score were used to evaluate the patients after admission. Although there was a tendency for decreased T cytotoxic cells and natural killer cells in the control group, no significant difference was observed between the 2 groups. However, an increase in lymphocyte and lymphocyte subgroups in the glutamine group was observed; but there was no difference between the groups. A low SAPS II score was observed on the sixth day in the glutamine group, whereas no difference in SAPS II and Acute Physiologic and Chronic Health Evaluation II scores was observed between the 2 groups. There was no difference in IgM, IgG, IgA, C 3, and C4 levels and numbers of B-lymphocytes between the groups. Glutamine-added TPN significantly decreases leukocyte and natural killer cell count and therefore suppresses inflammation. Furthermore, total lymphocyte count, B- and T-lymphocytes, and their subgroups (helper T-lymphocytes, cytotoxic T-lymphocytes) are increased; although not statistically significant, these increases might be playing a role in improving the immune system.

Glutamine Prevents Total Parenteral Nutrition-Associated Changes to Intraepithelial Lymphocyte Phenotype and Function: A Potential Mechanism for the Preservation of Epithelial Barrier Function

Total parenteral nutrition (TPN) results in a number of derangements to the intestinal epithelium, including a loss of epithelial barrier function (EBF). As TPN supplemented with glutamine has been thought to prevent this loss, this article further defined the impact of glutamine on EBF, and investigated potential mechanisms that contributed to the preservation of EBF. C57BL/6J male mice were randomized to enteral nutrition (control), TPN, or TPN supplemented with glutamine (TPN+GLN). Changes in intraepithelial lymphocyte (IEL)-derived cytokine expression were measured, and EBF was assessed with electrophysiologic methods and assessment of junctional protein expression. TPN resulted in a significant decline in EBF, and this loss of EBF was significantly prevented in the TPN+GLN group. Coincident with these changes was a loss of intraepithelial lymphocyte (IEL, mucosal lymphocyte)-derived IL-10 and increase in interferon-gamma (IFN-gamma) expression, and a decline in IEL numbers in the TPN group. A prevention in the increase in IFN-gamma and decline in IL-10 expression was seen in the TPN+GLN group. To determine the mechanism responsible for these glutamine-associated cytokine changes, we tested whether blockade of the IL-7 signaling pathway between epithelial cells (EC) and IEL would prevent these changes; however, blockade failed to influence IEL-derived cytokine changes. Glutamine-supplemented TPN leads to a specific IEL-derived cytokine profile, which may account for the preservation of EBF; and such action may be due to a direct action of glutamine on the IEL.

Does glutamine-supplemented total parenteral nutrition reduce the incidence of nosocomial pneumonia?

Does glutamine-supplemented total parenteral nutrition reduce the incidence of nosocomial pneumonia?

Does glutamine-supplemented total parenteral nutrition reduce the incidence of nosocomial pneumonia?

Does glutamine-supplemented total parenteral nutrition reduce the incidence of nosocomial pneumonia?

The Motogenic Effects of Cyclic Mechanical Strain on Intestinal Epithelial Monolayer Wound Closure Are Matrix Dependent

Complex deformation during normal digestion due to peristalsis or villous motility may be trophic for the intestinal mucosa. Because tissue fibronectin is increased in inflammatory states that may accompany mucosal injury, we evaluated the effects of cyclic mechanical strain and fibronectin on intestinal epithelial monolayer wound closure in Caco-2 and IEC-6 intestinal epithelial cells. Wounds created in intestinal epithelial monolayers were subjected to cyclic deformation. Wound closure was assessed by morphometry using microscopic imaging. Cell signals were assessed by Western blot and confocal microscopy. Mechanical strain stimulated wound closure on fibronectin but inhibited closure on collagen in Caco-2 and IEC-6 cells. The effect was independent of proliferation or cell spreading. Myosin light chain (MLC) and extracellular signal-regulated kinase (ERK) were phosphorylated in response to strain in confluent monolayers on both collagen and fibronectin. Blocking MLC or ERK phosphorylation inhibited the motogenic effect of strain on fibronectin. Although phosphorylated MLC was redistributed to the leading edge of migrating cells following 6 hours of strain on collagen and fibronectin, phosphorylated ERK was redistributed to the lamellipodial edge only on fibronectin. Strain promotes intestinal epithelial wound closure by a pathway requiring ERK and MLC kinase. Fibronectin-dependent ERK redistribution in response to strain in confluent migrating cells may explain the matrix dependence of the motogenic effect. Repetitive deformation stimulates intestinal epithelial proliferation on a collagen substrate, but not fibronectin. Deformation may exert matrix-dependent effects on intestinal epithelial cells, promoting epithelial restitution in fibronectin-rich tissue and proliferation in fibronectin-poor mucosa.

The effect of glutamine-supplemented total parenteral nutrition on nutrition and intestinal absorptive function in a rat model

The aim of the present study was to evaluate the effect of short-term (7 days) glycyl-glutamine-supplemented total parenteral nutrition (TPN) on nutrition and intestinal absorptive function in a rat model. Thirty Wistar rats, weighting 140-180 g, were divided into three groups (n=10) randomly. The animals received isonitrogenous and isocaloric TPN solutions for 7 days. The nitrogen was supplied by glycyl-glutamine dipeptide-supplemented amino acid solution (group G), and two standard amino acid solutions (group V, group N), respectively. Body weight, plasma glutamine level, nitrogen balance, total tissue water and intestinal absorptive function, assessed by (15-N)-glycine absorption, were investigated. Body weight decreased in three groups at the end of TPN; there was no significant difference in relative body-weight changes. There was a significant improvement of cumulative nitrogen balance and nitrogen retention in group G compared to other groups (P<0.05). There was no significant difference in intestinal glycine absorption (P>0.05) among the three groups. Total tissue water of left thigh muscle was significantly higher in group V and group N than that in group G (P<0.05). The results indicated that short-term (7 days) TPN supplemented with glycyl-glutamine improved plasma glutamine level and nitrogen balance, decreased water content of muscle, but had no beneficial effect on absorptive function in a rat model.

Glutamine-supplemented total parenteral nutrition attenuates plasma interleukin-6 in surgical patients with lower disease severity

Previous reports have shown that decrease in plasma glutamine (Gln) level following major surgery may contribute to the state of immunosuppression. Gln supplementation improves the depletion of body Gln pool, and may have indirect effect on reducing proinflammatory mediator release. This study evaluated whether the effect of Gln dipeptide-enriched total parenteral nutrition (TPN) on postoperative cytokine alteration depended on the disease severity of surgical patients. Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/kg per d) and isocaloric (30 kcal/kg per d) TPN for 6 d. Control group (Conv) using conventional TPN solution received 1.5 g amino acids/kg per day, whereas the test group received 0.972 g amino acids/kg per day and 0.417 g L-alanyl-L-glutamine (Ala-Gln)/kg per day. Blood samples were collected on d 1 and d 6 postoperatively for plasma interleukin (IL)-2, IL-6, IL-8, and interferon (IFN)-gamma analysis. Plasma IL-2 and IFN-gamma were not detectable. IL-6 concentrations were significantly lower on the 6(th) postoperative day in the Ala-Gln group than those in the Conv group in patients with APACHE II <=6, whereas no difference was noted in patients with APACHE II >6. There was no difference in IL-8 levels between the two groups. No difference in cumulative nitrogen balance was observed on d 2-5 after the operation between the two groups (Ala-Gln -3.2+/-1.6 g vs Conv -6.5+/-2.7 g). A significant inverse correlation was noted between plasma IL-6 levels and cumulative nitrogen balance postoperatively in the Ala-Gln group, whereas no such correlation was observed in the Conv group. TPN supplemented with Gln dipeptide had no effect on plasma IL-8 levels after surgery. However, Gln supplementation had a beneficial effect on decreasing systemic IL-6 production after surgery in patients with low admission illness severity, and lower plasma IL-6 may improve nitrogen balance in patients with abdominal surgery when Gln was administered.

Effect of total parenteral nutrition (TPN) with and without glutamine dipeptide supplementation on outcome in severe acute pancreatitis (SAP)

Objective: To investigate the effect of total parenteral nutrition (TPN) and glutamine-supplemented TPN in patients with serious acute pancreatitis (SAP). Methods: Sixty-four patients with SAP were randomly divided into three therapeutic groups. Twenty-three cases (group I) were treated by traditional therapeutic program combined with traditional therapy, the 21 cases in group II and 20 cases in group III were treated by TPN and glutamine-supplemented TPN, respectively. The concentration of serum albumin was determined, recovery time of blood amylase, the incidence of complications, mortality, length of hospital stay (LOS) and body mass of the patients in each group were monitored. Results: The concentrations of serum albumin were low in all three groups at admission. After 2 weeks of treatment, the serum albumin concentration increased in groups II and III, while it remained almost the same in group I. Mortalities for groups I, II, and III were 43.5% (10/23), 14.3% (3/21, vs. group I P<0.05) and 0% (vs. group I P<0.01), respectively. The incidence of complications in group I (21/23) was much higher than those in group II (11/21, P<0.01) and group III (4/20, P<0.01), and in group III they were less frequent than in group II (P<0.05). In fact no pancreatic infection occurred in group III with glutamine dipeptide supplementation. The loss of body mass in group I was more profound than in groups II and III, P<0.05. The length of stay (LOS) in group I (39.1±10.60 d) was longer than those of group II (28.6±6.90 d, P<0.05) and III (25.3±7.60 d, P<0.01). Conclusions: Combined with conventional therapy, TPN and glutamine dipeptide-supplemented TPN therapy can reduce mortality and the incidence of infectious complications, shorten the LOS, and improve the nutritional status of patients with SAP. Glutamine-supplemented TPN therapy can apparently prevent the occurrence of pancreatic infection.

Infection, multiple organ failure, and survival in the intensive care unit: influence of glutamine-supplemented parenteral nutrition on acquired infection

OBJECTIVE: We investigated the effect of a glutamine-supplemented parenteral nutrition on intensive-care-acquired infection (ICAI) and its relation to outcome. METHODS: We analyzed new data prospectively collected during a double-blind, randomized, and controlled trial in an adult general intensive care unit previously reported (Nutrition 1997;13:295). Eighty-four patients were randomized to receive glutamine-supplemented total parenteral nutrition or an isonitrogenous, isoenergetic control. Sepsis was present on admission in 71% of the patients. Clinical and microbiological data were collected on all new infective episodes and associated treatment decisions. Data were analyzed blind to the randomization and study outcome. RESULTS: There was no significant difference in the number of patients developing new infections or in the number occurring during the first 5 d. There was a non-significant trend to increased numbers of infections in those patients receiving the control feed for at least 5 d. In these patients the glutamine recipients showed significantly fewer catheter-related infections: 21 versus 12 ( P = 0.026). The difference in overall 6-mo mortality was almost completely described by those patients fed for at least 5 d: 9 of 25 versus 18 of 27 using the control nutrition ( P = 0.05). Of the deaths in the intensive care unit due to multiple organ failure, 8 of 8 in the glutamine group and 14 of 16 in the control group sustained one or more ICAI and accounted for 38% versus 74%, respectively, of the ICAIs occurring in those patients. In those patients, despite a similar high incidence of colonization with Candida, those receiving glutamine developed fewer Candida infections and none died, whereas six control patients who developed Candida infections died from multiple organ failure ( P = 0.02). Survival was not related to the reduced occurrence of the first acquired infection; however, binary logistic regression analysis of glutamine and the incidence of ICAI after starting total parenteral nutrition to outcome showed that only glutamine was significantly associated with improved 6-mo survival ( P = 0.027). CONCLUSIONS: In these severely ill patients, parenteral nutrition containing glutamine may not reduce the overall incidence of ICAI, but it may reduce the risk of dying from acquired infections. The improved survival seen at 6 mo appeared related mostly to reduced mortality in the intensive care unit from multiple organ failure in those patients in whom acquired infections are common.

The effect of glutamine-supplemented total parenteral nutrition on nitrogen economy depends on severity of diseases in surgical patients

Background: Gln is an important substrate for enterocyte and rapid proliferation cells. Studies have shown that parenteral supplementation of Gln maintains the intracellular Gln pool, improves nitrogen balance and shortens hospital stay. However, some studies showed Gln-supplemented TPN had no effect on restoring the Gln pool in critically ill patients. Objective: To evaluate the effect of glutamine (Gln) dipeptide supplementation of total parenteral nutrition (TPN) on postoperative nitrogen balance and immune response of patients undergoing surgery. Methods: This study is a prospective, randomized double-blind clinical trial. APACHE II score and TISS were used to evaluate the patients after admission. Forty-eight patients with major abdominal surgery were allocated to two groups to receive isonitrogenous (0.228 g nitrogen/kg/day) and isoenergetic (30 kcal/kg/day) TPN for 6 days. Two groups (Conv and Ala-Gln) were further divided to high (APACHE⩾6) and low (APACHE <6) groups. Control group (Conv) received 1.5 g amino acids/kg/day, whereas the Ala-Gln group received 0.972 g amino acids/kg/day and 0.417 g of L -alanyl- L -glutamine (Ala-Gln)/kg/day. Blood samples were collected on day 1 and day 6 after surgery for plasma amino acid and CD4, CD8 cell and T lymphocyte analysis. Cumulative nitrogen balance were also measured on day 2, 3, 4, 5 postoperatively. Results: Although there was a tendency to have better cumulative nitrogen balance on the postoperative days in the Ala-Gln group, no significant difference was observed between two groups. However, a better significant cumulative nitrogen balance was observed on the 2nd, 3rd and 5th postoperative day in the Ala-Gln group than in the Conv group in patients with APACHE II <6, whereas no significant difference was noted in patients with APACHE II ⩾ 6. No difference in urine 3-methylhistidine excretion were observed between the 2 groups. Patients in the Ala-Gln group had significant higher T lymphocyte and CD4 cells than did those in the Conv group.Conclusion: TPN supplemented with Gln dipeptide had beneficial effect on enhancing the immune response. However, the effect of Ala-Gln administration on improving nitrogen economy was only observed in patients with low APACHE II scores. These results may indicate that Gln required for reversing the catabolic condition may depend on the characteristics and severity of the diseases.

Total parenteral nutrition supplementation with glutamine improves survival after gut ischemia/reperfusion.

Total parenteral nutrition (TPN) alters gut cytokines and mucosal immunity and increases intercellular adhesion molecule-1 (ICAM-1) expression, gut neutrophil levels, and mortality after gut ischemia. Supplementation of TPN with glutamine partially supports mucosal immunity by preserving respiratory and intestinal IgA levels, maintaining the proper IgA-stimulating cytokine milieu within the intestine, and reducing intestinal ICAM-1 expression and neutrophil accumulation. This work investigates whether glutamine supplementation of TPN affects mortality in mice after gut ischemic insult. Thirty-eight mice were randomized to receive chow, TPN, or 2% glutamine-supplemented TPN (GLN-TPN) for 5 days. After feeding their respective diets, gut ischemia/reperfusion (I/R) was induced with superior mesenteric artery occlusion for 30 minutes followed by resuscitation with 1 mL saline. Survival was recorded until 72 hours after reperfusion. Survival time was significantly reduced in the TPN-fed mice compared with both chow-fed and GLN-TPN-fed mice (p < .05). Survival at 72 hours after reperfusion was also significantly lower in the TPN-fed mice than in the chow-fed and GLN-TPN-fed mice (p < .05) Glutamine supplementation of TPN significantly improves survival after gut I/R, suggesting modulation of the inflammatory response or improved gut tolerance to low-flow states.

Glutamine-supplemented total parenteral nutrition in major abdominal surgery

Glutamine-supplemented total parenteral nutrition in major abdominal surgery

Effects of glutamine-supplemented total parenteral nutrition on cytokine production and T cell population in septic rats.

This study was designed to investigate the effects of total parenteral nutrition (TPN) enriched with glutamine (GLN) on in vivo cytokine production and cellular immune response in early and late septic stages of rats. Male Wistar rats were divided into 2 experimental groups and received TPN solution at an energy level of 270 kcal/kg body weight. The TPN solutions were isonitrogenous and identical in nutrients composition except for differences in amino acid content. One group received 2% GLN, whereas the other group received glycine (Gly) instead. TPN was maintained for 5 or 6 days according to the sacrifice schedule of the rats. On day 5, sepsis was induced by cecal ligation and puncture (CLP). Respective groups of rats were sacrificed 2, 4, 6, and 24 hours after CLP. Sepsis resulted in a negative nitrogen balance in both groups, and nitrogen loss was significantly lower in the GLN than the Gly group. Interleukin (IL)-2 and interferon (IFN)-gamma in most of the samples collected at various time points were not detectable in plasma or peritoneal lavage fluid. No differences in plasma IL-6 and TNF-alpha concentrations were observed between the GLN and Gly groups. Also, there were no significant differences in IL-1beta, IL-6, and TNF-alpha concentrations in peritoneal lavage fluid between the 2 groups at various time points. The CD4+/CD8+ ratio was significantly higher in the GLN group than in the Gly group only at 4 hours after CLP, and no difference was observed at 24 hours after CLP. TPN preinfused with a GLN-supplemented solution had a beneficial effect in ameliorating the extent of negative nitrogen balance in septic rats. However, parenterally administered GLN did not reduce the production of inflammatory mediators systemically or at the site of injury, and the influence on enhancing cellular immunity was not obvious.

Glutamine supplementation in cancer patients

OBJECTIVES: Three series of studies investigated whether 1) glutamine deficiency occurs in tumor-bearing rats, 2) glutamine supplementation improves protein metabolism during chemotherapy in tumor-bearing rats, and 3) oral glutamine supplement improves systemic immune and gut-barrier function in patients with esophageal cancer receiving radiochemotherapy.METHODS: In the animal studies, AH109A hepatoma cells or Yoshida sarcoma cells were inoculated into male Donryu rats to induce tumors. Glutamine production was measured by U-14C-glutamine infusion and the conversion of arginine to glutamine was measured by infusion of U-14C-arginine. The effect of glutamine on protein metabolism was investigated by 1-14C-leucine infusion. In the clinical study, 13 patients with esophageal cancer were randomized into two groups, control and glutamine supplemented (30 g/d), for 4 wk.RESULTS: Glutamine levels in plasma and skeletal muscle were decreased in tumor-bearing rats, although glutamine production and the conversion of arginine to glutamine were increased. Glutamine-supplemented total parenteral nutrition reduced whole-body protein breakdown rate during chemotherapy in tumor-bearing rats. Oral supplementation of glutamine to the patients with esophageal cancer enhanced lymphocyte mitogenic function and reduced permeability of the gut during radiochemotherapy.CONCLUSIONS: Glutamine depletion in host tissues occurs in tumor-bearing rats. Glutamine supplementation can attenuate loss of protein in the muscle in tumor-bearing animals and protect immune and gut-barrier function during radiochemotherapy in patients with advanced cancer.

Glutamine: Role in the Fetus and Low-birthweight Infant

After completing this article, readers should be able to: 1. Describe the glutamine-glutamate shuttle. 2. Delineate the effects of glutamine supplementation during total parenteral nutrition, chemotherapy, and radiotherapy in animals. 3. Describe the beneficial effects of glutamine supplementation in low-birthweight infants and in critically ill adults. 4. List the primary actions of glutamine in the intestine. The importance of glutamine for optimal growth of cells in culture has been known since the 1950s, when Eagle published his landmark paper in Science .1 His work demonstrated that of all the amino acids, cell growth in culture relied most on glutamine. Numerous subsequent studies have established the importance of glutamine for a variety of metabolic processes in the entire organism and are beginning to demonstrate that nutritional supplementation of this amino acid may be highly beneficial under certain circumstances. Glutamine and glutamate are structurally similar five-carbon amino acids. Glutamine is a neutral amino acid at pH 7.0 that contains an alpha-amino group and a deltaamide group. In glutamate, the amide nitrogen of glutamine is replaced by a carboxy-group, conferring to it a net negative charge at pH 7.0. This at least partially accounts for the transport of these two amino acids across cell membranes via different transport systems. The presence or absence of the amide group is responsible for different metabolic interactions of these amino acids. The array of metabolic processes in which glutamine is involved is highlighted by its relationship to its metabolites and the citric acid cycle (Fig. 1⇓ ).Glutamine, via glutamate, is readily converted to alpha-ketoglutarate, an integral component of the citric acid cycle. Deamidation of glutamine via glutaminase produces glutamate, a precursor of gamma-amino butyric acid (GABA), a neurotransmission inhibitor. Proline also is produced by the cyclization of glutamate. Proline is an important amino acid component of collagen and …

Effect of Glutamine on Immune Function in the Surgical Patient

The beneficial effects of glutamine on immune function in vitro have been well described. Severely ill surgical patients undergo glutamine depletion and this has been implicated as a cause of immune dysfunction in vivo. With the introduction of the stable dipeptides of glutamine into total parenteral nutrition (TPN) regimens, the clinical effects of glutamine on the immune system have taken on an increased relevance and importance. In a randomized clinical trial, we have shown that glutamine-supplemented TPN increased the T cell mitogenic response in patients undergoing colorectal resection. This was not associated with an altered production of the pro-inflammatory cytokines interleukin-6 (IL-6) or tumor necrosis factor (TNF). In a subsequent clinical trial comparing glutamine-supplemented TPN with control TPN in patients with severe acute pancreatitis there was a similar modest enhancement of the T cell response in the glutamine-supplemented group. Although Il-6 and TNF production were again unchanged, there was a significant reduction in IL-8 production in the glutamine-supplemented group. Glutamine may exert its immunological effects by a direct action on the cells of the immune system. Possible indirect mechanisms by which glutamine may influence the immune system include the maintenance of gut barrier function, or the preservation of action of the antioxidant glutathione.

Effect of parenteral l-glutamine on muscle in the very severely Ill

Glutamine (Gln)-supplemented perioperative total parenteral nutrition (TPN) has been reported to reduce the loss of intramuscular glutamine following routine surgery. This study investigates whether glutamine-supplemented TPN can alter muscle biochemistry acutely in the very severely ill patient. Thirty-eight patients (age 19–77 yr; mean 55 yr), critically ill (APACHE II range 8–31; median 17) admitted to the intensive care unit (ICU) were recruited to receive either conventional TPN (CTPN) or an isonitrogenous, isoenergetic feed supplemented with 25 g crystalline l-glutamine per 24 h (GTPN) in a prospective, double blind, block-randomized study. In a representative sample of these patients, relatives consented to a paired muscle biopsy taken before feeding (10 GTPN/9 CTPN patients; ICU Day 2–4) and repeated 5 days later (16 patients; ICU Day 7–9). Muscle biopsies and matching plasma samples were analyzed using a coupled glutaminase-glutamate dehydrogenase enzymatic assay. A correction was made using sodium to account for the massive changes in extracellular fluid volume. The average muscle Gln content before feeding was very low. Between biopsies no consistent pattern of change was seen with or without exogenous Gln. It also proved difficult in these very sick patients to correct a low plasma Gln with l-Gln-TPN during the initial phase of the severe illness. TPN supplementation with 25 g/24 h, l-glutamine appears inadequate in the acute period to counteract the muscle and plasma biochemical changes seen in these patients. It is unknown whether any larger dose could alter this state.

Effect of Glutamine Supplement and Hepatectomy on DNA and Protein Synthesis in the Remnant Liver

One of the physiological roles of glutamine is as a precursor for DNA synthesis. The aims of this study were to determine (1) whether glutamine-supplemented total parenteral nutrition (TPN) enhanced DNA and protein synthesis in the liver and (2) whether glutamine uptake was increased following partial hepatectomy in rats. Male Donryu rats ( n = 59; body weight, 250-275 g) were randomized into four groups: (1) sham operation + standard TPN solution (C-STPN); (2) C + glutamine-supplemented TPN (C-GTPN); (3) 70% partial hepatectomy + STPN (H-STPN); (4) partial hepatectomy + GTPN (H-GTPN). On Day 0, rats underwent either a sham operation or 70% partial hepatectomy and concomitantly were catheterized in the jugular vein. TPN was begun immediately after the surgery. GTPN was isocaloric and isonitrogenous with STPN and 25% of total nitrogen was given as glutamine. On Day 2, the animals were sacrificed after either a continuous infusion of 1- 14C-leucine or a bolus iv injection of bromodeoxyuridine. The rate of hepatic regeneration was enhanced with glutamine supplementation (H-STPN, 60.8 ± 1.6% vs H-GTPN, 66.3 ± 2.0, P < 0.05) due to an increase in protein synthesis in the liver (H-STPN, 134.0 ± 10.3%/day vs H-GTPN, 160.9 ± 6.9, P < 0.05) and DNA synthesis in hepatocytes (H-STPN, 23.1 ± 2.5% vs H-GTPN, 31.4 ± 2.9, P < 0.05). The uptake of glutamine by the liver was increased following hepatectomy with GTPN supplementation. In conclusion, glutamine supplement and partial hepatectomy stimulated glutamine uptake in the liver and this results in an enhancement of protein and DNA synthesis in the remnant liver.