Enteral Glutamine Supplementation Research Articles

Effects of early enteral glutamine supplementation on lymphocyte subpopulations in Peyer’s patches in scalded rats

Effects of early enteral glutamine supplementation on lymphocyte subpopulations in Peyer’s patches in scalded rats

Glutamine-Enriched Enteral Nutrition in Very Low-Birth-Weight Infants: Effect on the Incidence of Allergic and Infectious Diseases in the First Year of Life

van den Berg A, van Zwol A, Moll HA, Fetter WP, van Elburg RM. Arch Pediatr Adolesc Med. 2007;161(11):1095–1101 PURPOSE OF THE STUDY. To determine the effect of glutamine-enriched enteral nutrition in very low birth weight infants on the incidence of allergic and infectious diseases during the first year of life. The authors hypothesized that glutamine may enhance maturation of the immune response by shifting the fetal T-helper 2 (Th2) response toward Th1 cytokine responses in early infancy, leading to decreased allergic disease later in life. STUDY POPULATION. Infants with a gestational age of <32 weeks and/or birth weight of <1500 g who were admitted to a level III NICU were randomly assigned to receive enteral glutamine or control (l-alanine) supplementation. METHODS. Enteral glutamine supplementation (l-glutamine, 0.3 g/kg per day) was administered to the intervention group from 3 through 30 days of life. Validated questionnaires were later sent to the parents of all eligible children, when they were a corrected age of 1 year, to assess the incidence of allergic and infectious diseases during the child's first year of life. Bronchial hyperreactivity was defined by report of at least 3 of the following physician-diagnosed symptoms: dyspnea, wheezing, humming/sawing breath sounds, or nightly dry cough without rhinitis. RESULTS. Of 90 eligible infants, 77 participated (response rate: 86%). The risk for atopic dermatitis (AD) was lower in the glutamine-supplemented group (odds ratio: 0.13 [95% confidence interval: 0.02–0.97]). However, other outcomes did not differ between the intervention and control groups, such as incidence of bronchial hyperreactivity, upper respiratory tract infections, lower respiratory tract infections, and gastrointestinal infections. CONCLUSIONS. Glutamine-enriched enteral nutrition in very low birth weight infants decreased the incidence of AD during the first year of life but had no effect on the incidence of bronchial hyperreactivity and infectious diseases during the first year of life. REVIEWER COMMENTS. The sample size was relatively small and was not powered sufficiently, specifically to assess the incidence of bronchial hyperreactivity. Moreover, the corrected age of 1 year is too early for assessing the incidence of development of atopy and infections. Therefore, it is unclear as to whether AD was prevented or simply delayed in onset among this cohort.

Monitoring the clinical introduction of a glutamine and antioxidant solution in critically ill trauma and burn patients

Objective Enteral glutamine supplementation and antioxidants have been shown to be beneficial in some categories of critically ill patients. This study investigated the impact on organ function and clinical outcome of an enteral solution enriched with glutamine and antioxidant micronutrients in patients with trauma and with burns. Methods This was a prospective study of a historical control group including critically ill, burned and major trauma patients ( n = 86, 40 patients with burns and 46 with trauma, 43 in each group) on admission to an intensive care unit in a university hospital (matching for severity, age, and sex). The intervention aimed to deliver a 500-mL enteral solution containing 30 g of glutamine per day, selenium, zinc, and vitamin E (Gln-AOX) for a maximum of 10 d, in addition to control treatment consisting of enteral nutrition in all patients and intravenous trace elements in all burn patients. Results Patients were comparable at baseline, except for more inhalation injuries in the burn-Gln-AOX group ( P = 0.10) and greater neurologic impairment in the trauma-Gln-AOX group ( P = 0.022). Intestinal tolerance was good. The full 500-mL dose was rarely delivered, resulting in a low mean glutamine daily dose (22 g for burn patients and 16 g for trauma patients). In burn patients intravenous trace element delivery was superior to the enteral dose. The evolution of the Sequential Organ Failure Assessment score and other outcome variables did not differ significantly between groups. C-reactive protein decreased faster in the Gln-AOX group. Conclusion The Gln-AOX supplement was well tolerated in critically ill, injured patients, but did not improve outcome significantly. The delivery of glutamine below the 0.5-g/kg recommended dose in association with high intravenous trace element substitution doses in burn patients are likely to have blunted the impact by not reaching an efficient treatment dose. Further trials testing higher doses of Gln are required.

Enteral glutamine supplementation impairs intestinal blood flow in rats

Background Clinical studies have shown that enteral immune-enhancing diets (IEDs) containing l-glutamine decrease septic complications and length of stay in some patient populations. Animal studies suggest IED benefits might include augmented gut blood flow. We hypothesized that enteral glutamine supplementation modulates gastrointestinal blood flow. Methods Blood flow was measured in male Sprague-Dawley rats via the colorimetric microsphere technique at baseline, 60, and 120 minutes. Four groups were studied: (1) control diet (CD) + enteral glutamine; (2) CD + enteral glycine; (3) CD + enteral saline; and (4) CD + intravenous glutamine. Results There were no differences in blood pressure or heart rate in any group. Group 1 blood flow was decreased at 120 minutes compared with controls (groups 2 and 3) in small intestine, colon, spleen, and pancreas, whereas the intravenous glutamine group (group 4) had no effect on blood flow. Conclusions Enteral glutamine supplementation (as in IEDs) appears to impair gastrointestinal blood flow. Because glutamine provides energy directly to active enterocytes, enteral glutamine availability might diminish metabolic stimuli of absorptive hyperemia. This finding might partially explain the benefits observed with parenteral versus enteral glutamine supplementation in clinical studies (such as bone-marrow–transplant patients).

Neurodevelopmental outcomes of very low‐birth‐weight infants after enteral glutamine supplementation in the neonatal period

To determine the effect of neonatal glutamine-enriched enteral nutrition in very low birth weight (VLBW) infants on neurodevelopmental outcome at 2 years of age. Eighty-eight out of one hundred two infants participating in the initial study were eligible for the follow-up study (13 died, one exclusion due to a chromosomal abnormality). Neurodevelopmental outcome (neurologic status, vision, hearing and Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II) was evaluated at the corrected age of 2 years. To adjust for potential confounders, data were analyzed by multiple linear or logistic regression (for continuous and dichotomous variables, respectively) Seventy-two out of eighty-eight (82%) infants participated in the follow-up study: 40 and 32 infants in glutamine-supplemented and control groups, respectively. The incidence of neither an MDI nor a PDI <or= 85 was different in glutamine-supplemented and control groups (MDI <or= 85: 27 and 19%, p = 0.17; PDI <or= 85: 28 and 16% p = 0.16, respectively). The incidence of neurodevelopmental impairment was not different between both groups (OR: 2.16, 95% CI: 0.64-7.28). A positive effect of neonatal glutamine-enriched enteral nutrition in VLBW infants on neurodevelopmental outcome at 2 years of age was not found in this study.

The effect of glutamine-enriched enteral nutrition on intestinal microflora in very low birth weight infants: A randomized controlled trial

In a previous study, we have found that glutamine supplementation decreased the infection rate in very low birth weight (VLBW) infants. In this study, we investigated whether this beneficial effect originated from increased number of bifidobacteria and lactobacilli in the intestinal microflora of these infants. In a randomized controlled trial, VLBW infants (gestational age <32 weeks and/or birth weight <1500g) received enteral glutamine supplementation (0.3g/kg/day) or isonitrogenous placebo supplementation between d3 and d30 of life. Faecal microflora was determined by fluorescent in situ hybridization <48h, at d7, d14 and d30 of life. In 43/52 (glutamine group) and 43/50 (control group) infants, > or = 2 samples were analyzed. Baseline characteristics were not different between groups. The prevalence of bifidobacteria, lactobacilli, Escheria coIi, streptococci and clostridia was not different between groups (p>0.05). In both groups, colonization with bifidobacteria was delayed, whereas potentially pathogenic bacteria such as E. coli, appeared rapidly after birth. Antibiotic treatment decreased the prevalence of all faecal bacteria (p<0.05). Decreased infectious morbidity in VLBW infants that received glutamine supplementation was not associated with alterations in the prevalence of bifidobacteria, lactobacilli, E. coIi, streptococci and clostridia. In general, colonization with health-promoting bacteria was delayed, whereas potentially pathogenic bacteria appeared rapidly after birth. Antibiotic treatment delayed the bacterial colonization.

Enteral Glutamine Supplementation in Critically Ill Patients with Burn Injuries: A Retrospective Case‐Control Evaluation

To evaluate the clinical application of enteral glutamine supplementation in critically ill patients and compare the frequency of nosocomial infections in these patients with a historical control group in a burn intensive care unit (BICU), and to assess lengths of stay in the hospital and BICU, mortality rates, and safety profile of glutamine. Retrospective case-control descriptive study. A university-affiliated hospital BICU. Seventeen patients receiving enteral glutamine supplementation and 15 historical control patients who were admitted to the BICU for thermal burn injuries from January 1, 2001-September 30, 2004. Data for patients receiving enteral glutamine supplementation were identified through the pharmacy database, and data for the control patients were identified through the BICU patient registry. No significant differences were noted in baseline characteristics or nutritional parameters and outcomes between the two groups. The mean daily dose and duration of glutamine were 0.52 g/kg and 21.6 days, respectively. The mean number of infections/patient between the glutamine and control groups was similar (2.47 and 2.73, respectively) as was the number of gram-negative infections (1.29 and 1.20, respectively). Bloodstream infections occurred more frequently in the glutamine group (24 vs 8 patients, p=0.0006); however, cellulitis (4 vs 11, p=0.05) and pneumonia (9 vs 15, p=0.15) occurred less often. For the glutamine group versus control group, BICU length of stay (17.9 vs 15.3 days, p=NS), hospital length of stay (32.3 vs 26 days, p=NS), and mortality rates (0% vs 6.7%, p=NS) were similar between groups. No adverse events were attributed to glutamine supplementation. Enteral glutamine supplementation was not associated with a change in the cumulative rate of infectious complications compared with the control group, but this was attributed to more cases of bloodstream infections and fewer cases of pneumonia and cellulitis in the glutamine group. Large, prospective, randomized trials designed to detect small but clinically relevant outcomes are needed to definitively determine the effect of enteral glutamine supplementation in the BICU population.

Glutamine Supplementation in Critical Illness: Evidence, Recommendations, and Implications for Clinical Practice in Burn Care

Glutamine is considered a conditionally essential amino acid in metabolic stress. Depletion of plasma and muscle glutamine is observed in acute burn injury and contributes to muscle wasting, weight loss, and infection. In critical illness, supplementation has been shown in patients to minimize these effects and reduce the rate of mortality and length of stay. The evidence for glutamine use and its implications for burn care practice are considered here. Work published to February 2006, which investigated enteral and parenteral glutamine supplementation in burns and critical care, is reviewed. Randomized controlled trials in burns, systematic reviews, and nutrition support practice guidelines are considered. Randomized controlled trials in burns suggest significant clinical benefit in terms of morbidity, mortality, and length of stay but are limited by sample size. Parenteral glutamine studies are under-represented. Systematic reviews and practice guidelines generally support glutamine supplementation in critical illness but vary in the level of recommendations for its use in burns. There also are features unique to burn injury that require consideration. Patients with severe burns or inhalation injury may have a prolonged critical illness phase. In large burns, inflammation and hypermetabolism may persist well beyond 4 weeks of injury. The justification and safety of long-term glutamine supplementation is yet to be established. The outlook for glutamine therapy in burns is promising. However, to strengthen recommendations for routine therapy in burns, further research focusing on larger-scale enteral glutamine studies, parenteral glutamine supplementation, and long-term use of the substrate is necessary.

The Effect of Glutamine‐Enriched Enteral Nutrition on Intestinal Permeability in Very‐Low‐Birth‐Weight Infants: A Randomized Controlled Trial

Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion. Glutamine depletion has negative effects on intestinal integrity. The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity, as reflected by decreased intestinal permeability. The aim of our study was to investigate whether glutamine-enriched enteral nutrition in VLBW infants enhances the normal decrease in intestinal permeability, as measured by the sugar absorption test (SAT). In a double-blind, randomized, placebo-controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1,500 g) received enteral glutamine supplementation (0.3 g/kg/d) or an isonitrogenous placebo supplementation (alanine) between days 3 and 30 of life. Intestinal permeability, determined from the urinary lactulose/mannitol (L/M) ratio after an oral dose of lactulose and mannitol, was assessed at 4 time points: before the start of the study, and at days 7, 14, and 30 of life. At least 2 SATs were performed in 45/52 (86%) and 45/50 (90%) infants in the glutamine-supplemented and control groups, respectively. Baseline patient and nutrition characteristics were not different between the groups. There was no effect of glutamine-enriched enteral nutrition on the decrease of the L/M ratio between the start and end of the study (p = .78). In both treatment groups, median urinary lactulose concentrations decreased (p < .001), whereas median urinary mannitol concentrations increased (p = .003). Glutamine-enriched enteral nutrition does not enhance the postnatal decrease in intestinal permeability in VLBW infants. Any beneficial effect of glutamine may involve other aspects of intestinal integrity; for example, modulation of the intestinal inflammatory response.

Glutamine in critical care: current evidence from systematic reviews

Glutamine, the most abundant amino acid in the body, is thought to become conditionally essential in critical illness. Some of the important roles for glutamine are as a carrier for inter-organ N, a preferred fuel for enterocytes and cells of the immune system, a substrate for renal NH3 formation and a precursor for glutathione. Mechanisms by which glutamine could improve recovery include attenuating oxidant damage and inflammatory cytokine production, reducing gut bacterial translocation and improving N balance. The present systematic review has found trends to suggest that parenteral and enteral glutamine supplementation reduce mortality, the development of infection and organ failure in critical illness. Trials of parenteral nutrition containing glutamine with patients after elective surgery also suggest reduction of infection, but it is unlikely that glutamine-containing parenteral nutrition would be used for such patients. The evidence base is limited by the quality of the reported trials and the suggestion that there is publication bias, with trials suggesting reduced infection being more likely to be published.

Metabolic effects of enteral versus parenteral alanyl‐glutamine (AG) dipeptide in critically ill tube‐fed patients

Enteral and parenteral glutamine (Gln) supplementation is being investigated in critically ill patients, but metabolic effects of different routes of administration are unknown. Methods This double-blind, randomized study compared enteral versus parenteral AG (EN-AG vs IV-AG) on plasma Gln, plasma antioxidants, intestinal permeability to lactulose/mannitol and nitrogen (N) balance over a 8-day period in 44 ICU patients requiring tube feeding. Subjects each received an identical, Gln-free, isocaloric tube feeding 24 h/day and randomized to control (no AG, n=12), EN-AG (n=16) or IV-AG (n=16) groups (AG at 0.5 g/kg/day). Results APACHE II scores were similar at entry in all groups as was energy and N delivery during study. Plasma Gln rose significantly in the IV-AG group. EN-AG subjects showed a significant increase in α-tocopherol (α-toc) levels over time (day 1, 1155±105 vs day 9, 1272±133 μg/dL; p=0.019) and maintained γ-tocopherol (γ-toc) levels. In contrast, α-toc levels were unchanged and γ-toc levels fell significantly in IV-AG and control groups. There were no differences between groups in levels of vitamin C and glutathione, intestinal permeability or N balance. In conclusion, this study shows that enteral Gln may maintain or increase plasma tocopherols in ICU patients. Route of Gln administration does not influence plasma vitamin C or glutathione levels, gut permeability or N balance in ICU patients over an 8-day period. Supported by NIH RO3 DK54823.

Does Enteral Glutamine Supplementation Decrease Infectious Morbidity?

Although some studies have demonstrated lower infectious morbidity in patients receiving supplemental glutamine, there remains no consensus on the utility of such treatment. This study was designed to investigate the effects of supplemental enteral glutamine on the rate and outcomes of infection in critically ill surgical patients. All 185 surgical and trauma patients admitted to a single university surgical trauma intensive care unit (STICU) over an approximately three-year period who were to receive enteral nutrition support were assigned sequentially to one of three diets: standard 1-kCal/mL feedings with added protein (Group 1), standard feedings with glutamine 0.6 g/kg per day (Group 2), or immune-modulated feedings with a similar amount of glutamine (Group 3). Group compositions and patient characteristics were similar at baseline. Data were collected prospectively on infections acquired during hospitalization. A total of 119 patients had at least one infection: 59% of the patients in Group 1, 64% of Group 2, and 69% of Group 3 (p = NS). There were no differences among the groups in the mean number of infections. The most common sites in all groups were the lungs, blood, and urine; and the frequencies of these infections did not differ between groups. Minor differences were found between groups in the organisms isolated. Antibiotic usage did not differ. Supplemental enteral glutamine in the dose studied does not appear to influence the acquisition or characteristics of infection in patients admitted to a mixed STICU.

A Randomized Controlled Trial of Enteral Glutamine Supplementation in Very Low Birth Weight Infants: Plasma Amino Acid Concentrations

Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very low birth weight (VLBW) infants are susceptible to glutamine depletion, as enteral nutrition is limited in the first weeks of life. Enteral glutamine supplementation may have a positive effect on feeding tolerance, infectious morbidity and short-term outcome. The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations, reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants. In a double-blind placebo-controlled randomized controlled trial, VLBW infants (gestational age <32 weeks or birth weight <1500 g) received enteral glutamine supplementation (0.3 g/kg per day) or isonitrogenous placebo supplementation (alanine) between day 3 and day 30 of life. Supplementation was added to breast milk or to preterm formula. Plasma amino acid concentrations were measured at four time points: before the start of the study and at days 7, 14 and 30 of life. Baseline patient and nutritional characteristics were not different in glutamine (n = 52) and control (n = 50) groups. Plasma concentrations of most essential and non-essential amino acids increased throughout the study period. There was no effect of enteral glutamine supplementation. In particular, the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups (P = 0.49 and P = 0.34 respectively, day 30). Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine, glutamate or other amino acids. Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants.

Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial

Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Very-low-birth-weight (VLBW) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life. The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity, and short-term outcome in VLBW infants. In a double-blind randomized controlled trial, VLBW infants (gestational age <32 wk or birth weight <1500 g) were allocated to receive enteral glutamine supplementation (0.3 g . kg(-1) . d(-1)) or isonitrogenous control supplementation (alanine) between days 3 and 30 of life. The supplementations were added to breast milk or to preterm formula. The primary endpoint for the study was time to full enteral feeding. Secondary endpoints were other variables of feeding tolerance, infectious morbidity, and short-term outcome. Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented (n = 52) and the control (n = 50) groups. The median time to full enteral feeding was 13 d (range: 7-31 d) in the glutamine-supplemented group and 13 d (range: 6-35 d) in the control group (hazard ratio: 1.19; 95% CI: 0.79, 1.79; P = 0.40). In the glutamine-supplemented group, 26 of 52 infants (50%) had >/=1 serious infection compared with 38 of 50 (76%) in the control group (odds ratio: 0.32; 95% CI: 0.14, 0.74; P = 0.008). Other variables of feeding tolerance and short-term outcome were not significantly different between groups. Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants. However, infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition.

Surgical manipulation of the intestine and distant organ damage—protection by oral glutamine supplementation

The intestine is increasingly recognized as a primary effector of distant organ damage, such as the lung, after any abdominal surgery. Earlier studies have shown that surgical manipulation of the intestine induces generation of reactive oxygen species in the intestine, resulting in mucosal and lung damage. Because glutamine is preferentially used by the small intestine as an energy source, this study examined the effect of glutamine and glutamic acid on intestinal and lung damage after surgical manipulation. Controls and rats were pretreated for 7 days with 2% glutamine or glutamic acid, or the isonitrogenous amino acids glycine or alanine in the diet and subjected to surgical manipulation of the intestine. The intestine and lung were assessed for damage, and protection offered by various amino acids was studied. Surgical manipulation resulted in oxidative stress in the intestine as evidenced by increased xanthine oxidase activity and decreased antioxidant status. Enterocyte mitochondria were also functionally impaired with altered calcium flux, decreased respiratory control ratio, and increased swelling. Gut manipulation also resulted in neutrophil infiltration and oxidative stress in the lung as assessed by an increase in myeloperoxidase activity, lipid peroxidation, and antioxidant status. Glutamine or glutamic acid supplementation for 7 days before surgical manipulation showed a protective effect against the intestinal and lung damage. This study suggests that preoperative enteral glutamine or glutamic acid supplementation attenuates intestinal and lung damage in rats during surgical manipulation and that this effect might offer protection from postsurgical complications.

P0120 PP GLUTAMINE-ENRICHED ENTERAL FEEDING IN VLBW INFANTS

Introduction: Glutamine may improve feeding tolerance and growth by providing oxidative substrate for enterocytes and increasing protein anabolism. Therefore, the aim of this study was to assess the effect of glutamine-enriched enteral feeding on feeding tolerance and growth in very low birth weight (VLBW) infants. Methods: In a randomised clinical trial (double blind) 102 VLBW infants (GA <32 weeks or BW <1500 grams) were allocated to receive enteral glutamine supplementation (to a maximum of 0.3 gram/kg/day) or isonitrogenous isocaloric placebo supplementation (alanine) between days 3 and 30 of life. Supplementation was added to breast-feeding or to preterm formula (2.4 gram protein/100 ml; casein-whey protein ratio 40:60). Analysis was performed on intention-to-treat basis. Results: Patients in the glutamine and control groups had similar mean BW (SD) (1175 (378) and 1156 (318) grams, respectively), and GA (29.3 (1.7) and 28.7 (1.9) weeks, respectively). A BW <p10 occured in 17/52 (33%) infants in the glutamine group and in 12/50 (8%) infants in the control group. 31/52 (60%) infants in the glutamine group and 31/50 (62%) infants in the control group received complete (expressed) breast-feeding during the study period. Feeding tolerance, growth and short-term outcome were not different in both groups (Table 1).Table 1: Feeding tolerance, growth and short-term outcome (mean (95% CI) or %).Conclusion: This randomised controlled trial did not show improved feeding tolerance, growth, or short-term outcome in VLBW infants receiving glutamine-enriched enteral feeding.

Short-term enteral glutamine does not enhance protein accretion in burned children: a stable isotope study

Objective Glutamine is a nonessential amino acid that, in recent years, has been found to play important roles in several metabolic and immunologic processes. It has been theorized that, in a stressed state, it may become “conditionally essential” because the patient's ability to manufacture glutamine may not be adequate to meet their needs under this condition. We chose to evaluate the ability of 48 hours of enteral glutamine to enhance immediate nitrogen accretion in stressed pediatric burn patients. Methods Nine children with serious burns who were tolerating tube feedings were enrolled in a human studies committee–approved protocol in which they received 48 hours of enteral feedings with glutamine replacing 20% of essential and nonessential amino acids and 48 hours of isonitrogenous, isocaloric standard enteral feedings. This interval was chosen to help ensure that the study periods were comparable from a metabolic perspective. At the end of each period, protein kinetics were determined by a primed constant infusion of L-[1- 13C] leucine tracer. The order of the studies was randomized. Seven children completed both phases of the study. Results were compared by paired t test and are presented as mean ± standard error of the mean. Results During the glutamine feeding period, the leucine flux and leucine oxidation rate were significantly lower than those in the conventional feeding period. This reflects a reduction in total leucine intake from 80 ± 11 to 62 ± 10 μmol/kg per hour. However, there was no significant difference in the net balance of leucine accretion into proteins between these 2 dietary periods, which indicated that enriched glutamine feeding for 48 hours did not result in an immediate whole body protein gain in this group of pediatric patients. In addition, plasma glutamine concentration showed a moderate increase after 48 hours of supplementation but did not reach significance. Conclusion Rapid protein accretion does not occur with short-term enteral glutamine supplementation. Several days of glutamine supplementation may be required to restore plasma glutamine levels and stimulate protein synthesis.

Enteral glutamine supplementation and morbidity in low birth weight infants

Objective To determine if glutamine-supplemented enteral nutrition decreased the incidence of nosocomial sepsis in neonates. Methods In a multicenter (n = 20) clinical trial, we randomly allocated infants (n = 649) with birth weight between 500 and 1250 g, who were <7 days of age, and had no major anomalies to receive enteral glutamine supplementation (0.3 g/kg/day) or sterile water (placebo) for the first 28 days. The primary outcome variable was the number of infants who had blood culture–proven nosocomial sepsis between 7 days' and 36 weeks' postmenstrual age. Results Infants were assigned to placebo (n = 335) or to glutamine supplementation (n = 314). Neonates assigned to glutamine were similar to those assigned placebo for demographic characteristics and nutritional support during the first week. There was no difference in the occurrence of culture-proven nosocomial sepsis (33.7% vs 30.9%) or suspected sepsis (51.6% vs 47.1%) between the placebo and glutamine groups; however, neonates treated with glutamine less often had gastrointestinal dysfunction (7.5% vs 2.5%, P < .01) and severe neurologic sequelae (15.1% vs 10.4%, P = .08). Conclusions At a dose of 0.3 g/kg/day, enteral glutamine does not appear to reduce nosocomial sepsis in premature neonates. (J Pediatr 2003;142:662-8)

Plasma taurine concentrations increase after enteral glutamine supplementation in trauma patients and stressed rats

Taurine is a unique amino acid with antioxidant and osmolytic properties. Glutamine serves as the preferred fuel for the gut, liver, and immune cells and as a precursor for antioxidants. Trauma patients have low glutamine concentrations. We investigated the effect of glutamine-enriched enteral nutrition on plasma taurine concentrations in patients with severe trauma (injury severity score >20). Additionally, plasma taurine concentrations and organ fluxes were studied in a stressed rat model. Twenty-nine patients with multiple trauma received glutamine-enriched nutrition and 31 patients received isocaloric, isonitrogenous control solution for 5 d. Plasma taurine and glutamine concentrations were measured. Male Wistar rats (250-300 g) received a glutamine-enriched diet (12%, by wt) or a control solution for 2 wk. Plasma taurine concentrations were measured. Taurine fluxes and fractional extraction rates in the liver, kidneys, and gut were assessed with a radioactive microsphere technique. Both patient groups had low taurine concentrations on day 1. From day 3 onward, the glutamine-fed patients had significantly higher taurine concentrations. Rats fed a glutamine-enriched diet had significantly higher plasma taurine concentrations than did the controls. A high taurine uptake was found in the liver, kidneys, and gut of the glutamine-fed rats. Fractional extraction rates were not significantly different between the rat groups. Glutamine enrichment increases plasma taurine in trauma patients and in stressed rats. Because of increased availability, organ fluxes showed a higher taurine uptake in the liver, kidneys, and gut. The reduction in morbidity with glutamine enrichment could be explained in part by increased taurine availability.

Immunonutrients and the Critically Ill Neonate

After completing this article, readers should be able to: 1. List the otherwise “nonessential” nutrients that may be required by the critically ill neonate. 2. Explain why omega-3 fatty acids do not cause as much inflammation as their omega-6 counterparts. 3. Define pre- and probiotics and describe how they can prevent colonization of the intestine by pathogenic organisms. 4. Describe the potential protective effects of lactoferrin on the neonatal gastrointestinal tract. In a critically ill individual, the intestinal barrier becomes compromised because of stress, lack of enteral feedings, and ischemic-reperfusion injury. In the preterm neonate, the mucosal barrier is not fully functional (see article on innate immunity in this issue of NeoReviews ). The combination of a damaged and immature gut barrier may lead to increased intestinal permeability, aberrant antigen transfer, and immune response, which can explain the vulnerability to infection, inflammation, and hypersensitivity at an early age. In patients dying of sepsis, there is clear evidence of an imbalance in pro- and anti-inflammatory cytokine production, a failure to maintain antioxidant defenses, and high levels of activation of nuclear factor- kappa-B (NF-kappa-B). Over the past several years, it has become more evident that the proinflammatory cytokine response, as part of an uncontrolled systemic inflammatory response syndrome (SIRS), plays an integral role in premature labor, chronic lung disease, cerebral palsy, necrotizing enterocolitis (NEC), and sepsis. Because the gut is a primary origin of SIRS, it is reasonable to suggest that nutritional agents might stabilize the intestinal mocosal barrier, alter the balance of pro- and anti- inflammatory cytokines, and prevent excessive activation of NF-kappa-B or other signaling pathways. Some nutrients, such as glutamine, arginine, omega-3 fatty acids, nucleotides, and probiotics, have been shown to have a considerable influence on immune function (eg, delayed hypersensitivity, lymphocyte subpopulation counts, immunologic test) and improve metabolic and nutritional indices such as …