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

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial

BACKGROUND: 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. OBJECTIVE: The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity, and short-term outcome in VLBW infants. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.     

Effect of enteral supplementation with glutamine on mesenteric blood flow in premature neonates

BACKGROUND AND AIMS: This study investigated the effects of enterally supplied glutamine on mesenteric blood flow in premature neonate. METHODS: Twenty-five neonates, aged at least 14 days and free of acute illness participated in a prospective, randomised, double-blind study. All were fed with total enteral nutrition enriched with glutamine (0.7 g kg(-1)day(-1), group 1) or isonitrogenous control (group 2). Blood flow velocities in the superior mesenteric artery were analysed by pulsed Doppler US before and after 21 days of supplemented feeding. Peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged mean velocity (TAV) were measured and resistance index (RI) and flow (Q) were calculated. RESULTS: Both groups were well matched clinically at inclusion. At inclusion, the velocimetry parameters were (mean +/- SD) : PSV:114.9 +/- -38 cms(-1), EDV:17.5 +/- 7.5 cm x s(-1), TAV:44.8 +/- 18.2 cms(-1), RI : 0.8 +/- 0.1, Q : 2.4 +/- 1.2 mls(-1). Mesenteric blood flow parameters remained stable between day 0 and day 21 with same values in both groups. CONCLUSIONS: Superior mesenteric blood flow remained stable in neonates after 14 days of life and did not appear to be influenced by enteral glutamine at that stage.     

Plasma glutamine response to enteral administration of glutamine in human volunteers (free glutamine versus protein-bound glutamine)

The goal of the present work was to compare the plasma glutamine response to exogenous glutamine administration in human volunteers; glutamine was provided as a free amino acid, bound to proteins, or in the form of peptides. Plasma glutamine concentrations were measured in eight human volunteers at 30, 60, 90, 120, and 240 min after receiving a drink containing 30 g of protein from one of the five different proteins tested (sodium caseinate, sodium caseinate + free glutamine, carob germ flour, carob protein concentrate, and carob protein hydrolysate). Peak plasma glutamine concentrations were 42% higher than postabsorptive basal values when exogenous glutamine was administered in the form of free glutamine added to caseinate (925.9 +/- 67.7 versus 651.3 +/- 44.0 micromol/L, respectively). In contrast, when glutamine was offered 100% bound to proteins (carob proteins), peak plasma glutamine concentration increased only between 18% and 23% from basal values, possibly because of the lower digestibility of carob proteins versus that of caseinate + free glutamine, to a different glutamine utilization at the gut level, or to a different response in endogenous glutamine kinetics to enteral administration of glutamine, depending on the molecular form of the glutamine source (free or protein bound).     

Long-term effects of neonatal glutamine-enriched nutrition in very-low-birth-weight infants

Several studies in very-low-birth-weight (VLBW) infants have investigated the effect of parenteral or enteral glutamine supplementation on morbidity, mortality, and outcome in the neonatal period. No evidence of toxicity of glutamine supplementation was found in these clinical trials, but the results for efficacy on a limited number of outcomes have been mixed. The use of glutamine supplementation in VLBW infants has not become routine. Some authors suggest that further study in this area is no longer warranted. In this review, more recent research in the area of glutamine supplementation is described, which suggests additional studies are warranted.     

口服布拉酵母菌对极低出生体质量儿的临床意义

目的 研究布拉酵母菌散剂对极低出生体质量儿的临床意义.方法 198例极低出生体质量儿中未服布拉酵母菌散剂早产儿93例（对照组）,口服布拉酵母菌散剂早产儿105例（观察组）,回顾性对照分析两组患儿的一般资料,观察两组患儿大便频次或腹泻（伴中重度脱水）情况、新生儿坏死性小肠结肠炎（NEC）发生率、院内感染（败血症、肺部感染）发生率、真菌感染率、静脉营养时间、总住院时间.结果 两组患儿一般资料比较差异无统计学意义（P＞0.05）.观察组和对照组患儿大便频次、静脉营养时间、住院时间比较差异有统计学意义[（1.8±0.4）次/d比（3.4±0.5）次/d、（30.21 ±3.43）d比（40.47±4.35）d、（33.5±6.8）d比（45.4±9.3）d]（P＜0.05）;两组新生儿腹泻、NEC、败血症或脓毒血症发生率比较差异有统计学意义[14.3％（15/105）比25.8％（24/93）、11.4％（12/105）比19.4％（18/93）、19.0％（20/105）比29.0％（27/93）] （P＜ 0.05）;两组肺炎发生率和真菌感染率比较差异无统计学意义（P＞0.05）.结论 口服布拉酵母菌散剂可以减少极低出生体质量儿腹泻发生率,减少NEC发生率,以及院内感染发生率（主要是败血症）,可以促进胃肠喂养,缩短住院时间,同时亦不会增加真菌感染率,有临床应用价值.     

Effect of severity of stress on whole-body protein kinetics in surgical patients receiving parenteral nutrition

A study was conducted to clarify the quantitative relationship between the alteration of protein metabolism and the severity of surgical stress to further understand the mechanisms of body nitrogen losses in surgical trauma. Twenty-one patients undergoing esophagectomy for esophageal cancer (group E), and 22 undergoing gastrectomy or colorectal operations for gastric or colorectal cancer (Group GC) were studied. All patients were fed exclusively by parenteral nutrition (PN) providing 1.5 g protein · kg⁻¹ · d⁻¹ and 35 kcal · kg⁻¹ before and after the operation. The measurements of whole-body protein turnover, synthesis, and breakdown were performed preoperatively and on postoperative days (PODs) 3 and 10. Urinary excretion of total nitrogen and total catecholamines was also measured. Urinary excretion of the total catecholamines of group E was twice as high as that of group GC on the POD 3 and well reflected the severity of surgical stress. Negative correlation of nitrogen retention to urinary excretion of the total catecholamines was also observed (r = 0.64; P < 0.01). The correlations between the urinary excretion of the total catecholamines and the whole-body protein flux, synthesis, and breakdown were statistically significant (r = 0.57, 0.27, and 0.57, respectively; P < 0.01 in all). Rate of elevation in breakdown according to the stress level was greater than that of synthesis. Consequently the progressive aggravation of nitrogen balance according to the severity of surgical stress was observed.     

Effect of intravenous amino acids on protein kinetics in preterm infants

PURPOSE OF REVIEW: To summarize recent findings of the effects of intravenous amino acids on protein kinetics in low-birth-weight infants and to describe the potential cellular mechanism for these observations. RECENT FINDINGS: Amino acids administered intravenously for 3-5 h in infants have been shown to suppress whole-body proteolysis. Recent data in low-birth-weight infants show that an increase in the dose of amino acid caused a suppression of proteolysis, and a decrease in the rate of glutamine and urea synthesis. These responses returned to basal state, however, when the amino acid infusion continued for 20-24 h. Supplementation with glutamine sustained the suppression of proteolysis after 3-5 days. Plasma insulin concentration did not change during the amino acid infusion. Data from studies in adults and from in vitro studies suggest that the amino acids impact protein breakdown and synthesis via the mammalian target of rapamycin pathway, stimulating initiation of translation and suppressing autophagic proteolysis. SUMMARY: Intravenous amino acids, by increasing extracellular amino acid concentration, transiently stimulate protein synthesis and suppress protein breakdown. These effects return to basal state when the amino acid infusions are prolonged. The mechanism of this adaptive response remains to be determined.     

Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants

BACKGROUND: Glutamine is one of the most abundant amino acids in both plasma and human milk and may be conditionally essential in premature infants. However, glutamine is not provided by standard intravenous amino acid solutions. OBJECTIVE: We assessed the effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants receiving parenteral nutrition (PN). DESIGN: A total of 141 infants with birth weights of 401-1000 g were randomly assigned to receive a standard intravenous amino acid solution that did not contain glutamine or an isonitrogenous amino acid solution with 20% of the total amino acids as glutamine. Blood samples were obtained just before initiation of study PN and again after the infants had received study PN (mean intake: 2.3 +/- 1.0 g amino acids x kg(-1) x d(-1)) for approximately 10 d. RESULTS: Infants randomly assigned to receive glutamine had mean plasma glutamine concentrations that increased significantly and were approximately 30% higher than those in the control group in response to PN (425 +/- 182 and 332 +/- 148 micromol/L for the glutamine and control groups, respectively). There was no significant difference between the 2 groups in the relative change in plasma glutamate concentration between the baseline and PN samples. In both groups, there were significant decreases in plasma phenylalanine and tyrosine between the baseline and PN samples; the decrease in tyrosine was greater in the group that received glutamine. CONCLUSIONS: In extremely low-birth-weight infants, parenteral glutamine supplementation can increase plasma glutamine concentrations without apparent biochemical risk. Currently available amino acid solutions are likely to be suboptimal in their supply of phenylalanine, tyrosine, or both for these infants.     

Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition

Continuous infusion of insulin was used to improve glucose tolerance in 30 premature (26.4+/-1.4 weeks) very-low-birth-weight (750+/-211.3 g) hyperglycaemic infants receiving parenteral nutrition. Infusion of insulin was started at 159.1+/-67 h of life; while glycaemia was 12.1+/-3.3 mmol/l. Normoglycaemia was restored within 31.4h (range 2-134 h). A maximum insulin dose of 0.4 (range 0.07-4.2)IU/kg/h was required to control the blood glucose, the mean cumulative doses of insulin required was 3.27 IU/kg (range 0.09-18.1). The mean glucose infusion rate during insulin treatment was 20.3+/-1.7 g/kg/day; lipid was 4.6+/-1.1 g/kg/day and non-protein caloric intake 121.7+/-16.5 kcal/kg/day. Infants reach 85 kcal/kg/day of non-protein energy intake at 179.5+/-71.2 h after birth. During continuous insulin infusion, enteral feeding was started in all infants at 124.9+/-75.8 h of life. Insulin was continued for 317.7+/-196.6 h. Only two infants lost weight during the first week of treatment, the remaining infant gained weight steadily. In conclusion, continuous insulin infusion can rapidly and safely improve intravenous glucose tolerance, allowing higher caloric intake and growth in very-low-birth-weight infants who develop hyperglycaemia during total parenteral nutrition.     

极低出生体重儿出院后营养与生长发育监测

目的　通过对极低出生体重儿出院后营养与生长发育监测研究,探讨半量强化母乳、早产儿出院后配方奶对极低出生体重儿出院后生长发育的影响。方法　对143例极低出生体重儿按照出院后个体化营养强化方式（半量强化母乳、早产儿出院后配方奶）分为两组,监测纠正周龄40周、52周时身长、体质量、头围生长发育情况。结果　143例早产极低出生体重儿纠正周龄40周时体质量、身长、头围宫外生长发育迟缓率分别为35.25%、32.43%、14.41%;纠正周龄52周时分别为9.52%、10.81%、2.7%;半量强化母乳组与早产儿出院后配方奶组生长发育比较,两者差异无统计学意义;在纠正周龄40周、52周、56周时,分别有18.67%、56.0%和68.75%的病例停用强化营养,改为普通配方奶或纯母乳喂养。结论　早产极低出生体重儿出院后营养强化管理能更快实现追赶生长,半量强化母乳与早产儿出院后配方奶对体格发育影响无差异。     

脐静脉导管置留对极低出生体重儿胃肠喂养影响的探讨

目的:探讨脐静脉导管(UVC)置留后对极低出生体重儿(VLBWl)胃肠喂养的影响。方法:选取2005年1月~2008年1月住院的VLBWl 86例,其中脐静脉导管置留者(UVC组)41例,无脐静脉导管置留者(N-UVC组)45例,观察两组患儿入院后经胃肠喂养时间、胎便排出和体重变化情况,以及低血糖持续时间和喂养后呕吐、腹胀、坏死性小肠结肠炎(NEC)等喂养不耐受情况发生。结果:UVC组患儿脐静脉置管一次操作均入血管(100%),导管置留时间(9·2±2·73)天;两组患儿开始经胃肠喂养的时间和胎便开始排出、排完时间以及呕吐、腹胀、NEC、血培养阳性例数、肝功能异常等并发症发生情况组间比较差异无统计学意义(P>0·05);UVC组患儿体重恢复至出生体重时间(11·55±3·26)天和低血糖持续时间(1·74±1·41)h较N-UVC组明显缩短,差异具有统计学意义(P<0·05)。结论:脐静脉导管置留在VLBWI治疗中能迅速有效的建立静脉通道,减少早产儿并发症的产生,且不会影响胃肠喂养。     

Synbiotics, prebiotics, glutamine, or peptide in early enteral nutrition: a randomized study in trauma patients

BACKGROUND: Since the hepatosplanchnic region plays a central role in development of multiple-organ failure and infections in critically ill trauma patients, this study focuses on the influence of glutamine, peptide, and synbiotics on intestinal permeability and clinical outcome. METHODS: One hundred thirteen multiple injured patients were prospectively randomized into 4 groups: group A, glutamine; B, fermentable fiber; C, peptide diet; and D, standard enteral formula with fibers combined with Synbiotic 2000 (Synbiotic 2000 Forte; Medifarm, Sweden), a formula containing live lactobacilli and specific bioactive fibers. Intestinal permeability was evaluated by measuring lactulose-mannitol excretion ratio on days 2, 4, and 7. RESULTS: No differences in days of mechanical ventilation, intensive care unit stay, or multiple-organ failure scores were found between the patient groups. A total of 51 infections, including 38 pneumonia, were observed, with only 5 infections and 4 pneumonias in group D, which was significantly less than combined infections (p = .003) and pneumonias (p = .03) in groups A, B, and C. Intestinal permeability decreased only in group D, from 0.148 (0.056-0.240) on day 4 to 0.061 (0.040-0.099) on day 7; (p < .05). In group A, the lactulose-mannitol excretion ratio increased significantly (p < .02) from 0.050 (0.013-0.116) on day 2 to 0.159 (0.088-0.311) on day 7. The total gastric retention volume in 7 days was 1150 (785-2395) mL in group D, which was significantly more than the 410 (382-1062) mL in group A (p < .02), and 620 (337-1190) mL in group C (p < .03). CONCLUSIONS: Patients supplemented with synbiotics did better than the others, with lower intestinal permeability and fewer infections.     

Effects of enteral nutrition supplemented with glutamine on intestinal mucosal immunity in burned mice

ObjectiveThe aim of this study was to investigate the effects of enteral nutrition (EN) supplemented with glutamine (GLN) on Peyer's patches and intestinal immunoglobulin A (IgA) response in burned mice.MethodsThirty-four mice were randomly assigned to a normal control group (n = 10), an EN group (n = 12), and an EN supplemented with GLN (EN + GLN) group (n = 12) and mice in the EN and EN + GLN groups received a 20% total body surface area, full-thickness scald burn on the back. Then the burned mice were fed with conventional EN or EN + GLN for 7 d. There was isonitrogenous and isocaloric intake in the EN and EN + GLN groups. On day 7 after injury, entire intestines were collected and intestinal IgA levels, total lymphocyte yield, lymphocyte subpopulations, and total apoptotic ratio in Peyer's patches were analyzed.ResultsTotal lymphocyte yield, numbers of lymphocyte subpopulations, and intestinal IgA levels in the EN + GLN group were significantly higher than those in the EN group (P < 0.05). The total apoptotic ratio in Peyer's patches was markedly decreased in the EN + GLN group compared with that in the EN group (P < 0.05).ConclusionThe results indicated that EN supplemented with GLN is superior to conventional EN with respect to improvement of intestinal immunity in burned mice.