Plasma Gln Research Articles

Plasma glutamine decreases immediately after surgery and is related to incisiveness

Glutamine (gln) is the most abundant free amino acid in the blood. It is involved in important metabolic and biochemical processes, like cell proliferation and oxidative stress. Previous studies have demonstrated that gln concentration in human plasma decreases in several conditions such as sepsis, ischemia-reperfusion, trauma, major surgery and burn. The aim of the present work was to compare the acute effects of different types of surgical interventions and of anesthetization on blood gln concentration. Plasma samples from 88 subjects (30 males and 58 females) were collected before and after major or minor surgery and the gln concentration was analyzed with high-performance liquid chromatography. The results showed that plasma gln concentration after surgery was lower than pre-surgery values and that in major surgery the decrease of gln was higher than in minor surgery. No significant effect was shown for sex or type of anesthesia. These results demonstrate the importance of a gln supplementation before a surgical intervention and show that the amount of gln supplementation should also be adjusted based on the type of surgery.

Understanding the mechanisms of glutamine action in critically ill patients

Glutamine (Gln) is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor)-kB activation, a balance between pro- and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day) demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.

Role of glutamine administration on T-cell derived inflammatory response after cardiopulmonary bypass

Cardiac surgery provokes an inflammatory response for which the endothelium, the myocardium, and monocytes/macrophages are primarily responsible. T cells are altered in a different way whereby the pro-inflammatory pathway is suppressed. From the results of experimental studies it was concluded that glutamine (Gln) enhances the production of T-cell cytokines in conditions of Gln deprivation. The aim of this clinical study was to evaluate the role of a perioperative Gln infusion on intracellular inflammatory T-cell cytokine expression in patients undergoing elective cardiac surgery and to evaluate the effects on systemic inflammation, organ dysfunction and ICU length of stay. In this prospective, randomized, double-blind study, we included 78 patients (age level older than 70 years, ejection fraction less than 40%, or mitral valve replacement) undergoing elective cardiosurgery with cardiopulmonary bypass. We randomly assigned each subject to receive an infusion with either Gln (0.5 g/kg/day, group A) or an isonitrogenous, isocaloric, isovolemic nutritional solution (group B) or physiological NaCl 0.9% (group C, to eliminate an unspecific nutritional effect). We started the infusion after the induction of anesthesia with 1000 ml/24 h and maintained this state for 3 days. On the first postoperative day plasma Gln levels in group A were significantly increased (958 +/- 331 microM) compared to group B (527 +/- 105 microM) and group C (489 +/- 104 microM), and remained higher until the third postoperative day. At the beginning and after surgery intracellular interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha levels in T cells showed no differences between the groups. Also, no differences could be observed with regard to C-reactive protein, SOFA score, heart and circulation support, postoperative ventilation time, and ICU length of stay. The elevation of Gln plasma levels as a result of 0.5 g/kg/day perioperative Gln infusion has no influence on the T-cell derived inflammatory response, indicating a sufficient supply of Gln. A Gln supplementation in cardiac surgery patients without a clear Gln deficiency seems not to affect the intracellular inflammatory T-cell cytokine expression.

Metabolic effects of enteral versus parenteral alanyl-glutamine dipeptide administration in critically ill patients receiving enteral feeding: A pilot study

Glutamine (Gln) may become conditionally indispensable during critical illness. The short-term metabolic effects of enteral versus parenteral Gln supplementation are unknown in this clinical setting. We studied metabolic effects of intravenous (i.v.) alanyl-Gln dipeptide (AG) supplementation and enteral (e.n.) AG supplementation on plasma Gln concentration, antioxidant status, plasma lymphocyte subset number, gut permeability and nitrogen balance in adult critically ill patients requiring tube feeding compared to a control group not receiving Gln supplementation. In a double-blind, pilot clinical trial, 44 medical and surgical ICU patients received identical Gln-free tube feedings 24 h/day and were randomized to either isonitrogenous control (n=15), e.n. AG (n=15) or i.v. AG (n=14) groups (AG). Twelve patients were discontinued from the study. The goal AG dose was 0.5 g/kg/day. Biochemical and metabolic endpoints were measured at baseline and on day 9 (plasma Gln, antioxidant indices, lymphocyte subsets; serum IGF-1 and IGF-binding protein-3; intestinal permeability). Nitrogen balance was determined between study days 6 and 8. Illness severity indices, clinical demographics, enteral energy and nitrogen intake and major biochemical indices were similar between groups during study. Plasma Gln was higher in the i.v. AG (565+/-119 microM, mean+/-SEM) vs the e.n. AG (411+/-27 microM) group by day 9 (p=0.039); however, subjects in the i.v. AG group received a higher dose of AG (i.v. AG 0.50 versus e.n. AG 0.32+/-0.02 g/kg/day; p<0.001). E.n. AG subjects showed a significant increase in plasma alpha-tocopherol levels over time and maintained plasma gamma-tocopherol concentrations. There were no differences between groups for plasma concentrations of vitamin C, glutathione, malondialdehyde (MDA), T-lymphocyte subsets, intestinal permeability or nitrogen balance. This study showed that alanyl-Gln administration by enteral or parenteral routes did not appear to affect antioxidant capacity or oxidative stress markers, T-lymphocyte subset (CD-3, CD-4, CD-8) number, gut barrier function or whole-body protein metabolism compared to unsupplemented ICU patients requiring enteral tube feeding. Enteral Gln appeared to maintain plasma tocopherol levels in this pilot metabolic study.

Effect of Glutamine Supplementation on Splanchnic Metabolism in Lactating Dairy Cows

The suggestion that glutamine (Gln) might become conditionally essential postpartum in dairy cows has been examined through increased postruminal supply of Gln. Net nutrient flux through the splanchnic tissues and mammary gland was measured in 7 multiparous Holstein cows receiving abomasal infusions of water or 300g/d of Gln for 21 d in a crossover design. Milk yield increased significantly (by 3%) in response to Gln supplementation, but the 2.4% increase in milk protein yield was not statistically significant. Glutamine treatment had no effect on portal or hepatic venous blood flows. Net portal appearance of Gln and Glu was increased by Gln supplementation, accounting for 83% of the infused dose with, therefore, only limited amounts available to provide additional energy to fuel metabolism of the portal-drained viscera. The extra net portal appearance of Gln was offset, however, by a corresponding increase in hepatic removal such that net Gln splanchnic release was not different between treatments. Nonetheless, the Gln treatment resulted in a 43% increase in plasma Gln concentration. Infusions of Gln did not affect splanchnic flux of other nonessential amino acids or of essential amino acids. Glutamine supplementation increased plasma urea-N concentration and tended to increase net hepatic urea flux, with a numerical increase in liver hepatic O2 consumption. There were no effects on glucose in terms of plasma concentration, net portal appearance, net liver release, or postliver supply, suggesting that Gln supplementation had no sparing effect on glucose metabolism. Furthermore, mammary uptake of glucose and amino acids, including Gln, was not affected by Gln supplementation. In conclusion, this study did not support the hypothesis that supplemental Gln would reduce glucose utilization across the gut or increase liver gluconeogenesis or mammary glutamine uptake to increase milk protein synthesis.

Dietary Glutamine Affects Mucosal Functions in Rats with Mild DSS-Induced Colitis , ,

The development of inflammatory bowel disease may involve immune dysfunction. Because enteral glutamine is the main source of amino acids for the intestinal mucosa and is metabolized at high rates by both enterocytes and immunocytes, the aim of this study was to ascertain the protective role of glutamine supplementation in a DSS-induced model of mild experimental colitis on metabolic, immune, and intestinal variables. Lewis rats were fed diets supplemented with glutamine (glutamine diet, G group) or an isoenergetic isonitrogenous control diet (C group) from postnatal d 21 (weaning) and continuing to d 35. On d 30, half of the rats from both groups were given 0.5% DSS in drinking water (G-DSS and C-DSS groups). Glutamine supplementation increased the plasma concentrations of Thr, Gln, Cit, His, and Arg and enhanced the ratio of essential to nonessential amino acids irrespective of DSS treatment. DSS administration increased the plasma Gln concentration, indicating a reduced utilization of this amino acid by the intestinal tissue. Regarding the gut-associated lymphoid tissue lymphocyte populations, DSS increased the percentages of CD3+ T lymphocytes from Peyer’s patches, NK and B lymphocytes from mesenteric lymph nodes, and NK CD8− cells from intraepithelial lymphocytes. The administration of glutamine did not affect the inductive populations nor did it modify T-cell subtypes or the percentage of intraepithelial lymphocytes of gut-associated lymphoid tissue. However, glutamine supplementation reduced the feces water contents in the DSS-treated but not in the untreated rats. These results indicate that glutamine supplementation can improve barrier function in rats with colitis.

Effect of ornithine α-ketoglutarate on glutamine pools in burn injury: evidence of component interaction

Ornithine alpha-ketoglutarate (OKG) has proved to be efficient in restoring glutamine (Gln) pools which are strongly depleted in hypercatabolic patients. Since its two components, alpha-ketoglutarate (alphaKG) and ornithine (Orn), give rise to glutamate (Glu), they are both considered as Gln precursors. The aim of this study was to assess the relative contributions of Orn and alphaKG to Gln generation in a rat model of burn injury. Forty-eight young Wistar rats were scalded to give a 20% burn surface area. They were fasted for 24 h and then refed by enteral nutrition for 48 h by gavages with Osmolite (Abbott-Ross, 210 kcal/kg day(-1), 1.18 N/kg day(-1)) supplemented with either 5 g OKG/kg day(-1) (B-OKG), Orn (isomolar to OKG; B-Orn), alphaKG (isomolar to OKG; B-KG) or glycine (as an isonitrogenous control; B-Gly). Rats in the B-KG group also received glycine to make all the groups isonitrogenous. Amino acid concentrations were determined in plasma, muscles, jejunal mucosa and liver. The alpha-KG-enriched diet had no effect on plasma Glu content or plasma and muscle Gln content compared with the burn-injured controls. The Orn-enriched diet significantly increased (p<0.01) muscle Glu and Gln contents but not plasma Gln content. In OKG-treated animals, plasma Gln as well as muscle Glu and Gln were significantly higher than in the control (p<0.01), alpha-KG-treated (p< 0.01) and Orn-treated (p<0.05 for muscle Gln and p<0.01 for plasma Gln) animals. OKG was more efficient than Orn or alphaKG alone in restoring Gln pools in plasma and muscle, which is evidence of metabolic interaction between the two components of this molecule.

Effect of Postruminal Glutamine Supplementation on Immune Response and Milk Production in Dairy Cows

Seventeen multiparous Holstein cows were used to examine the effect of an increased duodenal supply of Gln on immune function and production. Cows received continuous abomasal infusions of water (control: n = 8) or 300g/d of Gln (n = 9) for 21 d starting within 48h of calving. There were nonsignificant increases in milk and milk protein yields in response to Gln supplementation. Glutamine treatment had no effect on plasma glucose, nonesterified fatty acids (NEFA), or β-hydroxybutyrate (BHBA) concentrations but did tend to increase plasma urea N concentration. The Gln treatment resulted in an increase of 108μM in the plasma Gln concentration. Total essential AA concentrations decreased with the Gln treatment, whereas total nonessential AA concentrations were unaffected. T Lymphocyte proliferation did not differ between the control and Gln-treated cows. Treatment had no effect on the relative abundance of CD8 T cells but did increase the abundance of CD4 T cells. Cytokine production, as measured by IFN-γ concentration determined in vitro in concanavalin-A-stimulated peripheral blood mononuclear cells, was similar between the treatments. Over the first 3 wk following calving, Gln supplementation had limited effects on milk production, metabolic parameters, and immune function.

Effects of Biocom as a Replacement of Glutamine on Performance and Blood Biochemical Indexes of Early Weaned Piglets

The objective of this study was to evaluate Biocom (a protein source containing a high level of glutamine and alanyl- glutamine) as a replacement for glutamine (Gln) in nursery pig diets. Forty-two pigs (fourteen pigs per treatment) weaned at 28 d of age were used in a 28-d performance trial using three dietary treatments: control (no Gln), control supplemented with Gln or Biocom. The control diet was composed of corn, soybean meal, whey and fish meal. Individual body weight, pen feed disappearance and diarrhea were monitored. On d 0, 2, 7 and 14 postweaning, respectively, five pigs per treatment were selected and bled from the anterior vena cava to obtain five replicate samples of blood on each dietary treatment for determination of blood biochemical index. Dietary supplementation of Gln and Biocom did not influence performance, plasma Gln and total serum protein concentration (p>0.05). However, the addition of Gln and Biocom could prevent serum urea nitrogen and serum cortisol from increasing on d 2 postweaning (p 0.05) in any of the examined parameters between Gln- and Biocom-supplemented diets. In conclusion, dietary Gln did not influence the performance of early-weaned piglets owing to the complex diet containing whey, but could prevent the increase of serum urea and cortisol. Biocom could be used as a replacement for free pure Gln without any negative effect on early-weaned piglets. (Asian-Aust. J. Anim. Sci. 2006. Vol 19, No. 6 : 872-876)

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.

Glutamine: Do the Data Support the Cause for Glutamine Supplementation in Humans?

This review examines the preclinical rationale for using glutamine supplements and reviews the prospective randomized trials using glutamine to improve outcomes in patients. A special role for glutamine in gut physiology and in management of a variety of serious illnesses has been suggested, because it is the most abundant extracellular amino acid, and is used at high rates by the gut, liver, central nervous system, and immune cells. A state of relative Gln deficiency has been postulated in humans based on the decrease in plasma Gln in acute critical illness, but the decrease in plasma Gln is not specific for that amino acid, predicts only poorer outcome, and has not been validated to identify a deficiency state. Current evidence does not necessarily predict a special need or role for Gln in critical illness. Clinical efficacy of supplemental Gln has been difficult to demonstrate, possibly related to the lack of a Gln deficiency state, the wide range of end points used that reflect the lack of certainty of the predicted effect of supplementation, the heterogeneous patient populations studied, the lack of stable clinical course during the study, the lack of adequate power, and the relatively short follow-up period. Prospective randomized clinical trials of Gln supplementation were reviewed in patients with short-bowel syndrome, during cancer chemotherapy and in bone marrow transplantation, and in surgical, burn, and intensive care unit patients. No firm recommendation can be made at this time. Future studies should seek to develop a more standard and stable design for intervention in sufficiently powered studies.

Adaptive cellular mechanisms in response to Glutamine-starvation

Glutamine (Gln) utilising cells suffer from Gln-starvation during critical illness when plasma Gln levels are decreased. This study investigates whether such cells activate adaptive mechanisms. Monocytic U937 cells were cultured at 0.6 and 0.2 mM Gln for up to four days. Within the first day a decrease of ATP (78% of control), intracellular free Gln (13%), Hsp70 (74%) and proliferation rate (79%) was observed. A prolonged culture at 0.6 mM Gln for additional three days led to a recovery of ATP (97%), Hsp70 (91%) and proliferation (92%). The intracellular free Gln increased only to 41%. At 0.2 mM Gln, however, all levels remained decreased. The activation of the metabolic sensor AMP activated kinase (AMPK) increased immediately in Gln-starving cells but regained normal values only in cells cultured at 0.6 mM. A proteomic analysis identified 23 proteins, which were affected by Gln starvation including metabolic enzymes, proteins involved in synthesis and degradation of RNA and proteins, and stress proteins. These data show that Gln-utilising cells activate adaptive mechanisms in response to Gln-starvation, which enable them to overcome a Gln shortage. At very low Gln concentrations, these adaptive mechanisms are not sufficient to countervail the lack of the amino acid.

Effects of glutamine granules on immunofunction in trauma patients: a double-blind randomized controlled, multi-center clinical trail with 120 patients

To evaluate the effect of glutamine granules on immunofunction in severe burns and trauma patients. One hundred and twenty patients with severe burns, multiple trauma and post operation who met the requirements of the protocol joined this double-blind randomized controlled, multi-center clinical trail. Patients were randomly divided into two groups: placebo control group (P group, 60 patients) and glutamine granules treatment group (GLN group, 60 patients). There was isonitrogenous and isocaloric intake in both groups. GLN and P group patients had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(-1) for 7 days, respectively. The level of plasma glutamine and some index of immunofunction were determined, and the complication and side effect were also observed. After 7 days of taking glutamine granules orally, plasma GLN concentration was significantly higher than that in P group [(593 +/- 185) micromol/L vs (407 +/- 190) micromol/L)] (P < 0.01). IL-2 level, CD(4)/CD(8) ratio, PMN swallow ratio in GLN group were significantly higher than those in P group (P < 0.05-0.01), but the concentration of IgG, IgM, C(3)/C(4) were not significantly different when compared with P group (P > 0.05). In addition, the occurrence of side effect in both groups was seldom. Taking glutamine granules could increase plasma GLN concentration, enhance body immunofunction, and using glutamine granules is safe.

Does acute glutamine depletion enhance the response of glutamine synthesis to fasting in muscle in adult and old rats?

In earlier studies, skeletal muscle glutamine synthetase (GS) activity was shown to be enhanced by fasting and glucocorticoids, and inhibited by exogenous glutamine (Gln) supplementation. The current study was designed to determine whether phenylbutyrate (PhiB), a Gln-chelating agent in humans, (1) could trap Gln and produce a decline in plasma Gln in rats, as it does in humans, and (2) if so, whether (Phi)B would further enhance the response of muscle GS activity to fasting in rats. Adult (6-8 months) and aged (20-21 months) rats were fasted for 5 days and received two doses of 0.5 g(Phi)Bby orogastric route at times 0 and 4 h, and were then sacrificed at 5.5 h. Plasma Gln was measured by enzymatic methods, other amino acids were quantified by amino acid analysis. GS activity was measured in soleus (SO) and tibialis anterior (TA) muscles. (Phi)B treatment was associated with: (1) a 20% decline in plasma Gln concentration from 572+/-54 to 424+/-34 micromol/L (P<0.05) and from 476+/-49 to 360+/-80 micromol/L (P<0.05) in fasted adult and old rats, respectively; and (2) a preservation of GS up-regulation by fasting in TA and SO muscles in both adult and aged rats, with TA muscle GS activities of 198+/-65 vs. 203+/-68 ((Phi)B-treated vs. vehicle-treated, NS), and 244+/-81 vs. 274+/-59 (NS) nmol/h/mg protein in adult and aged rats, respectively. These data suggest that: (1) large doses of (Phi)B deplete plasma Gln in fasted rats, regardless of age, (2) Gln depletion induced by Phi)B does not alter GS activity.

Effects of glutamine granules on protein metabolism in trauma patients

To evaluate the effect of glutamine granules on protein metabolism in severe burns and trauma patients. 120 patients with severe burns, multiple trauma and post operation who met the requirements of the protocol joined this double-blind randomized controlled, multi-center clinical trail. Patients were randomly divided into two groups: placebo control group (P group, 60 patients) and glutamine granules treatment group (GLN group, 60 patients). There was isonitrogenous and isocaloric intake in both groups, GLN and P group patents had been given glutamine granules or placebo (glycine) at 0.5 g.kg(-1).d(-1) for 7 days, respectively. The level of plasma glutamine, protein and urine nitrogen exclude were determined, wound healing rate of burn area and hospital stay were recorded, and then observed the complication and side effect. After 7 days of taking glutamine granules orally, plasma GLN concentration was significant higher than that in P group (592.50 +/- 185.23 micro mol/L vs. 407.41 +/- 190.22 micro mol/L) (P < 0.01). Plasma prealbumin and transferrin in GLN group were significant higher than those in P group (P < 0.01), but the concentration of total protein and albumin were no marked changes compare with P group (P > 0.05). The capacity of urine nitrogen exclude in GLN group were significant lower than that in P group. Additional, the wound healing rate was faster and hospital stay days was shorter than P group (P < 0.05), and the occurrence of glutamine granules side effect was seldom. Taking glutamine could promote protein synthesis, abate protein decompose, ameliorate wound healing rate and reduce hospital stay obviously.

Glutamine starvation of monocytes inhibits the ubiquitin–proteasome proteolytic pathway

Peripheral blood monocytes utilize free glutamine (Gln) in addition to glucose as an important energy substrate. Although this demand increases upon activation, monocytes are commonly confronted with decreased plasma Gln during critical illness and thus suffer from Gln-starvation. Here we investigate the influence of Gln-starvation on protein stability and its effects on the monocyte proteome. Gln-starvation caused a reduction of protein degradation which was accompanied by an accumulation of ubiquitin–protein conjugates and a reduction of intracellular ATP. Similar effects were observed under ATP-reducing conditions and in the presence of a proteasome inhibitor. Using two-dimensional gel electrophoresis we identified the IL-1β precursor protein (pIL-1β) as the, by far, most induced protein in endotoxin-treated monocytes. The degradation of the short-lived pIL-1β was strongly reduced during Gln-starvation, while the degradation of the long-lived, constitutively expressed β-actin was less affected. This indicates that although Gln-starvation reduces protein breakdown on the overall proteasome level, it leads to differential changes in the stability of specific proteins. This selective effect is likely to contribute to the immunocompromised state of monocytes commonly observed during critical illness.

Effect of Dietary Glutamine Supplement on Performance and Intestinal Morphology of Weaned Pigs

Two experiments were conducted to investigate the effect of dietary glutamine (Gln) supplement on the performance and villus morphology of weaned pigs. In Exp. 1, 48 pigs were fed diets supplemented with 0, 0.5, 1.0, or 1.5% Gln for 28 days. Dietary Gln supplemented levels did not influence performance and plasma Gln concentration of weaned pigs. In Exp. 2, 48 weaned pigs were fed the same treatment diets of Exp. 1 for 7 or 14 days. Dietary Gln supplement reduced the ratio of small intestine weight to empty carcass weight at d 14 postweaning. However, the villus height and villus height/crypt depth ratio at the duodenum were increased. IgA and protein in the bile from d 7 and d 14 postweaning were higher in the pigs fed the diet supplemented with 0.5% Gln. Plasma IgA concentration was not influenced by dietary Gln levels. In conclusion, dietary Gln supplement might benefit the development of the small intestine and bile IgA production in weaned pigs. (Asian-Aust. J. Anim. Sci. 2003. Vol 16, No. 12 : 1770-1776)

Impact of oral l-glutamine on glutathione, glutamine, and glutamate blood levels in volunteers

OBJECTIVE: We investigated the effect of glutamine supplementation on plasma glutamine (Gln), glutamate (Glu), and whole-blood glutathione (GSH) concentrations in human volunteers. METHODS: Subjects first adapted to a standard diet with known intakes of protein, total GSH, cysteine, methionine, and total Glu (Glu values include Glu and Gln) for 3 d. Plasma Gln, Glu, and whole-blood GSH levels were then measured at 4-h intervals over 24 h. Supplemental oral Gln (0.3 g · kg −1 · d −1) was ingested for 10 d and then 24-h plasma levels of Gln, Glu, and whole-blood GSH were measured. RESULTS: The plasma concentrations of Glu (116%; P = 0.006) and Gln (20%; P = 0.046) were significantly higher, whereas concentrations of GSH were significantly lower (37%; P = 0.00091) after oral Gln supplementation. CONCLUSION: Oral Gln increases Glu and Gln levels in plasma of healthy subjects but does not increase GSH red cell (whole-blood) levels. Thus, GSH biosynthesis and preservation of GHS stores in red blood cells may involve rate-limiting substrates other than Gln.

Glutamine depletion impairs cellular stress response in human leucocytes.

During sepsis and major trauma the blood glutamine (Gln) level is reduced. The administration of Gln can improve the outcome of these patients. However, the mechanism of this beneficial effect of Gln is poorly understood. In the course of critical illness leucocytes are confronted with cytotoxic inflammatory mediators. To protect themselves against these factors, cells express heat shock proteins (HSP). Previous studies have shown that the expression of the major inducible HSP (HSP70) is improved by high Gln concentrations above 4 mM. In this study we investigated whether Gln depletion, such as observed during critical illness, has an effect on HSP70 expression. Human lymphocytes exposed for 2 h to 42 degrees C showed a 3-fold increase in HSP70 expression (P<0.01). A preceding Gln starvation period over 3 days had no influence on this increase. However, when Gln is reduced during the stress response, HSP70 expression is impaired. A reduction of Gln from 0.5 mM (physiological) to 0.125 mM (pathological) led to a 40% lower HSP70 level (P<0.002). In contrast, increasing Gln concentrations (up to 2 mM) had only minor stimulatory effects (about 15%). This Gln-dependency of heat mediated HSP70 expression was observed in resting as well as proliferating lymphocytes. Our data indicate that during periods of reduced plasma Gln levels the stress response of human lymphocytes is impaired. Thus, Gln may be essential to minimize the susceptibility of leucocytes to cytotoxic inflammatory mediators. This is a new aspect of the protective effect of Gln supplementation in critically ill patients.

Effect of post-ruminal infusion of glutamine on plasma amino acids, milk yield and composition in lactating dairy cows

The objectives of this study were to examine the effect of supplying post-ruminal L-glutamine in mid-lactation Holstein dairy cows on plasma amino acid profile, dry matter intake, milk yield and milk composition. The experiment was designed as a 4 × 4 Latin square with four 2-wk periods. Cows were continuously infused post-ruminally with graded levels of L-glutamine (L-Gln) for 5 consecutive days during the second week of each period. During the last 24 h of the infusion, blood plasma was collected every 6 h for the determination of plasma amino acid concentrations. Plasma Gln concentration increased (P &lt; 0.05) with increasing L-Gln daily infusions. Infusion of 0, 100, 200, and 300 g d–1 resulted in blood plasma Gln concentrations of 289.5, 299.2, 356.4 and 386.2 mmol L–1, respectively. The level of Gln infusion also resulted in a decrease in the blood plasma concentration of phenylalanine, but the concentrations of all other amino acids were not affected. The administration of Gln did not affect dry matter intake, milk yield and milk composition. Key words: Post-ruminal, L-glutamine, plasma amino acids, milk constituents