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1.
The Role of Immunonutrition in Patients Undergoing Pancreaticoduodenectomy.
Jabłońska, B, Mrowiec, S
Nutrients. 2020;(9)
Abstract
Pancreaticoduodenectomy (PD) is one of the most difficult and complex surgical procedures in abdominal surgery. Malnutrition and immune dysfunction in patients with pancreatic cancer (PC) may lead to a higher risk of postoperative infectious complications. Although immunonutrition (IN) is recommended for enhanced recovery after surgery (ERAS) in patients undergoing PD for 5-7 days perioperatively, its role in patients undergoing pancreatectomy is still unclear and controversial. It is known that the proper surgical technique is very important in order to reduce a risk of postoperative complications, such as a pancreatic fistula, and to improve disease-free survival in patients following PD. However, it has been proven that IN decreases the risk of infectious complications, and shortens hospital stays in patients undergoing PD. This is a result of the impact on altered inflammatory responses in patients with cancer. Both enteral and parenteral, as well as preoperative and postoperative IN, using various nutrients, such as glutamine, arginine, omega-3 fatty acids and nucleotides, is administered. The most frequently used preoperative oral supplementation is recommended. The aim of this paper is to present the indications and benefits of IN in patients undergoing PD.
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2.
Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis.
Nilsson, A, Haanstra, JR, Engqvist, M, Gerding, A, Bakker, BM, Klingmüller, U, Teusink, B, Nielsen, J
Proceedings of the National Academy of Sciences of the United States of America. 2020;(19):10294-10304
Abstract
Many cancer cells consume glutamine at high rates; counterintuitively, they simultaneously excrete glutamate, the first intermediate in glutamine metabolism. Glutamine consumption has been linked to replenishment of tricarboxylic acid cycle (TCA) intermediates and synthesis of adenosine triphosphate (ATP), but the reason for glutamate excretion is unclear. Here, we dynamically profile the uptake and excretion fluxes of a liver cancer cell line (HepG2) and use genome-scale metabolic modeling for in-depth analysis. We find that up to 30% of the glutamine is metabolized in the cytosol, primarily for nucleotide synthesis, producing cytosolic glutamate. We hypothesize that excreting glutamate helps the cell to increase the nucleotide synthesis rate to sustain growth. Indeed, we show experimentally that partial inhibition of glutamate excretion reduces cell growth. Our integrative approach thus links glutamine addiction to glutamate excretion in cancer and points toward potential drug targets.
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3.
Daily Supplementation of L-Glutamine in Atrial Fibrillation Patients: The Effect on Heat Shock Proteins and Metabolites.
Starreveld, R, Ramos, KS, Muskens, AJQM, Brundel, BJJM, de Groot, NMS
Cells. 2020;(7)
Abstract
Pharmaco-therapeutic strategies of atrial fibrillation (AF) are moderately effective and do not prevent AF onset and progression. Therefore, there is an urgent need to develop novel therapies. Previous studies revealed heat shock protein (HSP)-inducing compounds to mitigate AF onset and progression. Such an HSP inducing compound is L-glutamine. In the current study we investigate the effect of L-glutamine supplementation on serum HSP27 and HSP70 levels and metabolite levels in patients with AF patients (n = 21). Hereto, HSP27 and HSP70 levels were determined by ELISAs and metabolites with LC-mass spectrometry. HSP27 levels significantly decreased after 3-months of L-glutamine supplementation [540.39 (250.97-1315.63) to 380.69 (185.68-915.03), p = 0.004] and normalized to baseline levels after 6-months of L-glutamine supplementation [634.96 (139.57-3103.61), p < 0.001]. For HSP70, levels decreased after 3-months of L-glutamine supplementation [548.86 (31.50-1564.51) to 353.65 (110.58-752.50), p = 0.045] and remained low after 6-months of L-glutamine supplementation [309.30 (118.29-1744.19), p = 0.517]. Patients with high HSP27 levels at baseline showed normalization of several metabolites related to the carbohydrates, nucleotides, amino acids, vitamins and cofactors metabolic pathways after 3-months L-glutamine supplementation. In conclusion, L-glutamine supplementation reduces the serum levels of HSP27 and HSP70 within 3-months and normalizes metabolite levels. This knowledge may fuel future clinical studies on L-glutamine to improve cardioprotective effects that may attenuate AF episodes.
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4.
Glutamine supported early enteral therapy for severe acute pancreatitis: A systematic review and meta-analysis.
Jiang, X, Pei, LY, Guo, WX, Qi, X, Lu, XG
Asia Pacific journal of clinical nutrition. 2020;(2):253-261
Abstract
BACKGROUND AND OBJECTIVES Several studies have shown that glutamine (Gln) may play an important role in energy metabolism, inflammatory reactions, and immune processes in patients with severe acute pancreatitis (SAP). Nevertheless, the results of individual randomized controlled trials (RCTs) on Gln nutrition support for SAP are contradictory. This systematic review and meta-analysis evaluated the clinical benefit of Gln-supported early enteral nutrition (G+EEN) in patients with SAP. METHODS AND STUDY DESIGN Cochrane Library, PubMed, Embase, CNKI, Wan Fang, and Chinese Biomedical Literature Database were searched for relevant studies published before December 2018. RCTs of G+EEN versus standard early enteral nutrition (EEN) for SAP were selected, with both started within 48 h of admission. RESULTS Seven clinical RCTs including a total of 433 patients (EEN group: 218 patients; G+EEN group: 215 patients) were included. Compared with EEN, G+EEN increased serum albumin (standard mean difference [SMD]=0.74; 95% confidence interval [CI], 0.33-1.15; p<0.01), reduced serum hypersensitive C-reactive protein (SMD=-1.62; 95% CI, -1.98 to -1.26; p<0.01) and risks of mortality risk (risk ratio= 0.38; 95% CI, 0.16-0.90; p=0.03) and multiple organ dysfunction syndrome (MODS)(risk ratio=0.37; 95% CI, 0.15-0.94; p<0.01), and shortened length of hospital stay (SMD=-1.19; 95% CI, -1.88 to 0.49; p<0.01); moreover, it did not significantly increase the incidence of infection-related complications, operative interventions, or APACHE II scores. CONCLUSIONS G+EEN is beneficial in SAP management.
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Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections.
van Sadelhoff, JHJ, Wiertsema, SP, Garssen, J, Hogenkamp, A
Frontiers in immunology. 2020;:1007
Abstract
Breastfeeding is indicated to support neonatal immune development and to protect against neonatal infections and allergies. Human milk composition is widely studied in relation to these unique abilities, which has led to the identification of various immunomodulating components in human milk, including various bioactive proteins. In addition to proteins, human milk contains free amino acids (FAAs), which have not been well-studied. Of those, the FAAs glutamate and glutamine are by far the most abundant. Levels of these FAAs in human milk sharply increase during the first months of lactation, in contrast to most other FAAs. These unique dynamics are globally consistent, suggesting that their levels in human milk are tightly regulated throughout lactation and, consequently, that they might have specific roles in the developing neonate. Interestingly, free glutamine and glutamate are reported to exhibit immunomodulating capacities, indicating that these FAAs could contribute to neonatal immune development and to the unique protective effects of breastfeeding. This review describes the current understanding of the FAA composition in human milk. Moreover, it provides an overview of the effects of free glutamine and glutamate on immune parameters relevant for allergic sensitization and infections in early life. The data reviewed provide rationale to study the role of free glutamine and glutamate in human milk in the protection against neonatal allergies and infections.
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6.
Effects of carbohydrate and glutamine supplementation on cytokine production by monocytes after exercise in hypoxia: A crossover, randomized, double-blind pilot study.
Caris, AV, Tavares-Silva, E, Thomatieli-Santos, RV
Nutrition (Burbank, Los Angeles County, Calif.). 2020;:110592
Abstract
OBJECTIVES The aim of this study was to evaluate the combined effects of carbohydrate (CHO) and glutamine (Gln) supplementation on cytokine production by monocytes after exercise until exhaustion performed in hypoxia. METHODS Fifteen physically active men underwent three exercises until exhaustion with an intensity of 70% maximal oxygen intake at a simulated height of 4500 m under the following supplementation: placebo, CHO (maltodextrin 8%/200 mL for 20 min), and CHO + Gln (Gln 20 g/d for 6 d and maltodextrin 8%/200 mL for 20 min) during exercise and for 2 h of recovery. Analysis of variance for repeated measures followed by the Tukey's post hoc test was realized and P < 0.05 was considered statistically significant. RESULTS Oxygen saturation of arterial blood (SaO2%) decreased in the three trials compared with baseline. Two hours post-exercise, the SaO2% was high in CHO + Gln condition compared with placebo. Two hours after exercise, interleukin (IL)-1β decreased compared with post-exercise in placebo and was lower compared with baseline in the CHO + Gln condition. Tumor necrosis factor-α decreased 2 h after exercise compared with baseline and pre-exercise in the CHO + Gln condition. No changes were observed in myeloperoxidase or IL-6 production. Two hours after exercise, Gln decreased compared with baseline and post-exercise in placebo and decreased 2 h after exercise in relation to post-exercise in the CHO condition. Gln increased post-exercise compared with pre-exercise in the CHO + Gln condition. Although erythropoietin did not change in this condition, it was high post-exercise and 2 h after exercise in the placebo condition compared with baseline and 2 h after exercise compared with baseline and pre-exercise in the CHO condition. CONCLUSIONS Gln supplementation for 6 d before exercise, associated with CHO supplementation during exercise, was able to revert Gln reduction after exercise and after 2 h of recovery and may have contributed to reducing tumor necrosis factor-α production, suggesting a possible anti-inflammatory effect of supplementation.
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Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study.
Ogden, HB, Child, RB, Fallowfield, JL, Delves, SK, Westwood, CS, Millyard, A, Layden, JD
Nutrients. 2020;(10)
Abstract
l-Glutamine (GLN) is a conditionally essential amino acid which supports gastrointestinal (GI) and immune function prior to catabolic stress (e.g., strenuous exercise). Despite potential dose-dependent benefits, GI tolerance of acute high dose oral GLN supplementation is poorly characterised. Fourteen healthy males (25 ± 5 years; 1.79 ± 0.07 cm; 77.7 ± 9.8 kg; 14.8 ± 4.6% body fat) ingested 0.3 (LOW), 0.6 (MED) or 0.9 (HIGH) g·kg·FFM-1 GLN beverages, in a randomised, double-blind, counter-balanced, cross-over trial. Individual and accumulated GI symptoms were recorded using a visual analogue scale at regular intervals up to 24-h post ingestion. GLN beverages were characterised by tonicity measurement and microscopic observations. 24-h accumulated upper- and lower- and total-GI symptoms were all greater in the HIGH, compared to LOW and MED trials (p < 0.05). Specific GI symptoms (discomfort, nausea, belching, upper GI pain) were all more pronounced on the HIGH versus LOW GLN trial (p < 0.05). Nevertheless, most symptoms were still rated as mild. In comparison, the remaining GI symptoms were either comparable (flatulence, urge to regurgitate, bloating, lower GI pain) or absent (heart burn, vomiting, urge to defecate, abnormal stools, stitch, dizziness) between trials (p > 0.05). All beverages were isotonic and contained a dose-dependent number of GLN crystals. Acute oral GLN ingestion in dosages up to 0.9 g·kg·FFM-1 are generally well-tolerated. However, the severity of mild GI symptoms appeared dose-dependent during the first two hours post prandial and may be due to high-concentrations of GLN crystals.
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8.
Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.
Wischmeyer, PE, Mintz-Cole, RA, Baird, CH, Easley, KA, May, AK, Sax, HC, Kudsk, KA, Hao, L, Tran, PH, Jones, DP, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(2):563-573
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Abstract
BACKGROUND Nutrients, such as glutamine (GLN), have been shown to effect levels of a family of protective proteins termed heat shock proteins (HSPs) in experimental and clinical critical illness. HSPs are believed to serve as extracellular inflammatory messengers and intracellular cytoprotective molecules. Extracellular HSP70 (eHSP70) has been termed a chaperokine due to ability to modulate the immune response. Altered levels of eHSP70 are associated with various disease states. Larger clinical trial data on GLN effect on eHSP expression and eHSP70's association with inflammatory mediators and clinical outcomes in critical illness are limited. OBJECTIVE Explore effect of longitudinal change in serum eHSP70, eHSP27 and inflammatory cytokine levels on clinical outcomes such as pneumonia and mortality in adult surgical intensive care unit (SICU) patients. Further, evaluate effect of parenteral nutrition (PN) supplemented with GLN (GLN-PN) versus GLN-free, standard PN (STD-PN) on serum eHSP70 and eHSP27 concentrations. METHODS Secondary observational analysis of a multicenter clinical trial in 150 adults after cardiac, vascular, or gastrointestinal surgery requiring PN support and SICU care conducted at five academic medical centers. Patients received isocaloric, isonitrogenous PN, with or without GLN dipeptide. Serum eHSP70 and eHSP27, interleukin-6 (IL-6), and 8 (IL-8) concentrations were analyzed in patient serum at baseline (prior to study PN) and over 28 days of follow up. RESULTS eHSP70 declined over time in survivors during 28 days follow-up, but non-survivors had significantly higher eHSP70 concentrations compared to survivors. In patients developing pneumonia, eHSP70, eHSP27, IL-8, and IL-6 were significantly elevated. Adjusted relative risk for hospital mortality was reduced 75% (RR = 0.25, p = 0.001) for SICU patients with a faster decline in eHSP70. The area under the receiver operating characteristic curve was 0.85 (95% CI: 0.76 to 0.94) for the final model suggesting excellent discrimination between SICU survivors and non-survivors. GLN-PN did not alter eHSP70 or eHSP27 serum concentrations over time compared to STD-PN. CONCLUSION Our results suggest that serum HSP70 concentration may be an important marker for severity of illness and likelihood of recovery in the SICU. GLN-supplemented-PN did not increase eHSP70.
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Effect of Preoperative Administration of Oral Arginine and Glutamine in Patients with Enterocutaneous Fistula Submitted to Definitive Surgery: a Prospective Randomized Trial.
Martinez, JL, Bosco-Garate, I, Souza-Gallardo, LM, Méndez, JD, Juárez-Oropeza, MA, Román-Ramos, R, Ferat-Osorio, E
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2020;(2):426-434
Abstract
BACKGROUND The use of glutamine and arginine has shown several advantages in postoperative outcomes in patients after gastrointestinal surgery. We determined the effects of its use in patients with enterocutaneous fistula after operative treatment. PATIENTS AND METHODS Forty patients with enterocutaneous fistula were randomly assigned to one of two groups. The control group received the standard medical care while the patients of the experimental group were supplemented with enteral administration of 4.5 g of arginine and 10 g of glutamine per day for 7 days prior to the surgery. The primary outcome variable was the recurrence of the fistula and the secondary outcomes were preoperative and postoperative serum concentrations of interleukin 6 and C-reactive protein and postoperative infectious complications. RESULTS Twenty patients were assigned to each group. The fistula recurred in two patients (10%) of the experimental group and in nine patients (45%) of the control group (P < 0.001). We found a total of 13 infectious complications in six patients of the control group (all with fistula recurrence) and none in the experimental group. Mean preoperative serum concentrations of interleukin 6 and C-reactive protein were lower in patients from the experimental group. In addition, these levels were lower in patients who had recurrence if compared to patients that did not recur. CONCLUSION Preoperative administration of oral arginine and glutamine could be valuable in the postoperative recovery of patients with enterocutaneous fistulas submitted to definitive surgery.
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Carbohydrate and Glutamine Supplementation Attenuates the Increase in Rating of Perceived Exertion during Intense Exercise in Hypoxia Similar to 4200 m.
Caris, AV, Thomatieli-Santos, RV
Nutrients. 2020;(12)
Abstract
The rating of perceived exertion (RPE) indicates the feeling of fatigue. However, hypoxia worsens the condition and can worsen RPE. We evaluated whether carbohydrate and glutamine supplementation alters RPE and physiological markers in running at 70% peak oxygen uptake until exhaustion in a simulated altitude of 4500 m. Nine volunteers underwent three running tests at 70% peak oxygen uptake until exhaustion: (1) hypoxia and placebo, (2) hypoxia and 8% maltodextrin, and (3) hypoxia after six days of glutamine supplementation (20 g/day) and 8% maltodextrin. The exercise and supplementation were randomized and double-blinded. Lactate, heart rate, haemoglobin O2 saturation (SpO2%), and RPE (6-20 scale) were analyzed at the 15th and 30th min. The level of significance was set at p ≤ 0.05. SpO2% decreased at the 15th and 30th minutes compared to resting in placebo, carbohydrate, and glutamine supplementation. RPE increased at the 30th minute compared to the 15th minute in placebo and carbohydrate supplementation; however, there was no difference in the glutamine supplementation condition. Heart rate and lactate increased after the 15th and 30th minutes compared to resting, similar to the three conditions studied. We conclude that previous supplementation with glutamine and carbohydrate during intense exercise in hypoxia similar to 4500 m can attenuate the increase in RPE by the increase in glycemia and can be a useful strategy for people who exercise in these conditions.