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L-Glutamine Supplementation Enhances Strength and Power of Knee Muscles and Improves Glycemia Control and Plasma Redox Balance in Exercising Elderly Women.
Amirato, GR, Borges, JO, Marques, DL, Santos, JMB, Santos, CAF, Andrade, MS, Furtado, GE, Rossi, M, Luis, LN, Zambonatto, RF, et al
Nutrients. 2021;(3)
Abstract
We investigated the effects of oral L-glutamine (Gln) supplementation, associated or not with physical exercises, in control of glycemia, oxidative stress, and strength/power of knee muscles in elderly women. Physically active (n = 21) and sedentary (n = 23) elderly women aged 60 to 80 years were enrolled in the study. Plasma levels of D-fructosamine, insulin, reduced (GSH) and oxidized (GSSG) glutathione, iron, uric acid, and thiobarbituric acid-reactive substances (TBARs) (lipoperoxidation product), as well as knee extensor/flexor muscle torque peak and average power (isokinetic test), were assessed pre- and post-supplementation with Gln or placebo (30 days). Higher plasma D-fructosamine, insulin, and iron levels, and lower strength/power of knee muscles were found pre-supplementation in the NPE group than in the PE group. Post-supplementation, Gln subgroups showed higher levels of GSH, GSSG, and torque peak, besides lower D-fructosamine than pre-supplementation values. Higher muscle average power and plasma uric acid levels were reported in the PE + Gln group, whereas lower insulin levels were found in the NPE + Gln than pre-supplementation values. TBARs levels were diminished post-supplementation in all groups. Gln supplementation, mainly when associated with physical exercises, improves strength and power of knee muscles and glycemia control, besides boosting plasma antioxidant capacity of elderly women.
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Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease.
Harrison, SA, Baum, SJ, Gunn, NT, Younes, ZH, Kohli, A, Patil, R, Koziel, MJ, Chera, H, Zhao, J, Chakravarthy, MV
The American journal of gastroenterology. 2021;(12):2399-2409
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INTRODUCTION AXA1125 and AXA1957 are novel, orally administered endogenous metabolic modulator compositions, specifically designed to simultaneously support multiple metabolic and fibroinflammatory pathways associated with nonalcoholic fatty liver disease (NAFLD). This study assessed safety, tolerability, and biologic activity of AXA1125 and AXA1957 in NAFLD. METHODS In this multicenter, 16-week, placebo-controlled, single-blind, randomized clinical study in subjects with NAFLD stratified by type 2 diabetes, AXA1125 24 g, AXA1957 13.5 g or 20.3 g, or placebo was administered twice daily. Key metabolism (MRI-proton density fat fraction [MRI-PDFF] and homeostasis model assessment of insulin resistance [HOMA-IR]) and fibroinflammation markers (alanine aminotransferase [ALT], corrected T1 [cT1], keratin-18 [K-18] M65, and N-terminal type III collagen propeptide [Pro-C3]) were evaluated. Safety outcomes included adverse events and standard laboratory assessments. RESULTS Baseline characteristics of the 102 enrolled subjects, including 40 with type 2 diabetes, were consistent with presumed nonalcoholic steatohepatitis. AXA1125 showed consistently greater biologic activity than AXA1957 or placebo. Week 16 changes from baseline with AXA1125 vs placebo: MRI-PDFF -22.9% vs -5.7%, HOMA-IR -4.4 vs +0.7, ALT -21.9% vs -7.2%, K-18 M65 -13.6% vs +20.1%, cT1 -69.6 vs +18.3 ms (P < 0.05), and Pro-C3 -13.6% vs -3.6%. Week 16 changes from baseline with AXA1957 20.3 g: MRI-PDFF -8.1%, HOMA-IR +8.4, ALT -20.7%, K-18 M65 6.6%, cT1 -34.7 ms, and Pro-C3 -15.6%. A greater proportion of subjects treated with AXA1125 achieved clinically relevant thresholds: ≥30% MRI-PDFF, ≥17-IU/L ALT, and ≥80-ms cT1 reductions at week 16. Study products were safe and well tolerated with stable lipid and weight profiles. DISCUSSION Both compositions showed multitargeted activity on relevant NAFLD pathways. AXA1125 demonstrated the greatest activity over 16 weeks, warranting continued clinical investigation in nonalcoholic steatohepatitis subjects.
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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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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.
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Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome.
Zhou, Q, Verne, ML, Fields, JZ, Lefante, JJ, Basra, S, Salameh, H, Verne, GN
Gut. 2019;(6):996-1002
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BACKGROUND More effective treatments are needed for patients with postinfectious, diarrhoea-predominant, irritable bowel syndrome (IBS-D). Accordingly, we conducted a randomised, double-blind, placebo-controlled, 8-week-long trial to assess the efficacy and safety of oral glutamine therapy in patients who developed IBS-D with increased intestinal permeability following an enteric infection. METHODS Eligible adults were randomised to glutamine (5 g/t.i.d.) or placebo for 8 weeks. The primary end point was a reduction of ≥50 points on the Irritable Bowel Syndrome Severity Scoring System (IBS-SS). Secondary endpoints included: raw IBS-SS scores, changes in daily bowel movement frequency, stool form (Bristol Stool Scale) and intestinal permeability. RESULTS Fifty-four glutamine and 52 placebo subjects completed the 8-week study. The primary endpoint occurred in 43 (79.6%) in the glutamine group and 3 (5.8%) in the placebo group (a 14-fold difference). Glutamine also reduced all secondary endpoint means: IBS-SS score at 8 weeks (301 vs 181, p<0.0001), daily bowel movement frequency (5.4 vs 2.9±1.0, p<0.0001), Bristol Stool Scale (6.5 vs 3.9, p<0.0001) and intestinal permeability (0.11 vs 0.05; p<0.0001). 'Intestinal hyperpermeability' (elevated urinary lactulose/mannitol ratios) was normalised in the glutamine but not the control group. Adverse events and rates of study-drug discontinuation were low and similar in the two groups. No serious adverse events were observed. CONCLUSIONS In patients with IBS-D with intestinal hyperpermeability following an enteric infection, oral dietary glutamine supplements dramatically and safely reduced all major IBS-related endpoints. Large randomised clinical trials (RCTs) should now be done to validate these findings, assess quality of life benefits and explore pharmacological mechanisms. TRIAL REGISTRATION NUMBER NCT01414244; Results.
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The Effect of Acute Glutamine Supplementation on Markers of Inflammation and Fatigue During Consecutive Days of Simulated Wildland Firefighting.
Nava, RC, Zuhl, MN, Moriarty, TA, Amorim, FT, Bourbeau, KC, Welch, AM, McCormick, JJ, King, KE, Mermier, CM
Journal of occupational and environmental medicine. 2019;(2):e33-e42
Abstract
OBJECTIVE To examine the effect of oral glutamine supplementation on inflammation and fatigue during and after simulated wildland firefighting (WLFF) tasks in hot conditions over 2 consecutive days. METHODS Eleven men and women ingested a glutamine supplement or a placebo before and after simulated wildland firefighting in an environmental chamber (38 °C, 35% relative humidity). Subjective fatigue, markers of inflammation, and cellular stress were measured pre, post and 4 hours post-exercise on both days. RESULTS Gastrointestinal damage, subjective fatigue, and ratings of perceived exertion were lower after glutamine supplementation compared with placebo. Heat shock protein 70 (HSP70) and nuclear factor kappa-inhibitor alpha (IκBα) levels were higher on both days of the glutamine trial compared with placebo. CONCLUSIONS Glutamine supplementation may improve recovery after fire suppression in WLFFs. This may result from the upregulation of HSP70 which inhibits inflammation and protects against gastrointestinal (GI) barrier damage.
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Oral Supplementation with Beta-Hydroxy-Beta-Methylbutyrate, Arginine, and Glutamine Improves Lean Body Mass in Healthy Older Adults.
Ellis, AC, Hunter, GR, Goss, AM, Gower, BA
Journal of dietary supplements. 2019;(3):281-293
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Oral intake of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine may ameliorate muscle loss by stimulating protein synthesis and decreasing protein degradation while simultaneously decreasing inflammation. Previous studies provide evidence for improvement in body composition with dietary supplementation of these ingredients among patients with muscle-wasting diseases. The objectives of this study were to examine the effects of this amino acid mixture on lean body mass, muscle volume, and physical function among healthy older adults. Thirty-one community-dwelling men and women, aged 65-89 years, were randomized to either two oral doses of the amino acid supplement (totaling 3 g HMB, 14 g arginine, 14 g glutamine) or placebo daily for six months. At baseline and month six, lean body mass was measured by air displacement plethysmography, dual-energy X-ray absorptiometry (DXA), and four-compartment model. Muscle volume of quadriceps was quantified by magnetic resonance imaging (MRI), and participants performed a battery of tests to assess physical function. As compared to the placebo group, the treatment group exhibited improvement in a timed stair climb (p =.016) as well as significant increases in lean body mass by all methods of assessment (p <.05). Regional analysis by DXA revealed increased arm lean mass in the supplement group only (p =.035). However, no change was observed in MRI-derived quadriceps volume. Dietary supplementation with HMB, arginine, and glutamine improved total body lean mass among a small sample of healthy older adults. Further research is indicated to elucidate mechanisms of action and to determine whether supplementation may benefit frail elders. Registered under ClinicalTrials.gov identifier no. NCT01057082.
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Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.
Ma, C, Tsai, H, Su, W, Sun, L, Shih, Y, Wang, J
Journal of postgraduate medicine. 2018;(3):155-163
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BACKGROUND Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. MATERIALS AND METHODS This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. RESULTS No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). CONCLUSION Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.