No protective benefits of low dose acute L-glutamine supplementation on small intestinal permeability, epithelial injury and bacterial translocation biomarkers in response to subclinical exertional-heat stress: A randomized cross-over trial.

Exertional heat stress disrupts gastrointestinal permeability and, through subsequent bacterial translocation, can result in potentially fatal exertional heat stroke. Glutamine supplementation is a potential countermeasure although previously validated doses are not universally well tolerated. Ten males completed two 80-minute subclinical exertional heat stress tests (EHSTs) following either glutamine (0.3 g kg FFM-1) or placebo supplementation. Small intestinal permeability was assessed using the lactulose/rhamnose dual sugar absorption test and small intestinal epithelial injury using Intestinal Fatty-Acid Binding Protein (I-FABP). Bacterial translocation was assessed using the total 16S bacterial DNA and Bacteroides/total 16S DNA ratio. The glutamine bolus was well tolerated, with no participants reporting symptoms of gastrointestinal intolerance. Small intestinal permeability was not influenced by glutamine supplementation (p = 0.06) although a medium effect size favoring the placebo trial was observed (d = 0.73). Both small intestinal epithelial injury (p < 0.01) and Bacteroides/total 16S DNA (p = 0.04) increased following exertional heat stress, but were uninfluenced by glutamine supplementation. Low-dose acute oral glutamine supplementation does not protect gastrointestinal injury, permeability, or bacterial translocation in response to subclinical exertional heat stress.

Acute L-glutamine supplementation does not improve gastrointestinal permeability, injury or microbial translocation in response to exhaustive high intensity exertional-heat stress.

Purpose: Exertional-heat stress adversely distrupts (GI) barrier integrity and, through subsequent microbial translocation (MT), can result in potentially fatal exertional-heat stroke. Acute glutamine (GLN) supplementation is a potential nutritional countermeasure, although the practical value of current supplementation regimens is questionable.Method: Ten males completed two high-intensity exertional-heat stress tests (EHST) involving running in the heat (40°C and 40% relative humidity) at lactate threshold to volitional exhaustion. Participants ingested GLN (0.3 g kg FFM-1) or a non-calorific placebo (PLA) one hour prior to the EHST. Venous blood was drawn pre-, post- and one-hour post-EHST. GI permeability was assessed using a serum dual-sugar absorption test (DSAT) and small intestinal epithelial injury using plasma Intestinal Fatty-Acid Binding Protein (I-FABP). MT was assessed using the Bacteroides/total 16S DNA ratio.Results: Volitional exhaustion occurred after 22:19 ± 2:22 (minutes: seconds) in both conditions, during which whole-body physiological responses and GI symptoms were not different (p > 0.05). GI permeability (serum DSAT) was greater following GLN (0.043 ± 0.020) than PLA (0.034 ± 0.019) (p = 0.02; d = 0.47), but small intestine epithelial injury (I-FABP) increased comparably (p = 0.22; ηp2 = 0.16) following the EHST in both trials (GLN Δ = 1.25 ± 0.63 ng ml-1; PLA Δ = 0.92 ± 0.44 ng ml-1). GI MT (Bacteroides/total 16S DNA ratio) was unchanged in either condition following the EHST (p = 0.43).Conclusion: Acute low-dose (0.3 g kg-1 fat free mass) GLN supplementation ingested one hour before high-intesity exertional-heat stress worsened GI permeability, but did not influence either small intestinal epithilial injury or microbial translocation.Abbreviations: ANOVA: Analysis of variance; CV: Coefficient of Variation; DSAT: Dual Sugar Absorption Test; EDTA: Ethylenediaminetetraacetic acid; EHST: Exertional Heat Stress Test; ELISA: Enzyme Linked Immunosorbent Assay; FFM: Fat Free Mass; GI: Gastrointestinal; GFR: Glomerular Filtration Rate; GLN: Glutamine; HPLC: High Performance Liquid Chromatography; HR: Heart Rate; I-FABP: Intestinal Fatty-Acid Binding Protein; ISAK: International Society for the Advancement of Anthropometric Kinanthropometry; L/R: Lactulose-to-Rhamnose; LT: Lactate Threshold; MT: Microbial Translocation; mVAS: Modified Visual Analogue Scale; PBS: Phosphate-Buffered Saline; PLA: Placebo; qPCR: Quantitative Polymerase Chain Reaction; RH: Relative Humidity; RPE: Rate of Perceived Exertion; SD: Standard Deviation; SEM: Sensor Electronics Module; Tcore: Core Body Temperature; Tbody: Mean Body Temperature; Tskin: Mean Skin Temperature; TS: Thermal Sensation; V̇O2max: Maximal Oxygen Uptake.Highlights The pathophysiology of exertional-heat stroke is widely hypothesised to be at least in part attributable to a systemic inflammatory response caused by the leak of gastrointestinal microbes into the circulating blood.Acute high-dose (0.9 g kg FFM-1) L-glutamine supplementation is widely promoted as a practical strategy to protect gastrointestinal barrier integrity during exertional-heat stress. However, previously validated doses are often poorly tolerated and cannot be recommended for widespread implementation.This study examined the efficacy of low-dose (0.30 g kg FFM-1; ∼20 grams) acute L-glutamine supplementation on small intestinal injury, permeability, and microbial translocation in response a high-intensity exertional-heat stress test to exhaustion (20-30 min). This type of exercise accounts for the majority of exertional-heat stroke cases in the military.Despite being universally well-tolerated across all participants, acute low-dose L-glutamine supplementation worsened gastrointestinal permeability, without influencing either small intestinal injury or microbial translocation. These findings do not support the application of low-dose L-glutamine supplementation to help prevent exertional-heat stroke.

Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study.

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.

The Gastrointestinal Exertional Heat Stroke Paradigm: Pathophysiology, Assessment, Severity, Aetiology and Nutritional Countermeasures.

Exertional heat stroke (EHS) is a life-threatening medical condition involving thermoregulatory failure and is the most severe condition along a continuum of heat-related illnesses. Current EHS policy guidance principally advocates a thermoregulatory management approach, despite growing recognition that gastrointestinal (GI) microbial translocation contributes to disease pathophysiology. Contemporary research has focused to understand the relevance of GI barrier integrity and strategies to maintain it during periods of exertional-heat stress. GI barrier integrity can be assessed non-invasively using a variety of in vivo techniques, including active inert mixed-weight molecular probe recovery tests and passive biomarkers indicative of GI structural integrity loss or microbial translocation. Strenuous exercise is strongly characterised to disrupt GI barrier integrity, and aspects of this response correlate with the corresponding magnitude of thermal strain. The aetiology of GI barrier integrity loss following exertional-heat stress is poorly understood, though may directly relate to localised hyperthermia, splanchnic hypoperfusion-mediated ischemic injury, and neuroendocrine-immune alterations. Nutritional countermeasures to maintain GI barrier integrity following exertional-heat stress provide a promising approach to mitigate EHS. The focus of this review is to evaluate: (1) the GI paradigm of exertional heat stroke; (2) techniques to assess GI barrier integrity; (3) typical GI barrier integrity responses to exertional-heat stress; (4) the aetiology of GI barrier integrity loss following exertional-heat stress; and (5) nutritional countermeasures to maintain GI barrier integrity in response to exertional-heat stress.