Acute L‐glutamine supplementation does not improve gastrointestinal permeability, injury or microbial translocation in response to exhaustive high intensity exertional‐heat stress
Authors: Ogden Henry B. , Fallowfield Joanne L. , Child Robert B. , Davison Glen , Fleming Simon C. , Delves Simon K. , Millyard Alison , Westwood Caroline S. , Layden Joseph D. 
Published: November 2021

ABSTRACTPurpose: 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; = 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.