Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression

Abstract

The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P < 0.05). IκBα expression in peripheral blood mononuclear cells was higher 240 min after exercise in the GLN trial compared with the PLA trial (1.411 ± 0.523 vs. 0.9839 ± 0.343, respectively; P < 0.05). In vitro using the intestinal epithelial cell line Caco-2, we measured effects of GLN supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P < 0.05). Occludin levels increased after 4 mM supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P < 0.001). GLN supplementation prevented exercise-induced permeability, possibly through HSF-1 activation.

Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms

“…This is consistent with much of the recent laboratory-based research into single exercise sessions and markers of GI damage. Many of these have reported measures of increased intestinal damage but reported either low or mild scores of GI discomfort during acute exercise bouts (Lambert et al 2008;van Wijck et al 2011) or have not reported GI symptoms at all (Marchbank et al 2011;Zuhl et al 2014). Even 60 minutes of running in the heat, 30 minutes of which was a distance time trial, mean symptoms were rated as very mild to noticeable (Morrison et al 2014).…”

Heat acclimation: Gold mines and genes

“…On the other hand, ingestion of glutamine which increases HSP70 synthesis, prevented endotoxin release and the inflammatory response seen in the same unacclimated subjects without glutamine supplementation during an acute exercise bout in the heat. 44 It would be interesting to examine the effects of glutamine during a heat acclimation protocol.…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…However, human data supporting this assumption are either missing or contradictory [268]. Nevertheless, glutamine supplementation has convincingly been demonstrated to prevent exercise-induced intestinal permeability, possibly through HSF1 activation [269,270].…”

“…It is assumed that a derangement of the gut mucosal barrier function, which occurs during aging and critical illnesses, results in an amplification of the general inflammatory response predisposing patients to multiple organ failure [305]. In fact, chronic glutamine supplementation reduces exerciseinduced intestinal permeability while inhibiting NF-κB pro-inflammatory pathways in human PBMC, in a mechanism associated with the activation of HSP70 expression [269]. The same was confirmed in physically active subjects acutely treated with oral doses of glutamine prior to exercise [270].…”