Szymanski MC, Gillum TL, Gould LM, Morin DS, Kuennen MR. Short-term dietary curcumin supplementation reduces gastrointestinal barrier damage and physiological strain responses during exertional heat stress. J Appl Physiol 124: 330-340, 2018. First published September 21, 2017; doi: 10.1152/japplphysiol.00515.2017 .-This work investigated the effect of 3 days of 500 mg/day dietary curcumin supplementation on gastrointestinal barrier damage and systems-physiology responses to exertional heat stress in non-heat-acclimated humans. Eight participants ran (65% V̇o) for 60 min in a Darwin chamber (37°C/25% relative humidity) two times (Curcumin/Placebo). Intestinal fatty acid-binding protein (I-FABP) and associated proinflammatory [monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), interleukin-6] and anti-inflammatory [interleukin-1 receptor antagonist (IL-1RA), interleukin-10 (IL-10)] cytokines were assayed from plasma collected before (Pre), after (Post) and 1 (1-Post) and 4 (4-Post) h after exercise. Core temperature and HR were measured throughout exercise; the physiological strain index (PSI) was calculated from these variables. Condition differences were determined with 2-way (condition × time) repeated-measures ANOVAs. The interaction of condition × time was significant ( P = 0.05) for I-FABP and IL-1RA. Post hoc analysis indicated I-FABP increased more from Pre to Post (87%) and 1-Post (33%) in Placebo than in Curcumin (58 and 18%, respectively). IL-1RA increased more from Pre to 1-Post in Placebo (153%) than in Curcumin (77%). TNF-α increased ( P = 0.01) from Pre to Post (19%) and 1-Post (24%) in Placebo but not in Curcumin ( P > 0.05). IL-10 increased ( P < 0.01) from Pre to Post (61%) and 1-Post (42%) in Placebo not in Curcumin ( P > 0.05). The PSI, which indicates exertional heatstroke risk, was also lower ( P < 0.01) in Curcumin than Placebo from 40 to 60 min of exercise. These data suggest 3 days curcumin supplementation may improve gastrointestinal function, associated cytokines, and systems-level physiology responses during exertional heat stress. This could help reduce exertional heatstroke risk in non-heat-acclimated individuals. NEW & NOTEWORTHY Exercise-heat stress increases gastrointestinal barrier damage and risk of exertional heatstroke. Over the past decade at least eight different dietary supplements have been tested for potential improvements in gastrointestinal barrier function and systems-level physiology responses during exercise-heat stress. None have been shown to protect against both insults simultaneously. In this report 3 days of 500 mg/day dietary curcumin supplementation are shown to improve gastrointestinal barrier function, associated cytokine responses, and systems-level physiology parameters. Further research is warranted.

This work investigated the effect of a 6-day heat acclimation (HA) protocol on myotube metabolic responses at baseline and in response to a subsequent lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at 40 °C for 6 days (HA) or maintained at 37 °C (C). Following 24-h recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for analysis of protein markers of mitochondrial biogenesis and macronutrient storage. Functional significance of these changes was confirmed with mitochondrial respiration and glycolytic measurements on a Seahorse XF-96 analyzer. HA stimulated mitochondrial biogenesis and increased indicators of mitochondrial content [SIRT1 (+ 62%); PGC-1α (+ 57%); NRF-1 (+ 40%); TFAM (+ 141%); CS (+ 25%); CytC (+ 38%); all p < 0.05]. Altered lipid biosynthesis enzymes [p-ACCa:ACC (+ 59%; p = 0.04) and FAS (- 86%; p < 0.01)] suggest fatty acid generation may have been downregulated, whereas increased GLUT4 (+ 69%; p < 0.01) and LDH-B (+ 366%; p < 0.01) suggest aerobic glycolytic capacity may have been improved. Mitochondrial biogenesis signaling in HA myotubes was suppressed by 500 ng/ml LPS (PGC-1α, NRF-1, TFAM; all p > 0.05) but increased LDH-B (+ 30%; p = 0.02) and CPT-1 (+ 55%; p < 0.01) suggesting improved catabolic function. Basal respiration was increased in HA myotubes (+ 8%; p < 0.01) and HA myotubes maintained elevated basal respiration during LPS challenge (+ 8%; p < 0.01). LPS reduced peak respiration in C myotubes (- 6%; p < 0.01) but did not impair peak respiration in HA myotubes (p > 0.05). Oxidative reliance was elevated in HA over that in control (+ 25%; p < 0.01) and in HA + LPS over C + LPS (+ 30%; p < 0.01). In summary, HA stimulated mitochondrial biogenesis in C2C12 myotubes. HA myotubes exhibited (1) elevated basal/peak mitochondrial respiration capacities; (2) greater oxidative reliance; and (3) protection against LPS-mediated respiration impairment. Collectively, these data suggest HA may improve aerobic metabolism in skeletal muscle and protect against LPS-mediated energy deficit.

This work investigated the ability of a 6-day heat acclimation protocol to impart heat acclimation-mediated cross-tolerance (HACT) in C2C12 myotubes, as indicated by changes in inflammatory and apoptotic responses to subsequent lipopolysaccharide (LPS) challenge. Myotubes were incubated at 40 °C for 2 h/day over 6 days (HA) or maintained for 6 days at 37 °C (C). Following 24 h recovery, myotubes from each group received either no stimulation or 500 ng/ml LPS for 2 h (HA + LPS and C + LPS, respectively). Cell lysates were collected and analyzed for protein markers of the heat shock response, inflammation, and apoptosis. As compared to C, HA exhibited an elevated heat shock response [HSP70 (+ 99%); HSP60 (+ 216%); HSP32 (+ 40%); all p < 0.01] and reduced inflammatory and apoptotic signaling [p-NF-ĸB:NF-ĸB (- 99%%); p-JNK (- 49%); all p < 0.01]. When compared to C + LPS, HA + LPS also exhibited an elevated heat shock response [HSP70 (+ 68%); HSP60 (+ 32%); HSP32 (+ 38%); all p < 0.01]. However, inflammatory and apoptotic responses in HA + LPS were increased [p-IKBa:IKBa (+ 432%); p-NF-ĸB:NF-ĸB (+ 283%); caspase-8p18 (+ 53%); p-JNK (+ 41%); all p < 0.05]. This unanticipated finding may be due to increased TLR4-mediated signaling capacity in HA + LPS, as indicated by upregulation of TLR4 [(+ 24%); MyD88 (+ 308%); p-NIK (+ 199%); and p-IKKα/b (+ 81%); all p < 0.05]. Data suggest HA reduces inflammatory and apoptotic signaling in skeletal muscle cells that are maintained under basal conditions. However, HACT is selective and does not apply to TLR4 signaling in the present model.

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