Trevor Gillum

Thermotolerance and heat acclimation may share a common mechanism in humans

Thermotolerance and heat acclimation are key adaptation processes that have been hitherto viewed as separate phenomena. Here, we provide evidence that these processes may share a common basis, as both may potentially be governed by the heat shock response. We evaluated the effects of a heat shock response-inhibitor (quercetin; 2,000 mg/day) on established markers of thermotolerance [gastrointestinal barrier permeability, plasma TNF-α, IL-6, and IL-10 concentrations, and leukocyte heat shock protein 70 (HSP70) content]. Heat acclimation reduced body temperatures, heart rate, and physiological strain during exercise/heat stress) in male subjects (n = 8) completing a 7-day heat acclimation protocol. These same subjects completed an identical protocol under placebo supplementation (placebo). Gastrointestinal barrier permeability and TNF-α were increased on the 1st day of exercise/heat stress in quercetin; no differences in these variables were reported in placebo. Exercise HSP70 responses were increased, and plasma cytokines (IL-6, IL-10) were decreased on the 7th day of heat acclimation in placebo; with concomitant reductions in exercise body temperatures, heart rate, and physiological strain. In contrast, gastrointestinal barrier permeability remained elevated, HSP70 was not increased, and IL-6, IL-10, and exercise body temperatures were not reduced on the 7th day of heat acclimation in quercetin. While exercise heart rate and physiological strain were reduced in quercetin, this occurred later in exercise than with placebo. Consistent with the concept that thermotolerance and heat acclimation are related through the heat shock response, repeated exercise/heat stress increases cytoprotective HSP70 and reduces circulating cytokines, contributing to reductions in cellular and systemic markers of heat strain. Exercising under a heat shock response-inhibitor prevents both cellular and systemic heat adaptations.

Exercise, but not acute sleep loss, increases salivary antimicrobial protein secretion.

Abstract Gillum, TL, Kuennen, MR, Castillo, MN, Williams, NL, and Jordan-Patterson, AT. Exercise, but not acute sleep loss, increases salivary antimicrobial protein secretion. J Strength Cond Res 29(5): 1359–1366, 2015—Sleep deficiencies may play a role in depressing immune parameters. Little is known about the impact of exercise after sleep deprivation on mucosal immunity. The purpose of this study was to quantify salivary antimicrobial proteins (AMPs) in response to sleep loss before and after exercise. Four men and 4 women (age: 22.8 ± 2; : 49.1 ± 7.1 ml·kg−1·min−1) completed 2 exercise trials consisting of 45 minutes of running at 75% after a normal night of sleep (CON) and after a night without sleep (WS). Exercise trials were separated by 10 ± 3 days. Saliva was collected before, immediately after, and 1 hour after exercise. LL-37, HNP1-3, Lactoferrin (Lac), and Lysozyme (Lys) were measured. Sleep loss did not affect the concentration or secretion rate of AMPs before or in response to exercise. However, exercise increased the concentration from pre- to post-exercise of LL-37 (pre: 15.5 ± 8.7; post: 22.3 ± 16.2 ng·ml−1), HNP1-3 (pre: 2.2 ± 2.3; post: 3.3 ± 2.5 &mgr;g·ml−1), Lac (pre: 5,234 ± 4,202; post: 12,283 ± 10,995 ng·ml−1), and Lys (pre: 5,831 ± 4,465; post: 12,542 ± 10,755 ng·ml−1), p ⩽ 0.05. The secretion rates were higher immediately after and 1 hour after exercise compared with before exercise for LL-37 (pre: 3.1 ± 2.1; post: 5.1 ± 3.7; +1: 6.9 ± 8.4 ng·min−1), HNP1-3 (pre: 0.38 ± 0.38; post: 0.80 ± 0.75; +1: 0.84 ± 0.67 &mgr;g·min−1), Lac (pre: 1,096 ± 829; post: 2,948 ± 2,923; +1: 2,464 ± 3,785 ng·min−1), and Lys (pre: 1,534 ± 1,790; post: 3,042 ± 2,773; +1: 1,916 ± 1,682 ng·min−1), p ⩽ 0.05. These data suggest that the major constituents of the mucosal immune system are unaffected by acute sleep loss and by exercise after acute sleep loss. Exercise increased the concentration and secretion rate of each AMP suggesting enhanced immunity and control of inflammation, despite limited sleep.

Salivary antimicrobial protein response to prolonged running.

Introduction Prolonged exercise may compromise immunity through a reduction of salivary antimicrobial proteins (AMPs). Salivary IgA (IgA) has been extensively studied, but little is known about the effect of acute, prolonged exercise on AMPs including lysozyme (Lys) and lactoferrin (Lac). Objective To determine the effect of a 50-km trail race on salivary cortisol (Cort), IgA, Lys, and Lac. Methods 14 subjects: (6 females, 8 males) completed a 50km ultramarathon. Saliva was collected pre, immediately after (post) and 1.5 hrs post race (+1.5). Results Lac concentration was higher at +1.5 hrs post race compared to post exercise (p < 0.05). Lys was unaffected by the race (p > 0.05). IgA concentration, secretion rate, and IgA/Osm were lower +1.5 hrs post compared to pre race (p < 0.05). Cort concentration was higher at post compared to +1.5 (p < 0.05), but was unaltered from pre race levels. Subjects finished in 7.81±1.2 hrs. Saliva flow rate did not differ between time points. Saliva Osm increased at post (p < 0.05) compared to pre race. Conclusions The intensity could have been too low to alter Lys and Lac secretion rates and thus, may not be as sensitive as IgA to changes in response to prolonged running. Results expand our understanding of the mucosal immune system and may have implications for predicting illness after prolonged running.

Fit persons are at decreased (not increased) risk of exertional heat illness.

In the review entitled ‘‘Influence of Aerobic Fitness on Thermoregulation during Exercise in the Heat,’’ Dr. MoraRodgriguez (3) stated that ‘‘When individuals can self-pace exerciseI fit individuals will be producing more heat and may fall into the higher risk category [than unfit] for heatrelated injuries.’’ We wish to challenge this statement. McLellan et al. (2) recently levied a similar challenge, arguing that because ‘‘aerobic fitness enhances thermotolerance,’’ trained persons can tolerate higher core temperatures than untrained. Our previous work (1) reaffirms the challenge by McLellan et al. (2) and lends credence to our own. In that study, eight subjects exercised (in athletic shorts/socks/shoes) to a core temperature of 39-C or higher for seven consecutive days. As shown in Panel A of the Figure, plasma endotoxin, interleukin-6 (IL-6), and IL-10 were reduced and heat shock protein 70 (HSP70) content (peripheral blood mononuclear cells) was increased after 7 d of repeated exercise-heat stress. We attributed the lack of increase in urinary lactulose excretion, plasma endotoxin, and tumor necrosis factor-> (TNF->) (indicators of gut permeability) preacclimation to the fact that this exercise was undertaken in fit subjects who had acquired some level of thermotolerance. These subjects also exhibited improvements (reduced core, skin, and mean body temperatures, heart rate, and physiologic strain) on a standardized heat tolerance test (1). We also assessed the impact that inhibiting the thermotolerance machinery (in the same eight subjects) had on endotoxin spillover, the ensuing inflammatory response, and achievement of the ‘‘heat-acclimated’’ state. We inhibited thermotolerance with an oral HSP70 blocker, which subjects began ingesting immediately before the first day of exercise-heat stress. As shown in Panel B of the Figure, gut permeability markers (urinary lactulose excretion, plasma endotoxin, TNF->) were elevated on the first day of exercise-heat stress. They remained elevated on the seventh day. Core, skin, and mean body temperatures did not improve (1). Improvements in heart rate and physiologic strain were attenuated (1). These data effectively underscore: 1) the existence of ‘‘enhanced thermotolerance in fit populations’’ (2); 2) the importance of thermotolerance in the heat acclimation response; and 3) the potential for thermotolerance to reduce risk for ‘‘heat-related injuries’’ (3) in fit populations. We conclude our letter with three observations:

Prohormone supplement 3β-hydroxy-5α-androst-1-en-17-one enhances resistance training gains but impairs user health

Prohormone supplements (PS) are recognized not to impart anabolic or ergogenic effects in men, but the research supporting these conclusions is dated. The Anabolic Steroid Control Act was amended in 2004 to classify androstenedione and 17 additional anabolic compounds as controlled substances. The viability of PS that entered the market after that time have not been evaluated. Seventeen resistance-trained men (23 ± 1 yr; 13.1 ± 1.5% body fat) were randomly assigned to receive either 330 mg/day of 3β-hydroxy-5α-androst-1-en-17-one (Prohormone; n = 9) or sugar (Placebo; n = 8) per os and complete a 4-wk (16 session) structured resistance-training program. Body composition, muscular strength, circulating lipids, and markers of liver and kidney dysfunction were assessed at study onset and termination. Prohormone increased lean body mass by 6.3 ± 1.2%, decreased fat body mass by 24.6 ± 7.1%, and increased their back squat one repetition maximum and competition total by 14.3 ± 1.5 and 12.8 ± 1.1%, respectively. These improvements exceeded (P < 0.05) Placebo, which increased lean body mass by 0.5 ± 0.8%, reduced fat body mass by 9.5 ± 3.6%, and increased back squat one repetition maximum and competition total by 5.7 ± 1.7 and 5.9 ± 1.7%, respectively. Prohormone also experienced multiple adverse effects. These included a 38.7 ± 4.0% reduction in HDL (P < 0.01), a 32.8 ± 15.05% elevation in LDL (P < 0.01), and elevations of 120.0 ± 22.6 and 77.4 ± 12.0% in LDL-to-HDL and cholesterol-to-HDL ratios, respectively (both P < 0.01). Prohormone also exhibited elevations in serum creatinine (19.6 ± 4.3%; P < 0.01) and aspartate transaminase (113.8 ± 61.1%; P = 0.05), as well as reductions in serum albumin (5.1 ± 1.9%; P = 0.04), alkaline phosphatase (16.4 ± 4.7%; P = 0.04), and glomerular filtration rate (18.0 ± 3.3%; P = 0.04). None of these values changed (all P > 0.05) in Placebo. The oral PS 3β-hydroxy-5α-androst-1-en-17-one improves body composition and muscular strength. However, these changes come at a significant cost. Cardiovascular health and liver function are particularly compromised. Given these findings, we feel the harm associated with this particular PS outweighs any potential benefit.

Exercise does not increase salivary lymphocytes, monocytes, or granulocytes, but does increase salivary lysozyme

ABSTRACT An increase in salivary leukocytes may contribute to the exercise-induced increase in salivary antimicrobial proteins (AMPs). However, exercise-induced changes in salivary leukocytes have not been studied. The purpose of the study was to describe salivary leukocyte changes with exercise. Participants (n = 11, 20.3 ± 0.8 years, 57.2 ± 7.6 ml kg−1 min−1 peak oxygen uptake ((VO) ̇2peak), 11.1 ± 3.9% body fat) ran for 45 min at 75% of VO2peak. Stimulated saliva (12 mL) was collected pre- and immediately post exercise. Saliva was filtered through a 30 µm filter before analysis of leukocytes (CD45+), granulocytes (CD45+CD15+), monocytes (CD45+CD14+), T-cells (CD45+CD3+), and B-cells (CD45+CD20+) using flow cytometry. Saliva was analysed for Lysozyme (Lys) using ELISA. Exercise did not alter any leukocyte subset. The major constituent of leukocytes pre-exercise were granulocytes (57.9 ± 30.3% compared with monocytes: 5.1 ± 2.7%, T-cells: 17.1 ± 8.9%, B-cells: 12.1 ± 10.2%) (P < 0.05). In a subset of n = 6, Lys secretion rate increased after exercise (pre: 5,170 ± 5,215 ng/min; post: 7,639 ± 4,140 ng/min) (P < 0.05). Exercise does not result in increased granulocytes, but does increase Lys. Further, these data suggest that an increase in salivary leukocytes is not needed to increase Lys.

Sex differences in heat shock protein 72 expression in peripheral blood mononuclear cells to acute exercise in the heat.

Background: Heat shock protein 72 (Hsp72) is responsible for maintaining critical cellular function during heat stress. Hsp72 confers thermotolerance and may play a role in heat acclimation. Animal research suggests a difference between sexes in Hsp72 expression in response to exercise, however, human data is lacking. Objectives: To determine sex differences in intracellular heat shock protein 72 (Hsp72) following exercise in the heat. Patients and Methods: Nine non-heat acclimated women with normal menstrual cycles (VO2pk 58 ± 5 mL.kgFFM-1.min-1) and nine non-heat acclimated men (VO2pk 60 ± 7 ml.kgFFM-1.min-1) completed 2 treadmill bouts at 60% VO2pk for 60 min in a 42°C, 20% RH environment. Women were tested in follicular (fol) and luteal (lut) phases. The duplicate trials were separated by 12 days for men and women. Blood samples were drawn pre, immediately post, 1, and 4 hrs post-exercise. Results: Men and women differed in their Hsp72 response after exercise (time X sex X trial interaction; P < 0.05). Men increased Hsp72 after exercise more than women. Both men and women produced less Hsp72 during trial 2 compared to trial 1. Estrogen (r = 0.24; P > 0.05) and progesterone (r = 0.27, P > 0.05) concentrations were not correlated with Hsp72. Conclusion: Our findings suggest that men and women differ in their cellular stress response. Men up-regulated Hsp72 after a single bout of exercise in the heat, which persists for 12 days, suggesting an accumulation of Hsp72 which may lead to acquired cellular thermotolerance.

Short term dietary curcumin supplementation reduces gastrointestinal barrier damage and physiological strain responses during exertional heat stress

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% V̇o2max) 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.

Effects of Exercise Induced Dehydration and Glycerol Rehydration on Anaerobic Power in Male Collegiate Wrestlers.

Abstract McKenna, ZJ and Gillum, TL. Effects of exercise induced dehydration and glycerol rehydration on anaerobic power in male collegiate wrestlers. J Strength Cond Res 31(11): 2965–2968, 2017—Wrestlers attempting to reach a specific weight class often use rapid weight loss (RWL). Rapid weight loss is associated with high levels of dehydration, which may hinder athletic performance. Thus, there is a need for wrestlers to optimize rehydration after achieving a specific weight. We sought to observe the effects of RWL on anaerobic power and the impact of glycerol on rehydration and power in male collegiate wrestlers (n = 7, 19.75 ± 1.67 years, 76.8 ± 4.32 kg, 11.6 ± 4.32% body fat, 59.9 ± 6.42 ml·kg−1·min−1). Subjects were assessed for body mass (BM), hydration, and mean power output (Wmean) before exercise (pre), immediately after exercise (3% dehydrated), and 60 minutes after exercise (rehydrated). Participants ran at 70% of V[Combining Dot Above]O2max in a heated room (30° C) until 3% BM loss (BML). Subjects rehydrated drinking either 26 ml·kg−1 of water (control) or a 3% glycerol (treatment) solution containing 26 ml·kg−1 of water and 1 g·kg−1 of glycerol. Participants lost 3.00 ± 0.31% (control) and 2.89 ± 0.26% (treatment) of their BM from the pre- to dehydrated conditions. Wmean (control: 659.29 ± 79.12, 651.43 ± 70.71, 659.71 ± 82.78; treatment: 647.71 ± 110.64, 644.57 ± 118.15, 638.14 ± 100.71) did not differ across time (p = 0.87) nor condition (p = 0.80). In addition, glycerol had no significant impact on acute hydration (control: urine-specific gravity [SG] = 1.019 ± 0.010; treatment: SG = 1.017 ± 0.017). These data show that 3% BML did not impair anaerobic performance, and furthermore that glycerol proved ineffective for rehydration in a match like scenario for the competing wrestler.

Erratum to: Exercise increases lactoferrin, but decreases lysozyme in salivary granulocytes

Acute moderate intensity exercise has been shown to increase antimicrobial protein (AMP) concentration (from pre to immediately post exercise) in various exocrine solutions, most notably, saliva (Allgrove et al. 2008; Gillum et al. 2014, 2015, 2016). Lactoferrin (Lac) and lysozyme (Lys) are two AMPs that enhance immune protection and the prevention of upper respiratory infection symptoms (West et al. 2006a, b). Specifically, Lac and Lys exert immunomodulating effects that regulate inflammation, exemplify antimicrobial effects by preventing the growth of microorganisms, and directly eradicate microbes by a variety of mechanisms including DNA/RNA disruption, disruption of membranes, degradation of ATP, and initiation of autolysins (West et al. 2006). Abstract Introduction Intracellular lactoferrin (Lac) and lysozyme (Lys) content play an important role in regulating inflammation and promoting host protection. While exercise has demonstrated an increase in Lac and Lys concentration in exocrine solutions, little is known regarding intracellular concentration changes in response to exercise. Purpose To quantify intracellular Lac and Lys concentration before and after exercise in salivary CD45+CD15+ cells. Methods 11 males (20.3 ± 0.8 years, 57.2 ± 7.6 mL/kg/ min V̇O2pk, 11.1 ± 3.9% body fat) ran for 45 min at 75% of VO2pk. 12 mL of stimulated saliva were collected pre and immediately post exercise. Saliva was filtered through a 30-μm filter before analysis of leukocytes (CD45+) and granulocytes (CD45+CD15+) using flow cytometry. Results Median fluorescent intensity (MFI) of Lac increased from pre (64,268 ± 46,036 MFI) to post (117,134 ± 88,115 MFI) exercise (p <0.05). Lys MFI decreased with exercise (pre: 16,933 ± 8249; post: 11,616 ± 6875) (p <0.05). Conclusion Acute running resulted in an increased Lac concentration which could lead to a decrease in inflammation, adding further evidence of the anti-inflammatory effects of exercise. Conversely, the exercise-associated