Post-exercise hot or cold water immersion does not alter perception of effort or neuroendocrine responses during subsequent moderate-intensity exercise.

Post-exercise hot (HWI) and cold (CWI) water immersion are popular strategies used by athletes in a range of sporting contexts, such as enhancing recovery or adaptation. However, prolonged heating bouts increase neuroendocrine responses that are associated with perceptions of fatigue. Fourteen endurance-trained runners performed three trials consisting of two 45-min runs at 95% lactate threshold on a treadmill separated by 6 h of recovery. Following the first run, participants completed one of HWI (30 min, 40°C), CWI (15 min, 14°C) or control (CON, 30 min rest in ambient conditions) in a randomised order. Perceived effort and recovery were measured using ratings of perceived exertion (RPE) and the Acute Recovery and Stress Scale (ARSS), whilst physiological responses including venous concentrations of a range of neuroendocrine markers, superficial femoral blood flow, heart rate and rectal temperature were measured. Exercise increased neuroendocrine responses of interleukin-6, adrenaline and noradrenaline (all P < 0.001). Additionally, perceptions of overall recovery (P < 0.001), mental performance capacity (P = 0.02), physical performance capability (P = 0.01) and emotional balance (P = 0.03) were reduced prior to the second run. However, there was no effect of condition on these variables (P > 0.05), nor RPE (P = 0.68), despite differences in rectal temperature, superficial femoral blood flow following the first run, and participants' expected recovery prior to the intervention (all P < 0.001). Therefore, athletes may engage in post-exercise hot or cold-water immersion without negatively impacting moderate-intensity training sessions performed later the same day.

Effects of resistance exercise and whey protein supplementation on cognitive function in older men: secondary analysis of a randomised, double-blind, placebo-controlled trial.

PURPOSE: Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men. METHODS: In a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified. RESULTS: PRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35-0.51, P < 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention. CONCLUSION: In older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.

The effect of underwater massage during hot water immersion on acute cardiovascular and mood responses.

PURPOSE: There is emerging evidence that demonstrates the health benefits of hot water immersion including improvements to cardiovascular health and reductions in stress and anxiety. Many commercially available hot tubs offer underwater massage systems which purport to enhance many benefits of hot water immersion, however, these claims have yet to be studied. METHODS: Twenty participants (4 females) completed three, 30-min sessions of hot-water immersion (beginning at 39 °C) in a crossover randomized design: with air massage (Air Jet), water massage (Hydro Jet) or no massage (Control). Cardiovascular responses comprising; heart rate, blood pressure and superficial femoral artery blood flow and shear rate were measured. State trait anxiety, basic affect, and salivary cortisol were recorded before and after each trial. Data were analysed using a mixed effects model. RESULTS: Post immersion, heart rate increased (Δ31bpm, P < 0.001, d = 1.38), mean arterial blood pressure decreased (Δ16 mmHg, P < 0.001, d = -0.66), with no difference between conditions. Blood flow and mean shear rate increased following immersion (P < 0.001, Δ362 ml/min, d = 1.20 and Δ108 s-1, d = 1.00), but these increases were blunted in the Air Jet condition (P < 0.001,Δ171 ml/min, d = 0.43 and Δ52 s-1, d = 0.52). Anxiety and salivary cortisol were reduced (P = 0.003, d = -0.20, P = 0.014, d = -0.11), but did not vary between conditions. Enjoyment did not vary between conditions. CONCLUSION: These data demonstrate positive acute responses to hot water immersion on markers of cardiovascular function, anxiety, and stress. There was no additional benefit of water-based massage, while air-based massage blunted some positive vascular responses due to lower heat conservation of the water.

IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance.

The cytokine interleukin-6 (IL-6) is involved in a diverse set of physiological processes. Traditionally, IL-6 has been thought of in terms of its inflammatory actions during the acute phase response and in chronic conditions such as rheumatoid arthritis and obesity. However, IL-6 is also an important signaling molecule during exercise, being acutely released from working muscle fibers with increased exercise duration, intensity, and muscle glycogen depletion. In this context, IL-6 enables muscle-organ crosstalk, facilitating a coordinated response to help maintain muscle energy homeostasis, while also having anti-inflammatory actions. The range of actions of IL-6 can be explained by its dichotomous signaling pathways. Classical signaling involves IL-6 binding to a cell-surface receptor (mbIL-6R; present on only a small number of cell types) and is the predominant signaling mechanism during exercise. Trans-signaling involves IL-6 binding to a soluble version of its receptor (sIL-6R), with the resulting complex having a much greater half-life and the ability to signal in all cell types. Trans-signaling drives the inflammatory actions of IL-6 and is the predominant pathway in disease. A single nucleotide polymorphism (rs2228145) on the IL-6R gene can modify the classical/trans-signaling balance through increasing the levels of sIL-6R. This SNP has clinical significance, having been linked to inflammatory conditions such as rheumatoid arthritis and type 1 diabetes, as well as to the severity of symptoms experienced with COVID-19. This review will describe how acute exercise, chronic training and the rs2228145 SNP can modify the IL-6 signaling pathway and the consequent implications for health and athletic performance.

Sleep Deprivation: Cytokine and Neuroendocrine Effects on Perception of Effort.

INTRODUCTION: An increased perception of effort and subjective fatigue are thought to be central to decreased exercise performance observed after disrupted sleep. However, there is limited understanding of mechanisms that underpin these phenomena. We investigated the role of interleukin-6 (IL-6), the soluble IL-6 receptor, and neuroendocrine factors (cortisol, adrenaline, noradrenaline, and brain-derived neurotropic factor) in mediating these responses at rest and during exercise. METHODS: In a randomized order, 10 healthy active men completed three experimental trials following different sleep conditions: a single night of sleep deprivation, partial sleep deprivation equivalent to 4 h of sleep, and normal sleep. The experimental sessions consisted of physiological and perceptual measurements of exercise intensity throughout 45-min moderate intensity and 15-min maximal effort cycling. Cytokine and neuroendocrine factors were assessed at rest and in response to exercise. RESULTS: Sleep deprivation resulted in increased resting IL-6, lower blood glucose, increased perceived fatigue and perception of effort, lower free-living energy expenditure, and reduced maximal exercise performance. In contrast, sleep deprivation did not alter physiological, cytokine, or neuroendocrine responses to exercise. Variations in the resting concentration of IL-6 were associated with lowered blood glucose, an increased perception of effort, and impaired exercise performance. Resting concentrations of cortisol, adrenaline, noradrenaline, and BNDF showed subtle interactions with specific aspects of mood status and performance but were not affected by sleep deprivation. There were minimal effects of partial sleep deprivation. CONCLUSIONS: These findings demonstrate that cytokine and neuroendocrine responses to exercise are not altered by sleep deprivation but that changes in the resting concentration of IL-6 may play a role in altered perception of effort in this context.

One week of magnesium supplementation lowers IL-6, muscle soreness and increases post-exercise blood glucose in response to downhill running.

PURPOSE: Magnesium supplementation modulates glucose metabolism and inflammation, which could influence exercise performance and recovery. This study investigated the effect of magnesium intake on physiological responses and performance during eccentric exercise and recovery. METHODS: Nine male recreational runners completed a counterbalanced, double-blind, placebo-controlled, cross-over study, registered at ClinicalTrial.gov. Participants consumed low magnesium diets and were supplemented with 500 mg/day of magnesium (SUP) or placebo (CON) for 7 days prior to a 10 km downhill (- 10%) running time trial (TT), separated by a 2-week washout period. At baseline and 24 h post-TT, maximal muscle force was measured. Interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R) and creatine kinase (CK) were measured at rest, 0 h, 1 h and 24 h post-TT. Muscle soreness was measured at the previous times plus 48 h and 72 h post. Glucose and lactate were measured during the TT. RESULTS: The main effect of condition was detected for IL-6 (SUP: 1.36 ± 0.66 vs CON: 2.06 ± 1.14 pg/ml) (P < 0.05, η2 = 0.54), sIL-6R (SUP: 27,615 ± 8446 vs CON: 24,368 ± 7806 pg/ml) (P < 0.05, η2 = 0.41) and muscle soreness (P < 0.01, η2 = 0.67). Recovery of blood glucose and muscle soreness were enhanced in SUP post-TT. There were no differences in glucose and lactate during the TT, or post measures of CK and maximal muscle force. CONCLUSION: Magnesium supplementation reduced the IL-6 response, enhanced recovery of blood glucose, and muscle soreness after strenuous exercise, but did not improve performance or functional measures of recovery.

Characterization of extracellular redox enzyme concentrations in response to exercise in humans.

Redox enzymes modulate intracellular redox balance and are secreted in response to cellular oxidative stress, potentially modulating systemic inflammation. Both aerobic and resistance exercise are known to cause acute systemic oxidative stress and inflammation; however, how redox enzyme concentrations alter in extracellular fluids following bouts of either type of exercise is unknown. Recreationally active men (n = 26, mean ± SD: age 28 ± 8 yr) took part in either: 1) two separate energy-matched cycling bouts: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE) or 2) an eccentric-based resistance exercise protocol (RES). Alterations in plasma (study 1) and serum (study 2) peroxiredoxin (PRDX)-2, PRDX-4, superoxide dismutase-3 (SOD3), thioredoxin (TRX-1), TRX-reductase and interleukin (IL)-6 were assessed before and at various timepoints after exercise. There was a significant increase in SOD3 (+1.5 ng/mL) and PRDX-4 (+5.9 ng/mL) concentration following HIIE only, peaking at 30- and 60-min post-exercise respectively. TRX-R decreased immediately and 60 min following HIIE (-7.3 ng/mL) and MOD (-8.6 ng/mL), respectively. In non-resistance trained men, no significant changes in redox enzyme concentrations were observed up to 48 h following RES, despite significant muscle damage. IL-6 concentration increased in response to all trials, however there was no significant relationship between absolute or exercise-induced changes in redox enzyme concentrations. These results collectively suggest that HIIE, but not MOD or RES increase the extracellular concentration of PRDX-4 and SOD3. Exercise-induced changes in redox enzyme concentrations do not appear to directly relate to systemic changes in IL-6 concentration.NEW & NOTEWORTHY Two studies were conducted to characterize changes in redox enzyme concentrations after single bouts of exercise to investigate the emerging association between extracellular redox enzymes and inflammation. We provide evidence that SOD3 and PRDX-4 concentration increased following high-intensity aerobic but not eccentric-based resistance exercise. Changes were not associated with IL-6. The results provide a platform to investigate the utility of SOD3 and PRDX-4 as biomarkers of oxidative stress following exercise.

Acute responses of cytokines and adipokines to aerobic exercise in relapsing vs. remitting women with multiple sclerosis.

OBJECTIVE: To examine the acute effect of exercise on cytokines and adipokines during relapse and the remitting phase of multiple sclerosis (MS). METHODS: Thirty women with MS in the relapsing or remitting phase were matched with fifteen healthy controls. Participants performed a single-bout of aerobic exercise at 60-70% maximal heart rate. Furthermore, five women in the relapsing phase were enrolled (control relapse) and did not receive any intervention. Blood samples were taken before, immediately after, 1-h and 6-h after the exercise. RESULTS: Levels of IL-10 and TNF-α in response to exercise were similar in healthy and MS remitting subjects. Compared to baseline, TNF-α levels in relapsing subjects were significantly decreased immediately after exercise. Immediately following exercise, leptin levels significantly decreased in relapsing subjects. Adiponectin and IL-6 showed no significant difference between groups. CONCLUSION: After relapse, exercise does not induce inflammatory cytokine response and temporarily improves both cytokine and adipokine balance.

sIL-6R Is Related to Weekly Training Mileage and Psychological Well-being in Athletes.

INTRODUCTION: Interleukin 6 (IL-6) has been ascribed both positive and negative roles in the context of exercise and training. The dichotomous nature of IL-6 signaling seems to be determined by the respective concentration of its receptors (both membrane-bound [IL-6R] and soluble [sIL-6R] forms). The purpose of the present study was to investigate the response of sIL-6R to long-term training and to investigate the relationship between sIL-6R, self-reported measures of well-being, and upper respiratory symptoms in highly trained endurance athletes. METHODS: Twenty-nine athletes provided resting blood samples and completed well-being and illness monitoring questionnaires on a weekly basis for a period of 18 wk during a winter training block. RESULTS: Upper respiratory symptoms were not correlated to concentrations of sIL-6R or cortisol, but there was a nonsignificant trend (P = 0.08) for the most illness-prone athletes (as defined by self-reported illness questionnaire data) to exhibit higher average sIL-6R concentrations compared with the least ill (23.7 ± 4.3 vs 20.1 ± 3.8 ng·mL). Concentrations of sIL-6R were positively correlated to subjective measures of stress (r = 0.64, P = 0.004) and mood (r = 0.49, P = 0.02) but were negatively correlated to sleep quality (r = -0.43, P = 0.05) and cortisol concentration (r = -0.17, P = 0.04). In a subgroup of 10 athletes, weekly training distance was quantified by coaching staff, and this negatively correlated with sIL-6R in the following week (r = -0.74, P < 0.005). CONCLUSION: The findings of the current study suggest that sIL-6R is responsive to prolonged periods of exercise training, with sIL-6R levels varying related to the volume of training performed in the preceding week. Importantly, our data indicate that changes in sIL-6R levels could be linked to common symptoms of overreaching, such as high levels of stress, and/or depressed mood.

Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume.

Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6-related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise.