Effect of curcumin supplementation on exercise-induced muscle damage: a narrative review.

Curcumin, a natural polyphenol extracted from turmeric, is a potent antioxidant and anti-inflammatory agent. In the past few decades, curcumin's ability to impact chronic inflammatory conditions such as metabolic syndrome, arthritis, and cancer has been widely researched, along with growing interest in understanding its role in exercise-induced muscle damage (EIMD). EIMD impacts individuals differently depending on the type (resistance exercise, high-intensity interval training, and running), intensity, and duration of the exercise. Exercise disrupts the muscles' ultrastructure, raises inflammatory cytokine levels, and can cause swelling in the affected limb, a reduction in range of motion (ROM), and a reduction in muscular force-producing capacity. This review focuses on the metabolism, pharmacokinetics of various brands of curcumin supplements, and the effect of curcumin supplementation on EIMD regarding muscle soreness, activity of creatine kinase (CK), and production of inflammatory markers. Curcumin supplementation in the dose range of 90-5000 mg/day can decrease the subjective perception of muscle pain intensity, increase antioxidant capacity, and reduce CK activity, which reduces muscle damage when consumed close to exercise. Consumption of curcumin also improves muscle performance and has an anti-inflammatory effect, downregulating the production of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-8. Curcumin may also improve oxidative capacity without hampering training adaptations in untrained and recreationally active individuals. The optimal curcumin dose to ameliorate EIMD is challenging to assess as its effect depends on the curcumin concentration in the supplement and its bioavailability.

Bioengineered human skeletal muscle capable of functional regeneration.

BACKGROUND: Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology. RESULTS: Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl2) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo. CONCLUSIONS: This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.

Acute and chronic effects of hot water immersion on inflammation and metabolism in sedentary, overweight adults.

Regular exercise-induced acute inflammatory responses are suggested to improve the inflammatory profile and insulin sensitivity. As body temperature elevations partly mediate this response, passive heating might be a viable tool to improve the inflammatory profile. This study investigated the acute and chronic effects of hot water immersion on inflammatory and metabolic markers. Ten sedentary, overweight men [body mass index (BMI): 31.0 ± 4.2 kg/m2, mean ± SD] were immersed in water set at 39°C for 1 h (HWI) or rested for 1 h at ambient temperature (AMB). Venous blood was obtained before the session, immediately postsession, and 2 h postsession for assessment of monocyte intracellular heat shock protein-72 (iHsp72) and plasma concentrations of extracellular Hsp72 (eHsp72), interleukin-6 (IL-6), fasting glucose, insulin, and nitrite. Thereafter, participants underwent a 2-wk intervention period, consisting of 10 hot water immersion sessions (INT). Eight BMI-matched participants (BMI: 30.0 ± 2.5 kg/m2) were included as control (CON). Plasma IL-6 and nitrite concentrations were higher immediately following HWI compared with AMB (IL-6 P < 0.001, HWI: 1.37 ± 0.94 to 2.51 ± 1.49 pg/ml; nitrite P = 0.04, HWI: 271 ± 52 to 391 ± 72 nM), whereas iHsp72 expression was unchanged ( P = 0.57). In contrast to resting iHsp72 expression ( P = 0.59), fasting glucose ( P = 0.04; INT: 4.44 ± 0.93 to 3.98 ± 0.98 mmol/l), insulin ( P = 0.04; INT: 68.1 ± 44.6 to 55.0 ± 29.9 pmol/l), and eHsp72 ( P = 0.03; INT: 17 ± 41% reduction) concentrations were lowered after INT compared with CON. HWI induced an acute inflammatory response and increased nitric oxide bioavailability. The reductions in fasting glucose and insulin concentrations following the chronic intervention suggest that hot water immersion may serve as a tool to improve glucose metabolism. NEW & NOTEWORTHY A single hot water immersion (HWI) session induces an acute increase in plasma interleukin-6 and nitrite concentrations but does not acutely elevate heat shock protein-72 expression in monocytes [intracellular Hsp72 (iHsp72)]. A chronic HWI intervention reduces fasting glucose and insulin concentrations in the absence of changes in resting iHsp72. Therefore, HWI shows potential as a strategy to combat chronic low-grade inflammation and improve glucose metabolism in individuals without the physical capacity to do so using exercise.

Intestinal Barrier Disturbances in Haemodialysis Patients: Mechanisms, Consequences, and Therapeutic Options.

There is accumulating evidence that the intestinal barrier and the microbiota may play a role in the systemic inflammation present in HD patients. HD patients are subject to a number of unique factors, some related to the HD process and others simply to the uraemic milieu but with common characteristic that they can both alter the intestinal barrier and the microbiota. This review is intended to provide an overview of the current methods for measuring such changes in HD patients, the mechanisms behind these changes, and potential strategies that may mitigate these modifications. Lastly, intradialytic exercise is an increasingly employed intervention in HD patients; however the potential implications that this may have for the intestinal barrier are not known; therefore future research directions are also covered.

Hot water immersion induces an acute cytokine response in cervical spinal cord injury.

PURPOSE: The dysfunctional sympathetic nervous system in individuals with cervical spinal cord injury (CSCI) impairs adrenergic responses and may, therefore, contribute to the blunted post-exercise cytokine response. The purpose of this study was to investigate an alternative way to exercise to induce an acute cytokine response by passive core temperature elevation in CSCI. METHODS: Seven male participants with a motor complete CSCI and 8 male able-bodied controls were immersed for 60 min in water set at a temperature 2 °C above the individuals' resting oesophageal temperature. Blood was collected pre, post, and every hour up to 4 h post-immersion. RESULTS: Hot water immersion resulted in an IL-6 plasma concentration mean increase of 133 ± 144 % in both groups (P = 0.001). On a group level, IL-6 plasma concentrations were 68 ± 38 % higher in CSCI (P = 0.06). In both groups, IL-8 increased by 14 ± 11 % (P = 0.02) and IL-1ra by 18 ± 17 % (P = 0.05). Catecholamine plasma concentrations were significantly reduced in CSCI (P < 0.05) and did not increase following immersion. CONCLUSIONS: Passive elevation of core temperature acutely elevates IL-6, IL-8 and IL-1ra in CSCI despite a blunted adrenergic response, which is in contrast to earlier exercise interventions in CSCI. The present study lays the foundation for future studies to explore water immersion as an alternative to exercise to induce an acute cytokine response in CSCI.

Transport spectroscopy of low disorder silicon tunnel barriers with and without Sb implants.

We present transport measurements of silicon MOS split gate structures with and without Sb implants. We observe classical point contact (PC) behavior that is free of any pronounced unintentional resonances at liquid He temperatures. The implanted device has resonances superposed on the PC transport indicative of transport through the Sb donors. We fit the differential conductance to a rectangular tunnel barrier model with a linear barrier height dependence on source-drain voltage and non-linear dependence on gate bias. Effects such as Fowler-Nordheim (FN) tunneling and image charge barrier lowering (ICBL) are considered. Barrier heights and widths are estimated for the entire range of relevant biases. The barrier heights at the locations of some of the resonances for the implanted tunnel barrier are between 15-20 meV, which are consistent with transport through shallow partially hybridized Sb donors. The dependence of width and barrier height on gate voltage is found to be linear over a wide range of gate bias in the split gate geometry but deviates considerably when the barrier becomes large and is not described completely by standard 1D models such as FN or ICBL effects.

Spinal cord injury: known and possible influences on the immune response to exercise.

A spinal cord injury (SCI) can increase the risk of infection by impacting on many aspects of immune function; one particularly well-documented observation is a reduction in lymphocyte numbers. The vast majority of lymphoid cells express adrenergic receptors. Therefore, autonomic function loss and concomitant alterations in resting and post-exercise catecholamine concentrations, particularly so in individuals with a tetraplegia, may impact directly on immune cells and depress immunity. Other factors are further likely to contribute, examples including altered muscular, endocrine and cardiovascular function following SCI. However, some alterations, such as increases in natural killer cell cytotoxicity following exercise in those with a tetraplegia, are unrelated to the catecholamine response. Likewise, mucosal immunity in individuals with a tetraplegia appears to be similarly influenced by exercise as in the able-bodied population. Indeed, rehabilitation therapy and exercise can increase some measures of immunity and autonomic function in those with an SCI. It is therefore possible that compensatory mechanisms offset disability-related detriments. This may be by way of sympathetic reflex activity, receptor hypersensitivity, or parasympathetic and neuroendocrine adjustments. Future work needs to explore these mechanisms further to clarify the implications of an SCI on the immune response to exercise and susceptibility to infection. In this article, we review the impacts of an SCI on immune, and specifically, exercise immune function. The relevant anatomical and physiological foundations of the immune system are first briefly laid out in order to understand the potential impacts of neural and neuroendocrine dysfunction on the immune system. With the limited number of human studies available, we have then aimed specifically to gather all relevant existing literature on exercise immunology in individuals with an SCI in patient, recreationally active and athlete populations. We believe that an understanding of the impacts of exercise can provide a tool to help maintain or improve health in individuals with an SCI. A comprehensive literature search was conducted using the search engines PubMed, SPORTDiscus, Web of Science and Zetoc, search period June 2012-February 2013. Key words employed included spinal cord injury, immunology, exercise, paraplegic, tetraplegic, upper body exercise, interleukin, immunoglobulin, sympathetic, and parasympathetic. All articles and articles derived from their reference lists were checked for their suitability.

Mucosal immune responses during court training in elite tetraplegic athletes.

STUDY DESIGN: Experimental study. OBJECTIVES: To examine salivary secretory immunoglobulin A (sIgA) responses and α-amylase activity during court training in highly trained tetraplegic athletes. SETTING: Loughborough, UK. METHODS: Seven highly trained wheelchair rugby athletes with tetraplegia performed two separate wheelchair rugby court training sessions, lasting 23 and 41.5 min, respectively, with either an aerobic or an interval focus. Timed, unstimulated saliva samples were obtained pre, post and 30 min post exercise and analysed for sIgA and α-amylase. Furthermore, blood lactate concentration and rating of perceived exertion (RPE) immediately after training were measured. RESULTS: sIgA secretion rate and α-amylase were unaffected by exercise during both sessions. However, the increases of sIgA concentration (30 min post exercise: +67 ± 29%) during the aerobic session were accompanied by decreases in saliva flow rate (-35 ± 22%). Athletes' physiological responses to exercise document the highly strenuous nature of the sessions, with blood lactate concentrations reaching 8.1 ± 1.0 and 8.7 ± 1.6 mmol l(-1) and RPE reaching 18(17,18) and 16(15,17) for the aerobic and the interval session, respectively. CONCLUSION: Acute bouts of highly strenuous exercise do not have negative impacts on the mucosal immune response in tetraplegic athletes, nor do they influence the production of α-amylase, a marker of sympathetic nervous activity. This contrasts responses previously observed in able-bodied athletes. The disruption of the sympathetic nervous system may prevent the downregulation of sIgA secretion rate following intense exercise, which is a response previously observed in able-bodied athletes.

Caffeine ingestion and antigen-stimulated human lymphocyte activation after prolonged cycling.

This study investigated the effect of caffeine ingestion on antigen-stimulated T- (CD4(+) and CD8(+) ) and natural killer (NK)- (CD3(-) CD56(+) ) cell activation after prolonged, strenuous cycling. In a randomized cross-over design, nine male endurance cyclists (age: 22 ± 3 years, VO(2peak) : 62 ± 4 mL/kg/min, mean ± SD) cycled for 90 min at 70% VO(2peak) 60 min after ingesting 6 mg/kg body mass of caffeine (CAF) or placebo (PLA). Venous blood samples were obtained before supplementation, pre-exercise, immediately post-exercise and 1 h post-exercise. Whole blood was stimulated with Pediacel (five in one) vaccine. At 1 h post-exercise the number of antigen-stimulated CD4(+) cells expressing CD69 decreased on CAF compared with PLA [15 (17) × 10(6) vs 23 (22) × 10(6) cells/L, P<0.05]. In addition, the geometric mean fluorescence intensity (GMFI) of CD69 expression on antigen-stimulated CD8(+) cells decreased on CAF compared with PLA 1 h post-exercise [78 (10)% vs 102 (24)%, P<0.05]. At the same time-point GMFI of CD69 expression on antigen-stimulated CD3(-) CD56(+) cells was increased on CAF compared with PLA [103 (9)% vs 87 (8)%, P<0.05]. These findings suggest that caffeine reduces antigen-stimulated CD69 expression on T cells while at the same time increases NK-cell activation 1 h after intensive cycling.

Submaximal exercise responses in tetraplegic, paraplegic and non spinal cord injured elite wheelchair athletes.

It remains unclear whether similar exercise prescription, based on physiological markers, can be applied to subgroups of wheelchair athletes with different disabilities. Therefore, 25 wheelchair athletes, divided into three subgroups [eight tetraplegic (TETRA), nine paraplegic (PARA) and eight non spinal cord injured (NON-SCI)], performed an exercise test consisting of incremental submaximal stages, covering a range from 40% to 80% peak oxygen uptake (%VO(2peak) ). Oxygen uptake (VO(2)), heart rate (HR), blood lactate concentration (BLa) and rating of perceived exertion (RPE) were obtained for each stage. Expressed as a function of BLa, no differences were found between subgroups with respect to %VO(2peak) (group mean ± SD: 1.0 mmol/L: 53.9 ± 9.9%; 2.0 mmol/L: 70.7 ± 7.5%; 3.0 mmol/L: 78.5 ± 7.7%) and RPE [group mean (lower and upper quartile): 1.0 mmol/L: 10.8 (9.9, 12.2); 2.0 mmol/L: 13.6 (12.7, 14.3); 3.0 mmol/L: 14.9 (13.7, 16.5)]. Furthermore, no differences were found in the coefficient of determination (R(2) ) of the HR-VO(2) relationship in any of the subgroups (TETRA: 0.90 ± 0.12; PARA: 0.97 ± 0.02; NON-SCI: 0.96 ± 0.04). These results suggest that exercise prescription using measurements of VO(2), BLa or RPE can be based on the same recommendations in all the subgroups studied. This finding has added value for TETRA athletes, as it offers alternatives to HR monitoring.

Physical exercise in patients with severe kidney disease.

Patients with advanced chronic kidney disease (CKD), especially those on long-term dialysis, often suffer from muscle wasting and excessive fatigue. It is known that inactivity, muscle wasting and reduced physical functioning are associated with increased mortality in CKD. Known causes include uraemic myopathy and neuropathy, inactivity, and anaemia. Exercise in patients receiving regular dialysis treatment for end-stage renal disease was first introduced 3 decades ago, but is still only offered in a minority of renal units around the world, despite a significant body of evidence to support its use. Work is needed to increase awareness of the potential benefits of increased physical activity for patients with advanced CKD. This review summarizes the mechanisms of exercise intolerance and debility in advanced CKD patients, the methods used for the estimation of functional capacity, the options currently available for exercise training, and their influence on the well-being of this group of patients.

Effective mass suppression in dilute, spin-polarized two-dimensional electron systems.

We report effective mass (m*) measurements, via analyzing the temperature dependence of the Shubnikov-de Haas oscillations, for dilute, interacting, two-dimensional electron systems (2DESs) occupying a single conduction-band valley in AlAs quantum wells. When the 2DES is partially spin-polarized, m* is larger than its band value, consistent with previous results on various 2DESs. However, as we fully spin-polarize the 2DES by subjecting it to strong parallel magnetic fields, m* is unexpectedly suppressed and falls even below the band mass.

Valley polarization and susceptibility of composite fermions around a filling factor nu=3/2.

We report magnetotransport measurements of fractional quantum Hall states in an AlAs quantum well around a Landau level filling factor nu=3/2, demonstrating that the quasiparticles are composite fermions (CFs) with a valley degree of freedom. By monitoring the valley level crossings for these states as a function of applied symmetry-breaking strain, we determine the CF valley susceptibility and polarization. The data can be explained well by a simple Landau level fan diagram for CFs, and are in nearly quantitative agreement with the results reported for CF spin polarization.

Exercise-induced suppression of acylated ghrelin in humans.

Ghrelin is an orexigenic hormone secreted from endocrine cells in the stomach and other tissues. Acylation of ghrelin is essential for appetite regulation. Vigorous exercise induces appetite suppression, but this does not appear to be related to suppressed concentrations of total ghrelin. This study examined the effect of exercise and feeding on plasma acylated ghrelin and appetite. Nine male subjects aged 19-25 yr participated in two, 9-h trials (exercise and control) in a random crossover design. Trials began at 0800 in the morning after an overnight fast. In the exercise trial, subjects ran for 60 min at 72% of maximum oxygen uptake between 0800 and 0900. After this, they rested for 8 h and consumed a test meal at 1100. In the control trial, subjects rested for 9 h and consumed a test meal at 1100. Area under the curve values for plasma acylated ghrelin concentration (assessed from venous blood samples) were lower over the first 3 h and the full 9 h of the exercise trial compared with the control trial: 317+/-135 vs. 510+/-186 pg.ml(-1).3 h and 917+/-342 vs. 1,401+/-521 pg.ml(-1).9 h (means+/-SE) respectively (P<0.05). Area under the curve values for hunger (assessed using a visual scale) were lower over the first 3 h of the exercise trial compared with the control trial (P=0.013). These findings demonstrate that plasma acylated ghrelin concentration and hunger are suppressed during running.

Observation of quantum Hall "valley Skyrmions".

We report measurements of the interaction-induced quantum Hall effect in a spin-polarized AlAs two-dimensional electron system where the electrons occupy two in-plane conduction band valleys. Via the application of in-plane strain, we tune the energies of these valleys and measure the energy gap of the quantum Hall state at filling factor nu = 1. The gap has a finite value even at zero strain and, with strain, rises much faster than expected from a single-particle picture, suggesting that the lowest energy charged excitations at nu = 1 are "valley Skyrmions."

Spin-dependent resistivity at transitions between integer quantum hall states.

The longitudinal resistivity at transitions between integer quantum Hall states in two-dimensional electrons confined to AlAs quantum wells is found to depend on the spin orientation of the partially filled Landau level in which the Fermi energy resides. The resistivity can be enhanced by an order of magnitude as the spin orientation of this energy level is aligned with the majority spin. We discuss possible causes and suggest a new explanation for the spikelike features observed at the edges of quantum Hall minima near Landau level crossings.

No effect of fluid intake on neutrophil responses to prolonged cycling.

Ingesting carbohydrate beverages during prolonged exercise is associated with fewer numbers of circulating neutrophils and attenuated neutrophil functional responses, yet there is little information about the effect of fluid intake alone on immune responses to prolonged exercise. The aim of this study was to examine the influence of regular fluid ingestion compared with no fluid ingestion on plasma cortisol, circulating neutrophil and lipopolysaccharide (LPS)-stimulated neutrophil degranulation responses to prolonged cycling. In a randomized design, nine recreationally active males cycled for 2 h at 65% VO2max on two occasions with either fluid ingestion (lemon-flavoured water, fluid trial) before and during the exercise, or with no fluid intake at all (no fluid trial). Venous blood samples were obtained at rest, immediately after exercise and 1 h after exercise. Immediately after exercise, the plasma cortisol concentration was significantly higher in the no fluid trial than in the fluid trial (592 +/- 62 vs 670 +/- 63 nmol x l(-1), P < 0.05). Circulating numbers of neutrophils increased 4.5-fold (P < 0.01) and LPS-stimulated elastase release per neutrophil decreased 34 +/- 7% (P < 0.01) immediately after exercise; there were no differences between trials. These results suggest that in ambient environmental conditions, fluid ingestion alone has a negligible effect on circulating neutrophil and LPS-stimulated neutrophil degranulation responses to prolonged exercise.

Carbohydrate beverage ingestion and neutrophil degranulation responses following cycling to fatigue at 75% VO2 max.

Carbohydrate (CHO) beverage ingestion appears to influence neutrophil functional responses to prolonged exercise of a fixed duration. The aim of this randomised study was to examine the effect of CHO (5% w/v) beverage ingestion on lipopolysaccharide (LPS)-stimulated neutrophil degranulation responses in nine recreationally active males who cycled at 75% VO2 max until fatigue. On two separate occasions, subjects ingested either placebo (PLA) or CHO beverages before and at 15 min intervals during the exercise. Subjects exercised for 31% longer on the CHO trial compared with the PLA trial (P < 0.05). At fatigue plasma glucose concentration was significantly lower on the PLA trial compared with the CHO trial (P < 0.05). Plasma cortisol concentrations had increased similarly on both trials at this time. A marked neutrophilia was evident at fatigue and throughout the 4 h recovery period, the magnitude of which was similar on both trials. At fatigue LPS-stimulated elastase release per neutrophil had fallen similarly on both trials compared with pre-exercise values (47% and 50% on the PLA and CHO trials, respectively). In conclusion, our results suggest that CHO beverage ingestion has negligible influence on the hormonal, circulating neutrophil and LPS-stimulated neutrophil degranulation responses when exercise is performed to fatigue.

Pre-exercise carbohydrate status and immune responses to prolonged cycling: I. Effect on neutrophil degranulation.

Ingesting carbohydrate (CHO) beverages during heavy exercise is associated with smaller shifts in numbers of circulating neutrophils and attenuated changes in neutrophil functional responses. The influence of dietary CHO availability on these responses has not been determined. Therefore, the present study investigated the influence of pre-exercise CHO status on circulating neutrophil and lipopolysaccharide (LPS)-stimulated neutrophil degranulation responses to prolonged cycling. Twelve trained male cyclists performed a glycogen-lowering bout of cycling and were randomly assigned to follow a diet ensuring either greater than 70% (HIGH) or less than 10% (LOW) of daily energy intake from CHO for the next 3 days. On day 4, subjects performed an exercise test that comprised cycling for 1 hour at 60% Wmax immediately followed by a time-trial (TT) ensuring an energy expenditure equivalent to cycling for 30 min at 80% Wmax. Subjects repeated the protocol after 7 days, this time following the second diet. The order of the trials was counterbalanced. At TT completion, the HIGH compared with the LOW trial was associated with higher plasma glucose concentration, lower plasma cortisol concentration, and lower circulating neutrophil count. LPS-stimulated neutrophil degranulation per cell fell similarly on both trials. These findings suggest that pre-exercise CHO status influences neutrophil trafficking but not function in response to prolonged cycling.

Pre-exercise carbohydrate status and immune responses to prolonged cycling: II. Effect on plasma cytokine concentration.

Ingesting carbohydrate (CHO) beverages during heavy exercise is associated with smaller changes in the plasma concentrations of several cytokines. The influence of dietary CHO availability on these responses has not been determined. Therefore, the present study investigated the influence of pre-exercise CHO status on plasma interleukin (IL)-6, IL-10, and IL-1 receptor antagonist (IL-1ra) responses to prolonged cycling. Seven trained male cyclists performed a glycogen-lowering bout of cycling and were randomly assigned to follow a diet ensuring either greater than 70% (HIGH) or less than 10% (LOW) of daily energy intake from CHO for the next 3 days. On day 4 subjects performed an exercise test that comprised cycling for 1 hour at 60% Wmax immediately followed by a time-trial (TT) ensuring an energy expenditure equivalent to cycling for 30 min at 80% Wmax. Subjects repeated the protocol after 7 days, this time following the second diet. The order of the trials was counterbalanced. At 1 and 2 hours post-TT, plasma concentrations of IL-6 and IL-10 were 2-fold greater on the LOW trial than on the HIGH trial, and peak plasma concentrations of IL-1ra were 9-fold greater on the LOW trial than on the HIGH trial. These findings suggest that pre-exercise CHO status can influence the plasma cytokine response to prolonged cycling.