European Journal Of Applied Physiology[JOURNAL]
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200 papers
Trimethylamine N-oxide in exercise physiology: a gut microbiota-derived signal linking metabolic stress, redox balance and cardiometabolic health.
Olek RA, Radak Z
Eur J Appl Physiol · 2026 Jun · PMID 42287393 · Publisher ↗
Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite traditionally associated with cardiovascular and metabolic disease risk; however, emerging evidence from exercise physiology and metabolomics suggests...
Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite traditionally associated with cardiovascular and metabolic disease risk; however, emerging evidence from exercise physiology and metabolomics suggests a more complex and context-dependent biological role. This narrative review synthesizes findings from human observational studies, exercise interventions, supplementation trials, and animal models to examine TMAO metabolism, physiological functions, and its relationship with physical activity, training adaptations, and metabolic stress. Circulating TMAO concentrations are determined primarily by dietary precursor availability, gut microbial metabolism, hepatic flavin monooxygenase activity, and renal clearance. Across human studies, TMAO levels do not consistently correlate with aerobic fitness, habitual physical activity, or training status. Exercise-only interventions rarely produce significant changes in circulating TMAO concentrations, whereas dietary manipulation and precursor supplementation exert substantially stronger effects. Experimental evidence nevertheless suggests that TMAO may exert context-dependent biological actions related to protein stabilization, mitochondrial energy metabolism, redox regulation, and tolerance to physiological stress. Acute endurance exercise, high training load, and exercise-induced muscle damage have also been associated with transient alterations in circulating or urinary TMAO levels, although findings remain limited and heterogeneous. Collectively, current evidence does not support interpreting TMAO solely as a pathogenic metabolite. Instead, circulating TMAO may reflect interactions among diet, gut microbiota activity, metabolic stress, and host physiological status. However, the usefulness of TMAO or the TMAO/TMA ratio as biomarkers of exercise adaptation, training load, or recovery remains to be established in controlled longitudinal human studies.
Oxygen uptake on-kinetics during horizontal and uphill treadmill running in moderate- and severe-intensity domains.
Ventura TP, Borszcz FK, da Silva GR … +4 more , Lanzarini LDV, de Farias EAA, de Lucas RD, Turnes T
Eur J Appl Physiol · 2026 Jun · PMID 42287392 · Publisher ↗
PURPOSE: To compare pulmonary oxygen uptake ([Formula: see text]) on-kinetics during level and uphill treadmill running performed within moderate- and severe-intensity domains in trained trail runners. METHODS: Thirteen...
PURPOSE: To compare pulmonary oxygen uptake ([Formula: see text]) on-kinetics during level and uphill treadmill running performed within moderate- and severe-intensity domains in trained trail runners. METHODS: Thirteen trail runners completed: (I) a traditional 3 min stage treadmill incremental test and (II) an incremental test at a fixed treadmill speed (50% of participant's peak speed from the first test) with a 2% gradient increase every 3 min to determine the first lactate threshold (LT) and [Formula: see text]. On separate days, participants performed three 6-min square-wave transitions at 90% LT (moderate domain) and one 6-min transition at 70%Δ (severe domain) under both level and uphill conditions. Pulmonary [Formula: see text] was measured breath-by-breath to determine primary amplitude, time delay, time constant (τp), and slow component ([Formula: see text]), as well as blood lactate concentration ([La]) pre- and post-exercise. RESULTS: During moderate exercise, τp and time delay did not differ between level and uphill running, whereas the primary [Formula: see text] amplitude and post-exercise [La] were higher during uphill running (p < 0.05). In the severe domain, no differences were observed between conditions for τp, time delay, primary amplitude, or [Formula: see text] amplitude. Peak [Formula: see text] during severe exercise was higher in uphill compared with level running (p < 0.05), but values were similar to those obtained during the respective incremental tests. CONCLUSIONS: When exercise intensity domains are defined using slope-specific incremental testing, [Formula: see text] on-kinetics are similar between level and uphill running in trail runners. These findings support the validity of incline-based testing for physiological normalization and training prescription in uphill running contexts.
Imbalanced cortisol/BDNF signals and oxidative stress underscore temporary cognitive impairment in deep divers after in water/surface decompression: proof of concept.
Mrakic-Sposta S, Di Cianni S, Lombardi G … +5 more , Moccia E, Meloni G, Vezzoli A, Marzola M, Bosco G
Eur J Appl Physiol · 2026 Jun · PMID 42287391 · Publisher ↗
BACKGROUND: Military deep divers experience extreme environmental stressors, particularly with prolonged diving. Alterations such as hyperbaric conditions and variable O levels can prompt systemic/local oxidative stress...
BACKGROUND: Military deep divers experience extreme environmental stressors, particularly with prolonged diving. Alterations such as hyperbaric conditions and variable O levels can prompt systemic/local oxidative stress (OxS) and elevated nitric oxide (NO) post-dive release, heightening the risk of inflammation and cardiovascular events. Yet, deep diving (e.g. saturation diving) can also lead to cognitive impairment, whose mechanisms remain largely elusive but relevant to determine. METHODS: Three Deep Divers (Italian Navy-Comsubin), with an average age of 31.00 ± 2.64 years, carried out a technical surface-supplied bounce diving in open water (-89m) in the Mediterranean Sea. From them, we collected saliva and urine samples before diving (T0), after deep diving followed by water-surface decompression (T1), and after complete subemersion (T2). To assess for pro-inflammatory and stress conditions, we evaluated reactive oxygen species (ROS) production, DNA oxidation (8-OHdG), total antioxidant capacity (TAC), nitric oxide (NO) oxidation products, and the levels of interleukin-6, cortisol, brain-derived neurotrophic factor (BDNF), dopamine, and glutamate. RESULTS: At T1, ROS production increased (+ 121%) and continued to increase just to T2, coupled to a continuous rise in 8-OHdG, and a contemporary decline in TAC. Simultaneously, cortisol levels increased while those of dopamine decreased (-27%). BDNF levels were also sizably elevated (+ 175%). Conversely, no changes in pro-inflammatory markers and NO concentrations were evident. CONCLUSIONS: Oxidative stress and neurotransmitter increase and/or decrease (according to biomarkers evaluated) occur post-deep diving, suggesting preventative strategies to mitigate cognitive impairment.
Influence of age on walking performance among adults with bilateral spastic cerebral palsy.
Gravholt A, Fernandez B, Chauvet L … +5 more , Bessaguet H, Zeghoudi N, Millet GY, Buizer AI, Lapole T
Eur J Appl Physiol · 2026 Jun · PMID 42287390 · Publisher ↗
PURPOSE: To examine age-related differences in walking performance and its physiological determinants in adults with bilateral spastic cerebral palsy (CP) compared with typically developed (TD) peers. METHODS: Thirty adu...
PURPOSE: To examine age-related differences in walking performance and its physiological determinants in adults with bilateral spastic cerebral palsy (CP) compared with typically developed (TD) peers. METHODS: Thirty adults aged 18-50 years were included: younger (18-25 years; CP, n = 7) and older (35-50 years; CP, n = 8) ambulatory individuals with CP (GMFCS I-II), and age-matched TD controls (TD, n = 7; TD, n = 8). Assessments included maximal oxygen uptake (VO₂peak), walking performance (6-minute walk test, 10-m walk test, Timed Up-and-Go), energy cost of walking (CoW), lower-limb strength, balance, self-reported fatigue and quality of life, and actigraphy-derived activity levels. RESULTS: VO₂peak did not differ between groups. However, CP walked approximately 30-35% shorter distance during the 6-minute walk test compared with CP and TD peers, and showed similarly reduced performance in 10-m walk and Timed Up-and-Go tests. CP also exhibited a higher CoW (approximately 8 vs. 4 J·kg·m). Lower-limb strength was consistently reduced in CP compared with TD groups and was lower than CP in most contraction modes. Self-reported fatigue was greater in CP, whereas quality of life, daily step count, and sleep duration were similar across groups. CONCLUSION: Older adults with CP exhibit pronounced impairments in walking performance despite preserved aerobic capacity. These alterations are associated with increased walking cost, reduced strength, and impaired balance, suggesting accelerated mobility decline in adults with CP. Targeting neuromuscular function and walking economy may therefore represent key strategies to mitigate functional decline in adults with CP.
Mechanisms of dyspnoea and exercise intolerance in smokers with preserved ratio impaired spirometry.
Scussel A, Rodrigues NG, Santos AZ … +7 more , Trombin LCB, Pinto AC, Wagner LE, Knorst MM, Dean J, Singh D, Berton DC
Eur J Appl Physiol · 2026 Jun · PMID 42249935 · Publisher ↗
PURPOSE: Smokers with preserved ratio impaired spirometry (PRISm) present reduced forced expiratory volume in the first second (FEV₁ < 80% predicted) but preserved FEV/forced vital capacity (FVC) ≥ 0.7. Although they do...
PURPOSE: Smokers with preserved ratio impaired spirometry (PRISm) present reduced forced expiratory volume in the first second (FEV₁ < 80% predicted) but preserved FEV/forced vital capacity (FVC) ≥ 0.7. Although they do not meet diagnostic criteria for chronic obstructive pulmonary disease (COPD), they often report respiratory symptoms and exercise intolerance. We aimed to compare sensory and physiological responses to exercise between smokers with PRISm and matched healthy controls. Patients with mild-to-moderate COPD were included as a reference group. METHODS: In this cross-sectional study, smokers (> 10 pack-years) from a specialized outpatient clinic were evaluated. Thirteen participants (11 females; 62.4 ± 7.7 years) with PRISm and 13 age- and sex-matched patients with mild-to-moderate COPD (FEV₁/FVC < 0.7; FEV₁ > 50% predicted) underwent incremental cardiopulmonary exercise testing on a cycle ergometer. Data from healthy nonsmoking controls were obtained from previous studies. RESULTS: PRISm and COPD groups had similarly reduced FEV₁ (~ 72% predicted) compared to controls (97% predicted), whereas FVC was lower in PRISm (73% predicted) than in COPD and controls (~ 95% predicted). Both patient groups showed higher ventilation, reduced ventilatory reserve, and greater dyspnoea at a given submaximal workload versus controls. Increased tidal volume/inspiratory capacity ratios were also observed, contributing to greater dyspnoea for a given ventilation and lower peak work rate (42 ± 16 vs. 68 ± 11 vs. 94 ± 17% predicted, respectively; all P < 0.05). CONCLUSION: Smokers with PRISm exhibit increased dyspnoea and reduced exercise tolerance compared to healthy controls, largely driven by excessive ventilatory demand and reduced ventilatory capacity during submaximal exercise.
Effects of electrical cutaneous stimulation of the foot sole on voluntary plantarflexion rate of torque development after fatigue in males.
Marrelli LC, Sharma T, Vanderhaeghe AV … +2 more , Power GA, Bent LR
Eur J Appl Physiol · 2026 Jun · PMID 42249934 · Publisher ↗
PURPOSE: Fast rate of torque development (RTD) is crucial for all movements, from balance to athletics. Aging and fatigue decrease RTD, increasing fall and injury risk. Thus, finding accessible methods to increase RTD is...
PURPOSE: Fast rate of torque development (RTD) is crucial for all movements, from balance to athletics. Aging and fatigue decrease RTD, increasing fall and injury risk. Thus, finding accessible methods to increase RTD is necessary. Given the neuromechanical coupling that exists between foot-sole skin and lower-limb motor neurons, cutaneous stimulation may impact RTD. This work investigated whether foot-sole cutaneous stimulation could mitigate the fatigue-induced declines in plantarflexion RTD. METHODS: Adult males (n = 11, age = 28(7)) participated in three data collection sessions. Voluntary isometric plantarflexion RTD was measured during explosive plantarflexion contractions in a dynamometer. RTD was assessed at rest and post-fatigue, under three conditions: cutaneous electrical stimulation at the heel, metatarsal, or no stimulation. Fatigue was induced with a sustained maximal plantarflexion until torque dropped below 30% of maximum voluntary torque. RTD was calculated in cumulative 25ms epochs from contraction onset to 100ms. Post-fatigue, percent of rested RTD was compared between conditions. RESULTS: Post-fatigue RTD decreased across all conditions (p < 0.001) (mean = 31(12%)). No effect of stimulation was found for the change in RTD post-fatigue. (p = 0.174). However, when removing polarity of response by comparing absolute changes in RTD post-fatigue, a main effect of stimulation was found (p = 0.002) (mean difference from control: 14.6% with heel stimulation, and 17.5% with metatarsal stimulation). CONCLUSIONS: Although no clear location-dependent increase or decrease emerged, cutaneous stimulation did change fatigued RTD compared to control. Future work should focus on understanding the directional variability of responses across participants to isolate improved RTD as a mechanism to enhance performance and restore mobility.
Maximal glycolytic flux modulates metabolic thresholds independent of maximal oxygen uptake.
Meixner B, Leo P, Sperlich B
Eur J Appl Physiol · 2026 Jun · PMID 42249933 · Publisher ↗
PURPOSE: This study examined how maximal glycolytic flux, indexed by the peak lactate accumulation rate (vLa) from a 15-s sprint, relates to lactate- and gas-exchange derived endurance thresholds at a given V̇Omax in tra...
PURPOSE: This study examined how maximal glycolytic flux, indexed by the peak lactate accumulation rate (vLa) from a 15-s sprint, relates to lactate- and gas-exchange derived endurance thresholds at a given V̇Omax in trained cyclists. METHODS: Fifty cyclists (30 men, 20 women) completed two laboratory visits: a ramp test with verification to determine V̇Omax, and on a separate day, a 15-s all-out sprint with repeated post-exercise capillary blood sampling to determine peak lactate accumulation (ΔLa) and derived vLa, followed by a 3-min step-increment test with lactate and gas-exchange measurements. RESULTS: Partial correlations controlling for V̇Omax revealed moderate-to-strong negative associations between vLa and selected lactate- and gas-exchange-derived thresholds (r = - 0.37 to - 0.59, p < 0.01), whereas absolute and relative 15-s work showed consistently weaker or no relationships (r = 0.06 to - 0.48). No association was observed between vLa and peak fat oxidation. In general linear models, adding vLa to models with V̇Omax and sex as predictors significantly increased the explained variance in threshold power (ΔR ≈ 0.06 to 0.20). Sex contributed additional but consistently smaller effects. CONCLUSION: These findings indicate that the power output at several metabolic thresholds originates from the interaction of maximal oxidative and glycolytic flux. As such, vLa seems to be a promising parameter that complements traditional measures like V̇Omax and helps to improve metabolic profiling and exercise prescription. However, longitudinal studies are needed to verify these findings.
Excess of post-resistance exercise energy expenditure: a comparison between morning and evening.
An N, Watanabe D, Miyachi M
Eur J Appl Physiol · 2026 Jun · PMID 42249932 · Publisher ↗
PURPOSE: Excess post-exercise energy expenditure (EPEEE) refers to sustained elevation in energy expenditure above resting levels after exercise. This study compared the effect of morning (AM) and evening (PM) resistance...
PURPOSE: Excess post-exercise energy expenditure (EPEEE) refers to sustained elevation in energy expenditure above resting levels after exercise. This study compared the effect of morning (AM) and evening (PM) resistance exercise on EPEEE, with and without circadian rhythm (CR) adjustments. METHODS: In this randomized crossover study, 13 men with prior resistance training experience performed six resistance exercises, each with three sets of 10 repetitions at 60% one-repetition maximum, in separate AM and PM sessions. Resting energy expenditure (REE) and post-exercise energy expenditure (PEEE) were measured via exhaled gas analysis; EPEEE was calculated by subtracting REE from PEEE. CR-adjusted values were calculated using a sinusoidal model of energy expenditure across the day to derive REE-CR, PEEE-CR, and EPEEE-CR. RESULTS: REE did not differ significantly between AM and PM. Mean REE-CR values for AM and PM were similar. PEEE-CR in AM (194.4 ± 27.5 kcal/2 h) was significantly higher than that in PM (183.5 ± 32.2 kcal/2 h; P = 0.030), though insignificant in unadjusted PEEE. EPEEE was significantly higher in AM (49.8 ± 21.0 kcal/2 h) than in PM (30.1 ± 18.8 kcal/2 h; P = 0.049). CR adjustment attenuated EPEEE enhancement at AM; moreover, the difference in EPEEE-CR between AM and PM was no longer significant (AM: 47.3 ± 20.8 kcal/2 h; PM: 31.4 ± 18.9 kcal/2 h; P = 0.100). CONCLUSION: Compared to evening exercise, morning resistance exercise increases EPEEE; however, this difference diminishes when CRs are considered. These findings offer practical implications for optimizing resistance exercise prescriptions aimed at improving metabolism and cardiometabolic health.
Effect of six weeks ubiquinol supplementation on mitochondrial respiratory function and exercise capacity in healthy males.
Acton JP, Alsharif NS, Bond JW … +9 more , Cocksedge SP, Mclellan AG, Peden DL, Funnell MP, Dugdale HF, James LJ, Ferguson RA, Clifford T, Bailey SJ
Eur J Appl Physiol · 2026 Jun · PMID 42249931 · Publisher ↗
Coenzyme Q10 (CoQ) is an integral component of the mitochondrial electron transfer system. Most studies have administered the oxidised form of CoQ (ubiquinone) and observed no effects on mitochondrial respiratory functio...
Coenzyme Q10 (CoQ) is an integral component of the mitochondrial electron transfer system. Most studies have administered the oxidised form of CoQ (ubiquinone) and observed no effects on mitochondrial respiratory function or endurance exercise performance. The reduced form of CoQ, ubiquinol (UQH), has greater bioavailability than ubiquinone, but the effects of UQH supplementation on mitochondrial respiratory function and exercise capacity are unclear. Fifty-four healthy, recreationally active males were randomised to receive either 300 mg·day UQH or placebo (PLA) for 6 weeks in a double-blind independent-group design. Before and after the supplementation period, skeletal muscle mitochondrial respiration variables and protein content of the mitochondrial leak proteins, adenine nucleotide translocase1 + 2 (ANT1 + 2) and uncoupling protein-3 (UCP-3), were assessed. In addition, participants completed a severe-intensity cycle test to exhaustion to assess time to the limit of tolerance (T) and oxygen uptake (V̇O) kinetics. Compared to pre-supplementation and PLA, UQH supplementation increased plasma [CoQ] (P < 0.05), and lowered inverse respiratory control ratio (Pre-PLA: 0.064 ± 0.034 vs. Post-PLA: 0.072 ± 0.026; Pre- UQH: 0.073 ± 0.039 vs. Post-UQH: 0.044 ± 0.019; P < 0.05), suggestive of improved oxidative phosphorylation coupling efficiency. There were no differences in ANT1 + 2 or UCP-3 protein content post-supplementation compared to pre-supplementation between groups (P > 0.05). End-exercise V̇O, change in V̇O between 2 min and end-exercise, and T were not different between groups post-supplementation (P > 0.05). Six-weeks UQH supplementation increased plasma [CoQ] and oxidative phosphorylation coupling efficiency, but did not alter mitochondrial leak proteins, T or V̇O kinetics during severe-intensity exercise in healthy, active males.
Sex differences in climbing endurance emerge from combined physiological adaptation and neural strategies.
Borzelli D, Pstrag K, Carollo G … +2 more , Mena BB, Vieira TM
Eur J Appl Physiol · 2026 Jun · PMID 42249930 · Publisher ↗
BACKGROUND: Sport climbing imposes high endurance demands on finger flexor muscles, which sustain near-isometric loads for prolonged periods. Although women often demonstrate greater muscle endurance than men, the neurom...
BACKGROUND: Sport climbing imposes high endurance demands on finger flexor muscles, which sustain near-isometric loads for prolonged periods. Although women often demonstrate greater muscle endurance than men, the neuromuscular mechanisms underlying potential sex differences in climbing remain unclear. PURPOSE: Determine whether sex differences in climbing endurance are explained by physiological muscle adaptations, neural strategies of motor unit (MU) control, or both. METHODS: High-density surface electromyograms (HD-sEMG) were recorded from the dominant forearm of 9 female and 13 male intermediate climbers during sustained body suspension on a campus board until failure, using two grip depths (20 and 30 mm) to manipulate task demand. EMGs were decomposed into MU discharge trains. Physiological adaptation was assessed via temporal changes in MU action potential amplitude and median frequency (MDF), while neural strategies were evaluated using traditional MU discharge metrics and a mode-based analysis of MU firing patterns. RESULTS: Despite anthropometric differences, time to failure did not differ between sexes. MDF declined more slowly in women, indicating greater resistance to muscle fatigue. Traditional MU metrics showed greater discharge variability and intermittency in women. Mode analysis revealed three common temporal MU firing modes across sexes; however, men exhibited greater reliance on sustained early-phase MU activation, particularly under higher task demands. CONCLUSION: Sex differences in climbing endurance are not reflected in outcomes alone but arise from distinct neuromuscular mechanisms. Greater physiological fatigue resistance in women is complemented by sex-specific neural strategies of MU rate coding, underscoring the importance of integrating physiological and neural analyses when examining endurance performance in climbing.
Changes in the mechanical properties and pressure pain thresholds of muscles in patients with fibromyalgia and their relationship with clinical parameters: a case-control study.
Esen DH, Taş S, Eroğlu M
Eur J Appl Physiol · 2026 Jun · PMID 42249929 · Publisher ↗
PURPOSE: The association between fibromyalgia and changes in muscle mechanical properties is unclear. The primary objective of this study was to compare the mechanical properties (tone, stiffness, and elasticity) of the...
PURPOSE: The association between fibromyalgia and changes in muscle mechanical properties is unclear. The primary objective of this study was to compare the mechanical properties (tone, stiffness, and elasticity) of the upper trapezius (UT), extensor carpi radialis brevis (ECRB), and medial gastrocnemius (MG) muscles between patients with fibromyalgia (PwFM) and healthy controls. The secondary objective was to investigate the association between muscle mechanical properties and relevant clinical parameters. METHODS: Twenty-nine women and two men with fibromyalgia, and 31 age-matched healthy controls were included in this study. Muscle mechanical properties were assessed using myotonometry (MyotonPRO), pressure pain thresholds (PPTs) with a digital algometer (Commander Echo-Algometer), pain intensity using a visual analog scale, and disease impact using the Revised Fibromyalgia Impact Questionnaire. RESULTS: Muscle frequency (tone) and dynamic stiffness in the UT, ECRB, and MG were significantly higher in the PwFM group compared to controls (p < 0.05). Effect sizes were strong for the UT (|r|≥0.5), weak to moderate for the ECRB (|r|=0.293-0.306), and weak for the MG (|r|=0.293). No significant between-group differences were observed in logarithmic decrement (elasticity) (p > 0.05). In the PwFM group, a moderate positive correlation was found between the frequency of the MG muscle and its PPT (r = 0.508, p = 0.003). CONCLUSION: The present study revealed that the tone and stiffness of the UT, ECRB, and MG muscles were increased in PwFM. These findings indicate that altered muscle mechanical properties were associated with fibromyalgia and may warrant consideration in future research exploring clinical management approaches.
Effects of tyrosine kinase inhibitors on skeletal muscle metabolism: a link with muscle complaints.
Janssen L, Hoogstraten CA, Allard NAE … +4 more , Schirris TJJ, Hopman MTE, Blijlevens NMA, Timmers S
Eur J Appl Physiol · 2026 Jun · PMID 42249928 · Publisher ↗
Chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKIs) often report muscle complaints (MC). Strategies to prevent or attenuate these muscle complaints remain enigmatic as the underlying mecha...
Chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKIs) often report muscle complaints (MC). Strategies to prevent or attenuate these muscle complaints remain enigmatic as the underlying mechanism is unclear, although a central role for mitochondria is proposed. We investigated the effects of TKIs on cellular metabolism in muscle biopsies of CML patients (n = 20), compared with healthy controls (n = 10) and whether these changes may be linked to muscle complaints. C2C12 myotubes were used to further explore the effects of TKIs on muscle metabolism in vitro. We found that TKI muscle concentrations in CML patients aligned with the concentrations at which cytotoxicity could be observed in C2C12 myotubes, and that muscle to plasma ratios tended to correlate with the degree of MC in CML patients. In C2C12 myotubes, acute TKI incubation of C2C12 myotubes resulted in alterations in energy metabolism, showing a shift from glycolysis to oxidative phosphorylation. CML patients without MC showed higher oxidative capacity, characterized by higher mitochondrial complex activities in skeletal muscle and occurrence of the first ventilatory threshold at a higher percentage of peak oxygen uptake during maximal exercise compared to patients with MC. Taken together, these observations raise the possibility that TKIs may affect cellular energy metabolism and may contribute to muscle complaints.Trial registration The Netherlands Trial Registry identifier NTR6373.
Cadence effects on cardiorespiratory and muscular responses during eccentric cycling.
Villeneuve MÉ, Tremblay J, Julian V … +3 more , Coudeyre E, Costes F, Richard R
Eur J Appl Physiol · 2026 Jun · PMID 42249927 · Publisher ↗
PURPOSE: Eccentric cycling (ECC) enables high mechanical power output at a low metabolic cost, yet the influence of cadence on cardiorespiratory and neuromuscular responses during ECC remains poorly defined. This study e...
PURPOSE: Eccentric cycling (ECC) enables high mechanical power output at a low metabolic cost, yet the influence of cadence on cardiorespiratory and neuromuscular responses during ECC remains poorly defined. This study examined the interactive effects of cadence and power output on metabolic, cardiovascular, and muscle activation responses during ECC. METHODS: Fifteen healthy men performed randomized incremental ECC trials at 50 and 80 rpm, with successive 4-min stages at 80, 200, and 320 W. Oxygen uptake [Formula: see text], gross mechanical efficiency (GME), cardiac output [Formula: see text], heart rate (HR), stroke volume (Qs), arteriovenous O difference (a-v̄O), and quadriceps electromyographic activity were measured. Data were analysed using linear mixed-effects models with cadence, power output, and their interaction as fixed effects. RESULTS: A significant cadence × power interaction was observed for [Formula: see text] (p = 0.006). [Formula: see text] was lower at 80 rpm than at 50 rpm at 200 W (- 0.116 L·min, p = 0.007) and 320 W (- 0.187 L·min, p < 0.001), with no cadence effect at 80 W (p = 0.89). GME also showed a cadence × power interaction (p = 0.035), with lower GME at 80 rpm at 200 W (- 7.3%, p = 0.020) and 320 W (- 11.6%, p < 0.001). Cardiac output increased with power output (p < 0.001) but showed no cadence × power interaction (p = 0.13). Heart rate was modestly higher at 80 rpm only at 320 W (+ 9.1 bpm, p = 0.016). Arteriovenous O difference was consistently higher at 50 rpm across all workloads (p < 0.001). A cadence × power interaction was detected for vastus lateralis EMG (p = 0.039), with greater activation at 50 rpm at 320 W (+ 20.8 mV, p < 0.001), while no cadence effects were observed for vastus medialis or rectus femoris activity. CONCLUSION: During eccentric cycling, higher cadence reduces oxygen uptake and vastus lateralis activation at moderate to high power outputs, without altering fundamental cardiovascular-metabolic coupling. These findings indicate that cadence selection modulates the metabolic and neuromuscular cost of eccentric work primarily through contraction mechanics, supporting the use of higher cadences to optimize eccentric cycling in both rehabilitation and performance settings.
Exercise attenuates cisplatin-induced anorexia-cachexia via modulation of hypothalamic inflammation and orexigenic signaling.
Park SH, Ko JR, Yoon CS … +4 more , Park NM, Garcia MVFV, Kim HK, Han J
Eur J Appl Physiol · 2026 Jun · PMID 42249926 · Publisher ↗
PURPOSE: Chemotherapy-induced anorexia cachexia (CAC) is a common adverse effect of cancer treatment and is associated with poor prognosis and reduced treatment tolerance. Despite its clinical relevance, effective interv...
PURPOSE: Chemotherapy-induced anorexia cachexia (CAC) is a common adverse effect of cancer treatment and is associated with poor prognosis and reduced treatment tolerance. Despite its clinical relevance, effective interventions targeting central mechanisms of CAC remain limited. This study investigated whether aerobic exercise modulates hypothalamic appetite regulation and inflammatory signaling in a mouse model of cisplatin-induced CAC. METHODS: Eight-week-old C57BL/6 mice were assigned to a normal control (CON, n = 7), cisplatin-treated sedentary (CIS-CON, n = 7), or cisplatin-treated exercise group (CIS-EXE, n = 7). CAC was induced by daily intraperitoneal cisplatin administration (3.5 mg/kg). The CIS-EXE group performed treadmill running (14-16 m/min, 45 min/session, three times per week) for 12 weeks. RESULTS: Exercise attenuated cisplatin-induced reductions in food intake; however, final body weight was not significantly different between CIS-CON and CIS-EXE groups. In the hypothalamus, exercise increased mRNA expression of the orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related protein (AgRP), while suppressing the expression of anorexigenic markers cocaine- and amphetamine-regulated transcript (CART) and pro-opiomelanocortin (POMC). In addition, exercise significantly reduced the expression of pro-inflammatory cytokines IL-6, TNF-α, and NF-κB. These effects were accompanied by increased AMP-activated protein kinase (AMPK) activity and downregulation of protein kinase B (Akt) signaling. CONCLUSION: In conclusion, the findings suggest that exercise provides a potential therapeutic strategy for CAC, at least in part via increasing neuropeptide and inhibiting pro-inflammatory in the hypothalamus.
On the preserved muscle oxidative capacity in COPD patients with hypoxemia treated by long term O2 therapy.
Shan QQ
Eur J Appl Physiol · 2026 Jun · PMID 42249925 · Publisher ↗
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Cell-free DNA, cytokine, and catecholamine levels did not differ between sexes under a matched body core temperature increase, despite females exhibiting a more rapid increase in rectal temperature.
Juškevičiūtė E, Eimantas N, Daukšaitė G … +4 more , Neuberger E, Motiejūnaitė K, Simon P, Brazaitis M
Eur J Appl Physiol · 2026 Jun · PMID 42249924 · Publisher ↗
PURPOSE: To compare cell-free DNA (cfDNA), catecholamine (CAT), and cytokine concentrations and the perceptual responses following rectal temperature-matched hot water immersion (HWI) in females and males. METHODS: Twent...
PURPOSE: To compare cell-free DNA (cfDNA), catecholamine (CAT), and cytokine concentrations and the perceptual responses following rectal temperature-matched hot water immersion (HWI) in females and males. METHODS: Twenty-two healthy young adults (9 females, 13 males) underwent HWI (water temperature 43-44 °C) until body rectal temperature (Tre) reached 39 °C. Blood samples to determine cfDNA, CAT, and cytokine concentrations were collected. Thermal perceptions, Tre, and heart rate (HR) were assessed throughout the intervention. RESULTS: Females reached each Tre significantly faster than males (p < 0.001) and cooled more quickly during recovery (p = 0.023). HR and the physiological strain index increased similarly in both sexes. cfDNA increased twofold with rising Tre (main effect of time, p < 0.001) and no overall sex difference, although males showed higher values after 30 min of recovery (p = 0.046). Norepinephrine and epinephrine rose significantly during heating (p < 0.001), with no sex differences. Prolactin exhibited a stronger rise in females (sex × time interaction, p < 0.001), whereas tumor necrosis factor-α decreased only in males (p < 0.05). Interleukin-6 increased markedly in both sexes but was higher in males at baseline and early recovery (p < 0.05). CONCLUSION: When exposed to matched Tre elevation, females and males showed similar cfDNA, CAT, and perceptual responses, despite females reaching target temperatures faster and cooling more rapidly. These findings highlight cfDNA as a temperature-dependent marker of thermal strain and support its use alongside classical neuroendocrine and immune markers to characterize heat-stress physiology.
Low carbohydrate availability reduces power output at the moderate-to-heavy transition, impairs efficiency, and increases median power frequency during cycling in females.
Main E, Yoon S, James SL … +4 more , Mellor KM, Brick MJ, Leigh WB, Maunder E
Eur J Appl Physiol · 2026 Jun · PMID 42228164 · Publisher ↗
PURPOSE: Carbohydrate availability is reduced during prolonged exercise, and this may contribute to the loss of power output at the intensity domain transitions. The aim of this study was to investigate the effects of lo...
PURPOSE: Carbohydrate availability is reduced during prolonged exercise, and this may contribute to the loss of power output at the intensity domain transitions. The aim of this study was to investigate the effects of lowered carbohydrate availability on power output at intensity domain transitions, muscle activation, and gross cycling efficiency in endurance-trained female cyclists. METHODS: Nine well-trained female cyclists completed a randomised, counterbalanced crossover study consisting of two conditions. Participants completed an incremental cycling test and three-minute all-out test, preceded by glycogen-depleting exercise ~ 24 h beforehand and subsequent carbohydrate ingestion of either ≥ 9 g kg (HIGH) or ≤ 1 g kg (LOW). RESULTS: Power output at the first ventilatory threshold was reduced in LOW (133 ± 24 vs. 152 ± 28 W, ∆ - 19 ± 14 W, P = 0.011), with no between-trial difference in power output at the lactate threshold. Gross cycling efficiency during submaximal cycling was reduced in LOW (P = 0.003). Electromyographic median power frequency of the vastus lateralis (P = 0.025) and vastus medialis (P = 0.007) was higher in HIGH during submaximal cycling, with no between-trial differences in electromyographic amplitude. There was no between-trial difference in end-test power output during the three-minute all-out test. CONCLUSION: These data suggest lowered carbohydrate availability reduced power output at the moderate-to-heavy transition, possibly due to increased recruitment of higher-threshold motor units to compensate for glycogen-depleted fibres, impairing gross cycling efficiency. These data suggest that carbohydrate availability is likely important in 'durability' of the moderate-to-heavy intensity transition.
Impact of gelatin supplementation on indices of skeletal muscle recovery: a pilot study.
Graham RR, Salgado BE, Guerrero E … +2 more , Carrasco AP, D'Lugos AC
Eur J Appl Physiol · 2026 Jun · PMID 42228163 · Publisher ↗
PURPOSE: This pilot study examined whether collagen supplementation, via gelatin, influences indices of skeletal muscle recovery following strenuous exercise. METHODS: Using a double-blind, randomized, placebo-controlled...
PURPOSE: This pilot study examined whether collagen supplementation, via gelatin, influences indices of skeletal muscle recovery following strenuous exercise. METHODS: Using a double-blind, randomized, placebo-controlled design, recreationally-active adults (25.9 ± 4.6 yrs.; 11 F, 11 M) consumed gelatin (GEL; 15 g) or placebo (PLA) twice daily. Participants performed 150 maximal unilateral eccentric knee extensions. Muscle soreness (MS), assessed passively and dynamically (concentric, eccentric), peak isokinetic (PKT180, PKT60) and isometric torque (PMT), muscle morphology, and serum hydroxyproline (HYP) and procollagen-1 N-terminal peptide (P1NP) were assessed prior to- (Pre), 24 h, 72 h, and 168 h post-exercise. REPORTS: Exercise significantly increased soreness and impaired function over time (soreness: partial-eta-squared=0.56-0.76; torque: partial-eta-squared=0.34-0.61; all P<0.001), while group and group by time effects were not significant for these outcomes (P>0.05). Exploratory, pairwise comparisons suggested lower MS in GEL at select timepoints, including lower concentric MS at 24 h (P=0.029, d=0.97) and lower passive MS at 168 h (P = 0.028, d = 0.99). Differences in contractile function between groups were not statistically significant, though exploratory estimates favored GEL at 72 h for PKT60 (P = 0.067, d = 0.80) and PMT (P = 0.066, d = 0.81). HYP increased over time (partial-eta-squared=0.47, P<0.001) without group differences, and P1NP did not change over time or differ by group (P>0.05). CONCLUSION: GEL was associated with moderate-to-large time-specific effect estimates suggesting lower soreness and potentially improved force recovery at select timepoints; however, no significant group by time interactions were detected. These findings should be interpreted as preliminary and hypothesis-generating, supporting future trials into the effects of GEL as a recovery modality.
Multidimensional biomechanical modulation of walking reveals a threshold decline in distal ankle propulsion across aging.
Sangkarit N, Tapanya W
Eur J Appl Physiol · 2026 Jun · PMID 42228162 · Publisher ↗
PURPOSE: This study quantified biomechanical modulation of walking using a multidimensional framework and examined its association with aging, with emphasis on distal ankle propulsion. METHODS: An open-access three-dimen...
PURPOSE: This study quantified biomechanical modulation of walking using a multidimensional framework and examined its association with aging, with emphasis on distal ankle propulsion. METHODS: An open-access three-dimensional gait dataset of 240 healthy adults (18-91 years) was analyzed. Biomechanical modulation variables were defined as within-subject changes from comfortable to fast walking across spatiotemporal, kinetic, and joint-level measures. Principal component analysis (PCA) was utilized as an exploratory technique to derive composite modulation indices from a priori selected variables. Age associations were examined using linear regression and general linear models. RESULTS: Three modulation components explained 81.2% of total variance, representing global speed modulation, shock absorption, and distal ankle propulsion. Distal ankle propulsive modulation showed a significant, weak-to-moderate negative association with age (β = -0.31, R² = 0.10, p < 0.001) and a significant age-group effect (F(5,228) = 6.79, p < 0.001, partial η² = 0.13). Participants aged ≥ 70 years exhibited substantially lower distal propulsive modulation than younger groups (Δ = 1.06, 95% CI 0.84-1.28). Other modulation components showed weak or no age associations. CONCLUSION: Biomechanical modulation of walking is multidimensional and selectively affected by aging, with a pronounced threshold-like decline in distal ankle propulsion in later adulthood. Modulation-based assessment provides mechanistic insight beyond steady-state gait measures.
Hamstring-to-quadriceps ratio across menstrual cycle phases in physically active women: a repeated-measures study.
Heinrich C, Hofstaetter H, Puschkasch-Möck S … +1 more , Behringer M
Eur J Appl Physiol · 2026 Jun · PMID 42228161 · Publisher ↗
OBJECTIVE: To evaluate conventional hamstring-to-quadriceps ratio across the menstrual cycle in distinct angular velocities in an eumenorrheic, physically active population. DESIGN: Repeated measures within-subjects desi...
OBJECTIVE: To evaluate conventional hamstring-to-quadriceps ratio across the menstrual cycle in distinct angular velocities in an eumenorrheic, physically active population. DESIGN: Repeated measures within-subjects design. METHODS: Assessments were conducted in early follicular, ovulatory, and mid-luteal phase in n = 30 eumenorrheic females (age 27.2 yrs ± 4.1; height 168.3 cm ± 5.6; body mass 64.7 kg ± 7.5; body fat 25.9% ± 4.4; fat free mass 47.0 kg ± 4.7, training hours 6.98 ± 3.01, cycle length 28.2 ± 2.9). Isokinetic concentric peak torque values of leg extension and leg flexion at 60°∙s and 120°∙s angular velocity were recorded. Participants performed five consecutive maximum repetitions, and the highest values were obtained for further analysis. Subsequently, conventional hamstring-to-quadriceps peak torque ratio (HQ Ratio) was calculated by dividing the highest peak torque value of leg flexion by the highest peak torque value of leg extension. RESULTS: HQ Ratio did not differ significantly across menstrual cycle phases at 60°∙s (F (2,51) = 0.86, p = 0.43), or at 120°∙s (F (2, 52) = 0.46, p = 0.64). Peak torque values of leg flexion did not differ significantly between menstrual cycle phases at 60°∙s (F (2,50 = 2.43, p = 0.1) or at 120°∙s (F (2,52) = 0.48, p = 0.62). Furthermore, peak torque values of leg extension remained unaltered across distinct menstrual cycle phases at 60°∙s (F (2,50) = 0.5, p = 0.58), and at 120°∙s (F (2,51) = 0.29, p = 0.75). CONCLUSION: Strength ratios of leg extensors and flexors do not seem to differ between cycle phases. Isokinetic peak torque values of knee extension and flexions seem to remain constant across distinct menstrual cycle phases. Results indicated that conventional isokinetic peak torque testing does not need to be scheduled according to the menstrual cycle.
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