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Physical activity may reduce the risk of developing breast cancer via its effect on the insulin/insulin-like growth factor (IGF) signaling system. A systematic review searched for randomized controlled trials (RCT), Mendelian randomization and prospective cohort studies that examined the effects of physical activity on insulin/IGF signaling [IGFs, their binding proteins (IGFBP), and markers of insulin resistance] in adult women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the Grading of Recommendations Assessment, Development, and Evaluation system used to determine the overall quality of the evidence. Fifty-eight RCTs met our inclusion criteria, no observational or Mendelian randomization studies met the criteria for inclusion. Meta-analyses indicated that physical activity interventions (vs. control) reduced fasting insulin, the Homeostatic Model Assessment for Insulin Resistance and fasting glucose. Physical activity increased IGF-1, but there was no clear effect on IGFBP-3 or the ratio of IGF-1:IGFBP-3. Strong evidence was only established for fasting insulin and insulin resistance. Further research is needed to examine the effect of physical activity on C-peptide and HBA1c in women. Reductions in fasting insulin and insulin resistance following exercise suggest some biological plausibility of the first part of the physical activity-insulin/IGF signaling-breast cancer pathway. See related article by Drummond et al., p. 2116.

Background Lifestyle factors such as physical fitness, dietary habits, mental stress, and sleep quality, are strong predictors of the occurrence, clinical course, and overall treatment outcomes of common cardiovascular diseases. However, these lifestyle factors are rarely monitored, nor used in daily clinical practice and personalized cardiac care. Moreover, non-adherence to long-term self-reporting of these lifestyle factors is common. In the present study, we evaluate adherence to a continuous unobtrusive and patient-friendly lifestyle monitoring system using evidence-based assessment tools. Methods In a prospective observational trial (N = 100), the project investigates usability of and adherence to a monitoring system for multiple lifestyle factors relevant to cardiovascular disease, i.e., daily physical activity levels, dietary habits, mental stress, smoking, and sleep quality. Patients with coronary artery disease, valvular disease and arrhythmias undergoing an elective intervention are asked to participate. The monitoring system consists of a secured online platform with a custom-built conversational interface—a chatbot—and a wrist-worn wearable medical device. The wrist-worn device collects continuous objective data on physical activity and the chatbot is used to collect self-report data. Participants collect self-reported lifestyle data via the chatbot for a maximum of 4 days every other week; in the same week physiological data are collected for 7 days for 24 h. Data collection starts one week before the intervention and continues until 1-year after discharge. Via a dashboard, patients can observe their lifestyle measures and adherence to self-reporting, set and track personal goals, and share their lifestyle data with practitioners and relatives. The primary outcome of the trial is adherence to using the integrated platform for self-tracking data. The secondary outcomes include system usability, determinants of adherence and the relation between baseline lifestyle behaviour and long-term patient-relevant outcomes. Discussion Systematic monitoring during daily life is essential to gain insights into patients’ lifestyle behaviour. In this context, adherence to monitoring systems is critical for cardiologists and other care providers to monitor recovery after a cardiac intervention and to detect clinical deterioration. With this project, we will evaluate patients’ adherence to lifestyle monitoring technology. This work contributes to the understanding of patient-centered data collection and interpretation, to enable personalized care after cardiac interventions in order to ultimately improve patient-relevant outcomes and reduce health care costs. Trial registration Netherlands Trial Registry (NTR) NL9861. Registered 6th of November 2021.

The cross-stressor adaptation hypothesis—which posits that adjustment to physical stress as a result of regular physical activity and its effects on fitness crosses over to psychological stress reactivity—has been around for over four decades. However, the literature has been plagued by heterogeneities preventing definitive conclusions. We address these heterogeneity issues in a combined laboratory and daily life study of 116 young adults (M = 22.48 SD = 3.56, 57.76% female). The exposure, i.e., the potential driver of adaptation, was defined in three ways. First, a submaximal test was performed to obtain aerobic fitness measured as the VO2max (kg/ml/min). Second, leisure time exercise behavior, and third, overall moderate-to-vigorous physical activity (MVPA), were obtained from a structured interview. Outcomes were autonomic nervous system (ANS) reactivity and affective responsiveness to stressors. ANS activity was measured continuously and expressed as inter-beat-interval (IBI), pre-ejection-period (PEP), respiratory sinus arrythmia (RSA), and non-specific Skin Conductance Responses (ns.SCR). Negative and positive affect were recorded after each experimental condition in the laboratory and hourly in daily life with a nine-item digital questionnaire. Linear regressions were performed between the three exposure measures as predictors and the various laboratory and daily life stress measurements as outcomes. Our results support the resting heart rate reducing effect of aerobic fitness and total MVPA in both the laboratory and daily life. We did not find evidence for the cross-stressor adaptation hypothesis, irrespective of ANS or affective outcome measure or whether the exposure was defined as exercise/MVPA or aerobic fitness.

Impaired exercise capacity is the key symptom of heart failure (HF) and is associated with reduced quality of life and higher mortality rates. Unfortunately, current therapies, although generally lifesaving, have only small or marginal effects on exercise capacity. Specific strategies to alleviate exercise intolerance may improve quality of life, while possibly improving prognosis as well. There is overwhelming evidence that physical exercise improves performance in cardiac and skeletal muscles in health and disease. Unravelling the mechanistic underpinnings of exercise-induced improvements in muscle function could provide targets that will allow us to boost exercise performance in HF. With the current review we discuss: (i) recently discovered signalling pathways that govern physiological muscle growth as well as mitochondrial quality control mechanisms that underlie metabolic adaptations to exercise; (ii) the mechanistic underpinnings of exercise intolerance in HF and the benefits of exercise in HF patients on molecular, functional and prognostic levels; and (iii) potential molecular therapeutics to improve exercise performance in HF. We propose that novel molecular therapies to boost adaptive muscle growth and mitochondrial quality control in HF should always be combined with some form of exercise training.

Impaired exercise capacity is the key symptom of heart failure (HF) and is associated with reduced quality of life and higher mortality rates. Unfortunately, current therapies, although generally lifesaving, have only small or marginal effects on exercise capacity. Specific strategies to alleviate exercise intolerance may improve quality of life, while possibly improving prognosis as well. There is overwhelming evidence that physical exercise improves performance in cardiac and skeletal muscles in health and disease. Unravelling the mechanistic underpinnings of exercise-induced improvements in muscle function could provide targets that will allow us to boost exercise performance in HF. With the current review we discuss: (i) recently discovered signalling pathways that govern physiological muscle growth as well as mitochondrial quality control mechanisms that underlie metabolic adaptations to exercise; (ii) the mechanistic underpinnings of exercise intolerance in HF and the benefits of exercise in HF patients on molecular, functional and prognostic levels; and (iii) potential molecular therapeutics to improve exercise performance in HF. We propose that novel molecular therapies to boost adaptive muscle growth and mitochondrial quality control in HF should always be combined with some form of exercise training.

Glycogen particles are situated in key areas of the muscle cell in the vicinity of the main energy-consumption sites and may be utilised heterogeneously dependent on the nature of the metabolic demands. The present study aimed to investigate the time course of fibre type-specific utilisation of muscle glycogen in three distinct subcellular fractions (intermyofibrillar, IMF; intramyofibrillar, Intra; and subsarcolemmal, SS) during repeated high-intensity intermittent exercise. Eighteen moderately to well-trained male participants performed three periods of 10 × 45 s cycling at ∼105% watt max (EX1–EX3) coupled with 5 × 6 s maximal sprints at baseline and after each period. Muscle biopsies were sampled at baseline and after EX1 and EX3. A higher glycogen breakdown rate in type 2 compared to type 1 fibres was found during EX1 for the Intra (−72 vs. −45%) and IMF (−59 vs. −35%) glycogen fractions (P

Funder: Kjell och Märta Beijers Stiftelse (Kjell and Marta Beijer Foundation); doi: https://doi.org/10.13039/501100006353, Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

The purpose of the study was to develop prediction models to estimate physical activity (PA)-related energy expenditure (AEE) based on accelerometry and additional variables in free-living adults. In 50 volunteers (20–69 years) PA was determined over 2 weeks using the hip-worn Actigraph GT3X + as vector magnitude (VM) counts/minute. AEE was calculated based on total daily EE (measured by doubly-labeled water), resting EE (indirect calorimetry), and diet-induced thermogenesis. Anthropometry, body composition, blood pressure, heart rate, fitness, sociodemographic and lifestyle factors, PA habits and food intake were assessed. Prediction models were developed by context-grouping of 75 variables, and within-group stepwise selection (stage I). All significant variables were jointly offered for second stepwise regression (stage II). Explained AEE variance was estimated based on variables remaining significant. Alternative scenarios with different availability of groups from stage I were simulated. When all 11 significant variables (selected in stage I) were jointly offered for stage II stepwise selection, the final model explained 70.7% of AEE variance and included VM-counts (33.8%), fat-free mass (26.7%), time in moderate PA + walking (6.4%) and carbohydrate intake (3.9%). Alternative scenarios explained 53.8–72.4% of AEE. In conclusion, accelerometer counts and fat-free mass explained most of variance in AEE. Prediction was further improved by PA information from questionnaires. These results may be used for AEE prediction in studies using accelerometry

To assess total daily energy expenditure (TDEE) under daily living conditions, the doubly labelled water (DLW) technique is considered the gold standard. This technique is accurate but also costly and requires specific lab equipment and expertise. It also provides an average measure of TDEE over a period of one to two weeks and hence no information on physical activity (PA) patterns is available. To overcome these shortcomings, activity monitors can be used to assess activity patterns and an estimate of TDEE can be made, provided the activity monitor has been previously validated in daily life using DLW. Most activity monitors contain accelerometers, that measure the acceleration of the body and hence represent body movement. By definition, body movement leads to energy expenditure (EE) and hence the two always need to be related. Activity monitors that provide an estimate of EE need to be validated so that the contribution of the sensor output to the prediction of EE is known. Subject characteristics such as body mass, height, gender and age already explain most of the variation of TDEE; the accelerometer should then represent the physical activity component of TDEE and improve the explained variation. Many activity monitors also contain additional sensors measuring other (physiological) output parameters such as heart rate, skin temperature, galvanic skin response or gps positioning. Although promising, so far there is no compelling evidence that these additional sensors improve the prediction of EE, so careful consideration is needed whether or not these are worth the extra cost, and the extra battery power and storage capacity needed. Again, it is important to know the individual contribution of each outcome parameter to the prediction of TDEE. In conclusion, activity monitors are valuable tools in PA research but also in nutritional research when energy balance is studied.

To systematically review studies assessing (1) psychometric properties of the maximal oxygen uptake (VO2max) test in PD, (2) VO2max levels in persons with PD (pwPD) compared to healthy controls (HCs), and (3) reported VO2max associations in PD. Six databases were searched. Descriptive data synthesis was used to summarize psychometric properties and reported VO2max associations. The VO2max means and test end-criteria were calculated using linear mixed models. Simple linear regression was used for associations. The review included 25 studies. Psychometric properties of the VO2max test, reported in one study, showed intraclass correlations of 0.90–0.94 for VO2max. Thirteen studies reported test end-criteria, with only mean respiratory exchange ratio (on medication) and percentage of predicted maximal heart rate (off medication) fulfilling standardized minimum values for the VO2max test. The VO2max was comparable between pwPD and HC as well as between different PD-medication states. Associations between VO2max and age, sex, and fatigue were reported. In mildly to moderately affected pwPD, limited evidence exists on the psychometric properties of the VO2max test and end-criteria were sparsely reported. Surprisingly, VO2max was comparable between pwPD and HC as well as between different PD-medication states, and only age, sex, and fatigue were associated with VO2max. Implications for rehabilitationIn mildly to moderately affected persons with PD (pwPD), only one study has examined psychometric properties of the VO2max test, reporting excellent test–retest reliability.A general lack of consistency on how to measure and report VO2max end-criteria was observed, but when reported, the end-criteria were most often not met.No difference was found in VO2max between mildly to moderately affected pwPD and HC, or between pwPD across different medication states.The identified negative association between VO2max and fatigue suggests aerobic exercise as a potential symptomatic treatment of fatigue when rehabilitation professionals are treating pwPD. In mildly to moderately affected persons with PD (pwPD), only one study has examined psychometric properties of the VO2max test, reporting excellent test–retest reliability. A general lack of consistency on how to measure and report VO2max end-criteria was observed, but when reported, the end-criteria were most often not met. No difference was found in VO2max between mildly to moderately affected pwPD and HC, or between pwPD across different medication states. The identified negative association between VO2max and fatigue suggests aerobic exercise as a potential symptomatic treatment of fatigue when rehabilitation professionals are treating pwPD.

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes. ispartof: PEDIATRIC DIABETES vol:21 issue:8 pages:1375-1393 ispartof: location:Denmark status: published

As elite athletes demonstrate through the Olympic motto ‘Citius, Altius, Fortius- Communiter’, new performance records are driven forward by favourable skeletal muscle bioenergetics, cardiorespiratory, and endocrine system adaptations. At a recreational level, regular physical activity is an effective nonpharmacological therapy in the treatment of many endocrine conditions. However, the impact of physical exercise on endocrine function and how best to incorporate exercise therapy into clinical care are not well understood. Beyond the pursuit of an Olympic medal, elite athletes may therefore serve as role models for showcasing how exercise can help in the management of endocrine disorders and improve metabolic dysfunction. This review summarizes research evidence for clinicians who wish to understand endocrine changes in athletes who already perform high levels of activity as well as to encourage patients to exercise more safely. Herein, we detail the upper limits of athleticism to showcase the adaptability of human endocrine-metabolic-physiological systems. Then, we describe the growing research base that advocates the importance of understanding maladaptation to physical training and nutrition in males and females; especially the young. Finally, we explore the impact of physical activity in improving some endocrine disorders with guidance on how lessons can be taken from athletes training and incorporated into strategies to move more people more often.

Physical activity may reduce the risk of developing breast cancer via its effect on the insulin/insulin-like growth factor (IGF) signaling system. A systematic review searched for randomized controlled trials (RCT), Mendelian randomization and prospective cohort studies that examined the effects of physical activity on insulin/IGF signaling [IGFs, their binding proteins (IGFBP), and markers of insulin resistance] in adult women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the Grading of Recommendations Assessment, Development, and Evaluation system used to determine the overall quality of the evidence. Fifty-eight RCTs met our inclusion criteria, no observational or Mendelian randomization studies met the criteria for inclusion. Meta-analyses indicated that physical activity interventions (vs. control) reduced fasting insulin, the Homeostatic Model Assessment for Insulin Resistance and fasting glucose. Physical activity increased IGF-1, but there was no clear effect on IGFBP-3 or the ratio of IGF-1:IGFBP-3. Strong evidence was only established for fasting insulin and insulin resistance. Further research is needed to examine the effect of physical activity on C-peptide and HBA1c in women. Reductions in fasting insulin and insulin resistance following exercise suggest some biological plausibility of the first part of the physical activity–insulin/IGF signaling–breast cancer pathway. See related article by Drummond et al., p. 2116

Purpose: To investigate the effect of sex and load carriage on cardiorespiratory responses to high intensity exercise in male and female soldiers. Methods: Soldiers (9 women, 9 men) performed a graded treadmill test until exhaustion with no load (NL) and combat-gear with body armor (CG). Cohen's d effect sizes, paired t-tests and ANOVA were used to study differences between conditions. A mixed linear regression model analyzed the relationship between heart rate (HR) and oxygen uptake (V̇O2) with load and between sexes. Results: Wearing CG resulted in, for both sexes, a decreased time to exhaustion (−11 min), lower V̇O2peak (L/min) ES = 0.56; VO2peak (mL//kg/min) ES = 2.44, both p < 0.001, a net decrease in minute ventilation (ES = 3.53) and no change in HRmax. No sex-difference were present except for absolute V̇O2peak. The VO2 and HR relationship showed a cardiorespiratory reduction wearing CG vs. NL. Added load was equal between sexes, although female soldiers' CG relative to body mass was higher (25%) than male soldiers’ (20%), p < 0.01. Conclusion: Wearing CG reduces soldiers’ cardiorespiratory capacity and exercise performance level, although the reduction cannot be explained solely based on the added load of CG, instead CG seems to restrict the capacity to fully ventilate. No sex differences were found in relative cardiorespiratory responses to wearing CG compared to NL.

Purpose: High intensity occupational physical activity (OPA) seem to aggravate health and increase risk of sick leave and early retirement. Most intensity of OPA monitoring has been self-reported, e.g. by rating of perceived exertion (RPE). However, no studies have investigated the precision and risk of bias in RPE reporting during free-living OPA. This study investigated the agreement between OPA intensity in percentage of the heart rate reserve (%HRR) estimated from RPE and device-measured heart rate (HR), and potential bias factors on this agreement. Methods: The CR10 scale measured RPE at work. The Actiheart monitor measured HR during 24-h a day for 2–4 days. Both RPE and device-worn HR were converted to %HRR. The difference between both %HRR and their limits of agreement was determined in a Bland Altman plot. To detect bias factors, the difference between both %HRR was regressed on age, sex, cardiorespiratory fitness, occupational lifting, medication, consequences of musculoskeletal disorders and the interactions between these factors with device-work %HRR. Results: Six hundred and twenty-three participants were included in the analysis. Mean difference between RPE-based and device-worn %HRR was 54.6% (SD 19.5). The limits of agreement were wide (11.6–90.1%HRR). Age (0.48%HRR, 95% CI 0.18–0.79) occupational lifting (9.84%HRR, 95% CI 3.85–15.83) and cardiorespiratory fitness (0.41%HRR, 95% CI 0.03–0.79) significantly biased the agreement between the estimations of OPA intensity. Conclusion: RPE overestimated OPA intensity, and was biased by several factors. Device-worn %HRR should be preferred when evaluating OPA intensity among workers with physically demanding jobs.

Oxygen uptake (V̇o 2 ) at exercise onset is determined in part by acceleration of pulmonary blood flow ([Formula: see text]). Impairments in the [Formula: see text] response can decrease exercise tolerance. Prior research has shown that voluntary respiratory maneuvers can augment venous return, but the corollary impacts on cardiac function, [Formula: see text] and early-exercise V̇o 2 remain uncertain. We examined 1) the cardiovascular effects of three distinct respiratory maneuvers (abdominal, AB; rib cage, RC; and deep breathing, DB) under resting conditions in healthy subjects (Protocol 1, n = 13), and 2) the impact of pre-exercise DB on pulmonary O 2 transfer during initiation of moderate-intensity exercise (Protocol 2, n = 8). In Protocol 1, echocardiographic analysis showed increased right ventricular (RV) cardiac output and left ventricular (LV) cardiac output (RVCO and LVCO, respectively), following AB (by +23 ± 13 and +18 ± 15%, respectively, P < 0.05), RC (+23 ± 16; +14 ± 15%, P < 0.05), and DB (+27 ± 21; +23 ± 14%, P < 0.05). In Protocol 2, DB performed for 12 breaths produced a pre-exercise increase in V̇o 2 (+801 ± 254 mL·min -1 over ∼6 s), presumably from increased [Formula: see text], followed by a reduction in pulmonary O 2 transfer during early phase exercise (first 20 s) compared with the control condition (149 ± 51 vs. 233 ± 65 mL, P < 0.05). We conclude that 1) respiratory maneuvers enhance RVCO and LVCO in healthy subjects under resting conditions, 2) AB, RC, and DB have similar effects on RVCO and LVCO, and 3) DB can increase [Formula: see text] before exercise onset. These findings suggest that pre-exercise respiratory maneuvers may represent a promising strategy to prime V̇o 2 kinetics and thereby to potentially improve exercise tolerance in patients with impaired cardiac function.NEW & NOTEWORTHY We demonstrate that different breathing maneuvers can augment both right and left-sided cardiac output in healthy subjects. These maneuvers, when performed immediately before exercise, result in a pre-exercise "cardiodynamic" increase in oxygen uptake (V̇o 2 ) associated with a subsequent reduction in the "cardiodynamic" V̇o 2 normally seen during early exercise. We conclude that pre-exercise breathing maneuvers are a plausible tool worthy of additional study to prime V̇o 2 kinetics and improve exercise tolerance in patients with cardiovascular disease.

We evaluated the influence of a 32-day camping in Antarctica on physical performance and exercise-induced thermoregulatory responses. In Brazil, before and after the Antarctic camping, the volunteers performed an incremental exercise at temperate conditions and, two days later, an exercise heat stress protocol (45-min running at 60% of maximum aerobic speed, at 31°C and 60% of relative humidity). In Antarctica, core temperature was assessed on a day of fieldwork, and average values higher than 38.5°C were reported. At pre- and post-Antarctica, physiological (whole-body and local sweat rate, number of active sweat glands, sweat gland output, core and skin temperatures) and perceptual (thermal comfort and sensation) variables were measured. The Antarctic camping improved the participants’ performance and induced heat-related adaptations, as evidenced by sweat redistribution (lower in the chest but higher in grouped data from the forehead, forearm, and thigh) and reduced skin temperatures in the forehead and chest during the exercise heat stress protocol. Notwithstanding the acclimatization, the participants did not report differences of the thermal sensation and comfort. In conclusion, staying in an Antarctic camp for 32 days improved physical performance and elicited physiological adaptations to heat due to the physical exertion-induced hyperthermia in the field.

This study assesses the potential of workplace-based micro-exercise (brief and simple exercise bouts) to prevent long-term sickness absence (LTSA) at the population level. In the Work Environment and Health in Denmark Study (2012–2018), we followed 70,130 workers from the general working population, without prior LTSA, for two years in the Danish Register for Evaluation of Marginalisation. We used Cox regression with model-assisted weights and controlled for various confounders. From 2012 to 2018, the percentage of workers in Denmark using workplace-based micro-exercise during and outside of working hours increased from 7.1 to 10.9% and from 0.8 to 1.4%, respectively. The incidence of long-term sickness absence (at least 30 days) was 8.4% during follow-up. The fully adjusted model showed reduced risk of long-term sickness absence from using micro-exercise during working hours, (HR 0.86, 95% CI 0.77–0.96), but not when used outside of working hours. If used by all workers, micro-exercise during working hours could potentially prevent 12.8% of incident long-term sickness absence cases (population attributable fraction). In conclusion, micro-exercise performed during working hours holds certain potential to prevent incident long-term sickness absence in the general working population. Large-scale implementation of workplace-based micro-exercise may represent an unexploited opportunity for public health promotion.

In 2015, Uhrbrand et al. published the first review on Parkinson´s disease (PD) and exercise entirely based on randomized controlled trials (RCT) applying strict exercise definitions. The present review aimed to update the PD literature by assessing the effects of different intensive exercise modalities: resistance training (RT), endurance training (ET), and other intensive exercise modalities (OITM). An updated systematic literature search identified 33 new RCTs. Qualitative and quantitative analyses were performed. A total of 18 RT, 14 ET, and 1 OITM studies were identified (adding to the 8 RT, 6 ET, and 4 OITM studies identified by Uhrbrand et al. in 2015). RT, ET, and OITM were feasible, safe, and did not worsen PD symptoms. Furthermore, RT, ET, and OITM may positively affect functional outcomes (e.g., balance) and depressive symptoms in PD but inconsistencies across these findings warrant cautious conclusions. Meta-analyses showed that RT had a positive impact on muscle strength (standardized mean difference (SMD) = 0.83 [95% CI;0.54, 1.12]), functional capacity (Timed Up and Go Test (TUG): SMD = -0.62 [-1.01, -0.24]), and quality of life (SMD = -0.41 [-0.72, -0.09]), while ET had a positive impact on cardiorespiratory fitness (SMD = 0.27 [0.07, 0.47]) and functional capacity (TUG: SMD = -0.21 [-0.46, 0.04], 6-Min Walk Test: SMD = 0.89 [0.17, 1.62]), and a potentially positive impact on "on-medication" UPDRS-III (SMD = -0.15 [-0.38, 0.09]) and "off-medication" UPDRS-III (SMD = -0.19 [-0.41, 0.04]). In conclusion, RT, ET, and OITM all represent safe, feasible, and beneficial adjunct rehabilitation strategies in PD, with particularly RT and ET showing solid effects.

Objective The purpose of this systematic review was to investigate whether aerobic training (AT) or resistance training (RT) is most effective in terms of improving lower limb physical function and perceived fatigue in persons with multiple sclerosis (PwMS). Data Sources Nine databases (MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health, Allied and Complementary Medicine Database, Physiotherapy Evidence Database, SPORTDiscus, PsycINFO, Web of Science, and Scopus) were electronically searched in April 2020. Study Selection Included studies were randomized controlled trials (RCTs) involving PwMS attending 1 of 2 exercise interventions: AT or RT. Studies had to include at least 1 objective or self-reported outcome of lower extremity physical function and/or perceived fatigue. Data Extraction Data were extracted using a customized spreadsheet, which included detailed information on patient characteristics, interventions, and outcomes. The methodological quality of the included studies was independently assessed by 2 reviewers using the Tool for Assessment of Study Quality for Reporting on Exercise rating scale. Data Synthesis Twenty-seven articles reporting data from 22 RCTS (AT=14, RT=8) including 966 PwMS. The 2 modalities were found to be equally effective in terms of improving short walk test (AT: effect size [ES]=0.33 [95% confidence interval (CI), −1.49 to 2.06]; RT: ES=0.27 [95% CI, 0.07-0.47]) and long walk test performance (AT: ES=0.37 [95% CI, −0.04 to 0.78]; RT: ES=0.36 [95% CI, −0.35 to 1.08]), as well as in reducing perceived fatigue (AT: ES=−0.61 [95% CI, −1.10 to −0.11]; RT: ES=−0.41 [95% CI, −0.80 to −0.02]). Findings on other functional mobility tests along with self-reported walking performance were sparse and inconclusive. Conclusions AT and RT appear equally highly effective in terms of improving lower extremity physical function and perceived fatigue in PwMS. Clinicians can thus use either modality to target impairments in these outcomes. In a future perspective, head-to-head exercise modality studies are warranted. Future MS exercise studies are further encouraged to adapt a consensus “core battery” of physical function tests to facilitate a detailed comparison of results across modalities.

PURPOSE: Carbohydrate (CHO) mouth rinsing (MR) prior to exercise has been shown to elicit enhanced performance and energy availability in some studies. Previous literature has concentrated on examining CHO MR strategies for improving aerobic endurance performance in younger athletic adults. Knowledge of the impact of CHO MR on functional performance in older adults is scarce. The purpose of this investigation was to determine if CHO MR would improve 6-min walk test (6MWT) performance, perceived exertion, and blood glucose responses in older adults. METHOD: Thirty-three individuals (16 males, 17 females), age ≥ 70 years performed two 6MWT trials, one of which utilized a 6.4% maltodextrin CHO MR and one of which utilized a placebo MR. Participants held the MR in their mouth for 20 s prior to the 6MWT, and trials occurred in a counterbalanced fashion. Total distance walked and rating of perceived exertion (RPE) were recorded upon completion of each 6MWT. Heart rate (HR), peripheral blood oxygen saturation (SpO2), systolic and diastolic blood pressures (BP), blood glucose, and blood lactate were measured before and after each 6MWT. RESULT: CHO MR did not alter the response of any study parameter compared to the placebo MR (p = 0.13-0.94). HR, systolic BP, and blood lactate increased and SpO2 decreased across time (p

Background Reliable estimates of habitual sleep, physical activity, and sedentary time are essential to investigate the associations between these behaviours and health outcomes. While the number of days needed and hours/day for estimates of physical activity and sedentary time are generally known, the criteria for sleep estimates are more uncertain. The objective of this study was to identify the number of nights needed to obtain reliable estimates of habitual sleep behaviour using the GENEActiv wrist worn accelerometer. The number of days to obtain reliable estimate of physical activity was also examined. Methods Data was used from a two-year longitudinal study. Children wore an accelerometer for up to 8 days 24 h/day across three timepoints. The sample included 2,745 children (51 % girls) between the ages of 7-12-years-old (mean = 9.8 years, SD = 1.1 year) with valid accelerometer data from any timepoint. Reliability estimates were calculated for sleep duration, sleep efficiency, sleep onset, wake time, time in bed, light physical activity, moderate physical activity, moderate-to-vigorous physical activity, vigorous physical activity, and sedentary time. Results Intraclass correlations and the Spearman Brown prophecy formula were used to determine the nights and days needed for reliable estimates. We found that between 3 and 5 nights were needed to achieve acceptable reliability (ICC = 0.7) in sleep outcomes, while physical activity and sedentary time outcomes required between 3 and 4 days. Conclusions To obtain reliable estimates, researchers should consider these minimum criteria when designing their studies and prepare strategies to ensure sufficient wear time compliance.

PURPOSE. Convergence insufficiency (CI) is characterized by abnormal vergence eye movement frequently accompanied by abnormal accommodation and subjective symptoms, such as headache, blurred vision, and diplopia. CI is treated with vergence and accommodation exercises that are integrated so that the relative contributions of vergence and accommodation exercises to the outcome are concealed. The purpose of the present study was to determine the individual contributions of vergence and accommodation exercises for the treatment of CI in school children. METHODS. In a prospective crossover study 44 children aged 9 to 13 years with CI were randomized to perform either vergence exercises followed by accommodation exercises each for 6 weeks or the 2 treatment regimes in the reverse order. The outcome measures were recovery from CI and the parameters vergence facility, positive fusional vergence, near point of convergence, monocular amplitude, and facility of accommodation. RESULTS. After the first 6-week period, full recovery from CI was significantly more frequent in the group commencing vergence exercises than in the group commencing monocular accommodation exercises (p = 0.01), whereas there was no significant difference between these proportions after the second 6-week period (p = 0.45). Vergence facility and positive fusional vergence improved significantly more after the period with vergence exercises than after the accommodation exercises, whereas there was no significant difference between the effects of the two types of exercises on the other studied parameters. CONCLUSIONS. Vergence treatment induces a faster recovery of CI than accommodation treatment in school children. This may be used to improve compliance and success rate of the treatment.

PURPOSE. Recent evidence suggests that the smaller retinal vessels are significantly involved in the regulation of retinal blood flow and that this regulation may differ among the macular area and the retinal periphery. An alternative to studying blood flow regulation in smaller retinal vessels that are difficult to resolve is to assess the metabolic consequences of changes in the microcirculation using oximetry. METHODS. In 20 normal persons aged (mean ± SD, range) 30.1 ± 3.8 (24-37) years, the oxygen saturation and diameter of retinal arterioles and venules to the macular area and the retinal periphery were studied before and during an increase in the arterial blood pressure induced by isometric exercise. RESULTS. The isometric exercise increased the mean arterial blood pressure by (mean ± SEM) 10.0 ± 1.1 mm Hg but induced no significant changes in the diameter of the arterioles (P = 0.83). The isometric exercise had no significant effect on the oxygen saturation in the arterioles supplying the macular area and the retinal periphery (P > 0.42 for both comparisons). However, there was a significant increase in the oxygen saturation in venules draining the retinal periphery to reduce the oxygen extraction from (mean ± SEM) 36.0% ± 2.3% to 30.6% ± 2.1% (P = 0.002) but no significant change in the preexisting low oxygen extraction in the macular area that changed from (mean ± SEM) 18.2% ± 3.0% to 16.2% ± 1.9% (P = 0.37). CONCLUSIONS. Minor changes in the arterial blood pressure can induce changes in retinal rheology with significant regional variation. The finding may help explain regional variations in manifestations of retinal vascular disease such as hyperpermeability in the macular area and capillary occlusion in the retinal periphery.

ObjectiveTo determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS).MethodsWe conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired patients with MS aged 18–65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle.ResultsEighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% confidence interval [CI] −0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00–0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group.ConclusionThese findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted.Clinicaltrials.gov identifierNCT02661555.Classification of evidenceThis study provides Level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.

We evaluated the cardiometabolic effects of a 15-week combined exercise programme, implemented in sports clubs, for 50–70-year-olds with low aerobic fitness. In a randomized controlled trial, 45 participants (26 women) with low fitness were randomly assigned (2:1-ratio) to a training group (TG, n = 30) or inactive control group (CG, n = 15). TG had 15 weeks with one weekly 90-min supervised group-based session in a recreational sports club with combined aerobic exercise and strength training and were encouraged to perform home-based training 30 min/wk. Evaluations of relative VO2max (mLO2/min/kg), blood pressure, resting heart rate (HR), echocardiography, peripheral arterial tonometry, body composition, lipid profile and HbA1c were performed at 0 and 15 wks. Average HR during supervised training was 113 ± 13 bpm (68.6 ± 7.0%HRmax), with 4.3 ± 6.6% spent >90%HRmax. At 15-wk follow-up, intention-to-treat analyses revealed no between-group difference for VO2max/kg (0.4 mLO2/min/kg, 95%CI −0.8–1.5, P = 0.519; −3 mL/min, 95%CI −123–118, P = 0.966) or other cardiovascular outcomes (all P > 0.05). Compared to CG, total fat mass (−1.9 kg; 95%CI −3.2 to −0.5, P = 0.005), total fat percentage (−1.3%, 95%CI −2.2 to −0.3, P = 0.01) and total/HDL cholesterol ratio (P = 0.032) decreased in TG. Regular adherence to supervised training was high (81%), but 0% for home-based exercise. In conclusion, the group-based supervised training was associated with high adherence and moderate exercise intensity, whereas insufficiently supported home-based training was not feasible. Together, 15 wks of combined exercise training did not improve aerobic fitness or affected cardiovascular function in 50–70-yr-olds with low aerobic fitness, whereas some positive effects were observed in metabolic parameters. Highlights Combined exercise training implemented in a sports club elicited moderate aerobic intensity in 50-70-year-old untrained individuals. Supervised group-based training had high adherence whereas unsupported home-based training had very low adherence. 15 weeks of low-frequency combined moderate intensity exercise training improved lipid profile and fat mass, but had no effect on cardiovascular fitness.

Objectives We investigated associations between leisure-time physical activity (LTPA) at different intensities (moderate and vigorous or moderate-to-vigorous) and prospective weight gain in non-obese people. We also examined whether these associations were independent of other lifestyle factors and changes in muscle mass and whether they were age-dependent and changed over a person’s life course. Methods The data were extracted from the Lifelines cohort study (N = 52,498; 43.5% men) and excluded obese individuals (BMI > 30 kg/m2). We used the validated SQUASH questionnaire to estimate moderate-to-vigorous (MVPA; MET≥4), moderate (MPA; MET between 4 and 6.5) and vigorous PA (VPA; MET≥6.5). Body weight was objectively measured, and changes were standardized to a 4-year period. Separate analyses, adjusted for age, educational level, diet, smoking, alcohol consumption and changes in creatinine excretion (a marker of muscle mass), were performed for men and women. Results The average weight gain was + 0.45 ± 0.03 kg in women. Relative to each reference groups (No-MVPA, No-MPA and No-VPA), MVPA (Beta (95%CI): − 0.34 kg (− 0.56;-0.13)), MPA (− 0.32 kg (− 0.54;-0.10)) and VPA (− 0.30 kg (− 0.43;-0.18)) were associated with less gain in body weight in women after adjusting for potential confounders, described above. These associations were dose-dependent when physically active individuals were divided in tertiles. Beta-coefficients (95%CI) for the lowest, middle, and highest MVPA tertiles relative to the ‘No-MVPA’ were, respectively, − 0.24 (− 0.47;-0.02), − 0.31 (− 0.53;-0.08), and − 0.38 (− 0.61;-0.16) kg. The average weight gain in men was + 0.13 ± 0.03 kg, and only VPA, not MPA was associated with less body weight gain. Beta-coefficients (95%CI) for the VPA tertiles relative to the ‘No-VPA’ group were, respectively, − 0.25 (− 0.42;-0.09), − 0.19 (− 0.38;-0.01) and − 0.20 (− 0.38;-0.02) kg. However, after adjusting for potential confounders, the association was no longer significant in men. The potential benefits of leisure-time PA were age-stratified and mainly observed in younger adults (men Conclusion Higher leisure-time MVPA, MPA, and VPA were associated with less weight gain in women

Approximately 50% of patients with heart failure have preserved ejection fraction. Although a wide variety of conditions cause or contribute to heart failure with preserved ejection fraction, elevated left ventricular filling pressures, particularly during exercise, are common to all causes. Acute elevation in left‐sided filling pressures promotes lung congestion and symptoms of dyspnea, while chronic elevations often lead to pulmonary vascular remodeling, right heart failure, and increased risk of mortality. Pharmacologic therapies, including neurohormonal modulation and drugs that modify the nitric oxide/cyclic GMP‐protein kinase G pathway have thus far been limited in reducing symptoms or improving outcomes in patients with heart failure with preserved ejection fraction. Hence, alternative means of reducing the detrimental rise in left‐sided heart pressures are being explored. One proposed method of achieving this is to create an interatrial shunt, thus unloading the left heart at rest and during exercise. Currently available studies have shown 3‐ to 5‐mm Hg decreases of pulmonary capillary wedge pressure during exercise despite increased workload. The mechanisms underlying the hemodynamic changes are just starting to be understood. In this review we summarize results of recent studies aimed at elucidating the potential mechanisms of improved hemodynamics during exercise tolerance following interatrial shunt implantation and the current interatrial shunt devices under investigation.

Dietary nitrate (NO3−) supplementation, which can enhance performance in exercise settings involving repeated high-intensity efforts, has been linked to improved skeletal muscle contractile function. Although muscular strength is an important component of explosive movements and sport-specific skills, few studies have quantified indices of muscular strength following NO3− supplementation, particularly isokinetic assessments at different angular velocities. We performed a systematic review and meta-analysis to determine whether dietary NO3− supplementation improves peak torque, as assessed by the gold standard method of isokinetic dynamometry, and if this effect was linked to the angular velocity imposed during the assessment. Dialnet, Directory of Open Access Journals, MEDLINE, PubMed, SciELO, Scopus, and SPORTDiscus were searched for articles using the following search strategy: (nitrate OR beet*) AND (supplement* OR nutr* OR diet*) AND (isokinetic OR strength OR “resistance exercise” OR “resistance training” OR “muscular power”). The meta-analysis of data from 5 studies with 60 participants revealed an overall effect size of −0.01 for the effect of nitrate supplementation on isokinetic peak torque, whereas trivial effect sizes ranging from −0.11 to 0.16 were observed for independent velocity-specific (90°/s, 180°/s, 270°/s, and 360°/s) isokinetic peak torque. Four of the five studies indicated that dietary NO3− supplementation is not likely to influence voluntary knee extensor isokinetic torque across a variety of angular velocities. These results suggest that NO3− supplementation does not influence isokinetic peak torque, but further work is required to elucidate the potential of NO3− supplementation to influence other indices of muscular strength, given the dearth of experimental evidence on this topic.

Background: Advanced glycation end products (AGEs) are protein modifications that are predominantly formed from dicarbonyl compounds that arise from glucose and lipid metabolism. AGEs and sedentary behavior have been identified as a driver of accelerated (vascular) aging. The effect of physical activity on AGE accumulation is unknown. Therefore, we investigated whether plasma AGEs and dicarbonyl levels are different across older individuals that were active or sedentary and whether plasma AGEs are affected by high-intensity interval training (HIIT). Methods: We included healthy older active (HA, n=38, 44.7% female, 60.1 ± 7.7 years old) and healthy older sedentary (HS, n=36, 72.2% female, 60.0 ± 7.3 years old) individuals as well as older sedentary individuals with increased cardiovascular risk (SR, n=84, 50% female, 58.7 ± 6.6 years old). The SR group was randomized into a 12-week walking-based HIIT program or control group. We measured protein-bound and free plasma AGEs and dicarbonyls by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) at baseline and after the HIIT intervention. Results: Protein-bound AGE Nε-(carboxymethyl)lysine (CML) was lower in SR (2.6 ± 0.5 μmol/l) and HS (3.1 ± 0.5 μmol/l) than in HA (3.6 ± 0.6 μmol/l; P Discussion: Although lifestyle interventions may act as important modulators of cardiovascular risk, HIIT is not a potent short-term intervention to reduce glycation in older individuals, underlining the need for other approaches, such as pharmacological agents, to reduce AGEs and lower cardiovascular risk in this population.

AIMS/HYPOTHESIS: Plasma ATP is a potent vasodilator and is thought to play a role in the local regulation of blood flow. Type 2 diabetes is associated with reduced tissue perfusion. We aimed to examine whether individuals with type 2 diabetes have reduced plasma ATP concentrations compared with healthy control participants (case-control design).METHODS: We measured femoral arterial and venous plasma ATP levels with the intravascular microdialysis technique during normoxia, hypoxia and one-legged knee-extensor exercise (10 W and 30 W) in nine participants with type 2 diabetes and eight control participants. In addition, we infused acetylcholine (ACh), sodium nitroprusside (SNP) and ATP into the femoral artery to assess vascular function and ATP signalling.RESULTS: Individuals with type 2 diabetes had a lower leg blood flow (LBF; 2.9 ± 0.1 l/min) compared with the control participants (3.2 ± 0.1 l/min) during exercise (p CONCLUSIONS/INTERPRETATION: These findings demonstrate that individuals with type 2 diabetes have lower plasma ATP concentrations during exercise and hypoxia compared with control individuals, and this occurs in parallel with lower blood flow. Moreover, individuals with type 2 diabetes have a reduced vasodilatory response to infused ATP. These impairments in the ATP system are both likely to contribute to the reduced tissue perfusion associated with type 2 diabetes.TRIAL REGISTRATION: ClinicalTrials.gov NCT02001766.

Objective: Physical activity (PA) may influence acute stress reactivity in children differently depending on their weight. This randomized controlled trial investigated the impact of acute PA and of BMI status (overweight/obese (OB/OW) and normal weight (NW) on stress reactivity. Method: 50 prepubertal children (24 OW/OB and 26 NW) were randomly assigned to the PA or sedentary arm (SED) for 30 min followed by a stress task. Salivary cortisol, blood pressure (BP), and heart rate (HR) were measured. Results: An interaction effect between the randomization arms and weight status on salivary cortisol was found after the stress task (p = 0.04). Cortisol increased in the SED, but not in the PA arm (p = 0.004 for differences in time course) of NW children. Time course did not differ between both arms in OW/OB children (p = 0.7). OW/OB SED children had a flat cortisol course, and levels were reduced compared to the NW SED or the OW/OB PA children (p ≤ 0.03). Systolic BP increased only in the SED arm (p = 0.01). HR was higher in the PA than in the SED arm during stress (p < 0.001) and showed different time courses (p = 0.006). Conclusion: PA impacted on acute stress reactivity and influenced stress reactivity differently in NW and OW/OB children.

PURPOSE: The clinical relevance of abnormal exercise testing (ET) results (at least 0.1 mV ST segment depression measured during exercise or recovery in three consecutive beats) in athletes without obstructive coronary artery disease (CAD) is not well understood. It is unknown whether this phenomenon reflects a physiological adaptation to sport or a truly ischemic response and a concomitant attenuated stroke volume (SV) response. The aim of this study was to investigate if athletes with abnormal ET results without obstructive CAD showed signs of an attenuated SV response using cardiopulmonary ET parameters.METHODS: A total of 78 male master athletes with abnormal ET results without obstructive CAD underwent cardiopulmonary ET. ΔO2 pulse/Δwork rate (WR), ΔV˙O2/ΔWR, and Δheart rate (HR)/ΔWR were assessed and compared with data from 78 male master athletes with normal ET results, matched for age, sports characteristics, and exercise capacity.RESULTS: The ΔO2 pulse/ΔWR ratio beyond anaerobic threshold in athletes with abnormal ET results was lower than that in athletes with normal ET results (0.73 ± 0.41 vs 1.12 ± 0.54, respectively, P < 0.001). The ΔV˙O2/ΔWR ratio was also lower in athletes with abnormal ET results (0.9 ± 0.2 vs 1.0 ± 0.3, respectively, P = 0.041). Furthermore, these athletes showed a greater increase in HR in the last 2 min of exercise (ΔHR/ΔWR ratio: 1.19 ± 0.5 vs 0.80 ± 0.6, P < 0.001).CONCLUSION: Athletes with abnormal ET results without obstructive CAD showed an attenuated O2 pulse slope, decreased ΔV˙O2/ΔWR ratio, and increased ΔHR/ΔWR ratio beyond anaerobic threshold when compared with athletes with a normal ET result. These results support the hypothesis that at least a part of the athletes with an abnormal ET in absence of obstructive CAD have an attenuated SV response at high-intensity exercise.

NEW FINDINGS: What is the central question of this study? Is there an association of plasma concentration of asymmetric dimethylarginine, which is related to exercise capacity in patients with cardiovascular diseases, with oxygen delivery and subsequently exercise capacity in healthy subjects in the absence of the potentially confounding influence of inflammation and oxidative stress? What is the main finding and its importance? Plasma asymmetric dimethylarginine concentrations are not related to exercise capacity in healthy subjects, while O2 delivery in the working skeletal muscle during the maximal graded-exercise test is not associated with any of the l-arginine analogues. ADMA alone does not play a crucial role in local muscle perfusion and in maintaining exercise capacity. ABSTRACT: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis that could limit oxygen (O2 ) delivery in the working skeletal muscles by altering endothelium-dependent vasodilatation. Exercise capacity is associated with plasma ADMA concentrations in patients with cardiovascular diseases, but this issue has still not been investigated in healthy subjects. We aimed to determine whether plasma ADMA concentrations were negatively associated with exercise capacity in young healthy male subjects. Ten men with maximal oxygen uptake ( V ̇ O 2 max ) > 65 mL kg-1 min-1 were included in the high exercise capacity group (HI-FIT), and 10 men with V ̇ O 2 max < 45 mL kg-1 min-1 were included in the low exercise capacity group (LO-FIT). Plasma ADMA and other l-arginine analogue concentrations were measured before and after a maximal graded-exercise test by liquid chromatography-tandem mass spectrometry. Microvascular O2 delivery during exercise was estimated through the pattern from the sigmoid model of muscle deoxygenation in the vastus lateralis measured by near infrared spectroscopy. V ̇ O 2 max was 60% higher in the HI-FIT group (median: 70.2 mL kg-1 min-1 ; IQR: 68.0-71.9 mL kg-1 min-1 ) than in the LO-FIT group (median: 43.8 mL kg-1 min-1 ; IQR: 34.8-45.3 mL kg-1 min-1 ). Plasma ADMA concentrations did not differ between the LO-FIT and HI-FIT groups before (0.50 ± 0.06 vs. 0.54 ± 0.07 μmol L-1 , respectively) and after the maximal incremental exercise test (0.49 ± 0.08 vs. 0.55 ± 0.03 μmol L-1 ,respectively). There was no significant association of plasma ADMA concentrations with the pattern of local muscle deoxygenation and exercise capacity. Exercise capacity and microvascular O2 delivery are not related to plasma ADMA concentrations in young healthy male subjects. Our findings show that ADMA does not play a crucial role in local muscle perfusion and in maintaining exercise capacity without pathological conditions.