Personalized digital behaviour interventions increase short-term physical activity: a randomized control crossover trial substudy of the MyHeart Counts Cardiovascular Health Study.

Aims: Physical activity is associated with decreased incidence of the chronic diseases associated with aging. We previously demonstrated that digital interventions delivered through a smartphone app can increase short-term physical activity. Methods and results: We offered enrolment to community-living iPhone-using adults aged ≥18 years in the USA, UK, and Hong Kong who downloaded the MyHeart Counts app. After completion of a 1-week baseline period, e-consented participants were randomized to four 7-day interventions. Interventions consisted of: (i) daily personalized e-coaching based on the individual's baseline activity patterns, (ii) daily prompts to complete 10 000 steps, (iii) hourly prompts to stand following inactivity, and (iv) daily instructions to read guidelines from the American Heart Association (AHA) website. After completion of one 7-day intervention, participants subsequently randomized to the next intervention of the crossover trial. The trial was completed in a free-living setting, where neither the participants nor investigators were blinded to the intervention. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in a modified intention-to-treat analysis (modified in that participants had to complete 7 days of baseline monitoring and at least 1 day of an intervention to be included in analyses). This trial is registered with ClinicalTrials.gov, NCT03090321. Conclusion: Between 1 January 2017 and 1 April 2022, 4500 participants consented to enrol in the trial (a subset of the approximately 50 000 participants in the larger MyHeart Counts study), of whom 2458 completed 7 days of baseline monitoring (mean daily steps 4232 ± 73) and at least 1 day of one of the four interventions. Personalized e-coaching prompts, tailored to an individual based on their baseline activity, increased step count significantly (+402 ± 71 steps from baseline, P = 7.1⨯10-8). Hourly stand prompts (+292 steps from baseline, P = 0.00029) and a daily prompt to read AHA guidelines (+215 steps from baseline, P = 0.021) were significantly associated with increased mean daily step count, while a daily reminder to complete 10 000 steps was not (+170 steps from baseline, P = 0.11). Digital studies have a significant advantage over traditional clinical trials in that they can continuously recruit participants in a cost-effective manner, allowing for new insights provided by increased statistical power and refinement of prior signals. Here, we present a novel finding that digital interventions tailored to an individual are effective in increasing short-term physical activity in a free-living cohort. These data suggest that participants are more likely to react positively and increase their physical activity when prompts are personalized. Further studies are needed to determine the effects of digital interventions on long-term outcomes.

Mobile Health Study Incorporating Novel Fitness Test.

Mobile health (mHealth) is a rapidly expanding field within precision medicine and precision health that provides healthcare support and interventions using mobile technologies, such as smartphones and smartwatches. The growing ubiquity of commercial wireless signals and smartphones allows mHealth technologies to have a substantially broader reach than traditional healthcare networks. My Fitness Counts, a cross-platform My Heart Counts spinout study, is a pioneer cross-platform mHealth study for measuring cardiovascular fitness levels. The study uses Real-World Insights, a platform designed to host mHealth studies. In this paper, we present insights gained through the quality control process undertaken prior to the release of the cross-platform mHealth study My Fitness Counts. Through extensive testing of the 21 iOS and 11 Android builds of the application, over 70 bugs were identified and corrected during the 5-month development process of My Fitness Counts.

Physiological Factors of Importance for Load Carriage in Experienced and Inexperienced Men and Women.

INTRODUCTION: The ability to carry heavy loads is an important and necessary task during numerous outdoor activities and especially in military operations. The aim of this study was to investigate factors associated with load-carrying ability in men and women with and without extensive load-carrying experience. MATERIALS AND METHODS: The energy expenditure during carrying no load, 20, 35, and 50 kg at 2 walking speeds, 3 and 5 km h-1, was studied in 36 healthy participants, 19 men (30 ± 6 years, 82.5 ± 7.0 kg) and 17 women (29 ± 6 years, 66.1 ± 8.9 kg), experienced (>5 years) in carrying heavy loads (n = 16, 8 women) or with minor or no such experience (n = 20, 9 women). A standard backpack filled with weights to according carry load was used during the walks. Anthropometric data, leg muscle strength, as well as trunk muscle endurance and muscle fiber distribution of the thigh, were also obtained. Extra Load Index (ELI)-the oxygen uptake (VO2) during total load over unloaded walking-was used as a proxy for load-carrying ability at 20, 35, and 50 kg (ELI20, ELI35, and ELI50, respectively). In addition to analyzing factors of importance for the ELI values, we also conducted mediator analyses using sex and long-term carrying experience as causal variables for ELI as the outcome value. The study was approved by the Regional Ethics Committee in Stockholm, Sweden. RESULTS: For the lowest load (20 kg), ELI20, was correlated with body mass but no other factors. Walking with 35 and 50 kg load at 5 km h-1 body mass, body height, leg muscle strength, and absolute VO2max were correlated, while relative VO2max, trunk muscle endurance, and leg muscle fiber distribution were not correlated to ELI35 and ELI50.ELI50 at 5 km h-1 differed between the sexes. This difference was only mediated by the difference in body mass. Neither muscle fiber distribution, leg muscle strength, trunk muscle endurance, and body height nor did absolute or relative VO2max explain the difference.Participants with long-term experience of heavy load carrying had significant lower ELI20 and ELI50 values than those with minor or no experience, but none of the above studied factors could explain this difference. CONCLUSION: The study showed that body mass, without sex differences, and experience of carrying heavy loads are the dominant factors for the ability to carry heavy loads. Even though the effect of experience alludes to the need for extensive carrying training, no causality can be proven. Load carry training intervention studies is suggested for future investigations.

Performance and cardiac evaluation before and after a 3-week training camp for 400-meter sprinters - An observational, non-randomized study.

OBJECTIVE: To study the performance and cardiovascular function after a 3-week training camp in athletes competing in an anaerobically dominant sport. METHODS: Twenty-three competitive 400-m athletes were enrolled in this non-randomized study, 17 took part in a 3-week training camp in South-Africa (intervention), but one declined follow-up assessment, while 6 pursued in-door winter training in Sweden and served as controls. Electrocardiography, transthoracic echocardiography, blood test analyses, maximal exercise tolerance test, and a 300-m sprint test with lactate measurements ([La]peak) were performed before and after the training camp period. RESULTS: At baseline, there were no clinically significant pathological findings in any measurements. The training period resulted in improved 300m-sprint performance [n = 16; running time 36.71 (1.39) vs. 35.98 (1.13) s; p<0.01] and higher peak lactate values. Despite 48% more training sessions than performed on home ground (n = 6), myocardial biomarkers decreased significantly (NT-pro BNP -38%; p<0.05, troponin T -16%; p<0.05). Furthermore, resting heart rate (-7%; p<0.01) and left ventricular systolic and diastolic volumes decreased -6% (p<0.01) and -10% (p<0.05), respectively. CONCLUSIONS: Intense physical activity at training camp improved the performance level, likely due to improved anaerobic capacity indicated by higher [La]peak. There were no clinically significant adverse cardiac changes after this period of predominantly anaerobic training.

SR Ca2+ leak in skeletal muscle fibers acts as an intracellular signal to increase fatigue resistance.

Effective practices to improve skeletal muscle fatigue resistance are crucial for athletes as well as patients with dysfunctional muscles. To this end, it is important to identify the cellular signaling pathway that triggers mitochondrial biogenesis and thereby increases oxidative capacity and fatigue resistance in skeletal muscle fibers. Here, we test the hypothesis that the stress induced in skeletal muscle fibers by endurance exercise causes a reduction in the association of FK506-binding protein 12 (FKBP12) with ryanodine receptor 1 (RYR1). This will result in a mild Ca2+ leak from the sarcoplasmic reticulum (SR), which could trigger mitochondrial biogenesis and improved fatigue resistance. After giving mice access to an in-cage running wheel for three weeks, we observed decreased FKBP12 association to RYR1, increased baseline [Ca2+]i, and signaling associated with greater mitochondrial biogenesis in muscle, including PGC1α1. After six weeks of voluntary running, FKBP12 association is normalized, baseline [Ca2+]i returned to values below that of nonrunning controls, and signaling for increased mitochondrial biogenesis was no longer present. The adaptations toward improved endurance exercise performance that were observed with training could be mimicked by pharmacological agents that destabilize RYR1 and thereby induce a modest Ca2+ leak. We conclude that a mild RYR1 SR Ca2+ leak is a key trigger for the signaling pathway that increases muscle fatigue resistance.

Effects of Flywheel Training on Strength-Related Variables: a Meta-analysis.

BACKGROUND: Strength and power development are abilities important for athletic performance in many sports. Generally, resistance training based on gravity is used to improve these qualities. Flywheel training instead utilizes kinetic energy transferred to a flywheel. This allows for eccentric overload and variable resistance throughout the movement. The aim of this review was to identify the effects of flywheel training on multiple strength-related variables affecting athletic performance. The meta-analysis investigates the effects on (1) muscle growth (cross-sectional area (CSA) and volume/mass), (2) maximum dynamic strength, (3) development of power, (4) development of horizontal movement, and (5) development of vertical movement. METHODS: The meta-analysis includes 20 experimental studies that met the inclusion criteria. The quality of included studies was ranked according to the PEDro scale. Possible bias was identified in Funnel plot analyses. To enable the compilation of all results analyses, the random effect model was carried out using the software Review Manager Version 5.3 and presented with Forest plots. RESULTS: Flywheel training for a period of 4-24 weeks shows statistically significant increases in all strength aspects. Effect sizes were for hypertrophy, CSA 0.59; volume/mass 0.59; maximum strength 1.33; power 1.19; horizontal 1.01 and vertical movement 0.85. The evidence is particularly strong for beneficial effects from flywheel training in the development of maximal strength and power in trained younger individuals, and utilization of this training modality in shorter more intensive blocks. CONCLUSIONS: Flywheel training is an effective method for improving several aspects of strength and power with importance for sports performance.

Increased autophagy signaling but not proteasome activity in human skeletal muscle after prolonged low-intensity exercise with negative energy balance.

Little is known about the molecular regulation of skeletal muscle protein turnover during exercise in field conditions where energy is intake inadequate. Here, 17 male and 7 female soldiers performed an 8 days long field-based military operation. Vastus lateralis muscle biopsies, in which autophagy, the ubiquitin-proteasome system, and the mTORC1 signaling pathway were studied, were collected before and after the operation. The 187 h long operation resulted in a 15% and 29% negative energy balance as well as a 4.1% and 4.6% loss of body mass in women and men, respectively. After the operation protein levels of ULK1 as well as the phosphorylation of ULK1Ser317 and ULK1Ser555 had increased by 11%, 39%, and 13%, respectively, and this was supported by a 17% increased phosphorylation of AMPKThr172 (P < 0.05). The LC3b-I/II ratio was threefold higher after compared to before the operation (P < 0.05), whereas protein levels of p62/SQSTM1 were unchanged. The ß1, ß2, and ß5 activity of the proteasome and protein levels of MAFbx did not change, whereas levels of MuRF-1 were slightly reduced (6%, P < 0.05). Protein levels and phosphorylation status of key components in the mTORC1 signaling pathway remained at basal levels after the operation. Muscle levels of glycogen decreased from 269 ± 12 to 181 ± 9 mmol·kg dry·muscle-1 after the exercise period (P < 0.05). In conclusion, the 8 days of field-based exercise resulted in induction of autophagy without any increase in proteasome activity or protein ubiquitination. Simultaneously, the regulation of protein synthesis through the mTORC1 signaling pathway was maintained.

Regular moist snuff dipping does not affect endurance exercise performance.

Physiological and medical effects of snuff have previously been obtained either in cross-sectional studies or after snuff administration to non-tobacco users. The effects of snuff cessation after several years of daily use are unknown. 24 participants with >2 years of daily snuff-use were tested before and after >6 weeks snuff cessation (SCG). A control group (CO) of 11 snuff users kept their normal habits. Resting heart rate (HR) and blood pressure (BP) were significantly lower in SCG after snuff cessation, and body mass was increased by 1.4 ± 1.7 kg. Total cholesterol increased from 4.12 ± 0.54 (95% CI 3.89-4.35) to 4.46 ± 0.70 (95% CI 4.16-4.75) mM L-1 in SCG, due to increased LDL, and this change was significantly different from CO. Resting values of HDL, C-reactive protein, and free fatty acids (FFA) remained unchanged in both groups. In SCG group, both HR and BP were reduced during a four-stage incremental cycling test (from 50 to 80% of VO2max) and a prolonged cycling test (60 min at 50% of VO2max). Oxygen uptake (VO2), respiratory exchange ratio, blood lactate (bLa) and blood glucose (bGlu) concentration, and rate of perceived exertion (RPE) were unchanged. In CO group, all measurements were unchanged. During the prolonged cycling test, FFA was reduced, but with no significant difference between groups. During the maximal treadmill running test peak values of VO2, pulmonary ventilation (VE), time to exhaustion and bLa were unchanged in both groups. In conclusion, endurance exercise performance (VO2max and maximal endurance time) does not seem to be affected by prolonged snuff use, while effects on cardiovascular risk factors are contradictory. HR and BP during rest and submaximal exercise are reduced after cessation of regular use of snuff. Evidently, the long-time adrenergic stress on circulation is reversible.

Accuracy in Wrist-Worn, Sensor-Based Measurements of Heart Rate and Energy Expenditure in a Diverse Cohort.

The ability to measure physical activity through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown. The aim of this work is to assess the accuracy of seven commercially available wrist-worn devices in estimating heart rate (HR) and energy expenditure (EE) and to propose a wearable sensor evaluation framework. We evaluated the Apple Watch, Basis Peak, Fitbit Surge, Microsoft Band, Mio Alpha 2, PulseOn, and Samsung Gear S2. Participants wore devices while being simultaneously assessed with continuous telemetry and indirect calorimetry while sitting, walking, running, and cycling. Sixty volunteers (29 male, 31 female, age 38 ± 11 years) of diverse age, height, weight, skin tone, and fitness level were selected. Error in HR and EE was computed for each subject/device/activity combination. Devices reported the lowest error for cycling and the highest for walking. Device error was higher for males, greater body mass index, darker skin tone, and walking. Six of the devices achieved a median error for HR below 5% during cycling. No device achieved an error in EE below 20 percent. The Apple Watch achieved the lowest overall error in both HR and EE, while the Samsung Gear S2 reported the highest. In conclusion, most wrist-worn devices adequately measure HR in laboratory-based activities, but poorly estimate EE, suggesting caution in the use of EE measurements as part of health improvement programs. We propose reference standards for the validation of consumer health devices (http://precision.stanford.edu/).

Sports genetics moving forward: lessons learned from medical research.

Sports genetics can take advantage of lessons learned from human disease genetics. By righting past mistakes and increasing scientific rigor, we can magnify the breadth and depth of knowledge in the field. We present an outline of challenges facing sports genetics in the light of experiences from medical research. Sports performance is complex, resulting from a combination of a wide variety of different traits and attributes. Improving sports genetics will foremost require analyses based on detailed phenotyping. To find widely valid, reproducible common variants associated with athletic phenotypes, study sample sizes must be dramatically increased. One paradox is that in order to confirm relevance, replications in specific populations must be undertaken. Family studies of athletes may facilitate the discovery of rare variants with large effects on athletic phenotypes. The complexity of the human genome, combined with the complexity of athletic phenotypes, will require additional metadata and biological validation to identify a comprehensive set of genes involved. Analysis of personal genetic and multiomic profiles contribute to our conceptualization of precision medicine; the same will be the case in precision sports science. In the refinement of sports genetics it is essential to evaluate similarities and differences between sexes and among ethnicities. Sports genetics to date have been hampered by small sample sizes and biased methodology, which can lead to erroneous associations and overestimation of effect sizes. Consequently, currently available genetic tests based on these inherently limited data cannot predict athletic performance with any accuracy.

Personalized preventive medicine: genetics and the response to regular exercise in preventive interventions.

Regular exercise and a physically active lifestyle have favorable effects on health. Several issues related to this theme are addressed in this report. A comment on the requirements of personalized exercise medicine and in-depth biological profiling along with the opportunities that they offer is presented. This is followed by a brief overview of the evidence for the contributions of genetic differences to the ability to benefit from regular exercise. Subsequently, studies showing that mutations in TP53 influence exercise capacity in mice and humans are succinctly described. The evidence for effects of exercise on endothelial function in health and disease also is covered. Finally, changes in cardiac and skeletal muscle in response to exercise and their implications for patients with cardiac disease are summarized. Innovative research strategies are needed to define the molecular mechanisms involved in adaptation to exercise and to translate them into useful clinical and public health applications.

Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts.

BACKGROUND & AIMS: There is a demand for more sensitive, specific and predictive biomarkers for drug-induced liver injury (DILI) than the gold standard used today, alanine aminotransferase (ALT). The aim of this study was to qualify novel DILI biomarkers (keratin-18 markers M65/M30, microRNA-122, glutamate dehydrogenase and alpha-foetoprotein) in human DILI. METHODS: Levels of the novel biomarkers were measured by enzyme-linked immunosorbent assay or real-time quantitative reverse-transcription PCR (qRT-PCR) in two human DILI cohorts: a human volunteer study with acetaminophen and a human immunodeficiency virus (HIV)/tuberculosis (TB) study. RESULTS: In the acetaminophen study, serum M65 and microRNA-122 levels were significantly increased at an earlier time point than ALT. Furthermore, the maximal elevation of M65 and microRNA-122 exceeded the increase in ALT. In the HIV/TB study, all the analysed novel biomarkers increased after 1 week of treatment. In contrast to ALT, the novel biomarkers remained stable in a human cohort with exercise-induced muscular injury. CONCLUSIONS: M65 and microRNA-122 are potential biomarkers of DILI superior to ALT with respect to sensitivity and specificity.

Extensive inflammatory cell infiltration in human skeletal muscle in response to an ultraendurance exercise bout in experienced athletes.

The impact of a 24-h ultraendurance exercise bout on systemic and local muscle inflammatory reactions was investigated in nine experienced athletes. Blood and muscle biopsies were collected before (Pre), immediately after the exercise bout (Post), and after 28 h of recovery (Post28). Circulating blood levels of leukocytes, creatine kinase (CK), C-reactive protein (CRP), and selected inflammatory cytokines were assessed together with the evaluation of the occurrence of inflammatory cells (CD3(+), CD8(+), CD68(+)) and the expression of major histocompatibility complex class I (MHC class I) in skeletal muscle. An extensive inflammatory cell infiltration occurred in all athletes, and the number of CD3(+), CD8(+), and CD68(+) cells were two- to threefold higher at Post28 compared with Pre (P < 0.05). The inflammatory cell infiltration was associated with a significant increase in the expression of MHC class I in muscle fibers. There was a significant increase in blood leukocyte count, IL-6, IL-8, CRP, and CK at Post. At Post28, total leukocytes, IL-6, and CK had declined, whereas IL-8 and CRP continued to increase. Increases in IL-1ß and TNF-α were not significant. There were no significant associations between the magnitude of the systemic and local muscle inflammatory reactions. Signs of muscle degenerative and regenerative events were observed in all athletes with various degrees of severity and were not affected by the 24-h ultraendurance exercise bout. In conclusion, a low-intensity but very prolonged single-endurance exercise bout can generate a strong inflammatory cell infiltration in skeletal muscle of well-trained experienced ultraendurance athletes, and the amplitude of the local reaction is not proportional to the systemic inflammatory response.

Late cardiovascular drift observable during ultraendurance exercise.

INTRODUCTION: The present study investigates the adaptation of the central circulation to ultraendurance exercise, including the relative contributions of changes in stroke volume (SV) and arteriovenous oxygen difference to the increased oxygen pulse (VO2/HR). METHODS: We evaluated subjects undergoing 12 h of mixed exercise at controlled intensity (n=8) and a 53-h adventure race (n=20). HR, oxygen uptake (VO2), and cardiac output determined using noninvasive gas rebreathing were measured during cycling at a fixed work rate after 0, 4, 8, and 12 h and 0, 20, and 53 h of continuous exercise in the 12- and 53-h protocols, respectively. RESULTS AND CONCLUSIONS: The central circulation changed in several steps in response to ultraendurance exercise. Compared with initial levels, VO2 was increased at every time point measured. The increase was attributed to peripheral adaptations, confirmed by a close correlation between change in VO2 and change in arteriovenous oxygen difference. The first step of the circulatory response was typical of normal (early) cardiovascular drift, with increased HR and concomitantly decreased SV and VO2/HR, occurring during the first 4-6 h. The second step, which continued until approximately 12 h, included reversed HR drift, with normalization of SV and VO2/HR. When exercise continued until 50 h, late cardiovascular drift was noted, characterized by increased VO2/HR (indicating more efficient energy distribution), decreased peripheral resistance, increased SV, and decreased work of the heart. Because cardiac output was maintained at all time points, we interpret the changes as physiologically appropriate adaptations to ultraendurance exercise.

Rhabdomyolysis/myoglobinemia and NSAID during 48 h ultra-endurance exercise (adventure racing).

Our purpose is to determine whether rhabdomyolysis with myoglobinemia exists during a 48+ h adventure race and if there is a correlation with NSAID use, race time and perceived pain or exertion. Blood samples for analyses of myoglobin (Mb) were collected, and perception of exertion and pain was registered on the Borg-RPE and CR scales, from 20 subjects (3 female, 17 male) Pre-, Mid- and Post-race. Subjects were asked about NSAID use at each sampling and within 12 h pre-race. The result observed was a significant rise in Mb throughout the race, with the NSAID group (n = 6) having significantly lower Mb-Post than the no-NSAID group (n = 14). High Mb-Pre and Post correlated to shorter race time and high Mb-Pre to lower Pain-post. Race time also correlated to NSAID use, with the NSAID group having significantly longer race time than the no-NSAID group. Rhabdomyolysis with myoglobinemia, which might be reduced with NSAID use, exists during a 48+ h adventure race. Indications that high Mb-levels correlate with shorter race time and less pain, and the reasons for the NSAID groups longer race time, warrants further investigation.

Energy turnover during 24 hours and 6 days of adventure racing.

Energy turnover was assessed in two conditions of mixed ultra-endurance exercise. In Study 1, energy expenditure and intake were measured in nine males in a laboratory over 24 h. In Study 2, energy expenditure was assessed in six males during an 800-km Adventure race (mean race time 152.5 h). Individual correlations between heart rate and oxygen uptake (VO(2)) were established during pre-tests when kayaking, cycling, and running. During exercise, energy expenditure was estimated from continuous heart rate recordings. Heart rate and VO(2) were measured regularly during fixed cycling work rates to correct energy expenditure for drift in oxygen pulse. Mean energy expenditure was 18,050 +/- 2,390 kcal (750 +/- 100 kcal h(-1)) and 80,000 +/- 18,000 kcal (500 +/- 100 kcal h(-1)) in Study 1 and Study 2 respectively, which is higher than previously reported. Energy intake in Study 1 was 8,450 +/- 1,160 kcal, resulting in an energy deficit of 9,590 +/- 770 kcal. Body mass decreased in Study 1 (-2.3 +/- 0.8 kg) but was unchanged in Study 2. Fat mass decreased in Study 2 (-2.3 +/- 1.5 kg). In Study 1, muscle glycogen content decreased by only 60%. Adventure racing requires a high energy expenditure, with large inter-individual variation. A large energy deficit is caused by inadequate energy intake, possibly due to suppressed appetite and gastrointestinal problems. The oxygen pulse, comparing start to 12 h of exercise and beyond, increased by 10% and 5% in Study 1 and Study 2 respectively. Hence, estimations of energy expenditure from heart rate recordings should be corrected according to this drift.

Ultraendurance exercise increases the production of reactive oxygen species in isolated mitochondria from human skeletal muscle.

Exercise-induced oxidative stress is important for the muscular adaptation to training but may also cause muscle damage. We hypothesized that prolonged exercise would increase mitochondrial production of reactive oxygen species (ROS) measured in vitro and that this correlates with oxidative damage. Eight male athletes (24-32 yr) performed ultraendurance exercise (kayaking/running/cycling) with an average work intensity of 55% V(O(2peak)) for 24 h. Muscle biopsies were taken from vastus lateralis before exercise, immediately after exercise, and after 28 h of recovery. The production of H(2)O(2) was measured fluorometrically in isolated mitochondria with the Amplex red and peroxidase system. Succinate-supported mitochondrial H(2)O(2) production was significantly increased after exercise (73% higher, P = 0.025) but restored to the initial level at recovery. Plasma level of free fatty acids (FFA) increased fourfold and exceeded 1.2 mmol/l during the last 6 h of exercise. Plasma FFA at the end of exercise was significantly correlated to mitochondrial ROS production (r = 0.74, P < 0.05). Mitochondrial content of 4-hydroxy-nonenal-adducts (a marker of oxidative damage) was increased only after recovery and was not correlated with mitochondrial ROS production. Total thiol group level and glutathione peroxidase activity were elevated after recovery. In conclusion, ultraendurance exercise increases ROS production in isolated mitochondria, but this is reversed after 28 h recovery. Mitochondrial ROS production was not correlated with oxidative damage of mitochondrial proteins, which was increased at recovery but not immediately after exercise.

Reduced efficiency, but increased fat oxidation, in mitochondria from human skeletal muscle after 24-h ultraendurance exercise.

The hypothesis that ultraendurance exercise influences muscle mitochondrial function has been investigated. Athletes in ultraendurance performance performed running, kayaking, and cycling at 60% of their peak O(2) consumption for 24 h. Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration), with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate (Pyr). Electron transport chain activity was measured with NADH in permeabilized mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% (P < 0.05) when related to mitochondrial protein and to electron transport chain activity, respectively. State 3 respiration with Pyr was not changed (P > 0.05). State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec (P < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% (P < 0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec. Muscle uncoupling protein 3, measured with Western blotting, was not changed Post-Ex but tended to decrease at Rec (P = 0.07 vs. Pre-Ex). In conclusion, extreme endurance exercise decreases mitochondrial efficiency. This will increase oxygen demand and may partly explain the observed elevation in whole body oxygen consumption during standardized exercise (+13%). The increased mitochondrial capacity for PC oxidation indicates plasticity in substrate oxidation at the mitochondrial level, which may be of advantage during prolonged exercise.