Key pointsr Recent studies have indicated that antioxidant supplementation may blunt adaptations to exercise, such as mitochondrial biogenesis induced by endurance training. However, studies in humans are sparse and results are conflicting.r Isolated vitamin C and E supplements are widely used, and unravelling the interference of these vitamins in cellular and physiological adaptations to exercise is of interest to those who exercise for health purposes and to athletes.r Our results show that vitamin C and E supplements blunted the endurance training-induced increase of mitochondrial proteins (COX4), which is important for improving muscular endurance.r Training-induced increases inV O 2 max and running performance were not detectably affected by the supplementation.r The present study contributes to understanding of how antioxidants may interfere with adaptations to exercise in humans, and the results indicate that high dosages of vitamins C and E should be used with caution.Abstract In this double-blind, randomised, controlled trial, we investigated the effects of vitamin C and E supplementation on endurance training adaptations in humans. Fifty-four young men and women were randomly allocated to receive either 1000 mg of vitamin C and 235 mg of vitamin E or a placebo daily for 11 weeks. During supplementation, the participants completed an endurance training programme consisting of three to four sessions per week (primarily of running), divided into high-intensity interval sessions [4-6 × 4-6 min; >90% of maximal heart rate (HR max )] and steady state continuous sessions (30-60 min; 70-90% of HR max ). Maximal oxygen uptake (V O 2 max ), submaximal running and a 20 m shuttle run test were assessed and blood samples and muscle biopsies were collected, before and after the intervention. Participants in the vitamin C and E group increased theirV O 2 max (mean ± S.D.: 8 ± 5%) and performance in the 20 m shuttle test (10 ± 11%) to the same degree as those in the placebo group (mean ± S.D.: 8 ± 5% and 14 ± 17%, respectively). However, the mitochondrial marker cytochrome c oxidase subunit IV (COX4) and cytosolic peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC-1α) increased in the m. vastus lateralis in the placebo group by 59 ± 97% and 19 ± 51%, respectively, but not in the vitamin C and E group (COX4: −13 ± 54%; PGC-1α: −13 ± 29%; P ࣘ 0.03, between groups). Furthermore, mRNA levels of CDC42 and mitogen-activated protein kinase 1 (MAPK1) in the trained muscle were lower in the vitamin C and E group than in the placebo group (P ࣘ 0.05). Daily vitamin C and E supplementation attenuated increases in markers of mitochondrial biogenesis following endurance training. However, no clear interactions were detected for improvements inV O 2 max and running performance. Consequently, vitamin C and E supplementation hampered cellular adaptations in the exercised muscles, and although this did not translate to the performance tests applied in this study, we advocate caution when considering antioxidant supplemen...

It has been hypothesized that one reason for decreased .VO(2max) in hypoxia could be the lower maximal exercise intensity achieved in incremental, time or distance trial tests. We hypothesized that (1).VO(2max) would be decreased at altitude even when exercising at the same absolute maximal exercise intensity as at sea level and; (2) the decline in .VO(2max) in endurance-trained athletes (ETA) would be linear across the range from sea level through moderate altitudes. Eight ETA performed combined .VO(2max) and performance tests running to exhaustion at the same speed in a randomized double blind fashion at simulated altitudes of 300, 800, 1,300, 1,800, 2,300 and 2,800 m above sea level using a hypobaric chamber. Douglas bag system was used for respiratory measurements and pulse oximetry was used to estimate arterial O(2) saturation. .VO(2max) declined linearly from 66+/-1.6 ml kg(-1) min(-1) at 300 m to 55+/-1.6 ml kg(-1) min(-1) at 2,800 m corresponding to a 6.3% decrease per 1,000 m increasing altitude (range 4.6-7.5%). Time to exhaustion (performance) at a constant velocity associated with 107% of sea level .VO(2max) decreased with 14.5% (P<0.001) per 1,000 m altitude between 300 and 2,800 m. Both .VO(2max) and performance decreased from 300 to 800 m (P<0.01; P<0.05). Arterial haemoglobin oxygen saturation at test cessation (SpO(2min)) declined from 89.0+/-2.9% at 300 m to 76.5+/-4.0% at 2,800 m (P=0.001). This study report that in ETA during acute exposure to altitude both performance and .VO(2max) decline from 300 to 800 m above sea level and continued to decrease linearly to 2,800 m.

Heart transplant (HTx) recipients usually have reduced exercise capacity with reported VO 2peak levels of 50-70% predicted value. Our hypothesis was that highintensity interval training (HIIT) is an applicable and safe form of exercise in HTx recipients and that it would markedly improve VO 2peak.Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO 2peak increase. Forty-eight clinically stable HTx recipients >18 years old and 1-8 years after HTx underwent maximal exercise testing on a treadmill and were randomized to either exercise group (a 1-year HIIT-program) or control group (usual care). The mean ± SD age was 51 ± 16 years, 71% were male and time from HTx was 4.1 ± 2.2 years. The mean VO 2peak difference between groups at follow-up was 3.6 [2.0, 5.2] mL/kg/min (p < 0.001). The exercise group had 89.0 ± 17.5% of predicted VO 2peak versus 82.5 ± 20.0 in the control group (p < 0.001). There were no changes in cardiac function measured by echocardiography. We have demonstrated that a long-term, partly supervised and community-based HIIT-program is an applicable, effective and safe way to improve VO 2peak , muscular exercise capacity and general health in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future.Key words: Aerobic exercise, chronotropic response, heart transplantation, maximum oxygen uptake, muscle strength, VO 2peak Abbreviations: % HR max , percent of age-predicted maximum heart rate; AT, anaerobic threshold (ventilatory threshold); BIA, bioelectrical impedance analysis; CG, control group; CO, cardiac output; CRI, chronotropic response index; CRP, C-reactive protein; DXA, dual-emission X-ray absorptiometry; EG, exercise group; eGFR, estimated glomerular filtration rate; Hb, hemoglobin; HF, heart failure; HIIT, high-intensity interval training; HR, heart rate; HR max , maximum heart rate; HRQoL, health-related quality of life; HTx, heart transplant; J, Joule; LV, left ventricle; LVe', left ventricle early diastolic mitral annular velocity; LVEF, left ventricle ejection fraction; Nm, Newtonmeter; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; RER, respiratory exchange ratio; RPE, rated perceived exertion; VAS scale, visual analog scale; VE max , maximum ventilation; VO 2peak , peak oxygen uptake.

In this study the stress protein response to unaccustomed maximal eccentric exercise in humans was investigated. Eleven healthy males performed 300 maximal eccentric actions with the quadriceps muscle. Biopsies from vastus lateralis were collected at 30 min and 4, 8, 24, 96, and 168 h after exercise. Cellular regulation and localization of heat shock protein (HSP) 27, αB-crystallin, and HSP70 were analyzed by immunohistochemistry, ELISA technique, and Western blotting. Additionally, mRNA levels of HSP27, αB-crystallin, and HSP70 were quantified by Northern blotting. After exercise (30 min), 81 ± 8% of the myofibers showed strong HSP27 staining ( P < 0.01) that gradually decreased during the following week. αB-Crystallin mimicked the changes observed in HSP27. After exercise (30 min), the ELISA analysis showed a 49 ± 13% reduction of the HSP27 level in the cytosolic fraction ( P < 0.01), whereas Western blotting revealed a 15-fold increase of the HSP27 level in the myofibrillar fraction ( P < 0.01). The cytosolic HSP70 level increased to 203 ± 37% of the control level 24 h after exercise ( P < 0.05). After 4 days, myofibrillar-bound HSP70 had increased ∼10-fold ( P < 0.01) and was accompanied by strong staining on cross sections. mRNA levels of HSP27, αB-crystallin, and HSP70 were all elevated the first day after exercise ( P < 0.01); HSP70 mRNA showed the largest increase (20-fold at 8 h). HSP27 and αB-crystallin seemed to respond immediately to maximal eccentric exercise by binding to cytoskeletal/myofibrillar proteins, probably to function as stabilizers of disrupted myofibrillar structures. Later, mRNA and total HSP protein levels, especially HSP70, increased, indicating that HSPs play a role in skeletal muscle recovery and remodeling/adaptation processes to high-force exercise.

To investigate the effect of supplementing high-volume endurance training with heavy strength training on muscle adaptations and physical performance in elite cross country skiers. Eleven male (18-26 years) and eight female (18-27 years) were assigned to either a strength group (STR) (n=9) or a control group (CON) (n=10). STR performed strength training twice a week for 12 weeks in addition to their normal endurance training. STR improved 1 repetition maximum (RM) for seated pull-down and half squat (19 ± 2% and 12 ± 2%, respectively), while no change was observed in CON. Cross-sectional area (CSA) increased in m. triceps brachii for both STR and CON, while there was no change in the m. quadriceps CSA. VO(2max) during skate-rollerskiing increased in STR (7 ± 1%), while VO(2max) during running was unchanged. No change was observed in energy consumption during rollerskiing at submaximal intensities. Double-poling performance improved more for STR than for CON. Both groups showed a similar improvement in rollerski time-trial performance. In conclusion, 12 weeks of supplemental heavy strength training improved the strength in leg and upper body muscles, but had little effect on the muscle CSA in thigh muscles. The supplemental strength training improved both VO(2max) during skate-rollerskiing and double-poling performance.

Brown adipose tissue has gained interest as a potential target to treat obesity and metabolic diseases. Irisin is a newly identified hormone secreted from skeletal muscle enhancing browning of white fat cells, which improves systemic metabolism by increasing energy expenditure in mice. The discovery of irisin raised expectations of its therapeutic potential to treat metabolic diseases. However, the effect of irisin in humans is unclear. Analyses of genomic DNA, mRNA and expressed sequence tags revealed that FNDC5, the gene encoding the precursor of irisin, is present in rodents and most primates, but shows in humans a mutation in the conserved start codon ATG to ATA. HEK293 cells transfected with a human FNDC5 construct with ATA as start codon resulted in only 1% full-length protein compared to human FNDC5 with ATG. Additionally, in vitro contraction of primary human myotubes by electrical pulse stimulation induced a significant increase in PGC1α mRNA expression. However, FNDC5 mRNA level was not altered. FNDC5 mRNA expression in muscle biopsies from two different human exercise studies was not changed by endurance or strength training. Preadipocytes isolated from human subcutaneous adipose tissue exhibited differentiation to brite human adipocytes when incubated with bone morphogenetic protein (BMP) 7, but neither recombinant FNDC5 nor irisin were effective. In conclusion, our findings suggest that it is rather unlikely that the beneficial effect of irisin observed in mice can be translated to humans.

The aims of this study were to investigate the sarcomeric accumulation and expression of heat shock proteins (HSPs) after two bouts of maximal eccentric exercise. Twenty-four subjects performed two bouts of 70 maximal voluntary eccentric actions using the elbow flexors in one arm. The bouts were separated by 3 wk. The changes in concentric (60 degrees/s) and isometric (90 degrees) force-generating capacity were monitored for 9 days after each bout, and biopsies were taken 1 and 48 h and 4 and 7 days after bout 1 and 1 and 48 h after bout 2. The content of HSP27, alphaB-crystallin, HSP70, and desmin in the cytosolic and cytoskeleton/myofibrillar fractions of homogenized muscle samples was determined by immunoassays, and the cellular and subcellular localization of the HSPs in the myofibrillar structure was analyzed by conventional and confocal immunofluorescence microscopy and quantitative electron microscopy. The force-generating capacity was reduced by approximately 50% and did not recover completely during the 3 wk following bout 1. After bout 2, the subjects recovered within 4 days. The HSP levels increased in the cytosolic fraction after bout 1, especially HSP70 (approximately 300% 2-7 days after exercise). Increased levels of HSP27, alphaB-crystallin, and HSP70 were found in the cytoskeletal/myofibrillar fraction after both bouts, despite reduced damage after bout 2. At the ultrastructural level, HSP27 and alphaB-crystallin accumulated in Z-disks, in intermediate desmin-like structures (alphaB-crystallin), and in areas of myofibrillar disruption. In conclusion, HSP27 and alphaB-crystallin accumulated in myofibrillar structures, especially in the Z-disks and the intermediate structures (desmin). The function of the small HSPs is possibly to stabilize and protect the myofibrillar structures during and after unaccustomed eccentric exercise. The large amount of HSP27, alphaB-crystallin, and HSP70 in the cytoskeletal/myofibrillar fraction after a repeated bout of exercise suggests a protective role as part of the repeated-bout effect.

Exercise-induced muscle damage initiated a rapid local inflammatory response that gradually increased over the next days. Halted recovery of muscle function was associated with local accumulation of leukocytes, whereas muscle soreness could not be explained by the presence of leukocytes.