Aerobic exercise training resets the human skeletal muscle methylome 10 years after breast cancer treatment and survival.

Cancer survivors suffer impairments in skeletal muscle in terms of reduced mass and function. Interestingly, human skeletal muscle possesses an epigenetic memory of earlier stimuli, such as exercise. Long-term retention of epigenetic changes in skeletal muscle following cancer survival and/or exercise training has not yet been studied. We, therefore, investigated genome-wide DNA methylation (methylome) in skeletal muscle following a 5-month, 3/week aerobic-training intervention in breast cancer survivors 10-14 years after diagnosis and treatment. These results were compared to breast cancer survivors who remained untrained and to age-matched controls with no history of cancer, who undertook the same training intervention. Skeletal muscle biopsies were obtained from 23 females before(pre) and after(post) the 5-month training period. InfiniumEPIC 850K DNA methylation arrays and RT-PCR for gene expression were performed. The breast cancer survivors displayed a significant retention of increased DNA methylation (i.e., hypermethylation) at a larger number of differentially methylated positions (DMPs) compared with healthy age-matched controls pre training. Training in cancer survivors led to an exaggerated number of DMPs with a hypermethylated signature occurring at non-regulatory regions compared with training in healthy age-matched controls. However, the opposite occurred in important gene regulatory regions, where training in cancer survivors elicited a considerable reduction in methylation (i.e., hypomethylation) in 99% of the DMPs located in CpG islands within promoter regions. Importantly, training was able to reverse the hypermethylation identified in cancer survivors back toward a hypomethylated signature that was observed pre training in healthy age-matched controls at 300 (out of 881) of these island/promoter-associated CpGs. Pathway enrichment analysis identified training in cancer survivors evoked a predominantly hypomethylated signature in pathways associated with cell cycle, DNA replication/repair, transcription, translation, mTOR signaling, and the proteosome. Differentially methylated region (DMR) analysis also identified genes: BAG1, BTG2, CHP1, KIFC1, MKL2, MTR, PEX11B, POLD2, S100A6, SNORD104, and SPG7 as hypermethylated in breast cancer survivors, with training reversing these CpG island/promoter-associated DMRs toward a hypomethylated signature. Training also elicited a largely different epigenetic response in healthy individuals than that observed in cancer survivors, with very few overlapping changes. Only one gene, SIRT2, was identified as having altered methylation in cancer survivors at baseline and after training in both the cancer survivors and healthy controls. Overall, human skeletal muscle may retain a hypermethylated signature as long as 10-14 years after breast cancer treatment/survival. Five months of aerobic training reset the skeletal muscle methylome toward signatures identified in healthy age-matched individuals in gene regulatory regions.

Determinants and reference values for blood volume and total hemoglobin mass in women and men.

Blood volume (BV) is an important clinical parameter and is usually reported per kg of body mass (BM). When fat mass is elevated, this underestimates BV/BM. One aim was to study if differences in BV/BM related to sex, age, and fitness would decrease if normalized to lean body mass (LBM). The analysis included 263 women and 319 men (age: 10-93 years, body mass index: 14-41 kg/m2 ) and 107 athletes who underwent assessment of BV and hemoglobin mass (Hbmass ), body composition, and cardiorespiratory fitness. BV/BM was 25% lower (70.3 ± 11.3 and 80.3 ± 10.8 mL/kgBM ) in women than men, respectively, whereas BV/LBM was 6% higher in women (110.9 ± 12.5 and 105.3 ± 11.2 mL/kgLBM ). Hbmass /BM was 34% lower (8.9 ± 1.4 and 11.5 ± 11.2 g/kgBM ) in women than in men, respectively, but only 6% lower (14.0 ± 1.5 and 14.9 ± 1.5 g/kgLBM )/LBM. Age did not affect BV. Athlete's BV/BM was 17.2% higher than non-athletes, but decreased to only 2.5% when normalized to LBM. Of the variables analyzed, LBM was the strongest predictor for BV (R2 = .72, p < .001) and Hbmass (R2 = .81, p < .001). These data may only be valid for BV/Hbmass when assessed by CO re-breathing. Hbmass /LBM could be considered a valuable clinical matrix in medical care aiming to normalize blood homeostasis.

Effects of adding high-intensity training during an 8-week period on maximal oxygen uptake in 12-year-old youth athletes.

PURPOSE: Maximal oxygen uptake (V̇O2max ) increases during adolescence parallel to the increase in fat-free mass (FFM). How much endurance training adds to this effect is still controversial. Our aim was to investigate if inclusion of high-intensity training (HIT) during an 8-week training period was superior to low-intensity strength and coordination training in 12-year-old youth athletes concerning the effect on V̇O2max . METHODS: Thirty-five cross-country skiers were randomized into a HIT group (ET) and a strength and coordination group (SC), while 29 less active peers served as controls for growth and maturation (C). Anthropometrics and V̇O2max were assessed before and after the training period, and level of physical activity and training were monitored with accelerometers, training logs and a questionnaire. RESULTS: The number of weekly training sessions were higher for ET (4.6 ± 1.2) and SC (4.1 ± 1.0) compared with C (1.8 ± 2.0) (p < 0.01), with only ET conducting HIT sessions (1.9 ± 0.2 per week). C spent more time sedentary and less time in moderate and vigorous activity compared with ET (p < 0.05). All groups had a similar %-change pre-post in absolute V̇O2max (mL min-1 ) of 6% ± 6% for ET (p < 0.01), 5% ± 7 for SC (p = 0.14), and 5% ± 13% for C (p = 0.03), with no significant differences between groups. V̇O2max relative to FFM did not change significantly for any groups. CONCLUSION: The change in V̇O2max paralleled the change in FFM for all groups, questioning the effect of HIT on V̇O2max over an 8-week period in youth athletes.

Changes in cycling economy and fractional utilization of V̇O2peak during a 40-min maximal effort exercise test with acute hypobaric hypoxia corresponding to 2800 m of altitude.

INTRODUCTION: Peak oxygen uptake (V̇O2peak ) declines by ~7% per 1000 m of increasing altitude, whereas exercise performance seems reduced to a lesser extent. For example, 800-10 000 m track and field performances are decreased by 0.4%-2.4% above 1000 m as compared to below and some studies show similar drops in cycling performance. A greater decline in V̇O2peak than in endurance performance with altitude suggests a higher fractional utilization of V̇O2peak (%V̇O2peak ). Therefore, we hypothesized that the %V̇O2peak is higher with acute hypoxic exposure than near sea level. METHODS: Sixteen lowlanders (8 women, age: 31 ± 7 years [mean ± SD], body mass: 68 ± 8 kg, V̇O2peak : 60 ± 8 mL min-1 kg-1 ) underwent cycling testing in a hypobaric hypoxic chamber on 6 test days, three conducted at 300 m and three at 2800 m of acute altitude. At both altitudes, V̇O2peak was determined, and during a 40-min all out maximal effort time trial (TT), mean power output (MPO) and mean V̇O2 (%V̇O2peak ) were assessed. RESULTS: V̇O2peak decreased by 11.2 ± 3.0% (p < 0.001), while MPO during the TT declined by 10.7 ± 3.1% (p < 0.001) at 2800 m as compared to 300 m. During the TT, %V̇O2peak was higher at altitude, corresponding to 75.9 ± 4.5% at 300 m and 78.8 ± 4.2% at 2800 m (p = 0.011), and cycling economy (mL O2 kJ-1 ) was poorer (+3.4 ± 2.7%, p < 0.001). CONCLUSION: The %V̇O2peak was higher during a cycling TT at 2800 m of altitude than near sea level, while cycling economy was poorer. This resulted in a similar reduction in performance and V̇O2peak . Future studies should address the physiological mechanisms underlying the elevated %V̇O2peak .

Endurance Training Improves Leg Proton Release and Decreases Potassium Release During High-Intensity Exercise in Normoxia and Hypobaric Hypoxia.

AIM: To assess the impact of endurance training on skeletal muscle release of H+ and K+. METHODS: Nine participants performed one-legged knee extension endurance training at moderate and high intensities (70%-85% of Wpeak), three to four sessions·week-1 for 6 weeks. Post-training, the trained and untrained (control) leg performed two-legged knee extension at low, moderate, and high intensities (40%, 62%, and 83% of Wpeak) in normoxia and hypoxia (~4000 m). The legs were exercised simultaneously to ensure identical arterial inflow concentrations of ions and metabolites, and identical power output was controlled by visual feedback. Leg blood flow was measured (ultrasound Doppler), and acid-base variables, lactate- and K+ concentrations were assessed in arterial and femoral venous blood to study K+ and H+ release. Ion transporter abundances were assessed in muscle biopsies. RESULTS: Lactate-dependent H+ release was similar in hypoxia to normoxia (p = 0.168) and was lower in the trained than the control leg at low-moderate intensities (p = 0.060-0.006) but similar during high-intensity exercise. Lactate-independent and total H+ releases were higher in hypoxia (p < 0.05) and increased more with power output in the trained leg (leg-by-power output interactions: p = 0.02). K+ release was similar at low intensity but lower in the trained leg during high-intensity exercise in normoxia (p = 0.024) and hypoxia (p = 0.007). The trained leg had higher abundances of Na+/H+ exchanger 1 (p = 0.047) and Na+/K+ pump subunit α (p = 0.036). CONCLUSION: Moderate- to high-intensity endurance training increases lactate-independent H+ release and reduces K+ release during high-intensity exercise, coinciding with increased Na+/H+ exchanger 1 and Na+/K+ pump subunit α muscle abundances.

Individual variations in pre-altitude hemoglobin mass influence hemoglobin mass responses to repeated altitude sojourns.

INTRODUCTION: Previous studies have shown variable within-subject hemoglobin mass (Hbmass ) responses to altitude training. We investigated whether Hbmass responses depend on individual variations in pre-altitude Hbmass during repeated altitude sojourns. METHODS: Nine elite endurance athletes carried out 3-5 altitude sojourns over 17 ± 10 months (mean ± 95% confidence interval), at an altitude of 1976 ± 62 m, for 21 ± 1 days, and a total hypoxic dose of 989 ± 46 km·h, with Hbmass assessed before and after each sojourn (carbon monoxide rebreathing). The individual mean baseline was calculated as the mean of all pre-altitude Hbmass values for an athlete, and it was investigated whether the percent deviation from the individual mean baseline affected the altitude-induced Hbmass response. RESULTS: On average, Hbmass increased by 3.4 ± 1.1% (p < 0.001) from pre- to post-altitude. The intra-individual changes in Hbmass were highly inconsistent (coefficient of variation, CV: 88%), and we found no relationship between Hbmass changes in successive altitude sojourns (r = 0.01; p = 0.735). However, the percent increase in Hbmass was highly correlated with the pre-altitude Hbmass , expressed as the percent deviation from the individual mean baseline (y = -0.7x + 3.4; r = 0.75; p < 0.001). Linear mixed-model analysis confirmed a -0.6 ± 0.2% smaller increase in Hbmass for each 1% higher pre-altitude Hbmass than the individual mean baseline (p < 0.001) after adjusting for the covariates hypoxic dose (p = 0.032) and the relative Hbmass (g·kg-1 body weight; p = 0.031). CONCLUSION: Individual variations in pre-altitude Hbmass significantly influence the athletes' Hbmass responses to repeated altitude sojourns, with a potentiated response after traveling to altitude with a low pre-altitude Hbmass .

Kinematic differences between uphill roller skiing and on-snow skiing using the V2 skating technique.

PURPOSE: Roller skiing is the primary sport-specific training and testing mode during pre-competition periods for cross-country skiers, biathletes, and Nordic combined athletes. The present study aimed to compare the kinematics between uphill roller skiing and on-snow skiing using the V2 sub-technique. METHODS: In a cross-over design, nine well-trained male skiers performed short trials (< 40 s) at constant inclination (8.0°), speed (3.0 m‧s-1), and controlled rolling/gliding friction on asphalt (in the fall), on the treadmill (in the fall and winter), and during on-snow skiing (in the winter). Kinematic data were collected using a validated inertial measurement unit system. RESULTS: Repeated-measures ANOVAs revealed no differences between treadmill and asphalt roller skiing. Further, including on-snow skiing showed moderate to good reliability (ICC ≥ 0.63, p ≤ 0.001) for ground-contact temporal variables. However, on-snow skiing moderately increased hip range of motion around the longitudinal axis (22.2 ± 7.7° vs. 14.1 ± 4.7°), lateral hip displacement (44.1 ± 7.1 cm vs. 37.2 ± 6.6 cm) and pole push times (422 ± 41 ms vs. 386 ± 31 ms), and on-snow skiing was characterized by altered hip rotational patterns compared to roller skiing. CONCLUSION: V2 roller ski skating simulates on-snow ski skating to a large extent, but the mechanical properties of the skis and/or surface hardness systematically alter skiers' hip movements and pole push times. This implies a potential for equipment optimization to increase training specificity during pre-competition periods and highlights a need for future studies to examine the kinematic effects of snow hardness on all sub-techniques.

Functional reserve and sex differences during exercise to exhaustion revealed by post-exercise ischaemia and repeated supramaximal exercise.

KEY POINTS: Females have lower fatigability than males during single limb isometric and dynamic contractions, but whether sex-differences exist during high-intensity whole-body exercise remains unknown. This study shows that males and females respond similarly to repeated supramaximal whole-body exercise, and that at task failure a large functional reserve remains in both sexes. Using post-exercise ischaemia with repeated exercise, we have shown that this functional reserve depends on the glycolytic component of substrate-level phosphorylation and is almost identical in both sexes. Metaboreflex activation during post-exercise ischaemia and the O2 debt per kg of active lean mass are also similar in males and females after supramaximal exercise. Females have a greater capacity to extract oxygen during repeated supramaximal exercise and reach lower PETCO2 , experiencing a larger drop in brain oxygenation than males, without apparent negative repercussion on performance. Females had no faster recovery of performance after accounting for sex differences in lean mass. ABSTRACT: The purpose of this study was to ascertain what mechanisms explain sex differences at task failure and to determine whether males and females have a functional reserve at exhaustion. Exercise performance, cardiorespiratory variables, oxygen deficit, and brain and muscle oxygenation were determined in 18 males and 18 females (21-36 years old) in two sessions consisting of three bouts of constant-power exercise at 120% of V̇O2max until exhaustion interspaced by 20 s recovery periods. In one of the two sessions, the circulation of both legs was occluded instantaneously (300 mmHg) during the recovery periods. Females had a higher muscle O2 extraction during fatiguing supramaximal exercise than males. Metaboreflex activation, and lean mass-adjusted O2 deficit and debt were similar in males and females. Compared to males, females reached lower PETCO2 and brain oxygenation during supramaximal exercise, without apparent negative consequences on performance. After the occlusions, males and females were able to restart exercising at 120% of V̇O2max , revealing a similar functional reserve, which depends on glycolytic component of substrate-level phosphorylation and its rate of utilization. After ischaemia, muscle O2 extraction was increased, and muscle V̇O2 was similarly reduced in males and females. The physiological response to repeated supramaximal exercise to exhaustion is remarkably similar in males and females when differences in lean mass are considered. Both sexes fatigue with a large functional reserve, which depends on the glycolytic energy supply, yet females have higher oxygen extraction capacity, but reduced PETCO2 and brain oxygenation.

Longitudinal changes in maximal oxygen uptake in adolescent girls and boys with different training backgrounds.

The purpose of this study was to investigate the effects of high-volume endurance training on the development of maximal oxygen uptake (VO2max ) in physically active boys and girls between the ages of 12 and 15 years, using a longitudinal design. The children participated in organized training in sports clubs for an average of 7-10 hours per week, with one group undertaking a high volume of endurance training (~7 hours per week; End boys, n = 23 and End girls, n = 17) and the other group having a primary focus on technical and tactical skill development, undertaking low volumes of endurance training (~1.6 hours per week; non-End boys, n = 29 and non-End girls, n = 9). VO2max and anthropometrics were assessed at age 12, 13, and 15. At age 12, VO2max was 58.9 (5.6), 65.5 (7.2), 56.5 (6.5), and 58.8 (7.9) mL·kg-1 ·min-1 in End girls, End boys, non-End girls, and non-End boys, respectively. Over the three years, there was no difference between the training groups in the development of VO2max independent of scaling. In boys, VO2max relative to body mass (BM) did not change from age 12 to 15, while VO2max tended to decrease relative to fat-free mass (FFM). In girls, VO2max relative to BM decreased slightly from age 12 to 15, with no changes over the years relative to FFM. The present longitudinal study suggests that in growing active children during puberty, high volumes of systematic endurance training do not have an additional effect on VO2max compared with similar volume of training mainly aiming at developing motor skills.

Impact of baseline serum ferritin and supplemental iron on altitude-induced hemoglobin mass response in elite athletes.

The present study explored the impact of pre-altitude serum (s)-ferritin and iron supplementation on changes in hemoglobin mass (ΔHbmass) following altitude training. Measures of Hbmass and s-ferritin from 107 altitude sojourns (9-28 days at 1800-2500 m) with world-class endurance athletes (males n = 41, females n = 25) were analyzed together with iron supplementation and self-reported illness. Altitude sojourns with a hypoxic dose [median (range)] of 1169 (912) km·h increased Hbmass (mean ± SD) 36 ± 38 g (3.7 ± 3.7%, p < 0.001) and decreased s-ferritin -11 (190) µg·L-1 (p = 0.001). Iron supplements [27 (191) mg·day-1 ] were used at 45 sojourns (42%), while only 11 sojourns (10%) were commenced with s-ferritin <35 µg/L. Hbmass increased by 4.6 ± 3.7%, 3.4 ± 3.3%, 4.2 ± 4.3%, and 2.9 ± 3.4% with pre-altitude s-ferritin ≤35 µg·L-1 , 36-50 µg·L-1 , 51-100 µg·L-1 , and >100 µg·L-1 , respectively, with no group difference (p = 0.400). Hbmass increased by 4.1 ± 3.9%, 3.0 ± 3.0% and 3.7 ± 4.7% without, ≤50 mg·day-1 or >50 mg·day-1 supplemental iron, respectively (p = 0.399). Linear mixed model analysis revealed no interaction between pre-altitude s-ferritin and iron supplementation on ΔHbmass (p = 0.906). However, each 100 km·h increase in hypoxic dose augmented ΔHbmass by an additional 0.4% (95% CI: 0.1-0.7%; p = 0.012), while each 1 g·kg-1 higher pre-altitude Hbmass reduced ΔHbmass by -1% (-1.6 to -0.5; p < 0.001), and illness lowered ΔHbmass by -5.7% (-8.3 to -3.1%; p < 0.001). In conclusion, pre-altitude s-ferritin or iron supplementation were not related to the altitude-induced increase in Hbmass (3.7%) in world-class endurance athletes with clinically normal iron stores.

Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.

Achieving energy balance with a high-fat meal does not enhance skeletal muscle adaptation and impairs glycaemic response in a sleep-low training model.

NEW FINDINGS: What is the central question of this study? Does achieving energy balance mainly with ingested fat in a 'sleep-low' model of training with low muscle glycogen affect the early training adaptive response during recovery? What is the main finding and its importance? Replenishing the energy expended during exercise mainly from ingested fat to achieve energy balance in a 'sleep-low' model does not enhance the response of skeletal muscle markers of early adaptation to training and impairs glycaemic control the morning after compared to training with low energy availability. These findings are important for optimizing post-training dietary recommendations in relation to energy balance and macronutrient intake. ABSTRACT: Training with low carbohydrate availability (LCHO) has been shown to acutely enhance endurance training skeletal muscle response, but the concomitant energy deficit (ED) in LCHO interventions has represented a confounding factor in past research. This study aimed at determining if achieving energy balance with high fat (EB-HF) acutely enhances the adaptive response in LCHO compared to ED with low fat (ED-LF). In a crossover design, nine well-trained males completed a 'sleep-low' protocol: on day 1 they cycled to deplete muscle glycogen while reaching a set energy expenditure (30 kcal (kg of fat free mass (FFM))-1 ). Post-exercise, low carbohydrate, protein-matched meals completely (EB-HF, 30 kcal (kg FFM)-1 ) or partially (ED-LF, 9 kcal (kg FFM)-1 ) replaced the energy expended, with the majority of energy derived from fat in EB-HF. In the morning of day 2, participants exercised fasted, and skeletal muscle and blood samples were collected and a carbohydrate-protein drink was ingested at 0.5 h recovery. Muscle glycogen showed no treatment effect (P < 0.001) and decreased from 350 ± 98 to 192 ± 94 mmol (kg dry mass)-1 between rest and 0.5 h recovery. Phosphorylation status of the mechanistic target of rapamycin and AMP-activated protein kinase pathway proteins showed only time effects. mRNA expression of p53 increased after exercise (P = 0.005) and was higher in ED-LF at 3.5 h compared to EB-HF (P = 0.027). Plasma glucose and insulin area under the curve (P < 0.04) and peak values (P ≤ 0.05) were higher in EB-HF after the recovery drink. Achieving energy balance with a high-fat meal in a 'train-low' ('sleep-low') model did not enhance markers of skeletal muscle adaptation and impaired glycaemia in response to a recovery drink following training in the morning.

Increased oxygen extraction and mitochondrial protein expression after small muscle mass endurance training.

When exercising with a small muscle mass, the mass-specific O2 delivery exceeds the muscle oxidative capacity resulting in a lower O2 extraction compared with whole-body exercise. We elevated the muscle oxidative capacity and tested its impact on O2 extraction during small muscle mass exercise. Nine individuals conducted six weeks of one-legged knee extension (1L-KE) endurance training. After training, the trained leg (TL) displayed 45% higher citrate synthase and COX-IV protein content in vastus lateralis and 15%-22% higher pulmonary oxygen uptake ( V ˙ O 2 peak ) and peak power output ( W ˙ peak ) during 1L-KE than the control leg (CON; all P < .05). Leg O2 extraction (catheters) and blood flow (ultrasound Doppler) were measured while both legs exercised simultaneously during 2L-KE at the same submaximal power outputs (real-time feedback-controlled). TL displayed higher O2 extraction than CON (main effect: 1.7 ± 1.6% points; P = .010; 40%-83% of W ˙ peak ) with the largest between-leg difference at 83% of W ˙ peak (O2 extraction: 3.2 ± 2.2% points; arteriovenous O2 difference: 7.1 ± 4.8 mL· L-1 ; P < .001). At 83% of W ˙ peak , muscle O2 conductance (DM O2 ; Fick law of diffusion) and the equilibration index Y were higher in TL (P < .01), indicating reduced diffusion limitations. The between-leg difference in O2 extraction correlated with the between-leg ratio of citrate synthase and COX-IV (r = .72-.73; P = .03), but not with the difference in the capillary-to-fiber ratio (P = .965). In conclusion, endurance training improves O2 extraction during small muscle mass exercise by elevating the muscle oxidative capacity and the recruitment of DM O2, especially evident during high-intensity exercise exploiting a larger fraction of the muscle oxidative capacity.

Blood volume expansion does not explain the increase in peak oxygen uptake induced by 10 weeks of endurance training.

PURPOSE: The endurance training (ET)-induced increases in peak oxygen uptake ([Formula: see text]O2peak) and cardiac output ([Formula: see text]peak) during upright cycling are reversed to pre-ET levels after removing the training-induced increase in blood volume (BV). We hypothesised that ET-induced improvements in [Formula: see text]O2peak and [Formula: see text]peak are preserved following phlebotomy of the BV gained with ET during supine but not during upright cycling. Arteriovenous O2 difference (a-[Formula: see text]O2diff; [Formula: see text]O2/[Formula: see text]), cardiac dimensions and muscle morphology were studied to assess their role for the [Formula: see text]O2peak improvement. METHODS: Twelve untrained subjects ([Formula: see text]O2peak: 44 ± 6 ml kg-1 min-1) completed 10 weeks of supervised ET (3 sessions/week). Echocardiography, muscle biopsies, haemoglobin mass (Hbmass) and BV were assessed pre- and post-ET. [Formula: see text]O2peak and [Formula: see text]peak during upright and supine cycling were measured pre-ET, post-ET and immediately after Hbmass was reversed to the individual pre-ET level by phlebotomy. RESULTS: ET increased the Hbmass (3.3 ± 2.9%; P = 0.005), BV (3.7 ± 5.6%; P = 0.044) and [Formula: see text]O2peak during upright and supine cycling (11 ± 6% and 10 ± 8%, respectively; P ≤ 0.003). After phlebotomy, improvements in [Formula: see text]O2peak compared with pre-ET were preserved in both postures (11 ± 4% and 11 ± 9%; P ≤ 0.005), as was [Formula: see text]peak (9 ± 14% and 9 ± 10%; P ≤ 0.081). The increased [Formula: see text]peak and a-[Formula: see text]O2diff accounted for 70% and 30% of the [Formula: see text]O2peak improvements, respectively. Markers of mitochondrial density (CS and COX-IV; P ≤ 0.007) and left ventricular mass (P = 0.027) increased. CONCLUSION: The ET-induced increase in [Formula: see text]O2peak was preserved despite removing the increases in Hbmass and BV by phlebotomy, independent of posture. [Formula: see text]O2peak increased primarily through elevated [Formula: see text]peak but also through a widened a-[Formula: see text]O2diff, potentially mediated by cardiac remodelling and mitochondrial biogenesis.

Cardiac output with modified cardio-impedance against inert gas rebreathing during sub-maximal and maximal cycling exercise in healthy and fit subjects.

PURPOSE: We measured cardiac output ([Formula: see text]) during sub-maximal and supra-maximal exercise with inert gas rebreathing ([Formula: see text]) and modified cardio-impedance ([Formula: see text]) and we evaluated the repeatability of the two methods. METHODS: [Formula: see text]O2 and [Formula: see text] were measured twice in parallel with the two methods at sub-maximal (50-250 W) and supra-maximal exercise in 7 young subjects (25 ± 1 years; 74.4 ± 5.2 kg; 1.84 ± 0.07 m). RESULTS: [Formula: see text] and [Formula: see text] increased by 3.4 L·min-1 and by 5.1 L·min-1 per 1 L·min-1 of increase in [Formula: see text], respectively. Mean [Formula: see text] (23.3 ± 2.5 L·min-1) was 9% lower than [Formula: see text] (25.8 ± 2.2 L·min-1) during supra-maximal exercise. Bland-Altman analysis showed that: (i) bias ([Formula: see text]-[Formula: see text]) was significantly different from zero (- 0.65 ± 2.61 L·min-1) and; (ii) the ratios [Formula: see text] ÷ [Formula: see text] were linearly related with [Formula: see text], indicating that [Formula: see text] tended to overestimate [Formula: see text] in comparison with [Formula: see text] for values ranging from 10.0 to 15.0 L·min-1 and to underestimate it for larger values. The coefficient of variation was similar for sub-maximal values (8.6% vs. 7.7%; 95% CL: ×/÷1.31), but lower for [Formula: see text] (7.6%; 95% CL: ×/÷ 2.05) than for [Formula: see text] (27.7%; 95% CL: ×/÷2.54) at supra-maximal intensity. CONCLUSIONS: [Formula: see text] seems to represent a valuable alternative to invasive methods for assessing [Formula: see text] during sub-maximal exercise. The [Formula: see text] underestimation with respect to [Formula: see text] during supra-maximal exercise suggests that [Formula: see text] might be less optimal for supra-maximal intensities.

Technique analysis in elite athletes using principal component analysis.

The aim of this study was to advance current movement analysis methodology to enable a technique analysis in sports facilitating (1) concurrent comparison of the techniques between several athletes; (2) identification of potentially beneficial technique modifications and (3) a visual representation of the findings for feedback to the athletes. Six elite cross-country skiers, three world cup winners and three national elite, roller ski skated using the V2 technique on a treadmill while their movement patterns were recorded using 41 reflective markers. A principal component analysis performed on the marker positions resulted in multi-segmental "principal" movement components (PMs). A novel normalisation facilitated comparability of the PMs between athletes. Additionally, centre of mass (COM) trajectories were modelled. We found correlations between the athletes' performance levels (judged from race points) and specific features in the PMs and in the COM trajectories. Plausible links between COM trajectories and PMs were observed, suggesting that better performing skiers exhibited a different, possibly more efficient use of their body mass for propulsion. The analysis presented in the current study revealed specific technique features that appeared to relate to the skiers' performance levels. How changing these features would affect an individual athlete's technique was visualised with animated stick figures.

Kinematical analysis of the V2 ski skating technique: A longitudinal study.

To characterise timing of movements and evaluate performance effects of technique alterations in V2 ski skating, 13 elite male cross-country skiers (age, 23 ± 2 years; stature, 182 ± 6 cm; body mass, 76 ± 8 kg; V2 V̇O2max, 79.3 ± 4.4 mL · kg-1 · min-1) were tested four times during the preparation and competition phase on a roller ski treadmill. Each test consisted of submaximal intensities of exercise for determination of oxygen cost followed by one 1000-m performance test. Hip movement (from accelerometer data) and joint angles (2D video) were determined for high-intensity exercise (6° and 3.5 m · s-1; ~ 97-100% of V̇O2peak). Each ski thrust consisted of three phases: gliding phase (18-50% of cycle time), poling phase (50-70% of cycle time), and kick phase (70-78% of cycle time). Flexion/extension of the hip initiated all phases, followed by the respective joints in legs and arms. Mixed-model analysis, adjusting for systematic time-point effects, identified that both reduced vertical hip acceleration and increased cycle time gave a small likely reduction in oxygen cost and 1000-m time. In conclusion, well-developed hip movement is a key characteristic of the V2 technique for elite-standard skiers' long-term performance development.

Hemoglobin Mass and Aerobic Performance at Moderate Altitude in Elite Athletes.

Fore more than a decade, the live high-train low (LHTL) approach, developed by Levine and Stray-Gundersen, has been widely used by elite endurance athletes. Originally, it was pointed out, that by living at moderate altitude, athletes should benefit from an increased red cell volume (RCV) and hemoglobin mass (Hbmass), while the training at low altitudes should prevent the disadvantage of reduced training intensity at moderate altitude. VO2max is reduced linearly by about 6-8 % per 1000 m increasing altitude in elite athletes from sea level to 3000 m, with corresponding higher relative training intensities for the same absolute work load. With 2 weeks of acclimatization, this initial deficit can be reduced by about one half. It has been debated during the last years whether sea-level training or exposure to moderate altitude increases RCV and Hbmass in elite endurance athletes. Studies which directly measured Hbmass with the optimized CO-rebreathing technique demonstrated that Hbmass in endurance athletes is not influenced by sea-level training. We documented that Hbmass is not increased after 3 years of training in national team cross-country skiers. When athletes are exposed to moderate altitude, new studies support the argument that it is possible to increase Hbmass temporarily by 5-6 %, provided that athletes spend >400 h at altitudes above 2300-2500 m. However, this effect size is smaller than the reported 10-14 % higher Hbmass values of endurance athletes living permanently at 2600 m. It remains to be investigated whether endurance athletes reach these values with a series of LHTL camps.

Validity of Ski Skating Center-of-Mass Displacement Measured by a Single Inertial Measurement Unit.

In regard to simplifying motion analysis and estimating center of mass (COM) in ski skating, this study addressed 3 main questions concerning the use of inertial measurement units (IMU): (1) How accurately can a single IMU estimate displacement of os sacrum (S1) on a person during ski skating? (2) Does incorporating gyroscope and accelerometer data increase accuracy and precision? (3) Moreover, how accurately does S1 determine COM displacement? Six world-class skiers roller-ski skated on a treadmill using 2 different subtechniques. An IMU including accelerometers alone (IMU-A) or in combination with gyroscopes (IMU-G) were mounted on the S1. A reflective marker at S1, and COM calculated from 3D full-body optical analysis, were used to provide reference values. IMU-A provided an accurate and precise estimate of vertical S1 displacement, but IMU-G was required to attain accuracy and precision of < 8 mm (root-mean-squared error and range of displacement deviation) in all directions and with both subtechniques. Further, arm and torso movements affected COM, but not the S1. Hence, S1 displacement was valid for estimating sideways COM displacement, but the systematic amplitude and timing difference between S1 and COM displacement in the anteroposterior and vertical directions inhibits exact calculation of energy fluctuations.

Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial.

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 (HRmax)] and steady state continuous sessions (30-60 min; 70-90% of HRmax). Maximal oxygen uptake (VO2 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 their VO2 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 in VO2 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 supplementation combined with endurance exercise.