Low-Volume Speed Endurance Training with Reduced Volume Improves Short-Term Exercise Performance in Highly Trained Cyclists.

PURPOSE: We investigated the effects of low and high volume speed endurance training (SET), with a reduced training volume, on sprint ability, short- and long-term exercise capacity, muscle mitochondrial properties, ion transport proteins and maximal enzyme activity in highly trained athletes. METHODS: Highly-trained male cyclists (V̇O2max: 68.3 ± 5.0 mL × min-1 × kg-1, n = 24) completed six weeks of either low (SET-L; 6x30-s intervals, n = 8) or high (SET-H; 12 × 30-s intervals, n = 8) volume SET twice per week with a 30%-reduction in training volume. A control group (CON, n = 8) maintained their training. Exercise performance was evaluated by i) 6-s sprinting, ii) a 4-min time trial, iii) a 60-min preload at 60% V̇O2max followed by a 20-min time trial. A biopsy of m. vastus lateralis was collected before and after the training intervention. RESULTS: In SET-L, 4-min time trial performance was improved (P < 0.05) by 3.8%, with no change in SET-H and CON. Sprint ability, prolonged endurance exercise capacity, V̇O2max, muscle mitochondrial respiratory capacity, maximal citrate synthase activity, fiber-type specific mitochondrial proteins (complex I - V) and PFK content did not change in any of the groups. In SET-H, maximal activity of muscle PFK and abundance of Na+-K+ pump-subunit α1, α2, ß1, and phospholemman (FXYD1) were 20%, 50%, 19%, 24%, and 42 % higher (P < 0.05), respectively after compared to before the intervention, with no changes in SET-L or CON. CONCLUSIONS: Low SET volume combined with a reduced aerobic low and moderate intensity training volume does improve short duration intense exercise performance and maintain sprinting ability, V̇O2max, endurance exercise performance and muscle oxidative capacity, whereas, high volume of SET appears necessary to upregulate muscle ion transporter content and maximal PFK activity in highly trained cyclists.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

BACKGROUND: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects. METHODS: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 50.2 ± 3.4 mL kg-1 min-1) to 5 days of creatine monohydrate (0.3 g kg-1 per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg-1) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg-1), sodium bicarbonate (0.3 g kg-1), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial. RESULTS: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects. CONCLUSION: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance.

Beyond bronchodilation: Illuminating the performance benefits of inhaled beta2 -agonists in sports.

Given the prevalent use of inhaled beta2 -agonists in sports, there is an ongoing debate as to whether they enhance athletic performance. Over the last decades, inhaled beta2 -agonists have been claimed not to enhance performance with little consideration of dose or exercise modality. In contrast, orally administered beta2 -agonists are perceived as being performance enhancing, predominantly on muscle strength and sprint ability, but can also induce muscle hypertrophy and slow-to-fast fiber phenotypic switching. But because inhaled beta2 -agonists are more efficient to achieve high systemic concentrations than oral delivery relative to dose, it follows that the inhaled route has the potential to enhance performance too. The question is at which inhaled doses such effects occur. While supratherapeutic doses of inhaled beta2 -agonists enhance muscle strength and short intense exercise performance, effects at low therapeutic doses are less apparent. However, even high therapeutic inhaled doses of commonly used beta2 -agonists have been shown to induce muscle hypertrophy and to enhance sprint performance. This is concerning from an anti-doping perspective. In this paper, we raise awareness of the circumstances under which inhaled beta2 -agonists can constitute a performance-enhancing benefit.

Importance of training volume during intensified training in elite cyclists: Maintained vs. reduced volume at moderate intensity.

INTRODUCTION: Male elite cyclists (average VO2 -max: 71 mL/min/kg, n = 18) completed 7 weeks of high-intensity interval training (HIT) (3×/week; 4-min and 30-s intervals) during the competitive part of the season. The influence of a maintained or lowered total training volume combined with HIT was evaluated in a two-group design. Weekly moderate-intensity training was lowered by ~33% (~5 h) (LOW, n = 8) or maintained at normal volume (NOR, n = 10). Endurance performance and fatigue resistance were evaluated via 400 kcal time-trials (~20 min) commenced either with or without prior completion of a 120-min preload (including repeated 20-s sprints to simulate physiologic demands during road races). RESULTS: Time-trial performance without preload was improved after the intervention (p = 0.006) with a 3% increase in LOW (p = 0.04) and a 2% increase in NOR (p = 0.07). Preloaded time-trial was not significantly improved (p = 0.19). In the preload, average power during repeated sprinting increased by 6% in LOW (p < 0.01) and fatigue resistance in sprinting (start vs end of preload) was improved (p < 0.05) in both groups. Blood lactate during the preload was lowered (p < 0.001) solely in NOR. Measures of oxidative enzyme activity remained unchanged, whereas the glycolytic enzyme PFK increased by 22% for LOW (p = 0.02). CONCLUSION: The present study demonstrates that elite cyclists can benefit from intensified training during the competitive season both with maintained and lowered training volume at moderate intensity. In addition to benchmarking the effects of such training in ecological elite settings, the results also indicate how some performance and physiological parameters may interact with training volume.

Asthma and exercise-induced bronchoconstriction in athletes: Diagnosis, treatment, and anti-doping challenges.

Athletes often experience lower airway dysfunction, such as asthma and exercise-induced bronchoconstriction (EIB), which affects more than half the athletes in some sports, not least in endurance sports. Symptoms include coughing, wheezing, and breathlessness, alongside airway narrowing, hyperresponsiveness, and inflammation. Early diagnosis and management are essential. Not only because untreated or poorly managed asthma and EIB potentially affects competition performance and training, but also because untreated airway inflammation can result in airway epithelial damage, remodeling, and fibrosis. Asthma and EIB do not hinder performance, as advancements in treatment strategies have made it possible for affected athletes to compete at the highest level. However, practitioners and athletes must ensure that the treatment complies with general guidelines and anti-doping regulations to prevent the risk of a doping sanction because of inadvertently exceeding specified dosing limits. In this review, we describe considerations and challenges in diagnosing and managing athletes with asthma and EIB. We also discuss challenges facing athletes with asthma and EIB, while also being subject to anti-doping regulations.

Inhaled beta2 -agonist, formoterol, enhances intense exercise performance, and sprint ability in elite cyclists.

PURPOSE: Many athletes use long-acting beta2 -agonist formoterol in treatment of asthma. However, studies in non-athlete cohorts demonstrate that inhaled formoterol can enhance sprint performance calling into question whether its use in competitive sports should be restricted. We investigated whether formoterol at upper recommended inhaled doses (54 µg) would enhance sprint ability and intense exercise performance in elite cyclists. METHODS: Twenty-one male cyclists (V̇O2max : 70.4 ± 4.3 mL × min-1 × kg-1 , mean ± SD) completed two 6-s all-out sprints followed by 4-min all-out cycling after inhaling either 54 µg formoterol or placebo. We also assessed cyclists' leg muscle mass by dual-energy X-ray absorptiometry and muscle fiber type distribution of vastus lateralis biopsies. RESULTS: Peak and mean power output during the 6-s sprint was 32 W (95% CI, 19-44 W, p < 0.001) and 36 W (95% CI, 24-48 W, p < 0.001) higher with formoterol than placebo, corresponding to an enhancing effect of around 3%. Power output during 4-min all-out cycling was 9 W (95% CI, 2-16 W, p = 0.01) greater with formoterol than placebo, corresponding to an enhancing effect of 2.3%. Performance changes in response to formoterol were unrelated to cyclists' VO2max and leg lean mass, whereas muscle fiber Type I distribution correlated with change in sprinting peak power in response to formoterol (r2 = 0.314, p = 0.012). CONCLUSION: Our findings demonstrate that an inhaled one-off dose of 54 µg formoterol has a performance-enhancing potential on sprint ability and short intense performance in elite male cyclists, which is irrespective of training status but partly related to muscle fiber type distribution for sprint ability.

Inhaled salbutamol induces leanness in well-trained healthy females but not males during a period of endurance training: a randomised controlled trial.

Introduction: Many athletes use short-acting inhaled ß2-agonists multiple times weekly during training sessions to prevent exercise-induced bronchoconstriction, but it is unclear if treatment impairs training outcomes. Herein, we investigated performance adaptations in well-trained females and males training with prior inhalation of salbutamol. Methods: 19 females and 21 males with maximal oxygen uptake (V'O2max) of 50.5±3.3 and 57.9±4.9 mL·min-1·kg-1, respectively, participated in this double-blinded, placebo-controlled, parallel-group study. We randomised participants to placebo or salbutamol inhalation (800-1600 µg·training day-1) for 6 weeks of combined endurance (1× per week) and high-intensity interval training (2× per week). We assessed participants' body composition, V'O2max and muscle contractile function, and collected vastus lateralis muscle biopsies. Results: Salbutamol induced a sex-specific loss of whole-body fat mass (sex×treatment: p=0.048) where only salbutamol-treated females had a fat mass reduction compared to placebo (-0.8 kg at 6 weeks; 95% CI: -0.5 to -1.6; p=0.039). Furthermore, salbutamol-treated females exhibited a repartitioning effect, lowering fat mass while gaining lean mass (p=0.011), which was not apparent for males (p=0.303). Salbutamol negatively impacted V'O2max in both sexes (treatment main effect: p=0.014) due to a blunted increase in V'O2max during the initial 4 weeks of the intervention. Quadriceps contractile strength was impaired in salbutamol-treated females (-39 N·m; 95% CI: -61 to -17; p=0.002) compared to placebo at 6 weeks. Muscle electron transport chain complex I-V abundance increased with salbutamol (treatment main effect: p=0.035), while content of SERCAI, ß2-adrenoceptor and desmin remained unchanged. Conclusion: Inhaled salbutamol appears to be an effective repartitioning agent in females but may impair aerobic and strength-related training outcomes.

The effect of aerobic exercise training on asthma control in postmenopausal women (ATOM): a randomized controlled pilot study.

Objective: To evaluate if high-intensity interval training three times weekly for 12 weeks improves asthma control in overweight, postmenopausal women with uncontrolled, late-onset asthma. Methods: The reported study is a randomized clinical pilot study (www.clinicaltrials.gov; NCT03747211) that compared 12 weeks of high-intensity interval training (spinning) with usual care. The five-question Asthma Control Questionnaire (ACQ-5) was used as primary outcome. Secondary measures included systemic inflammation and inflammation of the airways, body composition, and cardiac function during exercise. Results: We included 12 women with asthma (mean age 65 years (SD 6); mean body mass index 30 kg/m2 (SD 2)) from whom eight were randomized to exercise and four to control. Baseline ACQ-5 was 1.95 (SD 0.53) in the control group and 2.03 (0.54) in the exercise group. Patients had a mean blood eosinophil level of 0.16 × 109cells/L (SD 0.07) and a mean fraction of exhaled nitric oxide of 23 ppb (SD 25). Mixed models showed that participants in the exercise group reduced their ACQ-5 by 0.55 points (95%CI -1.10 to -0.00; P = 0.08) compared with the control group. The exercise group significantly reduced their mean body fat percentage (-2.7%; 95%CI -4.5 to -0.8; P = 0.02), fat mass (-2.8 kg; 95%CI -5.1 to -0.4; P = 0.044) and android fat mass (-0.33 kg; 95%CI -0.60- -0.06; P = 0.038). In analyses of cardiac measures, we saw no significant effects on right ventricular function (fractional area change), diastolic function or left ventricular function. Conclusions: Although changes in ACQ-5 were slightly insignificant, these preliminary findings indicate that aerobic exercise training can be used as a means to improve asthma control in overweight, postmenopausal women with asthma.

Effect of High-Intensity Interval Training on Inhaled Corticosteroid Dose in Asthma Patients: A Randomized Controlled Trial.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment. However, ICS has side effects, and dose reduction is recommended when possible. Physical exercise improves asthma control, but it is unknown whether it reduces the reliance on ICS. OBJECTIVE: To assess whether supervised high-intensity interval training reduces the need for ICS in untrained asthma patients. METHODS: An assessor-blinded single-center randomized controlled trial, Copenhagen, Denmark. One hundred fifty untrained ICS-treated adults with symptomatic asthma were randomly assigned (2:1) to 6 months of supervised exercise 3 times weekly or a lifestyle as usual control group. Every second month, a clinical algorithm based on symptom control was applied in both groups to adjust ICS dose. Primary outcome was the proportion who had their ICS dose reduced by 25% or more after 6 months. Secondary outcomes included actual ICS dosage in micrograms per day. RESULTS: Between October 2017 and December 2019, 102 patients were allocated to exercise intervention (86% completed) and 48 to the control (85% completed). At the 6-month visit, 63% versus 50% met the primary outcome in the exercise and control groups, respectively (adjusted risk difference 9.6% [95% CI -3.8 to 18.8]; P = .15). Daily ICS dose was reduced in favor of the exercise group, with a mean difference of -234 µg (95% CI -391 to -77; P = .0037), corresponding to a 24% reduction from baseline. This effect was sustained at 12 months. The intervention was safe and well tolerated. CONCLUSIONS: Six months of regular exercise results in reduction in daily ICS dose without compromising asthma control.

Inhaled formoterol impairs aerobic exercise capacity in endurance-trained individuals: a randomised controlled trial.

Background: The 2022 Global Initiative for Asthma guidelines emphasise the inhaled long-acting ß2-agonist formoterol as part of the first treatment step, and therefore formoterol use among athletes will probably increase. However, prolonged supratherapeutic use of inhaled ß2-agonists impairs training outcomes in moderately trained men. We investigated whether inhaled formoterol, at therapeutic doses, imposes detrimental effects in endurance-trained individuals of both sexes. Methods: 51 endurance-trained participants (31 male, 20 female; mean±sd maximal oxygen consumption (V̇ O2 max) 62±6 mL·min-1·kg bw-1 and 52±5 mL·min-1·kg bw-1, respectively) inhaled formoterol (24 µg; n=26) or placebo (n=25) twice daily for 6 weeks. At baseline and follow-up, we assessed V̇ O2 max and incremental exercise performance during a bike-ergometer ramp-test; body composition by dual-energy X-ray absorptiometry; muscle oxidative capacity by high-resolution mitochondrial respirometry, enzymatic activity assays and immunoblotting; intravascular volumes by carbon monoxide rebreathing; and cardiac left ventricle mass and function by echocardiography. Results: Compared to placebo, formoterol increased lean body mass by 0.7 kg (95% CI 0.2-1.2 kg; treatment×trial p=0.022), but decreased V̇ O2 max by 5% (treatment×trial p=0.013) and incremental exercise performance by 3% (treatment×trial p<0.001). In addition, formoterol lowered muscle citrate synthase activity by 15% (treatment×trial p=0.063), mitochondrial complex II and III content (treatment×trial p=0.028 and p=0.007, respectively), and maximal mitochondrial respiration through complexes I and I+II by 14% and 16% (treatment×trial p=0.044 and p=0.017, respectively). No apparent changes were observed in cardiac parameters and intravascular blood volumes. All effects were sex-independent. Conclusion: Our findings demonstrate that inhaled therapeutic doses of formoterol impair aerobic exercise capacity in endurance-trained individuals, which is in part related to impaired muscle mitochondrial oxidative capacity. Thus, if low-dose formoterol fails to control respiratory symptoms in asthmatic athletes, physicians may consider alternative treatment options.

Airway hyperresponsiveness reflects corticosteroid-sensitive mast cell involvement across asthma phenotypes.

BACKGROUND: Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the airways, suggesting inhaled corticosteroids to be effective in reducing the response to mannitol, despite low levels of type 2 inflammation. OBJECTIVE: We sought to investigate the relationship between airway hyperresponsiveness and infiltrating mast cells, and the response to inhaled corticosteroid treatment. METHODS: In 50 corticosteroid-free patients with airway hyperresponsiveness to mannitol, mucosal cryobiopsies were obtained before and after 6 weeks of daily treatment with 1600 µg of budesonide. Patients were stratified according to baseline fractional exhaled nitric oxide (Feno) with a cutoff of 25 parts per billion. RESULTS: Airway hyperresponsiveness was comparable at baseline and improved equally with treatment in both patients with Feno-high and Feno-low asthma: doubling dose, 3.98 (95% CI, 2.49-6.38; P < .001) and 3.85 (95% CI, 2.51-5.91; P < .001), respectively. However, phenotypes and distribution of mast cells differed between the 2 groups. In patients with Feno-high asthma, airway hyperresponsiveness correlated with the density of chymase-high mast cells infiltrating the epithelial layer (ρ, -0.42; P = .04), and in those with Feno-low asthma, it correlated with the density in the airway smooth muscle (ρ, -0.51; P = .02). The improvement in airway hyperresponsiveness after inhaled corticosteroid treatment correlated with a reduction in mast cells, as well as in airway thymic stromal lymphopoietin and IL-33. CONCLUSIONS: Airway hyperresponsiveness to mannitol is related to mast cell infiltration across asthma phenotypes, correlating with epithelial mast cells in patients with Feno-high asthma and with airway smooth muscle mast cells in patients with Feno-low asthma. Treatment with inhaled corticosteroids was effective in reducing airway hyperresponsiveness in both groups.

High-Intensity Training Represses FXYD5 and Glycosylates Na,K-ATPase in Type II Muscle Fibres, Which Are Linked with Improved Muscle K+ Handling and Performance.

Na+/K+ ATPase (NKA) comprises several subunits to provide isozyme heterogeneity in a tissue-specific manner. An abundance of NKA α, ß, and FXYD1 subunits is well-described in human skeletal muscle, but not much is known about FXYD5 (dysadherin), a regulator of NKA and ß1 subunit glycosylation, especially with regard to fibre-type specificity and influence of sex and exercise training. Here, we investigated muscle fibre-type specific adaptations in FXYD5 and glycosylated NKAß1 to high-intensity interval training (HIIT), as well as sex differences in FXYD5 abundance. In nine young males (23.8 ± 2.5 years of age) (mean ± SD), 3 weekly sessions of HIIT for 6 weeks enhanced muscle endurance (220 ± 102 vs. 119 ± 99 s, p < 0.01) and lowered leg K+ release during intense knee-extensor exercise (0.5 ± 0.8 vs. 1.0 ± 0.8 mmol·min-1, p < 0.01) while also increasing cumulated leg K+ reuptake 0-3 min into recovery (2.1 ± 1.5 vs. 0.3 ± 0.9 mmol, p < 0.01). In type IIa muscle fibres, HIIT lowered FXYD5 abundance (p < 0.01) and increased the relative distribution of glycosylated NKAß1 (p < 0.05). FXYD5 abundance in type IIa muscle fibres correlated inversely with the maximal oxygen consumption (r = -0.53, p < 0.05). NKAα2 and ß1 subunit abundances did not change with HIIT. In muscle fibres from 30 trained males and females, we observed no sex (p = 0.87) or fibre type differences (p = 0.44) in FXYD5 abundance. Thus, HIIT downregulates FXYD5 and increases the distribution of glycosylated NKAß1 in type IIa muscle fibres, which is likely independent of a change in the number of NKA complexes. These adaptations may contribute to counter exercise-related K+ shifts and enhance muscle performance during intense exercise.

Effect of sample fractionation and normalization when immunoblotting for human muscle Na+/K+-ATPase subunits and glycogen synthase.

Immunoblotting is widely used in muscle physiology to determine protein regulation and abundance. However, research groups use different protocols, which may result in differential outcomes. Herein, we investigated the effect of various homogenization procedures on determination of protein abundance in human m. vastus lateralis biopsies. Furthermore, we investigated differences in abundance between young healthy males (n = 12) and type-2 diabetics (n = 4), and the effect of data normalization. Fractionated lysates had the lowest variation in total protein determination as compared to non-fractionated homogenates. Abundance of NKAα2, NKAß1, FXYD1, and glycogen synthase was higher (P < 0.05) in young healthy than in type-2 diabetics determined in both fractionated and non-fractionated samples for which normalization to the stain-free signal and/or standard curve did not affect outcomes. Precision and reliability of protein abundance determination between sample types showed a moderate to good reliability for these proteins, whereas the commonly used house-keeping protein, actin, showed poor reliability. In conclusion, fractionated and non-fractionated immunoblotting samples yield similar data for several sarcolemmal and cytosolic proteins, except for actin, which, therefore appears inappropriate for data normalization in immunoblotting of human skeletal muscle. Thus, fractionation does not seem to be a major source of bias when immunoblotting for NKA subunits and GS.

Urine concentrations of vilanterol and its metabolites, GSK932009 and GW630200, after inhalation of therapeutic and supratherapeutic doses.

The 2023 Prohibited List issued by the World Anti-Doping Agency (WADA) permits athletes to inhale the beta2 -agonist vilanterol at a standard dose of 25 µg daily. However, given limited data on urine pharmacokinetics, vilanterol has no urinary threshold or decision limit to discriminate therapeutic from supratherapeutic use. We investigated urine concentrations of vilanterol and its main metabolites GSK932009 and GW630200 over 0-72 h following inhalation of therapeutic (25 µg) or supratherapeutic (100 µg) doses and repeat-dose administration for 7 days of 25 or 100 µg·day-1 in 25 trained men and women. Vilanterol administration was followed by 1 h of exercise. GW630200 urine concentrations were low and insufficient for threshold purposes, and while GSK932009 had higher urine concentrations, it could not discriminate between therapeutic and supratherapeutic use. Mean (range) maximum urine concentrations of parent vilanterol were 1.2 (0.2-4.1) and 6.2 (1.4-14.3) ng·ml-1 for single-dose 25 and 100 µg vilanterol, respectively, and 2.0 (0.3-4.8) and 22.4 (6.4-42.1) ng·ml-1 for repeat-dose 25 and 100 µg·day-1 vilanterol. In 333 samples collected 6 h post-administration and considering WADA TD2022DL, a 3.1 ng·ml-1 vilanterol cut-off showed 30% sensitivity in detecting supratherapeutic use at 100 µg versus therapeutic use at 25 µg. Considering inter- and intra-individual variability and guard bands in doping analysis, a 6 ng·ml-1 decision limit, which could be shifted upwards in samples with specific gravity >1.018, appears sufficiently high to minimize risk of samples exceeding the decision limit after therapeutic use of vilanterol, while demonstrating the ability to detect supratherapeutic use at 100 µg.

Assay validation for vilanterol and its metabolites in human urine with application for doping control analysis.

A bioanalytical method for detecting the ultra-long-acting beta2 -agonist (U-LABA) inhaled vilanterol and its metabolites, GSK932009 and GW630200, in urine was developed to potentially monitor permitted therapeutic versus prohibited supratherapeutic use in sport. The World Anti-Doping Agency (WADA) has established urinary concentration thresholds for the beta2 -agonists salbutamol and formoterol. Therapeutic use of vilanterol (25 µg once daily) was recently permitted by WADA; however, there is no established decision limit for adverse analytical findings due to insufficient urine concentration data. In this study, we validated an assay to detect vilanterol in urine collected from four healthy male and female athletes 0-72 h who received inhaled corticosteroid fluticasone furoate/U-LABA vilanterol (800/100 µg) combination, four times the normal therapeutic dose. After administration, subjects performed 1 h of bike ergometer exercise. The experiment was conducted again after repeat dosing for 1 week. Our method utilised liquid chromatography with tandem mass spectrometry and was validated over urine concentrations of 5-5000 (vilanterol) and 50-50,000 pg/ml (GSK932009 and GW630200). Plasma samples were analysed for vilanterol, using a previously validated assay. The peak concentration values for urine vilanterol, GSK932009 and GW630200 were 9.5, 10.4 and 0.17 ng/ml, for single dosing, and 18.6, 19.5 and 0.20 ng/ml, for repeat dosing. Urine samples from four volunteers using the final validated method are reported, demonstrating this assay has sensitivity to detect vilanterol or GSK932009 in urine for ≥72 h post single or repeat dosing with 800/100 µg fluticasone furoate/vilanterol, whereas GW630200 was quantifiable ≤4 h post dose.

Microdoses of Recombinant Human Erythropoietin Enhance Time Trial Performance in Trained Males and Females.

PURPOSE: We investigated the effects of recombinant human erythropoietin (rHuEPO) administration on exercise endurance, maximal aerobic performance, and total hemoglobin mass (tHb). We hypothesized that frequent, small intravenous injections of epoetin ß would increase time trial performance, peak oxygen uptake (V̇O 2peak ), and tHb in both males and females. METHODS: We included 48 healthy, recreational to trained males ( n = 24, mean ± SD V̇O 2peak = 55 ± 5 mL O 2 ·kg -1 ⋅min -1 ) and females ( n = 24; V̇O 2peak of 46 ± 4 mL O 2 ·kg -1 ⋅min -1 ) in a counterbalanced, double-blind, randomized, placebo-controlled study design stratified by sex. Time trial performance, V̇O 2peak , and tHb were determined before and after intravenous injections of either rHuEPO (9 IU·kg bw -1 epoetin ß) or saline (0.9% NaCl) three times weekly for 4 wk. RESULTS: A time-treatment effect ( P < 0.05) existed for time trial performance. Within the rHuEPO group, mean power output increased by 4.1% ± 4.2% ( P < 0.001). Likewise, a time-treatment effect ( P < 0.001) existed for V̇O 2peak , where the rHuEPO group improved V̇O 2peak and peak aerobic power by 4.2% ± 6.1% ( P < 0.001) and 2.9% ± 4.0% ( P < 0.01), respectively. A time-treatment effect ( P < 0.001) existed for tHb, where the rHuEPO group increased tHb by 6.7% ± 3.4% ( P < 0.001). A main effect of "sex" alone was also evident ( P < 0.001), but no sex-specific interactions were found. No changes were observed in the placebo group for mean power output, V̇O 2peak , peak aerobic power, or tHb. CONCLUSIONS: Microdoses with intravenous rHuEPO provide a sufficient erythropoietic stimuli to augment tHb and enhance aerobic-dominated performance in both trained males and females.

Performance Adaptations to Intensified Training in Top-Level Football.

Because physical demands are surging in football (soccer, USA), clubs are more and more seeking players who have a high capacity to perform repeated intense exercise. High-intensity interval training (HIIT), comprising exercise performed at intensities near or exceeding the capacity of aerobic energy systems, effectively enhances the physical conditioning of players. But given that HIIT imposes high loads, it increases the risk of overload-associated match performance decline and injury. This makes some coaches inclined to conduct HIIT in the weeks leading up to the season and during the season. Therefore, the challenge is how to optimize and dose HIIT during these phases, as they can be decisive. Studies have highlighted the utility of conducting periods of intensified training to overcome the risk of overload while at the same time enhancing performance. During intensified training periods of typically a few weeks, intensity is increased by enlarging the amount of HIIT, for example, aerobic high-intensity training or speed endurance training, while volume at low-to-moderate intensity is significantly reduced. The outcome depends on training composition and prescription-most notably, intensity and duration of bouts and recovery. When work intervals are prescribed for a few minutes at intensities > 90% heart rate max (i.e., aerobic high-intensity training), then beneficial adaptations pertaining to aerobic power and capacity are apparent. But when work intervals are conducted at much higher intensities, as all-out efforts or sprinting of typically 10- to 40-s duration with longer recovery periods (i.e., speed endurance training), beneficial adaptations pertaining to anaerobic energy systems, ion handling, and fatigue resilience are commonly observed. In this review, we discuss the utility of conducting intensified training periods to enhance performance in elite football players during the late preparation phase and competitive season.

The Effect of Monophasic Oral Contraceptives on Muscle Strength and Markers of Recovery After Exercise-Induced Muscle Damage: A Systematic Review.

CONTEXT: Oral contraceptives (OCs) manipulate hormonal fluctuations of the menstrual cycle and affect physical performance. Most investigations on the effect of OCs on physical performance did not discriminate between different types of OCs. Thus, the effects of monophasic OCs (MOCs) - the most common type of OCs - on muscle strength and recovery from exercise are largely unknown. OBJECTIVE: To examine the effect of MOC use on muscle strength and markers of recovery after exercise-induced muscle damage (EIMD) in premenopausal women. DATA SOURCES: Electronic databases Embase, PubMed, SportDiscus, and Web of Science were searched for studies examining the effect of MOCs on acute muscle strength and recovery. STUDY SELECTION: Keywords applied for the study selection were oral contraceptive* AND muscle strength or oral contraceptive* AND muscle damage. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Lowest quality assessed for an included study in this review was serious risk of bias using ROBINS-I tool made from Cochrane for nonrandomized studies. DATA EXTRACTION: A total of 104 studies on muscle strength were identified, of which 11 met the inclusion criteria. Concerning recovery, 51 studies were identified, of which 4 met the inclusion criteria. RESULTS: Of the 11 studies included, 10 showed no effect of MOCs on acute muscle strength. Of the 4 studies on recovery, 2 found a greater decrease in muscle strength, and 3 found higher creatine kinase (CK) levels after EIMD in MOC users than in nonusers. The included studies were all rated with moderate-to-serious risk of bias. CONCLUSION: These findings suggest that MOCs may impair recovery from EIMD as indicated by lowered muscle strength and elevated CK levels. There is insufficient evidence to conclude whether MOCs acutely affect muscle strength. Moderate-to-serious risk of bias in studies makes interpretation challenging.

Myonuclear addition is associated with sex-specific fiber hypertrophy and occurs in relation to fiber perimeter not cross-sectional area.

It is unclear whether resistance training-induced myofiber hypertrophy is affected by sex, and whether myonuclear addition occurs in relation to the myonuclear domain and can contribute to explaining a potential sex-specific hypertrophic response. This study investigated the effect of 8 wk of resistance training on myofiber hypertrophy and myonuclear addition in 12 males (28 ± 7 yr; mean ± SD) and 12 females (27 ± 7 yr). Muscle biopsies were collected from m. vastus lateralis before and after the training intervention and were analyzed by immunohistochemistry for fiber type and size, satellite cells, and myonuclei. Hypertrophy of type I fibers was greater in males than females (P < 0.05), whereas hypertrophy of type II fibers was similar between sexes (P = 0.158-0.419). Expansion of the satellite cell pool (P = 0.132-0.667) and myonuclear addition (P = 0.064-0.228) did not differ significantly between sexes, irrespective of myofiber type. However, when individual responses to resistance training were assessed, myonuclear addition was strongly correlated with fiber hypertrophy (r = 0.68-0.85, P < 0.001). Although myofiber hypertrophy was accompanied by an increase in myonuclear domain (P < 0.05), fiber perimeter per myonucleus remained constant throughout the study (P = 0.096-0.666). These findings indicate that myonuclear addition occurs in relation to the fiber perimeter per myonucleus, not the myonuclear domain, and has a substantial role in resistance training-induced muscle hypertrophy but does not fully explain greater hypertrophy of type I fibers in males than females.NEW & NOTEWORTHY Here, we show that resistance training-induced hypertrophy of type I fibers is greater in males than females. Myonuclear addition was strongly associated with fiber hypertrophy but did not differ between sexes in type I fibers. Furthermore, whereas muscle hypertrophy was accompanied by an increase in myonuclear domain, fiber perimeter per myonucleus remained constant. Thus, myonuclear addition occurs in relation to fiber perimeter during muscle hypertrophy but does not explain sex-specific hypertrophy of type I fibers.

Four Weeks of Intensified Training Enhances On-Ice Intermittent Exercise Performance and Increases Maximal Oxygen Consumption of Youth National-Team Ice Hockey Players.

PURPOSE: We investigated whether 4 weeks of intensified training consisting of speed endurance training (SET) enhanced high-intensity exercise performance in youth national-team ice hockey players. METHODS: Utilizing a randomized crossover design, we subjected 17 players to 4 weeks of SET, comprising 6 to 10 × 20 seconds at maximal effort (>95% maximum ice skating speed) with 120-second recovery performed 3 times weekly, or maintenance of regular training (control period). Before and after each period, players completed ice-hockey-specific tests on ice, including a Yo-Yo Intermittent Recovery Level 1 test, a 30-m sprint test, and an agility test. On a separate day, players were assessed for body composition with dual-energy X-ray absorptiometry and performed countermovement jump, maximal voluntary isometric knee extensor contraction, a 15-second maximal sprint test, and a submaximal and incremental test on a bike ergometer in which pulmonary oxygen consumption was determined. RESULTS: Yo-Yo Intermittent Recovery Level 1 test performance increased (P < .001) by 14% (95% CI, 201-496 m) during the SET period. Maximal pulmonary oxygen consumption (P < .05) and time to exhaustion (P < .05) were 4.8% and 6.5% higher, respectively, after the SET period than before. Fat-free mass increased (P < .01) during the SET period by 1.7 kg (95% CI, 1.0-2.5), whereas fat mass remained unchanged. These effects were superior to the control period. CONCLUSIONS: These findings underpin the effectiveness of SET for improving on-ice high-intensity performance and highlight that elite ice hockey players can benefit from implementing SET.