Muscle glycogen unavailability and fat oxidation rate during exercise: Insights from McArdle disease.

Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild-type male mice. Peak oxygen uptake ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ ), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ (24.7 ± 4 vs. 42.5 ± 11.4 mL kg-1  min-1 , respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min-1 , P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ , P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg-1 , P = 0.020) than controls. No between-group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near-maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease. KEY POINTS: Physically active McArdle patients show an exceptional fat oxidation capacity. Maximal fat oxidation rate occurs near-maximal exercise capacity in these patients. McArdle patients' exercise tolerance might rely on maximal fat oxidation rate capacity. Hyperpnoea might cloud substrate oxidation measurements in some patients. An animal model revealed overall no higher molecular markers of lipid transport/metabolism.

High-intensity Actions in Elite Soccer: Current Status and Future Perspectives.

Over the years, soccer has become more physically demanding; the number and frequency of high-intensity actions have increased, and these activities are decisive in determining the match outcome. Importantly, the reductionist approach commonly used to analyze high-intensity actions does not contemplate a more contextualized perspective on soccer performance. Traditionally, most investigations have only provided quantitative data regarding sprints (i. e. time, distances, frequency) without examining "how" (e. g. type of trajectory or starting position) and "why" (e. g. tactical role) soccer players sprint. In fact, other high-intensity actions, apart from running, are not even mentioned (i. e. curve sprints, change of direction, and specific-jump tasks). This has led to the use of tests and interventions that do not accurately reflect real game actions. Given the true technical-tactical-physical demands of each playing position, this narrative review collected a wide-spectrum of current soccer-related articles and provided a discussion regarding high-intensity actions, with a positional-based approach. In this narrative review, practitioners are encouraged to contemplate and consider the different elements that characterize high-intensity actions in soccer, in order to assess and train soccer players under a more sport-specific and integrative perspective.

Identification of Potential Muscle Biomarkers in McArdle Disease: Insights from Muscle Proteome Analysis.

Glycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The pathobiology of GSDV is still not fully understood, especially with regard to some features such as persistent muscle damage (i.e., even without prior exercise). We aimed at identifying potential muscle protein biomarkers of GSDV by analyzing the muscle proteome and the molecular networks associated with muscle dysfunction in these patients. Muscle biopsies from eight patients and eight healthy controls showing none of the features of McArdle disease, such as frequent contractures and persistent muscle damage, were studied by quantitative protein expression using isobaric tags for relative and absolute quantitation (iTRAQ) followed by artificial neuronal networks (ANNs) and topology analysis. Protein candidate validation was performed by Western blot. Several proteins predominantly involved in the process of muscle contraction and/or calcium homeostasis, such as myosin, sarcoplasmic/endoplasmic reticulum calcium ATPase 1, tropomyosin alpha-1 chain, troponin isoforms, and alpha-actinin-3, showed significantly lower expression levels in the muscle of GSDV patients. These proteins could be potential biomarkers of the persistent muscle damage in the absence of prior exertion reported in GSDV patients. Further studies are needed to elucidate the molecular mechanisms by which PYGM controls the expression of these proteins.

How does curve sprint evolve across different age categories in soccer players?

Research has shown that soccer players regularly execute curved sprints during matches. The purpose of this study was to determine the age-related effects on curve sprint (CS) performance to both sides, asymmetry, and association with linear sprint (LS). Eighty-four soccer players (aged 16.1 ± 1.6 categorized in U15, U17, and U20) were recruited, who performed CS and LS tests. One-way analysis of variance (ANOVA) and effect size (ES) were used to compare CS performance between age categories, and relationships between physical performance measures were calculated using Pearson's correlation coefficient. The main findings of this study were that: 1) there were significant differences in the "good" side CS among age groups (p < 0.001; ES from moderate to large), but not in the "weak" side CS, 2) curve asymmetry was significantly higher in U20 than U15 (p < 0.05; ES large) and U17 players (p < 0.05; ES moderate), and 3) relationships between CS and LS times decreased with age (from significant and very large [p < 0.001] to non-significant and smallmoderate [p > 0.05]). This study highlights the importance of assessing and training CS in different age categories, an action that becomes less correlated with LS as age increases, with the aim of mitigating the increase in asymmetries as a result of the specialization process, focusing interventions mainly on improving the CS "weak" side.

Curve Sprinting in Soccer: Kinematic and Neuromuscular Analysis.

Sprinting in curvilinear trajectories is an important soccer ability, corresponding to ~85% of the actions performed at maximum velocity in a soccer league. We compared the neuromuscular behavior and foot contact-time between outside leg and inside leg during curve sprinting to both sides in soccer players. Nine soccer players (age=23±4.12 years) performed: 3×Sprint linear, 3×Sprint right curve, and 3×Sprint left curve. An ANOVA with repeated measures was used to compare the differences between inside and outside leg, and Cohen's d was used to calculate the effect-size. Considering the average data, the performance classification (from best to worst) was as follows: 1. Curve "good" side (2.45±0.11 s), 2. Linear (2.47±0.13 s), and 3. Curve "weak" side (2.56±0.17 s). Comparing linear with curve sprinting, inside leg recorded significant differences ("good" and "weak"; effect size=1.20 and 2, respectively); in contrast, for outside leg, there were no significant differences ("good" and "weak"; effect size=0.30 and 0.49, respectively). Electromyography activity showed significant differences (p≤0.05) during curve sprinting between outside (higher in biceps femoris and gluteus medius) and inside leg (higher activity in semitendinosus and adductor). In summary, inside and outside leg play different roles during curved sprints, but inside leg is more affected by the change from straight to curve sprint.

New curve sprint test for soccer players: Reliability and relationship with linear sprint.

The speed performance is involved not only in linear sprints, but also in a wide spectrum of multi-directional movements, such as curve sprinting. Curved sprint can be defined as sprint with gradual and continuous change of direction (COD). Although ~85% of the actions performed at maximum velocity in a professional soccer league are curvilinear sprints, there is not any specific test to assess this ability. This study aimed to analyse the reliability of a new curve sprint test, and compare its results with those obtained by soccer players in linear sprint. Forty experienced soccer players performed 3 attempts of curve sprint (using the penalty arc) to right and left side (17 m), and 3 linear sprints (17 m) in two different days. The ICCs (inter-session reliability) were 0.93 for sprint curve right side (CSRS) and 0.89 for sprint curve left side (CSLS), considered "acceptable". The CVs (intra-session reliability) were 0.87% in CSRS and 1.15% in CSLS. The coefficient of determination (R2) between linear and curve sprinting was ~35%. The association between curve sides was "very large" (r = 0.878; p < 0.01). In summary, we showed that "curve sprint test" is highly reliable, and that curvilinear and linear sprints are different and independent actions.

Correction to: Manifesting heterozygotes in McArdle disease: a myth or a reality-role of statins.

Unfortunately the name of one of the authors was spelled incorrectly in the published original article. The correct name is Alejandro Santos-Lozano. The original article got updated.

Manifesting heterozygotes in McArdle disease: a myth or a reality-role of statins.

McArdle disease is an autosomal recessive condition caused by deficiency of the PYGM gene-encoded muscle isoform of glycogen phosphorylase. Some cases of "manifesting" heterozygotes or carriers (i.e., patients who show some McArdle-like symptoms or signs despite being carriers of only one mutated PYGM allele) have been reported in the literature but there is controversy, with misdiagnosis being a possibility. The purpose of our study was to determine if there are actually "manifesting" heterozygotes of McArdle disease and, if existing, whether statin treatment can trigger such condition. Eighty-one relatives of McArdle patients (among a total of 16 different families) were studied. We determined whether they were carriers of PYGM mutations and also collected information on exercise tests (second wind and modified Wingate anaerobic test) and statin intake. We found 50 carriers and 31 non-carriers of PYGM mutations. Although we found existence of heterozygotes manifesting some exercise-related muscle problems such as exacerbated myalgia or weakness, they only accounted for 14% of the carriers and muscle symptoms were milder than those commonly reported in patients. Further, no carrier (whether reporting symptoms or not) showed the second wind phenomenon or a flat blood lactate response to maximal-intensity exercise, both of which are hallmarks of McArdle disease. On the other hand, statin myotoxicity was not associated with muscle symptom onset.

Ventilatory efficiency response is unaffected by fitness level, ergometer type, age or body mass index in male athletes.

The aim of this study was to evaluate the ventilatory efficiency (V E/VCO2 slope) and the respiratory control (Vt/Ti slope) in a wide range of athletes and describe the influence of fitness level, age, ergometer type or BMI on these parameters. Ninety-one males (30.4±10.53 years; 175.52±7.45 cm; 71.99±9.35 kg) were analysed retrospectively for the study. Ventilatory efficiency reacted similarly in athletes independently of the fitness level, age, BMI or the ergometer used for testing. No significant differences were found in V E/VCO2 slope and the Vt/Ti slope between variables analyzed (P>0.05). The slope of the predictive equations was similar in all cases studied in V E/VCO2 slope and the Vt/Ti slope. Moreover, the central control impulse of respiration was not affected by the variables studied. These observations suggest that ventilatory efficiency (V E/VCO2 slope) could be a variable fixed by the respiratory system which tends to respond similarly in athletes.

Genotypic and phenotypic features of all Spanish patients with McArdle disease: a 2016 update.

BACKGROUND: We recently described the genotype/phenotype features of all Spanish patients diagnosed with McArdle disease as of January 2011 (n = 239, prevalence of ~1/167,000) (J Neurol Neurosurg Psychiatry 2012;83:322-8). Several caveats were however identified suggesting that the prevalence of the disease is actually higher. METHODS: We have now updated main genotype/phenotype data, as well as potential associations within/between them, of all Spanish individuals currently diagnosed with McArdle disease (December 2016). RESULTS: Ninety-four new patients (all Caucasian) have been diagnosed, yielding a prevalence of ~1/139,543 individuals. Around 55% of the mutated alleles have the commonest PYGM pathogenic mutation p.R50X, whereas p.W798R and p.G205S account for 10 and 9% of the allelic variants, respectively. Seven new mutations were identified: p.H35R, p.R70C, p.R94Q, p.L132WfsX163, p.Q176P, p.R576Q, and c.244-3_244-2CA. Almost all patients show exercise intolerance, the second wind phenomenon and high serum creatine kinase activity. There is, however, heterogeneity in clinical severity, with 8% of patients being asymptomatic during normal daily life, and 21% showing limitations during daily activities and fixed muscle weakness. A major remaining challenge is one of diagnosis, which is often delayed until the third decade of life in 72% of new patients despite the vast majority (86%) reporting symptoms before 20 years. An important development is the growing proportion of those reporting a 4-year improvement in disease severity (now 34%) and following an active lifestyle (50%). Physically active patients are more likely to report an improvement after a 4-year period in the clinical course of the disease than their inactive peers (odds ratio: 13.98; 95% confidence interval: 5.6, 34.9; p < 0.001). Peak oxygen uptake is also higher in the former (20.7 ± 6.0 vs. 16.8 ± 5.3 mL/kg/min, p = 0.0013). Finally, there is no association between PYGM genotype and phenotype manifestation of the disease. CONCLUSIONS: The reported prevalence of McArdle disease grows exponentially despite frequent, long delays in genetic diagnosis, suggesting that many patients remain undiagnosed. Until a genetic cure is available (which is not predicted in the near future), current epidemiologic data support that adoption of an active lifestyle is the best medicine for these patients.

Off-Season Effects on Functional Performance, Body Composition, and Blood Parameters in Top-Level Professional Soccer Players.

Requena, B, García, I, Suárez-Arrones, L, Sáez de Villarreal, E, Naranjo Orellana, J, and Santalla, A. Off-season effects on functional performance, body composition, and blood parameters in top-level professional soccer players. J Strength Cond Res 31(4): 939-946, 2017-To examine the effects of a standard off-season period (OSP) on aerobic, sprint, and jumping performances, and body and blood composition in a top-level soccer team. Nineteen soccer players were measured. The OSP included to 2 weeks of no training (resting phase) and a 4-week period of moderate-training load (phase in which each player performed the vacation exercise plan). Player's functional performance (15- and 30-m sprint times [seconds], vertical jump [meter], and incremental field test Vam-Eval [kilometer per hour]), percentage of body fat (%) and blood composition (hematological and biochemical data) were measured at mid-season, end-season, and after the OSP. The percentage of body fat was nonaltered during the competitive season (10.8 ± 3.6 and 10.5 ± 3.5%) and increased significantly after the OSP (11.6 ± 3.6%, p ≤ 0.05). Similarly, the maximal aerobic speed (VVam-Eval) velocity (kilometer per hour) decreased (p ≤ 0.05) from 17.4 ± 1 and 17.3 ± 1.2 during the competitive season to 16.6 ± 0.9 after the OSP. The hematocrit and blood hemoglobin concentration increased (p ≤ 0.05) during the OSP, showing a blood hemoconcentration adaptation. However, sprint time (seconds) and jump height (meters) showed no significant changes after the OSP. Soccer players maintained their functional performance during high-intensity activities such as jumping or sprinting after the OSP proposed. By contrast, there was a decrease in aerobic performance (VVam-Eval) accompanied by a blood hemoconcentration, and an increase of body fat mass associated with a reduction of fat-free mass of the lower limbs. Our data suggest that an end-season evaluation is needed to design holiday training programs focused on regaining aerobic capacity and body composition.

Genes and exercise intolerance: insights from McArdle disease.

McArdle disease (glycogen storage disease type V) is caused by inherited deficiency of a key enzyme in muscle metabolism, the skeletal muscle-specific isoform of glycogen phosphorylase, "myophosphorylase," which is encoded by the PYGM gene. Here we review the main pathophysiological, genotypic, and phenotypic features of McArdle disease and their interactions. To date, moderate-intensity exercise (together with pre-exercise carbohydrate ingestion) is the only treatment option that has proven useful for these patients. Furthermore, regular physical activity attenuates the clinical severity of McArdle disease. This is quite remarkable for a monogenic disorder that consistently leads to the same metabolic defect at the muscle tissue level, that is, complete inability to use muscle glycogen stores. Further knowledge of this disorder would help patients and enhance understanding of exercise metabolism as well as exercise genomics. Indeed, McArdle disease is a paradigm of human exercise intolerance and PYGM genotyping should be included in the genetic analyses that might be applied in the coming personalized exercise medicine as well as in future research on genetics and exercise-related phenotypes.

McArdle Disease: Update of Reported Mutations and Polymorphisms in the PYGM Gene.

McArdle disease is an autosomal-recessive disorder caused by inherited deficiency of the muscle isoform of glycogen phosphorylase (or "myophosphorylase"), which catalyzes the first step of glycogen catabolism, releasing glucose-1-phosphate from glycogen deposits. As a result, muscle metabolism is impaired, leading to different degrees of exercise intolerance. Patients range from asymptomatic to severely affected, including in some cases, limitations in activities of daily living. The PYGM gene codifies myophosphoylase and to date 147 pathogenic mutations and 39 polymorphisms have been reported. Exon 1 and 17 are mutational hot-spots in PYGM and 50% of the described mutations are missense. However, c.148C>T (commonly known as p.R50X) is the most frequent mutation in the majority of the studied populations. No genotype-phenotype correlation has been reported and no mutations have been described in the myophosphorylase domains affecting the phosphorylated Ser-15, the 280's loop, the pyridoxal 5'-phosphate, and the nucleoside inhibitor binding sites. A newly generated knock-in mouse model is now available, which renders the main clinical and molecular features of the disease. Well-established methods for diagnosing patients in laboratories around the world will shorten the frequent ∼20-year period stretching from first symptoms appearance to the genetic diagnosis.

The pathogenomics of McArdle disease--genes, enzymes, models, and therapeutic implications.

Numerous biomedical advances have been made since Carl and Gerty Cori discovered the enzyme phosphorylase in the 1940s and the Scottish physician Brian McArdle reported in 1951 a previously 'undescribed disorder characterized by a gross failure of the breakdown in muscle of glycogen'. Today we know that this disorder, commonly known as 'McArdle disease', is caused by inherited deficiency of the muscle isoform of glycogen phosphorylase (GP). Here we review the main aspects of the 'pathogenomics' of this disease including, among others: the spectrum of mutations in the gene (PYGM) encoding muscle GP; the interplay between the different tissue GP isoforms in cellular cultures and in patients; what can we learn from naturally occurring and recently laboratory-generated animal models of the disease; and potential therapies.

Rationale and Design of a Randomized Controlled Trial Evaluating Whole Muscle Exercise Training Effects in Outpatients with Pulmonary Arterial Hypertension (WHOLEi+12).

BACKGROUND AND AIMS: Physical exercise is an important component in the management of pulmonary artery hypertension (PAH). The aim of this randomized controlled trial (RCT) is to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure load exercises in PAH outpatients. METHODS: The RCT will be conducted from September 2015 to September 2016 following the recommendations of the Consolidated Standards of Reported Trials (CONSORT), with a total sample size of n ≥ 48 (≥24 participants/group). We will determine the effects of the intervention on: (i) skeletal-muscle power and mass (primary end points); and (ii) NT-proBNP, cardiopulmonary exercise testing variables (VO2peak, ventilatory equivalent for CO2 at the anaerobic threshold (VE/VCO2 at the AT), end-tidal pressure of CO2 at the anaerobic threshold (PETCO2 at the AT), 6-min walking distance (6MWD), maximal inspiratory pressure (PImax), health-related quality of life (HRQoL), objectively-assessed spontaneous levels of physical activity, and safety (secondary end points). CONCLUSIONS AND PERSPECTIVES: This trial will provide insight into biological mechanisms of the disease and indicate the potential benefits of exercise in PAH outpatients, particularly on muscle power.

Validity and reliability of rating perceived exertion in women with fibromyalgia: exertion-pain discrimination.

The present study aimed (1) to assess the validity and reliability of the Borg category-ratio (CR-10) scale for monitoring exercise intensity in women with fibromyalgia (FM) and (2) to examine whether women with FM can discriminate between perceived exertion and exercise-induced pain. Thirty-three women with FM performed two incremental treadmill tests (1 week separated). Heart rate, oxygen uptake, minute ventilation and respiratory quotient were measured. The ratings of perceived exertion (RPE: CR-10 scale) and exercise-induced pain were obtained at each workload. The Spearman's correlation of RPE with the physiological responses ranged from 0.69 to 0.79. The regression models explained ~50% of the variability of the studied physiological responses. We found "perfect acceptable" agreement in 69% of the observations. Weighted Kappa was 0.66 (95% confidence interval [CI]: 0.59-0.72). There were differences between RPE and pain at workloads 3 (1.50; 95% CI: 0.85-2.16), 4 (2.10; 95% CI: 1.23-2.96), 5 (3.40; 95% CI: 1.29-5.51) and 6 (3.97; 95% CI: 1.61-6.33). The main findings of the present study suggest that the Borg CR-10 scale is valid and moderately reliable for monitoring exercise intensity in women with FM, and these patients were able to discriminate between exertion and exercise-induced pain.

Forced inspiratory volume in the first second as predictor of front-crawl performance in young sprint swimmers.

The purposes of this study were to determine the extent to which specific anthropometric, conditional, and pulmonary function variables predict 100-m front-crawl performance in national swimmers and compare anthropometric, conditional, and pulmonary function variables between both genders. Two groups (male, n = 8 and female, n = 9) of sprint swimmers (mean age ± SD = 19.4 ± 0.7 years and 16.9 ± 3.2 years, respectively) of national competitive level volunteered for this study. Swimmers performed an all-out 100-m front-crawl swimming test. Physiological parameters of lung function were measured using portable spirometer. Basic anthropometry included body height, body mass, and skinfold thickness. Lower limb strength was measured by countermovement and squat jump tests. Correlation and regression analyses were calculated to quantify the relationships between trial time and each variable potentially predictive. Differences between means of both gender groups were analyzed. Results showed that 100-m race performance correlated significantly with forced inspiratory volume in the first second (FIV1) in male swimmers and with FIV1 and forced vital capacity in female swimmers. Stepwise multiple regressions revealed that FIV1 was the only predictor of 100-m race performance, explaining 66% of 100-m time trial variance in male swimmers and 58% in female swimmers. Gender comparisons indicated significant differences in anthropometric, conditional, pulmonary function, and performance variables. The findings suggest that FIV1 could be a good predictor of performance and it should be evaluated routinely and used by coaches in front-crawl sprint swimmers.

Fatigue and associated factors in 172 patients with McArdle disease: An international web-based survey.

McArdle disease is an autosomal recessive inherited disease caused by pathogenic variants in the PYGM gene, resulting in virtual absence of the myophosphorylase enzyme in skeletal muscle. Patients experience physical activity intolerance, muscle pain, and muscle fatigue. This study aimed to investigate other fatigue domains with the Multidimensional Fatigue Inventory (MFI-20) along with an investigation of potential contributing factors, including relevant disease and lifestyle-related factors. We conducted a survey in an international cohort of patients with McArdle disease. The survey included questions on demographics and McArdle disease-related symptoms, and the questionnaires: MFI-20, Insomnia Severity Index (ISI), and International Physical Activity Questionnaire Short-Form (IPAQ-SF). One hundred seventy-four responses were included in the data analyses. We found relatively high fatigue scores in all five domains (general fatigue (12.9 ± 2.2), mental fatigue (10.1 ± 4.1), physical fatigue (13.7 ± 4.1), reduced activity (12.1 ± 4.1), and reduced motivation (10.4 ± 3.4)). Fatigue associated with McArdle symptom severity (p < 0.005), lower levels of physical activity (assessed by IPAQ-SF) (p < 0.05), and poor sleep (assessed by ISI) (p < 0.05). These findings call for clinical focus and future research into fatigue, sleep and mental health in patients with McArdle disease.

Acute ketone supplementation in the absence of muscle glycogen utilization: Insights from McArdle disease.

BACKGROUND & AIMS: Ketone supplementation is gaining popularity. Yet, its effects on exercise performance when muscle glycogen cannot be used remain to be determined. McArdle disease can provide insight into this question, as these patients are unable to obtain energy from muscle glycogen, presenting a severely impaired physical capacity. We therefore aimed to assess the effects of acute ketone supplementation in the absence of muscle glycogen utilization (McArdle disease). METHODS: In a randomized cross-over design, patients with an inherited block in muscle glycogen breakdown (i.e., McArdle disease, n = 8) and healthy controls (n = 7) underwent a submaximal (constant-load) test that was followed by a maximal ramp test, after the ingestion of a placebo or an exogenous ketone ester supplement (30 g of D-beta hydroxybutyrate/D 1,3 butanediol monoester). Patients were also assessed after carbohydrate (75 g) ingestion, which is currently considered best clinical practice in McArdle disease. RESULTS: Ketone supplementation induced ketosis in all participants (blood [ketones] = 3.7 ± 0.9 mM) and modified some gas-exchange responses (notably increasing respiratory exchange ratio, especially in patients). Patients showed an impaired exercise capacity (-65 % peak power output (PPO) compared to controls, p < 0.001) and ketone supplementation resulted in a further impairment (-11.6 % vs. placebo, p = 0.001), with no effects in controls (p = 0.268). In patients, carbohydrate supplementation resulted in a higher PPO compared to ketones (+21.5 %, p = 0.001) and a similar response was observed vs. placebo (+12.6 %, p = 0.057). CONCLUSIONS: In individuals who cannot utilize muscle glycogen but have a preserved ability to oxidize blood-borne glucose and fat (McArdle disease), acute ketone supplementation impairs exercise capacity, whereas carbohydrate ingestion exerts the opposite, beneficial effect.

Durability in Professional Cyclists: A Field Study.

PURPOSE: To assess durability in professional cyclists, as well as potential associated indicators. METHODS: Twelve male professional cyclists participated in the study (age: 26 [5] y, VO2max: 83.0 [3.6] mL·kg-1·min-1). They performed a 20-minute time trial (TT) on 2 different sessions separated by a 48-hour period: (1) with no previous fatigue (TTFresh) and (2) immediately after a long submaximal ride (approximately 4 h, 40 kJ/kg) (TTFatigue). We then assessed the decay (in percentage) in mean power output (PO) from TTFresh to TTFatigue and its association with different laboratory-based endurance indicators (ventilatory threshold, peak PO, and VO2max) determined through a previous maximal incremental cycling test, as well as with training loads during the 4 weeks preceding the TTs. RESULTS: While no differences were noted in the average heart rate (177 [7] vs 176 [6] beats·min-1, P = .118), there was a significant decay in PO between TTFresh and TTFatigue (386 [29] W vs 375 [28] W [-2.9%], respectively; P = .007), albeit with signs of interindividual variability (range = -8.5% to 1.1%; coefficient of variation = 105%). No significant associations were found between the PO decay and any of the analyzed indicators (all P > .05). CONCLUSIONS: Performance is significantly impaired after a certain amount of work completed (approximately 40 kJ·kg-1) in professional cyclists, and the magnitude of this impairment seems to be not related to "traditional" laboratory-based endurance indicators or to markers of training load. These findings might support the need for specifically assessing durability in cyclists and confirming potential determinants of this parameter.