High-dose short-term creatine supplementation without beneficial effects in professional cyclists: a randomized controlled trial.

BACKGROUND: Growing evidence supports the ergogenic effects of creatine supplementation on muscle power/strength, but its effects on endurance performance remain unclear. We assessed the effects of high-dose short-term creatine supplementation in professional cyclists during a training camp. METHODS: The study followed a double-blind, randomized parallel design. Twenty-three professional U23 cyclists (19 ± 1 years, maximum oxygen uptake: 73.0 ± 4.6 mL/kg/min) participated in a 6-day training camp. Participants were randomized to consume daily either a recovery drink (containing carbohydrates and protein) with a 20-g creatine supplement (creatine group, n = 11) or just the recovery drink (placebo group, n = 12). Training loads and dietary intake were monitored, and indicators of fatigue/recovery (Hooper index, countermovement jump height), body composition, and performance (10-second sprint, 3-, 6-, and 12-minute time trials, respectively, as well as critical power and W') were assessed as study outcomes. RESULTS: The training camp resulted in a significant (p < 0.001) increase of training loads (+50% for total training time and + 61% for training stress score, compared with the preceding month) that in turn induced an increase in fatigue indicators (significant time effect [p < 0.001] for delayed-onset muscle soreness, fatigue, and total Hooper index) and a decrease in performance (significant time effect [p = 0.020] for critical power, which decreased by -3.8%). However, no significant group-by-time interaction effect was found for any of the study outcomes (all p > 0.05). CONCLUSIONS: High-dose short-term creatine supplementation seems to exert no consistent beneficial effects on recovery, body composition or performance indicators during a strenuous training period in professional cyclists.

Is all work the same? Performance after accumulated work of differing intensities in male professional cyclists.

OBJECTIVES: Although the ability to attenuate power output (PO) declines after accumulated work (i.e., 'durability') is increasingly recognized as a major determinant of cycling performance, the potential role of the intensity of the previous work is unclear. We assessed the effect of work-matched levels of accumulated work at different intensities on performance in male professional cyclists. DESIGN: Observational field-based study. METHODS: PO data was registered in 17 cyclists during a competition season, and the critical power (CP) was repeatedly determined every 4 weeks from training sessions and competitions. Participants' maximum mean power (MMP) for different durations (5 s, 5 min, 10 min, and 20 min) and the CP were determined under 'fresh' conditions (0 kJ·kg-1) and after varying levels of accumulated work (2.5, 5.0 and 7.5 kJ·kg-1) at intensities below and above the CP. RESULTS: A significant decline was found for all MMP values following all levels of accumulated work above the CP (-4.0 %, -1.7 %, -1.8 %, and -3.2 % for 30s, 5 min, 10 min and 20 min-MMP, respectively; all p < 0.001), versus no change after any level of accumulated work below the CP (all p > 0.05). Similar results were observed for the CP, which decreased after all levels of accumulated work above (-2.2 %, -6.1 %, and -16.2 %, after 2.5, 5.0 and 7.5 kJ·kg-1, p < 0.001) but not below this indicator (p > 0.05). CONCLUSIONS: In male professional cyclists, accumulated work above the CP impairs performance compared with work-matched, albeit less intense efforts. This raises concerns on the use of mechanical work per se as a single fatigue/stress indicator in these athletes.

The Influence of High-Intensity Work on the Record Power Profile of Under-23, Pro Team, and World Tour Cyclists.

BACKGROUND: Durability (ie, the ability to attenuate the decline in performance after accumulated work) has been identified as a performance determinant in elite cyclists. The aim of the present study was to compare durability in elite cyclists of various performance levels, particularly after high-intensity work, referred to as "high-intensity durability." METHODS: Forty-nine (N = 49) male road cyclists were categorized as either under 23 years of age (U23) (N = 11), Pro Team (N = 13), or World Tour (N = 24). The participants' critical power (CP) was assessed during the preseason. Thereafter, the participants' maximum mean power (MMP) values were determined for efforts of different durations (from 5 s to 30 min) after different levels of accumulated work above CP (from 0 to 7.5 kJ·kg-1). RESULTS: U23 cyclists showed a significant reduction of all relative MMP values for durations ≥1 minute after ≥5 kJ·kg-1 above CP compared with the "fresh" state (0 kJ·kg-1), whereas in Pro Team and World Tour cyclists, a significant reduction was not observed until 7.5 kJ·kg-1 above CP. In the "fresh" state, both Pro Team and particularly World Tour cyclists attained higher MMP values for efforts ≥10 minutes than U23 riders. However, more differences emerged with greater previous work levels, and indeed after 7.5 kJ·kg-1 above CP World Tour cyclists attained higher MMP values than both U23 and Pro Team cyclists for most efforts (≥30 s). CONCLUSION: Pro Team and particularly World Tour cyclists tolerate greater levels of accumulated work at high intensity, which might support the importance of high-intensity durability for performance.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Two Lactones Non-toxic to Humans Are Effective Repellents for the German Cockroach.

Lactones are cyclic esters of hydroxy carboxylic acids, present in several fruits and animals consumed by humans. There is evidence that some lactones modify insect behavior. The aim of the present study was to evaluate the repellent effect of four lactones (γ- and δ-nonalactone, and γ- and δ-dodecalactone) in first instar nymphs of the German cockroach, Blattella germanica (Linnaeus). To assess repellency, a nymph was placed on a circle of filter paper, half of which had been treated with lactone dissolved in acetone and the other half with acetone alone. The behavior of the nymph was recorded and the time the nymph spent in each half of the paper was quantified using Ethovision XT 10.1 software. Values of Distribution Coefficient (DC) were calculated: DC = (Tt - TA) / Tt, where Tt is the experimental time and TA is the time the nymph spent in the area treated with the repellent agent. DC can vary between 0 and 1. Values significantly higher than 0.5 indicate repellency. N,N-diethyl-meta-toluamide (DEET) was used as a positive control. DEET, δ- and γ-nonalactone caused repellency as from 77.9 µg/cm2, whereas γ- and δ-dodecalactone had a repellent effect starting at 779.0 µg/cm2. The values of DC for these concentrations were 0.89 (DEET), 0.86 (γ-nonalactone), 0.87 (δ-nonalactone), 0.83 (γ-dodecalactone), and 0.72 (δ-dodecalactone). To our knowledge, this is the first report of repellency produced by lactones in the German cockroach. This work allowed to identify two lactones that have a repellent effect similar to DEET.

Exercise is also medicine for iron homeostasis.

High-intensity interval training (HIIT) is gaining popularity as an effective exercise modality to improve cardiometabolic health. Combining high-throughput/sensitivity proteome analyses in subcutaneous adipose tissue with biochemical blood measures, Larsen et al. recently provided mechanistic insights into a potential beneficial role of this exercise modality on iron homeostasis at the whole-body level.

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.

Lifestyle and cardiovascular risk in working young adults: insights from a nationwide Spanish cohort.

INTRODUCTION AND OBJECTIVES: This study aimed to describe the cardiovascular risk profile of working young adults from Spain and its association with lifestyle. METHODS: Participants (18-30 years) were recruited from a nationwide cohort of economically active adults insured by a large occupational risk prevention company, with data obtained from routine medical assessments. The participants were categorized as having an "unhealthy" cardiovascular risk profile based on the presence of prediabetes/diabetes, prehypertension/hypertension, or hypercholesterolemia, or a "healthy" profile if these conditions were completely absent. The association with lifestyle factors (weight, physical activity, sleeping characteristics, alcohol consumption, smoking) was assessed. RESULTS: A total of 78 421 young adults (27±2 years, 36% female) were evaluated at baseline. The "unhealthy" cardiovascular risk profile was prevalent (18%) and inversely associated (OR, 0.64; 95%CI, 0.57-0.80) with an optimal lifestyle (normal weight, regular physical activity, no drinking/smoking, and good sleep). The latter condition was found in only 3.5% of the participants. On the other hand, prospective analyses in 44 776 participants (median follow-up=2 [range 2-5] years) showed that 2.0% transitioned from a "healthy" to an "unhealthy" profile. Being physically active (OR, 0.95; 95%CI, 0.81-0.99) and having a normal weight (OR, 0.61; 95%CI, 0.51-0.70) were associated with a lower likelihood of this transition. No consistent associations were found for other lifestyle factors. CONCLUSIONS: The prevalence of cardiovascular risk factors is high in economically active young Spanish adults. An unhealthy cardiovascular risk profile is inversely associated with an optimal lifestyle, but the latter is highly infrequent in this population.

Association of physical behaviours with sarcopenia in older adults: a systematic review and meta-analysis of observational studies.

BACKGROUND: Physical behaviours (ie, physical activity and sedentary behaviour) might have a role in the development of sarcopenia, although the evidence is unclear. We aimed to explore the association of total and intensity-specific levels of physical activity and sedentary behaviour with sarcopenia and its components (ie, muscle mass, muscle strength, and physical performance) in older adults. METHODS: We conducted a systematic review and meta-analysis and searched MEDLINE (via PubMed), Scopus, and Web of Science from inception to July 26, 2022, for peer-reviewed, observational studies or baseline data from randomised clinical trials conducted in older adults (ie, individual age ≥60 years or mean age ≥65 years) and published in English that reported on the association of physical activity or sedentary behaviour or both with sarcopenia (or its determinants: muscle mass or strength, and physical performance). Physical activity and sedentary behaviour were measured by any method. The main outcome was sarcopenia, which could be diagnosed by any means. Estimates were extracted and pooled using Bayesian meta-analytic models and publication bias was assessed using the Egger's test. This study is registered with PROSPERO, CRD42022315865. FINDINGS: We identified 15 766 records, of which 124 studies (230 174 older adults; 121 301 [52·7%] were female and 108 873 [47·3%] were male) were included in the systematic review. 86 studies were subsequently included in the meta-analysis. Higher levels of total physical activity were inversely associated with sarcopenia both cross-sectionally (21 studies, n=59 572; odds ratio 0·49, 95% credible interval 0·37-0·62) and longitudinally (four studies, n=7545; 0·51, 0·27-0·94). A protective association was also identified for moderate-to-vigorous physical activity in cross-sectional research (five studies, n=6787; 0·85, 0·71-0·99), whereas no association was identified for the remaining physical behaviours (ie, steps, light physical activity, or sedentary behaviour). INTERPRETATION: Total and moderate-to-vigorous physical activity are inversely associated with sarcopenia. These findings might support the importance of moderate-to-vigorous, rather than light, intensity physical activity-based interventions to prevent sarcopenia. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Exercise Intervention and Hospital-Associated Disability: A Nonrandomized Controlled Clinical Trial.

Importance: Inpatient exercise interventions may prevent, at least partly, hospital-associated disability (HAD) in older adults, but whether they also confer clinical benefits in the months following discharge is unclear. Objective: To examine the association of exercise and health education with HAD incidence in hospitalized older adults receiving acute hospital care at discharge and 3 months later. Design, Setting, and Participants: This single-center open-label, nonrandomized controlled clinical trial included patients aged 75 years or older seen at an acute care for elders unit at a tertiary public hospital in Madrid, Spain, from May 1, 2018, to June 30, 2022. Interventions: Patients were allocated to an intervention or control group. Both groups received usual care, but the intervention group also performed a supervised multicomponent exercise program (daily strength, balance, and walking exercises along with inspiratory muscle training) during hospitalization and received health education on how to exercise at home and telephone counseling during follow-up. Main Outcomes and Measures: The primary outcome was HAD incidence (determined by the Katz Index of Independence in Activities of Daily Living [hereafter, Katz Index]) at discharge and after 3 months compared with baseline (ie, 2 weeks before admission). Secondary outcomes included HAD incidence determined by the Barthel Index for Activities of Daily Living, ambulatory capacity decline at discharge and follow-up, changes in physical performance at discharge, and incidence of falls, readmissions, and mortality during the follow-up period. Results: The study included 260 patients (134 women [51.5%]; mean [SD] age, 87.4 [4.9] years [range, 75-105 years]; median hospital length of stay, 7 days [IQR, 5-10 days]), of whom 130 received the intervention and 130 were in the control group. Differences in HAD incidence did not reach statistical significance at discharge (odds ratio [OR], 0.62; 95% CI, 0.37-1.05; P = .08) or follow-up (OR, 0.65; 95% CI, 0.36-1.17; P = .15) when using the Katz Index. A lower HAD incidence was observed in the intervention group at discharge (OR, 0.47; 95% CI, 0.27-0.81; P = .01) and at follow-up (OR, 0.36; 95% CI, 0.20-0.66; P = .001) when using the Barthel Index for Activities of Daily Living. The intervention was also associated with a lesser decline in ambulatory capacity (OR, 0.55; 95% CI, 0.32-0.96; P = .03) and improved physical performance at discharge (Cohen d, 0.39; 95% CI, 0.12-0.65; P = .004). No significant associations were observed for readmissions, falls, or mortality. Conclusions and Relevance: In this nonrandomized controlled clinical trial, an exercise and health education intervention was not significantly associated with reduced HAD incidence when measured by the Katz Index. However, the benefits found for several secondary outcomes might support the implementation of in-hospital exercise programs for older patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03604640.

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

Digging into the intrinsic capacity concept: Can it be applied to Alzheimer's disease?

Historically, aging research has largely centered on disease pathology rather than promoting healthy aging. The World Health Organization's (WHO) policy framework (2015-2030) underscores the significance of fostering the contributions of older individuals to their families, communities, and economies. The WHO has introduced the concept of intrinsic capacity (IC) as a key metric for healthy aging, encompassing five primary domains: locomotion, vitality, sensory, cognitive, and psychological. Past AD research, constrained by methodological limitations, has focused on single outcome measures, sidelining the complexity of the disease. Our current scientific milieu, however, is primed to adopt the IC concept. This is due to three critical considerations: (I) the decline in IC is linked to neurocognitive disorders, including AD, (II) cognition, a key component of IC, is deeply affected in AD, and (III) the cognitive decline associated with AD involves multiple factors and pathophysiological pathways. Our study explores the application of the IC concept to AD patients, offering a comprehensive model that could revolutionize the disease's diagnosis and prognosis. There is a dearth of information on the biological characteristics of IC, which are a result of complex interactions within biological systems. Employing a systems biology approach, integrating omics technologies, could aid in unraveling these interactions and understanding IC from a holistic viewpoint. This comprehensive analysis of IC could be leveraged in clinical settings, equipping healthcare providers to assess AD patients' health status more effectively and devise personalized therapeutic interventions in accordance with the precision medicine paradigm. We aimed to determine whether the IC concept could be extended from older individuals to patients with AD, thereby presenting a model that could significantly enhance the diagnosis and prognosis of this disease.

Physical activity, chronic kidney disease, and cardiovascular risk: A study in half a million adults.

OBJECTIVE: There is a growing prevalence of chronic kidney disease (CKD), a condition associated with a higher cardiovascular disease (CVD) risk. We assessed the association between self-reported physical activity (PA) and CKD and also studied whether PA attenuates CKD-associated CVD risk. METHODS: A cohort of Spanish adults (18-64 years) participated in this nationwide study. Participants were categorized at baseline as being either inactive (performing no PA), regularly, or insufficiently active (meeting or not, respectively, international PA recommendations) and were followed for up to 5 years. The presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 ) and major CVD risk factors (diabetes, hypercholesterolemia, hypertension, obesity) was determined at baseline and at follow-up. RESULTS: 517 917 participants (44 ± 9 years, 67% male, CKD prevalence = 7%) were studied at baseline, with prospective analyses (median follow-up = 2 years, range = 2-5) in a subcohort of 264 581 individuals. Compared to physical inactivity, cross-sectional analyses at baseline showed that regular PA (odds ratio = 0.80; 95% confidence interval = 0.79-0.81), but not insufficient PA (1.02; 0.99-1.04) was associated with lower CKD prevalence. However, prospective analyses failed to confirm this association (p > 0.1). In turn, CKD was associated with a higher prevalence of hypertension (+3%) and diabetes (+5%) at baseline and with a greater incidence of hypertension at follow-up (+37%). Among those participants with CKD, regular PA was associated with a lower prevalence (-45% to -7%) and incidence (-38% to -4%) of all CVD risk factors. CONCLUSION: Although PA might not reduce incident CKD in the middle term (~2 years), it can attenuate the CVD risk linked to this condition.

The Tour de France, also possible for mortals? A comparison of a recreational and a World Tour cyclist.

Cycling Grand Tours are arguably the epitome of strenuous endurance exercise, and they have been reported to represent the ceiling of sustained energy expenditure for humans. It remains unknown, however, if an average recreational athlete could endure such an event. Through the analysis of power output (PO), we compared data from the 2023 Tour de France (21 stages, total distance = 3,405 km, elevation gain = 51,815 m) in a recreational (male, age = 58 yr; height = 191 cm; body mass = 96.1 kg; estimated maximum oxygen uptake = 45.4 mL·kg-1·min-1) and a sex-matched professional (World-Tour) cyclist (28 yr; 180 cm; 67.0 kg; 80.5 mL·kg-1·min-1). The recreational and professional cyclist completed the event in 191 and 87 h, respectively (average PO of 1.50 and 3.45 W·kg-1), with the latter spending a greater proportion of time in high-intensity zones. The recreational cyclist showed an estimated total daily energy expenditure (TDEE) of 35.9 MJ [or 8,580 kcal, or ∼4.3× his daily basal metabolic rate (BMR)], whereas lower absolute values were estimated for the professional cyclist (29.7 MJ, 7,098 kcal, ∼3.8× his BMR). Despite such high TDEE values, both individuals lost minimal body mass during the event (0-2 kg). The present report therefore suggests that, partly due to differences in exercise intensity and duration, not only professional cyclists but also recreational athletes can reach currently known ceilings of TDEE for humans.NEW & NOTEWORTHY This case report indicates that a recreationally trained 58-year-old man can reach similar or even higher values of energy expenditure (∼4 times their basal metabolic rate) than professional cyclists, who are likely near the ceiling of sustained energy expenditure for humans. This was possible owing to a total longer exercise time coupled with a lower absolute and relative intensity in the recreational athlete.

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.