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Acute ketone supplementation in the absence of muscle glycogen utilization: Insights from McArdle disease.
Valenzuela, PL, Santalla, A, Alejo, LB, Bustos, A, Ozcoidi, LM, Castellote-Bellés, L, Ferrer-Costa, R, Villarreal-Salazar, M, Morán, M, Barranco-Gil, D, et al
Clinical nutrition (Edinburgh, Scotland). 2024;(3):692-700
Abstract
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.
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2.
Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.
Western, B, Ivarsson, A, Vistad, I, Demmelmaier, I, Aaronson, NK, Radcliffe, G, van Beurden, M, Bohus, M, Courneya, KS, Daley, AJ, et al
Scandinavian journal of medicine & science in sports. 2024;(2):e14575
Abstract
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.
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High-dose short-term creatine supplementation without beneficial effects in professional cyclists: a randomized controlled trial.
Barranco-Gil, D, Alejo, LB, Revuelta, C, Górriz, M, Pagola, I, Ozcoidi, LM, Lucia, A, Valenzuela, PL
Journal of the International Society of Sports Nutrition. 2024;(1):2340574
Abstract
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.
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Integrative metabolomics science in Alzheimer's disease: Relevance and future perspectives.
Lista, S, González-Domínguez, R, López-Ortiz, S, González-Domínguez, Á, Menéndez, H, Martín-Hernández, J, Lucia, A, Emanuele, E, Centonze, D, Imbimbo, BP, et al
Ageing research reviews. 2023;:101987
Abstract
Alzheimer's disease (AD) is determined by various pathophysiological mechanisms starting 10-25 years before the onset of clinical symptoms. As multiple functionally interconnected molecular/cellular pathways appear disrupted in AD, the exploitation of high-throughput unbiased omics sciences is critical to elucidating the precise pathogenesis of AD. Among different omics, metabolomics is a fast-growing discipline allowing for the simultaneous detection and quantification of hundreds/thousands of perturbed metabolites in tissues or biofluids, reproducing the fluctuations of multiple networks affected by a disease. Here, we seek to critically depict the main metabolomics methodologies with the aim of identifying new potential AD biomarkers and further elucidating AD pathophysiological mechanisms. From a systems biology perspective, as metabolic alterations can occur before the development of clinical signs, metabolomics - coupled with existing accessible biomarkers used for AD screening and diagnosis - can support early disease diagnosis and help develop individualized treatment plans. Presently, the majority of metabolomic analyses emphasized that lipid metabolism is the most consistently altered pathway in AD pathogenesis. The possibility that metabolomics may reveal crucial steps in AD pathogenesis is undermined by the difficulty in discriminating between the causal or epiphenomenal or compensatory nature of metabolic findings.
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Pre-sleep protein supplementation in professional cyclists during a training camp: a three-arm randomized controlled trial.
Valenzuela, PL, Alejo, LB, Montalvo-Pérez, A, Ojanguren, D, Górriz, M, Pagola, I, Ozcoidi, LM, Lucia, A, Barranco-Gil, D
Journal of the International Society of Sports Nutrition. 2023;(1):2166366
Abstract
BACKGROUND The effects of pre-sleep protein supplementation on endurance athletes remain unclear, particularly whether its potential benefits are due to the timing of protein intake or solely to an increased total protein intake. We assessed the effects of pre-sleep protein supplementation in professional cyclists during a training camp accounting for the influence of protein timing. METHODS Twenty-four professional U23 cyclists (19 ± 1 years, peak oxygen uptake: 79.8 ± 4.9 ml/kg/min) participated in a six-day training camp. Participants were randomized to consume a protein supplement (40 g of casein) before sleep (n = 8) or in the afternoon (n = 8), or an isoenergetic placebo (40 g of carbohydrates) before sleep (n = 8). Indicators of fatigue/recovery (Hooper index, Recovery-Stress Questionnaire for Athletes, countermovement jump), body composition, and performance (1-, 5-, and 20-minute time trials, as well as the estimated critical power) were assessed as study outcomes. RESULTS The training camp resulted in a significant (p < 0.001) increase in training loads (e.g. training stress score of 659 ± 122 per week during the preceding month versus 1207 ± 122 during the training camp), which induced an increase in fatigue indicators (e.g. time effect for Hooper index p < 0.001) and a decrease in performance (e.g. time effect for critical power p = 0.002). Protein intake was very high in all the participants (>2.5 g/kg on average), with significantly higher levels found in the two protein supplement groups compared to the placebo group (p < 0.001). No significant between-group differences were found for any of the analyzed outcomes (all p > 0.05). CONCLUSIONS Protein supplementation, whether administered before sleep or earlier in the day, exerts no beneficial effects during a short-term strenuous training period in professional cyclists, who naturally consume a high-protein diet.
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Prevention of cardiorenal damage: importance of albuminuria.
Ruilope, LM, Ortiz, A, Lucia, A, Miranda, B, Alvarez-Llamas, G, Barderas, MG, Volpe, M, Ruiz-Hurtado, G, Pitt, B
European heart journal. 2023;(13):1112-1123
Abstract
Chronic kidney disease (CKD) is projected to become a leading global cause of death by 2040, and its early detection is critical for effective and timely management. The current definition of CKD identifies only advanced stages, when kidney injury has already destroyed >50% of functioning kidney mass as reflected by an estimated glomerular filtration rate <60 mL/min/1.73 m2 or a urinary albumin/creatinine ratio >six-fold higher than physiological levels (i.e. > 30 mg/g). An elevated urinary albumin-excretion rate is a known early predictor of future cardiovascular events. There is thus a 'blind spot' in the detection of CKD, when kidney injury is present but is undetectable by current diagnostic criteria, and no intervention is made before renal and cardiovascular damage occurs. The present review discusses the CKD 'blind spot' concept and how it may facilitate a holistic approach to CKD and cardiovascular disease prevention and implement the call for albuminuria screening implicit in current guidelines. Cardiorenal risk associated with albuminuria in the high-normal range, novel genetic and biochemical markers of elevated cardiorenal risk, and the role of heart and kidney protective drugs evaluated in recent clinical trials are also discussed. As albuminuria is a major risk factor for cardiovascular and renal disease, starting from levels not yet considered in the definition of CKD, the implementation of opportunistic or systematic albuminuria screening and therapy, possibly complemented with novel early biomarkers, has the potential to improve cardiorenal outcomes and mitigate the dismal 2040 projections for CKD and related cardiovascular burden.
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Obesity, cardiovascular risk, and lifestyle: cross-sectional and prospective analyses in a nationwide Spanish cohort.
Valenzuela, PL, Santos-Lozano, A, Saco-Ledo, G, Castillo-García, A, Lucia, A
European journal of preventive cardiology. 2023;(14):1493-1501
Abstract
AIMS: To assess whether overweight and obesity are independently associated with cardiometabolic health [as categorized based on the presence/absence of cardiovascular disease (CVD) risk factors (diabetes, hypercholesterolaemia, or hypertension)], and the role of lifestyle on this association. METHODS AND RESULTS A nationwide cohort of Spanish adults (18-64 years) was studied using a cross-sectional design and prospective observational design. Lifestyle-related factors (physical activity, sleeping characteristics, alcohol drinking, and smoking) were registered, and participants were classified as having an 'unhealthy' or 'healthy' cardiometabolic status attending to the presence or absence, respectively, of ≥1 CVD risk factor. A number of 596 111 participants (44 ± 9 years, 67% male) were studied at baseline, with prospective analyses in a subcohort [n = 302 061; median follow-up, 2 years (range, 2 to 5)]. Compared to normal weight, overweight and obesity were associated with a higher prevalence [odds ratio, 1.67 (95% confidence interval, 1.61-1.67) and 2.70 (2.69-2.78), respectively] and incidence [1.62 (1.59-1.67) and 2.70 (2.63-2.78)] of an unhealthy cardiometabolic status. Meeting physical activity guidelines reduced the odds of an unhealthy cardiometabolic status at baseline [0.87 (0.85-0.88)] among individuals with overweight/obesity, as well as of transitioning from a healthy status to an unhealthy status during the follow-up [0.87 (0.84-0.94)]. No significant associations were found for the remainder of lifestyle factors. CONCLUSION Overweight and obesity are independently associated with an unhealthy cardiometabolic status. Regular physical activity attenuates not only the prevalence but also the incidence of CVD risk factors.
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Data from the European registry for patients with McArdle disease (EUROMAC): functional status and social participation.
Karazi, W, Scalco, RS, Stemmerik, MG, Løkken, N, Lucia, A, Santalla, A, Martinuzzi, A, Vavla, M, Reni, G, Toscano, A, et al
Orphanet journal of rare diseases. 2023;(1):210
Abstract
BACKGROUND The European registry for individuals with GSD5 and other muscle glycogenosis (EUROMAC) was launched to register rare muscle glycogenosis in Europe, to facilitate recruitment for research trials and to learn about the phenotypes and disseminate knowledge about the diseases. A network of twenty collaborating partners from eight European countries and the US contributed data on rare muscle glycogenosis in the EUROMAC registry. METHODS Following the initial report on demographics, neuromuscular features and comorbidity (2020), we here present the data on social participation, previous and current treatments (medication, supplements, diet and rehabilitation) and limitations. Furthermore, the following questionnaires were used: Fatigue severity scale (FSS), WHO Disability Assessment Scale (DAS 2.0), health related quality of life (SF36) and International Physical Activity Questionnaire (IPAQ). RESULTS Of 282 participants with confirmed diagnoses of muscle glycogenosis, 269 had GSD5. Of them 196 (73%) completed all questionnaires; for the others, the data were incomplete. The majority, 180 (67%) were currently working. Previous medical treatments included pain medication (23%) and rehabilitation treatment (60%). The carbohydrate-rich diet was reported to be beneficial for 68%, the low sucrose diet for 76% and the ketogenic diet for 88%. Almost all participants (93%) reported difficulties climbing stairs. The median FSS score was 5.22, indicating severe fatigue. The data from the WHODAS and IPAQ was not of sufficient quality to be interpreted. CONCLUSIONS The EUROMAC registry have provided insight into the functional and social status of participants with GSD5: most participants are socially active despite limitations in physical and daily life activities. Regular physical activity and different dietary approaches may alleviate fatigue and pain.
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Defining and assessing intrinsic capacity in older people: A systematic review and a proposed scoring system.
López-Ortiz, S, Lista, S, Peñín-Grandes, S, Pinto-Fraga, J, Valenzuela, PL, Nisticò, R, Emanuele, E, Lucia, A, Santos-Lozano, A
Ageing research reviews. 2022;:101640
Abstract
INTRODUCTION The World Health Organization has introduced the term 'intrinsic capacity' (IC) as a marker of healthy ageing. However, controversy exists on the definition and assessment of IC. We aimed to review the definitions and methods used for the assessment of IC in older adults. In addition, we proposed a new IC scoring method. METHODS A systematic search was performed in PubMed, Web of Science, Cochrane Library, Scopus and SPORTDiscus (up to February 10th, 2022) for studies assesing IC in older adults (>60 years). RESULTS Thirty-three studies were included. There is overall consensus on the definition of IC as well as on its different dimensions, that is: locomotion, vitality, sensory, cognition and psychological. However, the methods for assessing each of these five dimensions differ substantially across studies and there is no consensus on the best method to compute an eventual global compound score to evaluate IC taking into account all its different dimensions. CONCLUSIONS The IC represents a highly relevant clinical concept that has been unfortunately underutilized. We propose a standardization for the assessment of each dimension of IC, with a global 0 (worst) to 10 (highest) score.
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Exerkines in health, resilience and disease.
Chow, LS, Gerszten, RE, Taylor, JM, Pedersen, BK, van Praag, H, Trappe, S, Febbraio, MA, Galis, ZS, Gao, Y, Haus, JM, et al
Nature reviews. Endocrinology. 2022;(5):273-289
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Abstract
The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways. A multitude of organs, cells and tissues release these factors, including skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (baptokines) and neurons (neurokines). Exerkines have potential roles in improving cardiovascular, metabolic, immune and neurological health. As such, exerkines have potential for the treatment of cardiovascular disease, type 2 diabetes mellitus and obesity, and possibly in the facilitation of healthy ageing. This Review summarizes the importance and current state of exerkine research, prevailing challenges and future directions.