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.

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.

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.

Pre-sleep protein supplementation in professional cyclists during a training camp: a three-arm randomized controlled trial.

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.

Acute effects of electrostimulation and blood flow restriction on muscle thickness and fatigue in the lower body.

Neuromuscular electrical stimulation (NMES) in combination with blood flow restriction (BFR) enhances muscle hypertrophy and force-generating capacity. The present study aimed to investigate the acute effects of BFR and NMES, both in isolation and in combination, on muscle thickness (MT) and fatigue in the lower body of 20 young healthy subjects. Different stimuli were applied for 25 min, defined by the combination of BFR with high- and low-frequency NMES, and also isolated BFR or NMES. Changes in MT were then evaluated by ultrasound of the rectus femoris (RF) and vastus lateralis (VL) muscles at the end of the session (POST) and 15 min later (POST 15'). Lower limb fatigue was evaluated indirectly by strength performance. Results showed that RF MT was higher under the combined protocol (BFR + NMES) or isolated BFR than under NMES - regardless of the frequency - both at POST (p ≤ 0.018) and POST 15' (p ≤ 0.016). No significant changes in MT were observed under isolated NMES or BFR at POST 15' when compared with basal values (p ≥ 0.067). No significant differences were observed for VL MT between conditions (p = 0.322) or for fatigue between conditions (p ≥ 0.258). Our results indicate that a combination of BFR and NMES acutely increases MT in sedentary subjects. Also, although not significantly, BFR conditions had a greater tendency to induce fatigue than isolated NMES.HighlightsThe combination of blood flow restriction (BFR) and neuromuscular electrical stimulation (NMES) produces higher acute cell swelling than the isolated application of either NMES or BFR.BFR in isolation appears to produce greater cell swelling than NMES, regardless of the frequency used.BFR conditions had a greater tendency to induce fatigue than isolated NMES.

Exercise Training and Natural Killer Cells in Cancer Survivors: Current Evidence and Research Gaps Based on a Systematic Review and Meta-analysis.

BACKGROUND: Exercise training can positively impact the immune system and particularly natural killer (NK) cells, at least in healthy people. This effect would be of relevance in the context of cancer given the prominent role of these cells in antitumor immunity. In this systematic review and meta-analysis, we aimed to summarize current evidence on the effects of exercise training on the levels and function of NK cells in cancer survivors (i.e., from the time of diagnosis until the end of life). METHODS: Relevant articles were searched in PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (until January 11, 2022). Randomized controlled trials (RCT) of exercise training (i.e., non-acute) interventions vs usual care conducted in cancer survivors and assessing NK number and/or cytotoxic activity (NKCA) before and upon completion of the intervention were included. Methodological quality of the studies was assessed with the PEDro scale, and results were meta-analyzed using a random effects (Dersimoian and Laird) model. RESULTS: Thirteen RCT including 459 participants (mean age ranging 11-63 years) met the inclusion criteria. Methodological quality of the studies was overall fair (median PEDro score = 5 out of 10). There was heterogeneity across studies regarding cancer types (breast cancer, non-small cell lung cancer and other solid tumors), treatment (e.g., receiving vs having received chemotherapy), exercise modes (aerobic or resistance exercise, Tai Chi, Yoga) and duration (2-24 weeks). No consistent effects were observed for NK number in blood (mean difference [MD]: 1.47, 95% confidence interval [CI] - 0.35 to 3.29, p = 0.113) or NKCA as assessed in vitro (MD: - 0.02, 95%CI - 0.17 to 0.14, p = 0.834). However, mixed results existed across studies, and some could not be meta-analyzed due to lack of information or methodological heterogeneity. CONCLUSIONS: Current evidence does not support a significant effect of exercise training intervention on NK cells in blood or on their 'static response' (as assessed in vitro) in cancer survivors. Several methodological issues and research gaps are highlighted in this review, which should be considered in future studies to draw definite conclusions on this topic.

Omics sciences for systems biology in Alzheimer's disease: State-of-the-art of the evidence.

Alzheimer's disease (AD) is characterized by non-linear, genetic-driven pathophysiological dynamics with high heterogeneity in biological alterations and disease spatial-temporal progression. Human in-vivo and post-mortem studies point out a failure of multi-level biological networks underlying AD pathophysiology, including proteostasis (amyloid-ß and tau), synaptic homeostasis, inflammatory and immune responses, lipid and energy metabolism, oxidative stress. Therefore, a holistic, systems-level approach is needed to fully capture AD multi-faceted pathophysiology. Omics sciences - genomics, epigenomics, transcriptomics, proteomics, metabolomics, lipidomics - embedded in the systems biology (SB) theoretical and computational framework can generate explainable readouts describing the entire biological continuum of a disease. Such path in Neurology is encouraged by the promising results of omics sciences and SB approaches in Oncology, where stage-driven pathway-based therapies have been developed in line with the precision medicine paradigm. Multi-omics data integrated in SB network approaches will help detect and chart AD upstream pathomechanistic alterations and downstream molecular effects occurring in preclinical stages. Finally, integrating omics and neuroimaging data - i.e., neuroimaging-omics - will identify multi-dimensional biological signatures essential to track the clinical-biological trajectories, at the subpopulation or even individual level.

Perspective: Ketone Supplementation in Sports-Does It Work?

Oral ketone supplements have gained popularity in recent years. There is biological rationale for a potential ergogenic effect of this type of supplement, as they might not only alter muscle fuel preference during exercise (and promote glycogen sparing, with potential benefits for endurance performance) but also favor cognition performance during exertion or muscle glycogen synthesis after exercise. However, as discussed in this Perspective, evidence to date does not support a benefit of acute ketone supplementation on sports performance, cognition, or muscle recovery [although further research with long-duration exercise (i.e., >60 min), is needed], and the evidence for chronic supplementation is sparse. In addition, acute intake of ketone supplements might be associated with gastrointestinal symptoms, and further research is warranted on the long-term safety of repeated use of ketone supplements. In summary, there is currently insufficient evidence to support the overall effectiveness of ketone supplements in sports.

Exercise Benefits Meet Cancer Immunosurveillance: Implications for Immunotherapy.

Regular exercise reduces the risk of cancer. One potential mechanism for this efficacy is improved antitumor immunity. This is an important issue because evading immune destruction is a hallmark of cancer and immunotherapy is reshaping cancer treatment. Here we review recent developments reported by Wennerberg et al., Garritson et al., Martín-Ruiz et al., and Rundqvist et al. on the effects of exercise on anticancer immune cell effectors.

Intradialytic neuromuscular electrical stimulation improves functional capacity and muscle strength in people receiving haemodialysis: a systematic review.

QUESTIONS: Does neuromuscular electrical stimulation (NMES) applied during haemodialysis sessions improve functional capacity in people with end-stage renal disease? Does NMES used in this way also improve muscle strength, muscle mass/architecture, psychological outcomes, cardiovascular outcomes and biochemical variables? Does it have any adverse effects? DESIGN: Systematic review of randomised controlled trials with meta-analysis. PubMed, Web of Science, Scopus and SPORTDiscus were searched from inception to 15 October 2019. PARTICIPANTS: Patients receiving haemodialysis for end-stage renal disease. INTERVENTION: NMES administered during haemodialysis sessions versus control. OUTCOMES MEASURES: Functional capacity, muscle strength, muscle mass, psychological outcomes, cardiovascular outcomes, biochemical variables and adverse events. DATA ANALYSIS: Data were meta-analysed where possible and results were expressed as the pooled mean difference between groups with a 95% confidence interval. RESULTS: Eight studies (221 patients) were included in the analysis. Overall, the methodological quality of the studies was fair to good. NMES improved functional capacity as assessed by the 6-minute walk distance test (MD 31 m, 95% CI 13 to 49) and peak workload attained in incremental exercise (MD 12.5 W, 95% CI 3.2 to 21.9). NMES increased knee extensor muscle strength (MD 3.5 kg, 95% CI 2.3 to 4.7) and handgrip strength (MD 2.4 kg, 95% CI 0.4 to 4.4). Muscle mass/architecture was not substantially affected. NMES was estimated to be beneficial for several domains of quality of life in several studies, although most of these estimates were imprecise. No benefits were found for cardiovascular outcomes. The available data did not establish any clear effects on cardiovascular outcomes or biochemical variables (dialysis efficiency, urea and creatinine). No major NMES-related adverse events were observed. CONCLUSIONS: NMES is safe, practical and effective for improving functional capacity and muscle strength in haemodialysis patients. Further research is needed to confirm the clinical relevance of these findings. REGISTRATION: PROSPERO CRD42018107323.

Does Beef Protein Supplementation Improve Body Composition and Exercise Performance? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Protein supplementation might improve body composition and exercise performance. Supplements containing whey protein (WP) have received the most attention, but other protein sources such as beef protein (BP) are gaining popularity. We conducted a systematic review and meta-analysis of randomized controlled trials that compared the effects of exercise training combined with BP, WP or no protein supplementation (NP), on body composition or exercise performance. Secondary endpoints included intervention effects on total protein intake and hematological parameters. Seven studies (n = 270 participants) were included. No differences were found between BP and WP for total protein intake (standardized mean difference (SMD) = 0.04, p = 0.892), lean body mass (LBM) (SMD = -0.01, p = 0.970) or fat mass (SMD = 0.07, p = 0.760). BP significantly increased total daily protein intake (SMD = 0.68, p < 0.001), LBM (SMD = 0.34, p = 0.049) and lower-limb muscle strength (SMD = 0.40, p = 0.014) compared to NP, but no significant differences were found between both conditions for fat mass (SMD = 0.15, p = 0.256), upper-limb muscle strength (SMD = 0.16, p = 0.536) or total iron intake (SMD = 0.29, p = 0.089). In summary, BP provides similar effects to WP on protein intake and body composition and, compared to NP, might be an effective intervention to increase total daily protein intake, LBM and lower-limb muscle strength.

Supplements with purported effects on muscle mass and strength.

PURPOSE: Several supplements are purported to promote muscle hypertrophy and strength gains in healthy subjects, or to prevent muscle wasting in atrophying situations (e.g., ageing or disuse periods). However, their effectiveness remains unclear. METHODS: This review summarizes the available evidence on the beneficial impacts of several popular supplements on muscle mass or strength. RESULTS: Among the supplements tested, nitrate and caffeine returned sufficient evidence supporting their acute beneficial effects on muscle strength, whereas the long-term consumption of creatine, protein and polyunsaturated fatty acids seems to consistently increase or preserve muscle mass and strength (evidence level A). On the other hand, mixed or unclear evidence was found for several popular supplements including branched-chain amino acids, adenosine triphosphate, citrulline, ß-Hydroxy-ß-methylbutyrate, minerals, most vitamins, phosphatidic acid or arginine (evidence level B), weak or scarce evidence was found for conjugated linoleic acid, glutamine, resveratrol, tribulus terrestris or ursolic acid (evidence level C), and no evidence was found for other supplements such as ornithine or α-ketoglutarate (evidence D). Of note, although most supplements appear to be safe when consumed at typical doses, some adverse events have been reported for some of them (e.g., caffeine, vitamins, α-ketoglutarate, tribulus terrestris, arginine) after large intakes, and there is insufficient evidence to determine the safety of many frequently used supplements (e.g., ornithine, conjugated linoleic acid, ursolic acid). CONCLUSION:  In summary, despite their popularity, there is little evidence supporting the use of most supplements, and some of them have been even proven ineffective or potentially associated with adverse effects.

Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors.

Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia-reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health.

Missense mutations have unexpected consequences: The McArdle disease paradigm.

McArdle disease is a disorder of muscle glycogen metabolism caused by mutations in the PYGM gene, encoding for the muscle-specific isoform of glycogen phosphorylase (M-GP). The activity of this enzyme is completely lost in patients' muscle biopsies, when measured with a standard biochemical test which, does not allow to determine M-GP protein levels. We aimed to determine M-GP protein levels in the muscle of McArdle patients, by studying biopsies of 40 patients harboring a broad spectrum of PYGM mutations and 22 controls. Lack of M-GP protein was found in muscle in the vast majority (95%) of patients, irrespective of the PYGM genotype, including those carrying missense mutations, with few exceptions. M-GP protein biosynthesis is not being produced by PYGM mutations inducing premature termination codons (PTC), neither by most PYGM missense mutations. These findings explain the lack of PYGM genotype-phenotype correlation and have important implications for the design of molecular-based therapeutic approaches.

Benefits of skeletal-muscle exercise training in pulmonary arterial hypertension: The WHOLEi+12 trial.

BACKGROUND: Pulmonary arterial hypertension is often associated with skeletal-muscle weakness. The purpose of this randomized controlled trial was to determine the effects of an 8-week intervention combining muscle resistance, aerobic and inspiratory pressure-load exercises on upper/lower-body muscle power and other functional variables in patients with this disease. METHODS: Participants were allocated to a control (standard care) or intervention (exercise) group (n=20 each, 45±12 and 46±11years, 60% women and 10% patients with chronic thromboembolic pulmonary hypertension per group). The intervention included five, three and six supervised (inhospital) sessions/week of aerobic, resistance and inspiratory muscle training, respectively. The primary endpoint was peak muscle power during bench/leg press; secondary outcomes included N-terminal pro-brain natriuretic peptide levels, 6-min walking distance, five-repetition sit-to-stand test, maximal inspiratory pressure, cardiopulmonary exercise testing variables (e.g., peak oxygen uptake), health-related quality of life, physical activity levels, and safety. RESULTS: Adherence to training sessions averaged 94±0.5% (aerobic), 98±0.3% (resistance) and 91±1% (inspiratory training). Analysis of variance showed a significant interaction (group×time) effect for leg/bench press (P<0.001/P=0.002), with both tests showing an improvement in the exercise group (P<0.001) but not in controls (P>0.1). We found a significant interaction effect (P<0.001) for five-repetition sit-to-stand test, maximal inspiratory pressure and peak oxygen uptake (P<0.001), indicating a training-induced improvement. No major adverse event was noted due to exercise. CONCLUSIONS: An 8-week exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables.

Influence of a Moderate-Intensity Exercise Program on Early NK Cell Immune Recovery in Pediatric Patients After Reduced-Intensity Hematopoietic Stem Cell Transplantation.

INTRODUCTION: After allogeneic hematopoietic stem cell transplantation (HSCT), NK cell reconstitution, which is crucial for positive outcomes, is dominated by the CD56bright subset with low NK cell cytotoxicity (NKCC) activity. Moderate exercise has been described as a potent NK cell stimulus in adults with cancer. PURPOSE: To determine the effects of a moderate-intensity exercise program on NK cell recovery early after HSCT and the feasibility of this intervention. METHODS: Six children undergoing allogeneic HSCT were randomized to an exercise program (EP) or control (CT) group. The EP group performed a 10-week training combining in-hospital and home-based EP. RESULTS: We observed a significant increase in the posttraining/pretraining ratio of the CD56dim subset (EP = 1.27 ± 0.07; CT = 0.99 ± 0.08; P < .005) of the EP group. The ratio of NKCC was 8 times greater in the EP group. CONCLUSION: Data suggest that a moderate-intensity EP program performed early after HSCT is feasible and might redistribute the CD56dim/CD56brigh NK cell subset, improving NKCC. The results are still preliminary and must be interpreted with caution.

Exercise and Preexercise Nutrition as Treatment for McArdle Disease.

McArdle disease is due to an inborn defect in the muscle isoform of glycogen phosphorylase (or "myophosphorylase"), the enzyme that catalyzes the first step of glycogenolysis. This condition is still not fully understood, and although advances in research would help patients immeasurably, these would also enhance our understanding of exercise metabolism. It has been 10 yr since the first published report demonstrating the benefits of regular aerobic exercise for these patients. However, misconceptions remain and the value of exercise prescription for patients with McArdle disease is still overlooked. Here, we review the role of exercise in McArdle disease with the aim to better inform health-care professionals and thus better serve the interests of patients. Recommendations for regular exercise together with preexercise nutrition in children and adult patients are also provided along with examples of exercise practice and its benefits.

Upper versus lower limb exercise training in patients with intermittent claudication: a systematic review.

Lower extremity (LE) exercise training has been shown to contribute to improvements in Maximum Walking Distance (MWD), Claudication Distance (CD), peak oxygen uptake (VO2peak) and Quality of Life (QoL) in patients with intermittent claudication (IC). However, little is known regarding the efficacy of upper extremity (UE) exercise training in comparison to the widely used LE training. The objective of this systematic literature review is to identify and synthesize the available literature on the effects of UE versus LE exercises using the International Classification of Functioning (ICF) conceptual framework. A total of 6 randomized controlled trials comparing UE to LE exercises were included in this study. Two of the articles were considered to be of high quality using the PEDro grading list. Both UE and LE training groups demonstrated significant improvements in MWD, CD, VO2peak and QoL in comparison to the control group but LE was not better than UE training. This supports the use of UE training as an alternative to LE, which could provide symptomatic relief to patients with IC without the discomfort caused during the LE training.

No association between ACTN3 R577X polymorphism and elite judo athletic status.

The authors compared ACTN3 R577X genotype and allele frequencies in the majority of all-time-best Spanish judo male athletes (n = 108) and 343 ethnically matched nonathletic men. No between-groups differences were found in allele (P = .077) or genotype distributions (P = .178). Thus, the R577X polymorphism was not significantly associated with the status of being an elite judo athlete, at least in the Spanish population. The contribution of genetics to sports-related phenotype traits is undeniable with some genotypes, of which ACTN3 R577X is currently the leading candidate, partly distinguishing individuals predisposed to either endurance or power sports. However, few athletic events can be categorized as purely power or endurance based. Although genetic testing (ie, for ACTN3 R577X) is already being marketed to predict sports talent and potential of young children, its usefulness is still questionable, at least in competitive judo.