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.

Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice.

BACKGROUND: Sarcopenia is defined by the progressive and generalized loss of muscle mass and function associated with aging. We have previously proposed that aging-related hyperphosphataemia is linked with the appearance of sarcopenia signs. Because there are not effective treatments to prevent sarcopenia, except for resistance exercise, we propose here to analyse whether the dietary restriction of phosphate could be a useful strategy to improve muscle function and structure in an animal model of aging. METHODS: Five-month-old (young), 24-month-old (old) and 28-month-old (geriatric) male C57BL6 mice were used. Old and geriatric mice were divided into two groups, one fed with a standard diet (0.6% phosphate) and the other fed with a low-phosphate (low-P) diet (0.2% phosphate) for 3 or 7 months, respectively. A phosphate binder, Velphoro®, was also supplemented in a group of old mice, mixed with a standard milled diet for 3 months. Muscle mass was measured by the weight of gastrocnemius and tibial muscles, and quality by nuclear magnetic resonance imaging (NMRI) and histological staining assays. Muscle strength was measured by grip test and contractile properties of the tibialis muscle by electrical stimulation of the common peroneal nerve. Gait parameters were analysed during the spontaneous locomotion of the mice with footprinting. Orientation and motor coordination were evaluated using a static rod test. RESULTS: Old mice fed with low-P diet showed reduced serum phosphate concentration (16.46 ± 0.77 mg/dL young; 21.24 ± 0.95 mg/dL old; 17.46 ± 0.82 mg/dL low-P diet). Old mice fed with low-P diet displayed 44% more mass in gastrocnemius muscles with respect to old mice (P = 0.004). NMRI revealed a significant reduction in T2 relaxation time (P = 0.014) and increased magnetization transfer (P = 0.045) and mean diffusivity (P = 0.045) in low-P diet-treated mice compared with their coetaneous. The hypophosphataemic diet increased the fibre size and reduced the fibrotic area by 52% in gastrocnemius muscle with respect to old mice (P = 0.002). Twitch force and tetanic force were significantly increased in old mice fed with the hypophosphataemic diet (P = 0.004 and P = 0.014, respectively). Physical performance was also improved, increasing gait speed by 30% (P = 0.032) and reducing transition time in the static rod by 55% (P = 0.012). Similar results were found when diet was supplemented with Velphoro®. CONCLUSIONS: The dietary restriction of phosphate in old mice improves muscle quantity and quality, muscle strength and physical performance. Similar results were found using the phosphate binder Velphoro®, supporting the role of phosphate in the impairment of muscle structure and function that occurs during aging.

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.

Individual responsiveness to a school-based karate intervention: An ancillary analysis of a randomized controlled trial.

INTRODUCTION: School-based sport interventions have shown beneficial effects on psychosocial functioning and academic performance in children. However, the inter-individual variability in response to these types of interventions remains unclear. We aimed to determine which children benefit most from a school-based sport intervention. METHODS: This is an ancillary analysis of a randomized controlled trial assessing the effects of a 1-year school-based karate intervention (versus "traditional" physical education lessons) in children (7-8 years) from twenty schools across five European countries. Outcomes included psychosocial functioning (Strengths and Difficulties Questionnaire [SDQ] for parents) and academic performance (grade point average). Only participants of the intervention group were included in the present ancillary analysis, and were categorized as responders or non-responders for the analyzed outcomes attending to whether improvements surpassed a minimal clinically important difference. RESULTS: About 388 children (187 girls) from the intervention group completed the study, of which 17% and 46% were considered responders for SDQ and academic performance, respectively. Responders for the SDQ presented higher SDQ scores (i.e., higher psychosocial difficulties) at baseline than non-responders (p < 0.001). Responders for academic performance were mostly males (p = 0.017), with an older age (p = 0.030), and with worse academic performance (p < 0.001) at baseline compared with non-responders, and tended to present higher SDQ scores (p = 0.055). Responders for one outcome obtained greater benefits from the intervention on the other outcome (e.g., responders for SDQ improved academic performance [p < 0.001] compared with non-responders). CONCLUSIONS: A school-based sport intervention (karate) seems particularly effective for children with psychosocial difficulties and low academic performance.

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.

Effects of Beef Protein Supplementation in Male Elite Triathletes: A Randomized, Controlled, Double-Blind, Cross-Over Study.

OBJECTIVE: Beef protein extracts are growing in popularity in recent years due to their purported anabolic effects as well as to their potential benefits on hematological variables. The present randomized, controlled, double-blind, cross-over study aimed to analyze the effects of beef protein supplementation on a group of male elite triathletes (Spanish National Team). METHODS: Six elite triathletes (age, 21 ± 3 years; VO2max, 71.5 ± 3.0 ml·kg·min-1) were randomly assigned to consume daily either 25 g of a beef supplement (BEEF) or an isoenergetic carbohydrates (CHO) supplement for 8 weeks, with both conditions being separated by a 5-week washout period. Outcomes, including blood analyses and anthropometrical measurements, were assessed before and after each 8-week intervention. RESULTS: No effects of supplement condition were observed on body mass nor on skinfold thicknesses, but BEEF induced significant and large benefits over CHO in the thigh cross-sectional area (3.02%, 95%CI = 1.33 to 4.71%; p = 0.028, d = 1.22). Contrary to CHO, BEEF presented a significant increase in vastus lateralis muscle thickness (p = 0.046), but differences between conditions were not significant (p = 0.173, d = 0.87). Although a significantly more favorable testosterone-to-cortisol ratio (TCR) was observed for BEEF over CHO (37%, 95% CI = 5 to 68%; p = 0.028, d = 1.29), no significant differences were found for the hematological variables (i.e., iron, ferritin, red blood cell count, hemoglobin or hematocrit). CONCLUSION: Beef protein supplementation seems to facilitate a more favorable anabolic environment (i.e., increased TCR and muscle mass) in male elite triathletes, with no impact on hematological variables.

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.

Caffeine Supplementation Improves Anaerobic Performance and Neuromuscular Efficiency and Fatigue in Olympic-Level Boxers.

BACKGROUND: this study examined the effects of caffeine supplementation on anaerobic performance, neuromuscular efficiency and upper and lower extremities fatigue in Olympic-level boxers. METHODS: Eight male athletes, members of the Spanish National Olympic Team, were enrolled in the study. In a randomized double-blind, placebo-controlled, counterbalanced, crossover design, the athletes completed 2 test sessions after the intake of caffeine (6 mg·kg-1) or placebo. Sessions involved initial measures of lactate, handgrip and countermovement jump (CMJ) performance, followed by a 30-seconds Wingate test, and then final measures of the previous variables. During the sessions, electromiography (EMG) data were recorded on the gluteus maximus, biceps femoris, vastus lateralis, gastrocnemius lateral head and tibialis anterior. RESULTS: caffeine enhanced peak power (6.27%, p < 0.01; Effect Size (ES) = 1.26), mean power (5.21%; p < 0.01; ES = 1.29) and reduced the time needed to reach peak power (-9.91%, p < 0.01; ES = 0.58) in the Wingate test, improved jump height in the CMJ (+2.4 cm, p < 0.01), and improved neuromuscular efficiency at peak power in the vastus lateralis (ES = 1.01) and gluteus maximus (ES = 0.89), and mean power in the vastus lateralis (ES = 0.95) and tibialis anterior (ES = 0.83). CONCLUSIONS: in these Olympic-level boxers, caffeine supplementation improved anaerobic performance without affecting EMG activity and fatigue levels in the lower limbs. Further benefits observed were enhanced neuromuscular efficiency in some muscles and improved reaction speed.

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.

Carbohydrate Availability and Physical Performance: Physiological Overview and Practical Recommendations.

Strong evidence during the last few decades has highlighted the importance of nutrition for sport performance, the role of carbohydrates (CHO) being of special interest. Glycogen is currently not only considered an energy substrate but also a regulator of the signaling pathways that regulate exercise-induced adaptations. Thus, low or high CHO availabilities can result in both beneficial or negative results depending on the purpose. On the one hand, the depletion of glycogen levels is a limiting factor of performance during sessions in which high exercise intensities are required; therefore ensuring a high CHO availability before and during exercise is of major importance. A high CHO availability has also been positively related to the exercise-induced adaptations to resistance training. By contrast, a low CHO availability seems to promote endurance-exercise-induced adaptations such as mitochondrial biogenesis and enhanced lipolysis. In the present narrative review, we aim to provide a holistic overview of how CHO availability impacts physical performance as well as to provide practical recommendations on how training and nutrition might be combined to maximize performance. Attending to the existing evidence, no universal recommendations regarding CHO intake can be given to athletes as nutrition should be periodized according to training loads and objectives.

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.