Physiological Roles of Carnosine in Myocardial Function and Health.

Carnosine is a pleiotropic histidine-containing dipeptide synthesized from ß-alanine and l-histidine, with the intact dipeptide and constituent amino acids being available from the diet. The therapeutic application of carnosine in myocardial tissue is promising, with carnosine playing a potentially beneficial role in both healthy and diseased myocardial models. This narrative review discusses the role of carnosine in myocardial function and health, including an overview of the metabolic pathway of carnosine in the myocardial tissue, the roles carnosine may play in the myocardium, and a critical analysis of the literature, focusing on the effect of exogenous carnosine and its precursors on myocardial function. By so doing, we aim to identify current gaps in the literature, thereby identifying considerations for future research.

Patterns of weight cycling in youth Olympic combat sports: a systematic review.

BACKGROUND: Patterns of weight cycling in adult combat sports have been extensively studied, yet data on this matter in youth combat athletes is rather scarce. METHODS: PubMed, EBSCOhost and Web of Science were used to retrieve relevant data. Eligible studies had to record the methods used to elicit rapid weight loss (RWL) and/or record the oscillations in bodyweight during the RWL phase. Only studies conducted in the context of an official competition were considered for inclusion in the present review. RESULTS: RWL is highly prevalent in children and adolescent combat athletes, ranging from 25 to 94% depending on the type of combat sport, age and level of competition. These athletes regularly prompt RWL by increasing exercise frequency and intensity, decreasing fluid and food intake, training in impermeable suits and using sauna frequently. Overall, the magnitude of RWL was ranging from ~ 1% to 6.3 ± 3.7% with significant RWL variations within individual studies and individuals within those studies. CONCLUSION: Acquired data indicated that RWL patterns in young combat athletes are similar to those found in their adult counterparts. Knowing that childhood and adolescence are critical periods for growth and development, RWL needs to be stringently regulated and ideally banned in this population.

Extracellular Buffering Supplements to Improve Exercise Capacity and Performance: A Comprehensive Systematic Review and Meta-analysis.

BACKGROUND: Extracellular buffering supplements [sodium bicarbonate (SB), sodium citrate (SC), sodium/calcium lactate (SL/CL)] are ergogenic supplements, although questions remain about factors which may modify their effect. OBJECTIVE: To quantify the main effect of extracellular buffering agents on exercise outcomes, and to investigate the influence of potential moderators on this effect using a systematic review and meta-analytic approach. METHODS: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Three databases were searched for articles that were screened according to inclusion/exclusion criteria. Bayesian hierarchical meta-analysis and meta-regression models were used to investigate pooled effects of supplementation and moderating effects of a range of factors on exercise and biomarker responses. RESULTS: 189 articles with 2019 participants were included, 158 involving SB supplementation, 30 with SC, and seven with CL/SL; four studies provided a combination of buffering supplements together. Supplementation led to a mean estimated increase in blood bicarbonate of + 5.2 mmol L-1 (95% credible interval (CrI) 4.7-5.7). The meta-analysis models identified a positive overall effect of supplementation on exercise capacity and performance compared to placebo [ES0.5 = 0.17 (95% CrI 0.12-0.21)] with potential moderating effects of exercise type and duration, training status and when the exercise test was performed following prior exercise. The greatest ergogenic effects were shown for exercise durations of 0.5-10 min [ES0.5 = 0.18 (0.13-0.24)] and > 10 min [ES0.5 = 0.22 (0.10-0.33)]. Evidence of greater effects on exercise were obtained when blood bicarbonate increases were medium (4-6 mmol L-1) and large (> 6 mmol L-1) compared with small (≤ 4 mmol L-1) [ßSmall:Medium = 0.16 (95% CrI 0.02-0.32), ßSmall:Large = 0.13 (95% CrI - 0.03 to 0.29)]. SB (192 outcomes) was more effective for performance compared to SC (39 outcomes) [ßSC:SB = 0.10 (95% CrI - 0.02 to 0.22)]. CONCLUSIONS: Extracellular buffering supplements generate large increases in blood bicarbonate concentration leading to positive overall effects on exercise, with sodium bicarbonate being most effective. Evidence for several group-level moderating factors were identified. These data can guide an athlete's decision as to whether supplementation with buffering agents might be beneficial for their specific aims.

International Society of Sports Nutrition position stand: sodium bicarbonate and exercise performance.

Based on a comprehensive review and critical analysis of the literature regarding the effects of sodium bicarbonate supplementation on exercise performance, conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society: 1. Supplementation with sodium bicarbonate (doses from 0.2 to 0.5 g/kg) improves performance in muscular endurance activities, various combat sports, including boxing, judo, karate, taekwondo, and wrestling, and in high-intensity cycling, running, swimming, and rowing. The ergogenic effects of sodium bicarbonate are mostly established for exercise tasks of high-intensity that last between 30 s and 12 min. 2. Sodium bicarbonate improves performance in single- and multiple-bout exercise. 3. Sodium bicarbonate improves exercise performance in both men and women. 4. For single-dose supplementation protocols, 0.2 g/kg of sodium bicarbonate seems to be the minimum dose required to experience improvements in exercise performance. The optimal dose of sodium bicarbonate dose for ergogenic effects seems to be 0.3 g/kg. Higher doses (e.g., 0.4 or 0.5 g/kg) may not be required in single-dose supplementation protocols, because they do not provide additional benefits (compared with 0.3 g/kg) and are associated with a higher incidence and severity of adverse side-effects. 5. For single-dose supplementation protocols, the recommended timing of sodium bicarbonate ingestion is between 60 and 180 min before exercise or competition. 6. Multiple-day protocols of sodium bicarbonate supplementation can be effective in improving exercise performance. The duration of these protocols is generally between 3 and 7 days before the exercise test, and a total sodium bicarbonate dose of 0.4 or 0.5 g/kg per day produces ergogenic effects. The total daily dose is commonly divided into smaller doses, ingested at multiple points throughout the day (e.g., 0.1 to 0.2 g/kg of sodium bicarbonate consumed at breakfast, lunch, and dinner). The benefit of multiple-day protocols is that they could help reduce the risk of sodium bicarbonate-induced side-effects on the day of competition. 7. Long-term use of sodium bicarbonate (e.g., before every exercise training session) may enhance training adaptations, such as increased time to fatigue and power output. 8. The most common side-effects of sodium bicarbonate supplementation are bloating, nausea, vomiting, and abdominal pain. The incidence and severity of side-effects vary between and within individuals, but it is generally low. Nonetheless, these side-effects following sodium bicarbonate supplementation may negatively impact exercise performance. Ingesting sodium bicarbonate (i) in smaller doses (e.g., 0.2 g/kg or 0.3 g/kg), (ii) around 180 min before exercise or adjusting the timing according to individual responses to side-effects, (iii) alongside a high-carbohydrate meal, and (iv) in enteric-coated capsules are possible strategies to minimize the likelihood and severity of these side-effects. 9. Combining sodium bicarbonate with creatine or beta-alanine may produce additive effects on exercise performance. It is unclear whether combining sodium bicarbonate with caffeine or nitrates produces additive benefits. 10. Sodium bicarbonate improves exercise performance primarily due to a range of its physiological effects. Still, a portion of the ergogenic effect of sodium bicarbonate seems to be placebo-driven.

Effect of Carnosine or ß-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis.

There is growing evidence that supplementation with carnosine, or its rate-limiting precursor ß-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or ß-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. We performed a systematic search of 6 electronic databases up to 31 December 2020. Primary outcomes were changes in 1) fasting glucose, 2) glycated hemoglobin (HbA1c), and 3) 2-h glucose following a glucose-tolerance test. A set of additional outcomes included fasting insulin and homeostatic model assessment of ß-cell function (HOMA-ß) and insulin resistance (HOMA-IR). We assessed risk of bias using the Cochrane risk of bias (RoB) 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) RoB (animal studies) tools; and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty. We used Bayesian hierarchical random-effects models, with informative priors for human data and noninformative priors for animal data. Inferences were made on posterior samples generated by Hamiltonian Markov Chain Monte Carlo using 90% credible intervals (90% CrI) and calculated probabilities. Twenty studies (n = 4 human, n = 16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-ß, and HOMA-IR). The model provides evidence that supplementation decreases fasting glucose [humans: mean difference (MD)0.5 = -0.95 mmol · L-1 (90% CrI: -2.1, 0.08); rodent: MD0.5 = -2.26 mmol · L-1 (90% CrI: -4.03, -0.44)], HbA1c [humans: MD0.5 = -0.91% (90% CrI: -1.46, -0.39); rodents: MD0.5 = -1.05% (90% CrI: -1.64, -0.52)], HOMA-IR [humans: standardized mean difference (SMD)0.5 = -0.41 (90% CrI: -0.82, -0.07); rodents: SMD0.5 = -0.63 (90% CrI: -1.98, 0.65)], and fasting insulin [humans: SMD0.5 = -0.41 (90% CrI: -0.77, -0.07)]. GRADE assessment showed our certainty in the effect estimate of each outcome to be moderate (human outcomes) or very low (rodent outcomes). Supplementation with carnosine or ß-alanine may reduce fasting glucose, HbA1c, and HOMA-IR in humans and rodents, and fasting insulin in humans; both compounds show potential as therapeutics to improve glycemic control and insulin resistance. This review was registered at PROSPERO as CRD42020191588.

High-Protein Plant-Based Diet Versus a Protein-Matched Omnivorous Diet to Support Resistance Training Adaptations: A Comparison Between Habitual Vegans and Omnivores.

BACKGROUND: Acute protein turnover studies suggest lower anabolic response after ingestion of plant vs. animal proteins. However, the effects of an exclusively plant-based protein diet on resistance training-induced adaptations are under investigation. OBJECTIVE: To investigate the effects of dietary protein source [exclusively plant-based vs. mixed diet] on changes in muscle mass and strength in healthy young men undertaking resistance training. METHODS: Nineteen young men who were habitual vegans (VEG 26 ± 5 years; 72.7 ± 7.1 kg, 22.9 ± 2.3 kg/m2) and nineteen young men who were omnivores (OMN 26 ± 4 years; 73.3 ± 7.8 kg, 23.6 ± 2.3 kg/m2) undertook a 12-week, twice weekly, supervised resistance training program. Habitual protein intake was assessed at baseline and adjusted to 1.6 g kg-1 day-1 via supplemental protein (soy for VEG or whey for OMN). Dietary intake was monitored every four weeks during the intervention. Leg lean mass, whole muscle, and muscle fiber cross-sectional area (CSA), as well as leg-press 1RM were assessed before (PRE) and after the intervention (POST). RESULTS: Both groups showed significant (all p < 0.05) PRE-to-POST increases in leg lean mass (VEG: 1.2 ± 1.0 kg; OMN: 1.2 ± 0.8 kg), rectus femoris CSA (VEG: 1.0 ± 0.6 cm2; OMN: 0.9 ± 0.5 cm2), vastus lateralis CSA (VEG: 2.2 ± 1.1 cm2; OMN: 2.8 ± 1.0 cm2), vastus lateralis muscle fiber type I (VEG: 741 ± 323 µm2; OMN: 677 ± 617 µm2) and type II CSA (VEG: 921 ± 458 µm2; OMN: 844 ± 638 µm2), and leg-press 1RM (VEG: 97 ± 38 kg; OMN: 117 ± 35 kg), with no between-group differences for any of the variables (all p > 0.05). CONCLUSION: A high-protein (~ 1.6 g kg-1 day-1), exclusively plant-based diet (plant-based whole foods + soy protein isolate supplementation) is not different than a protein-matched mixed diet (mixed whole foods + whey protein supplementation) in supporting muscle strength and mass accrual, suggesting that protein source does not affect resistance training-induced adaptations in untrained young men consuming adequate amounts of protein. CLINICAL TRIAL REGISTRATION: NCT03907059. April 8, 2019. Retrospectively registered.

The effect of carnosine or ß-alanine supplementation on markers of glycaemic control and insulin resistance in human and animal studies: a protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetes is a major public health issue and there is a need to develop low-cost, novel interventions to prevent or reduce disease progression. Growing evidence shows that supplementation with carnosine, or its rate-limiting precursor ß-alanine, can ameliorate aspects of the metabolic dysregulation that occurs in diabetes. There is, however, a need to develop a better understanding of the magnitude of effect and the factors associated with positive outcomes. The purpose of this systematic review and meta-analysis is to evaluate the effect of carnosine or ß-alanine supplementation on markers of glycaemic control and insulin resistance in humans and animals. METHODS: We will perform a systematic search for randomised and non-randomised controlled trials. Studies will be retrieved by searching electronic databases, clinical trial registers, author review, and cross-referencing. Primary outcomes include changes in (i) fasting glucose, (ii) glycated haemoglobin, and (iii) 2-h glucose following a glucose tolerance test. A set of additional outcomes includes other markers of glycaemic control and insulin resistance. Risk of bias (RoB) will be assessed using the Cochrane RoB 2.0 tool (human studies) and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) RoB tool (animal studies). Confidence in the cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. All meta-analyses will be conducted within a Bayesian framework, providing a flexible modelling approach to account for uncertainty in model parameters and underlying structures within the data. DISCUSSION: By including all available human and animal data, we will provide the most comprehensive overview on the topic to date. The results will have implications for those working in prediabetes, diabetes, and metabolic health in general and may lead to the development of new treatment approaches. DISSEMINATION: Study results will be presented at a professional conference and published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: CRD42020191588.

Muscular Atrophy and Sarcopenia in the Elderly: Is There a Role for Creatine Supplementation?

Sarcopenia is characterized by a loss of muscle mass, quality, and function, and negatively impacts health, functionality, and quality of life for numerous populations, particularly older adults. Creatine is an endogenously produced metabolite, which has the theoretical potential to counteract many of the morphological and metabolic parameters underpinning sarcopenia. This can occur through a range of direct and indirect mechanisms, including temporal and spatial functions that accelerate ATP regeneration during times of high energy demand, direct anabolic and anti-catabolic functions, and enhanced muscle regenerating capacity through positively impacting muscle stem cell availability. Studies conducted in older adults show little benefit of creatine supplementation alone on muscle function or mass. In contrast, creatine supplementation as an adjunct to exercise training seems to augment the muscle adaptive response to the training stimulus, potentially through increasing capacity for higher intensity exercise, and/or by enhancing post-exercise recovery and adaptation. As such, creatine may be an effective dietary strategy to combat age-related muscle atrophy and sarcopenia when used to complement the benefits of exercise training.

The Physiological Roles of Carnosine and ß-Alanine in Exercising Human Skeletal Muscle.

Carnosine (ß-alanyl-L-histidine) plays an important role in exercise performance and skeletal muscle homeostasis. Dietary supplementation with the rate-limiting precursor ß-alanine leads to an increase in skeletal muscle carnosine content, which further potentiates its effects. There is significant interest in carnosine and ß-alanine across athletic and clinical populations. Traditionally, attention has been given to performance outcomes with less focus on the underlying mechanism(s). Putative physiological roles in human skeletal muscle include acting as an intracellular pH buffer, modulating energy metabolism, regulating Ca handling and myofilament sensitivity, and scavenging of reactive species. Emerging evidence shows that carnosine could also act as a cytoplasmic Ca-H exchanger and form stable conjugates with exercise-induced reactive aldehydes. The enigmatic nature of carnosine means there is still much to learn regarding its actions and applications in exercise, health, and disease. In this review, we examine the research relating to each physiological role attributed to carnosine, and its precursor ß-alanine, in exercising human skeletal muscle.

A Systematic Risk Assessment and Meta-Analysis on the Use of Oral ß-Alanine Supplementation.

ß-Alanine supplementation is one of the world's most commonly used sports supplements, and its use as a nutritional strategy in other populations is ever-increasing, due to evidence of pleiotropic ergogenic and therapeutic benefits. Despite its widespread use, there is only limited understanding of potential adverse effects. To address this, a systematic risk assessment and meta-analysis was undertaken. Four databases were searched using keywords and Medical Subject Headings. All human and animal studies that investigated an isolated, oral, ß-alanine supplementation strategy were included. Data were extracted according to 5 main outcomes, including 1) side effects reported during longitudinal trials, 2) side effects reported during acute trials, 3) effect of supplementation on circulating health-related biomarkers, 4) effect of supplementation on skeletal muscle taurine and histidine concentration, and 5) outcomes from animal trials. Quality of evidence for outcomes was ascertained using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework, and all quantitative data were meta-analyzed using multilevel models grounded in Bayesian principles. In total, 101 human and 50 animal studies were included. Paraesthesia was the only reported side effect and had an estimated OR of 8.9 [95% credible interval (CrI): 2.2, 32.6] with supplementation relative to placebo. Participants in active treatment groups experienced similar dropout rates to those receiving the placebo treatment. ß-Alanine supplementation caused a small increase in circulating alanine aminotransferase concentration (effect size, ES: 0.274, CrI: 0.04, 0.527), although mean data remained well within clinical reference ranges. Meta-analysis of human data showed no main effect of ß-alanine supplementation on skeletal muscle taurine (ES: 0.156; 95% CrI: -0.38, 0.72) or histidine (ES: -0.15; 95% CrI: -0.64, 0.33) concentration. A main effect of ß-alanine supplementation on taurine concentration was reported for murine models, but only when the daily dose was ≥3% ß-alanine in drinking water. The results of this review indicate that ß-alanine supplementation within the doses used in the available research designs, does not adversely affect those consuming it.

Negligible Effects of ß-Hydroxy-ß-Methylbutyrate Free Acid and Calcium Salt on Strength and Hypertrophic Responses to Resistance Training: A Randomized, Placebo-Controlled Study.

This study evaluated the effects of ß-hydroxy-ß-methylbutyrate free acid (HMB-FA) and calcium salt (HMB-Ca) on strength, hypertrophy, and markers of muscle damage. In this randomized, double-blind, placebo-controlled study, 44 resistance-trained men (age: 26 ± 4 years; body mass: 84.9 ± 12.0 kg) consuming ≥1.7 g·kg-1·day-1 of protein received HMB-FA (3 g/day; n = 14), HMB-Ca (3 g/day; n = 15), or placebo (PL; cornstarch, 3 g/day; n = 15) for 12 weeks, while performing a periodized resistance training program. Before and after intervention, lean body mass (measured with dual X-ray absorptiometry), maximal dynamic strength (one-repetition maximum), knee extension maximal isometric strength (maximal voluntary isometric contraction [MVIC]), cross-sectional area (measured with ultrasound), and muscle soreness were assessed. MVIC was also measured 48 hr after the first and the last training sessions. All groups increased lean body mass (main time effect: p < .0001; HMB-FA: 1.8 ± 1.8 kg; HMB-Ca: 0.8 ± 1.4 kg; PL: 0.9 ± 1.4 kg), cross-sectional area (main time effect: p < .0001; HMB-FA: 6.6 ± 3.8%; HMB-Ca: 4.7 ± 4.4%; PL: 6.9 ± 3.8%), one-repetition maximum bench press (main time effect: p < .0001; HMB-FA: 14.8 ± 8.4 kg; HMB-Ca: 11.8 ± 7.4 kg; PL: 11.2 ± 6.6 kg), MVIC (main time effect: p < .0001; HMB-FA: 34.4 ± 39.3%; HMB-Ca: 32.3 ± 27.4%; PL: 17.7 ± 20.9%) after the intervention, but no differences between groups were shown. HMB-FA group showed greater leg press strength after the intervention than HMB-Ca and PL groups (Group × Time interaction: p < .05; HMB-FA: 47.7 ± 31.2 kg; HMB-Ca: 43.8 ± 31.7 kg; PL: 30.2 ± 20.9 kg). MVIC measured 48 hr after the first and the last sessions showed no attenuation of force decline with supplementation. Muscle soreness following the first and last sessions was not different between groups. The authors concluded that neither HMB-Ca nor HMB-FA improved hypertrophy or reduced muscle damage in resistance-trained men undergoing resistance training ingesting optimal amounts of protein. HMB-FA but not HMB-Ca resulted in a statistically significant yet minor improvement on leg press one-repetition maximum.

Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men.

ß-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day-1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day-1) improved isometric, but not isokinetic or isotonic endurance performance.

The Magnitude of Rapid Weight Loss and Rapid Weight Gain in Combat Sport Athletes Preparing for Competition: A Systematic Review.

Combat sport athletes typically engage in a process called making weight, characterized by rapid weight loss (RWL) and subsequent rapid weight gain (RWG) in the days preceding competition. These practices differ across each sport, but no systematic comparison of the size of the changes in body mass exists. The aim was to determine the magnitude of RWL and RWG in combat sport athletes preparing for competition. The review protocol was preregistered with PROSPERO (CRD42017055279). In eligible studies, athletes prepared habitually with a RWL period ≤7 days preceding competition. An electronic search of EBSCOhost (CINAHL Plus, MEDLINE, and SPORTDiscus) and PubMed Central was performed up to July 2018. Sixteen full-text studies (total 4,432 participants; 156 females and 4,276 males) were included, providing data from five combat sports (boxing, judo, mixed martial arts, taekwondo, and wrestling). Three studies reported RWL and 14 studies reported RWG. Duration permitted for RWG ranged 3-32 hr. The largest changes in body mass occurred in two separate mixed martial arts cohorts (RWL: 7.4 ± 1.1 kg [∼10%] and RWG: 7.4 ± 2.8 kg [11.7% ± 4.7%]). The magnitude of RWG appears to be influenced by the type of sport, competition structure, and recovery duration permitted. A cause for concern is the lack of objective data quantifying the magnitude of RWL. There is insufficient evidence to substantiate the use of RWG as a proxy for RWL, and little data are available in females. By engaging in RWG, athletes are able to exploit the rules to compete up to three weight categories higher than at the official weigh-in.

Exercise and ß-alanine supplementation on carnosine-acrolein adduct in skeletal muscle.

Previous studies have demonstrated that exercise results in reactive aldehyde production and that ß-alanine supplementation increases carnosine content in skeletal muscle. However, little is known about the influence exercise and ß-alanine supplementation have on the formation of carnosine-aldehydes. The goal of the present study was to monitor the formation of carnosine-aldehyde adducts, following high-intensity intermittent exercise, before and after ß-alanine supplementation. Vastus lateralis biopsy samples were taken from 14 cyclists, before and after a 28 day ß-alanine supplementation, following 4 bouts of a 30 s all-out cycling test, and carnosine and CAR-aldehyde adducts [carnosine-acrolein, CAR-ACR (m/z 303), carnosine-4-hydroxy-2-hexenal, CAR-HHE (m/z 341) and carnosine-4-hydroxy-2-nonenal, CAR-HNE (m/z 383)] were quantified by HPLC-MS/MS. ß-alanine supplementation increased muscle carnosine content by ~50% (p = 0.0001 vs. Pre-Supplementation). Interestingly, there was a significant increase in post-exercise CAR-ACR content following ß-alanine supplementation (p < 0.001 vs. post-exercise before supplementation), whereas neither exercise alone nor supplementation alone increased CAR-ACR formation. These results suggest that carnosine functions as an acrolein-scavenger in skeletal muscle. Such a role would be relevant to the detoxification of this aldehyde formed during exercise, and appears to be enhanced by ß-alanine supplementation. These novel findings not only have the potential of directly benefiting athletes who engage in intensive training regimens, but will also allow researchers to explore the role of muscle carnosine in detoxifying reactive aldehydes in diseases characterized by abnormal oxidative stress.

Effect of rapid weight loss and glutamine supplementation on immunosuppression of combat athletes: a double-blind, placebo-controlled study.

The role of plasma glutamine concentration and glutamine supplementation on immunosuppression was investigated in combat athletes. Twenty-three male athletes were randomly assigned to receive glutamine (21 g/day, n=12) or placebo (ovalbumin, n=11) for 10 days. Six athletes who did not lose weight served as controls. Athletes were assessed 21 days before (-21d), 1 day before (-1d) and 5 days after (+5d) a competition. Weight reduction was similar between glutamine (-8.2%± 4.1%) and placebo (-8.5%±2.4%) and negligible in control (-0.6%±1.4%). In both weight-loss groups, the majority of athletes reported symptoms of upper respiratory symptoms, as assessed by the Wisconsin upper respiratory symptom survey questionnaire. Only two athletes reported symptoms in the control group. Immune cell function remained unchanged throughout the study except for an increase in neutrophil phagocytic activity (placebo: -21d=5,251±2,986; -1d=17,428±22,374; +5d=21,125±21,934; glutamine: -21d=6,096±3,549; -1d=11,029±17,113; +5d=28,186±21,032 FI) and a minor change in monocyte phagocytic activity (placebo: -21d=4,421±3,634; -1d=3,329±6,283; +5d=3,243± 2,553; glutamine: -21d=4,051±3,186; -1d=3,106±2,625; +5d=4,981± 4,598) in both glutamine and placebo after weight loss. Plasma glutamine and cortisol remained unchanged across the study. creatine kinase levels were increased in placebo (-21d=125.2±54.1; -1d=187.2± 73.5; +5d=111.3±59.1 U/L) but not in glutamine (-21d=136.2±58.2; -1d= 168.8±65.0; +5d=129.7±64.0 U/L). Rapid weight loss increased the frequency and severity of infection symptoms, but this was neither associated with plasma glutamine depletion nor counteracted by glutamine supplementation.

A temperatura dos repositores hídricos pode influenciar a capacidade aeróbia? / Does the fluid replacers' temperature may influence the aerobic capacity?

O aumento da temperatura interna (Ti) é considerado importante causa da fadiga durante exercícios prolongados realizados no calor. Dentre as estratégias empregadas para atenuá-la, a reposição hídrica é a que mais se destaca por sua praticidade e baixo custo. Por outro lado, pouco se sabe a respeito da influência que a temperatura dos repositores hídricos exerce sobre respostas termorregulatórias e o desempenho aeróbio durante exercícios prolongados em ambientes quentes. Teoricamente, as bebidas em baixa temperatura poderiam conferir vantagem fisiológica, agindo como dissipadores de calor ou proporcionando uma sensação agradável, levando à manutenção da ativação do drive central. Combinados, esses mecanismos podem diminuir os efeitos deletérios da elevação da Ti ao desempenho. Mesmo assim, o número de estudos investigando tal hipótese é escasso. Logo, o objetivo deste Ponto de Vista foi examinar se as evidências existentes apoiam a hipótese de modulação da Ti e melhora do desempenho aeróbio a partir da ingestão de bebidas em baixas temperaturas durante os exercícios prolongados realizados no calor. Encontramos grande heterogeneidade na metodologia dos estudos, sobretudo no que diz respeito 1) ao baixo número amostral; 2) à ausência de soluções controle; 3) à falta de padronização do momento de administração dos repositores hídricos; e 4) ao protocolo de exercício utilizado. Isso dificulta o estabelecimento de conclusões definitivas sobre o assunto, e, portanto, mais estudos são necessários. Contudo, evidências oriundas de poucos estudos bem controlados sugerem que repositores hídricos em baixa temperatura podem atenuar o aumento na Ti e melhorar a capacidade aeróbia durante a realização de exercícios prolongados no calor....(AU)

The increase in internal temperature (Ti) is considered a major cause of fatigue during prolonged exercise in the heat. Among the strategies employed to attenuate it, the fluid replacement is the most used due its cost-effectiveness and practicality. On the other hand, little is known about the influence that the beverage temperature exerts on the thermoregulatory responses and aerobic capacity during prolonged exercise in hot environments. Theoretically, fluid replacers at a low temperature may provide a physiological advantage by acting as a 'heat sink', and providing a pleasant sensation, leading to increased central drive activation. These mechanisms would mitigate the side effects of an increased Ti on performance. Nevertheless, the number of studies dedicated to investigate this hypothesis is scarce. Thus, the aim of this Point of View was to examine whether the existing evidence support the modulation of Ti and improved aerobic capacity hypothesis from fluid replacers at low temperatures during prolonged exercise in hot environments. We have found substantial heterogeneity in the methodology inherent in these studies with regards to the 1) low sample size; 2) absence of control solutions; 3) lack of standardization of the moment of administration of the fluid replacers; and 4) exercise protocol. This causes difficulty in establishing definitive conclusions on this topic, and therefore more studies are required. However, the few existing evidence from well-controlled studies suggest that the fluid replacers at low temperatures can attenuate the increase in Ti and improve aerobic capacity during prolonged exercise in the heat....(AU)

ß-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the evidence on the effects of ß-alanine supplementation on exercise capacity and performance. DESIGN: This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data. DATA SOURCES: 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms ('ß-alanine' and 'Beta-alanine' combined with 'supplementation', 'exercise', 'training', 'athlete', 'performance' and 'carnosine'). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of ß-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses. RESULTS: 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI -0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of ß-alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)). SUMMARY/CONCLUSIONS: ß-alanine had a significant overall effect while subgroup analyses revealed a number of modifying factors. These data allow individuals to make informed decisions as to the likelihood of an ergogenic effect with ß-alanine supplementation based on their chosen exercise modality.

ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians.

Skeletal muscle strength and mass, major contributors to sprint/power athletic performance, are influenced by genetics. However, to date, only a handful of genetic variants have been associated with sprint/power performance. The ACVR1B A allele (rs rs2854464) has previously been associated with increased muscle-strength in non-athletic cohort. However, no follow-up and/or replications studies have since been conducted. Therefore, the aim of the present study was to compare the genotype distribution of ACVR1B rs2854464 between endurance athletes (E), sprint/power (S/P) athletes, mixed athletes (M), and non-athletic control participants in 1672 athletes (endurance athletes, n = 482; sprint/power athletes, n = 578; mixed athletes, n = 498) and 1089 controls (C) of both European Caucasians (Italian, Polish and Russians) and Brazilians. We have also compared the genotype distribution according to the athlete's level of competition (elite vs. sub-elite). DNA extraction and genotyping were performed using various methods. Fisher's exact test (adjusted for multiple comparisons) was used to test whether the genotype distribution of rs2854464 (AA, AG and GG) differs between groups. The A allele was overrepresented in S/P athletes compared with C in the Caucasian sample (adjusted p = 0.048), whereas there were no differences in genotype distribution between E athletes and C, in neither the Brazilian nor the Caucasian samples (adjusted p > 0.05). When comparing all Caucasian athletes regardless of their sporting discipline to C, we found that the A allele was overrepresented in athletes compared to C (adjusted p = 0.024). This association was even more pronounced when only elite-level athletes were considered (adjusted p = 0.00017). In conclusion, in a relatively large cohort of athletes from Europe and South America we have shown that the ACVR1B rs2854464 A allele is associated with sprint/power performance in Caucasians but not in Brazilian athletes. This reinforces the notion that phenotype-genotype associations may be ethnicity-dependent.

ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study.

BACKGROUND: To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. AIM: To examine the association between these variants and sprint time in elite athletes. METHODS: We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants. RESULTS: On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively. CONCLUSIONS: Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.