Sodium bicarbonate induces alkalosis, but improves high-intensity cycling performance only when participants expect a beneficial effect: a placebo and nocebo study.

The study aimed to investigate the effects of sodium bicarbonate (NaHCO3) intake with divergent verbal and visual information on constant load cycling time-to-task failure, conducted within the severe intensity domain. Fifteen recreational cyclists participated in a randomized double-blind, crossover study, ingesting NaHCO3 or placebo (i.e., dextrose), but with divergent information about its likely influence (i.e., likely to induce ergogenic, inert, or harmful effects). Performance was evaluated using constant load cycling time to task failure trial at 115% of peak power output estimated during a ramp incremental exercise test. Data on blood lactate, blood acid-base balance, muscle electrical activity (EMG) through electromyography signal, and the twitch interpolation technique to assess neuromuscular indices were collected. Despite reduced peak force in the isometric maximal voluntary contraction and post-effort peripheral fatigue in all conditions (P < 0.001), neither time to task failure, EMG nor, blood acid-base balance differed between conditions (P > 0.05). Evaluation of effect sizes of all conditions suggested that informing participants that the supplement would be likely to have a positive effect (NaHCO3/Ergogenic: 0.46; 0.15-0.74; Dextrose/Ergogenic: 0.45; 0.04-0.88) resulted in improved performance compared to control. Thus, NaHCO3 ingestion consistently induced alkalosis, indicating that the physiological conditions to improve performance were present. Despite this, NaHCO3 ingestion did not influence performance or indicators of neuromuscular fatigue. In contrast, effect size estimates indicate that participants performed better when informed that they were ingesting an ergogenic supplement. These findings suggest that the apparently ergogenic effect of NaHCO3 may be due, at least in part, to a placebo effect.

Energy constraint and compensation: Insights from endurance athletes.

The Constrained Model of Total Energy Expenditure predicts that increased physical activity may not influence total energy expenditure, but instead, induces compensatory energetic savings in other processes. Much remains unknown, however, about concepts of energy expenditure, constraint and compensation in different populations, and it is unclear whether this model applies to endurance athletes, who expend very large amounts of energy during training and competition. Furthermore, it is well-established that some endurance athletes consciously or unconsciously fail to meet their energy requirements via adequate food intake, thus exacerbating the extent of energetic stress that they experience. Within this review we A) Describe unique characteristics of endurance athletes that render them a useful model to investigate energy constraints and compensations, B) Consider the factors that may combine to constrain activity and total energy expenditure, and C) Describe compensations that occur when activity energy expenditure is high and unmet by adequate energy intake. Our main conclusions are as follows: A) Higher activity levels, as observed in endurance athletes, may indeed increase total energy expenditure, albeit to a lesser degree than may be predicted by an additive model, given that some compensation is likely to occur; B) That while a range of factors may combine to constrain sustained high activity levels, the ability to ingest, digest, absorb and deliver sufficient calories from food to the working muscle is likely the primary determinant in most situations and C) That energetic compensation that occurs in the face of high activity expenditure may be primarily driven by low energy availability i.e., the amount of energy available for all biological processes after the demands of exercise have been met, and not by activity expenditure per se.

Patterns of energy allocation during energetic scarcity; evolutionary insights from ultra-endurance events.

Exercise physiologists and evolutionary biologists share a research interest in determining patterns of energy allocation during times of acute or chronic energetic scarcity. Within sport and exercise science, this information has important implications for athlete health and performance. For evolutionary biologists, this would shed new light on our adaptive capabilities as a phenotypically plastic species. In recent years, evolutionary biologists have begun recruiting athletes as study participants and using contemporary sports as a model for studying evolution. This approach, known as human athletic palaeobiology, has identified ultra-endurance events as a valuable experimental model to investigate patterns of energy allocation during conditions of elevated energy demand, which are generally accompanied by an energy deficit. This energetic stress provokes detectable functional trade-offs in energy allocation between physiological processes. Early results from this modelsuggest thatlimited resources are preferentially allocated to processes which could be considered to confer the greatest immediate survival advantage (including immune and cognitive function). This aligns with evolutionary perspectives regarding energetic trade-offs during periods of acute and chronic energetic scarcity. Here, we discuss energy allocation patterns during periods of energetic stress as an area of shared interest between exercise physiology and evolutionary biology. We propose that, by addressing the ultimate "why" questions, namely why certain traits were selected for during the human evolutionary journey, an evolutionary perspective can complement the exercise physiology literature and provide a deeper insight of the reasons underpinning the body's physiological response to conditions of energetic stress.

Dietary ß-Alanine Intake Assessed by Food Records Does Not Associate With Muscle Carnosine Content in Healthy, Active, Omnivorous Men and Women.

ß-Alanine (BA) is one of the most widely used sport supplements, due to its capacity to improve high-intensity exercise performance by increasing muscle carnosine (MCarn) content, and consequently, the buffering capacity of the muscle. BA is also available in a variety of animal foods, but little is currently known about the influence of dietary BA intake on MCarn. The aim of the current study was to compile a detailed summary of available data on the BA content of commonly consumed foods, and to explore whether associations could be detected between self-reported dietary BA intake and skeletal MCarn in a group of 60 healthy, active, omnivorous men and women. Dietary BA intake was assessed via 3-day food records, and MCarn content assessed by high-performance liquid chromatography. A series of univariate and multivariate linear regression models were used to explore associations between estimated dietary BA and MCarn. No evidence of associations between dietary BA intake and MCarn were identified, with effect sizes close to zero calculated from models accounting for key demographic variables (f2 ≤ 0.02 for all analyses). These findings suggest that capacity to increase MCarn via dietary strategies may be limited, and that supplementation may be required to induce increases of the magnitude required to improve performance.

Acute and post-acute COVID-19 presentations in athletes: a systematic review and meta-analysis.

OBJECTIVE: To describe acute/postacute COVID-19 presentations in athletes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The search was conducted in four databases (MEDLINE, EMBASE, SCOPUS, SPORTDiscus) and restricted to studies published from 2019 to 6 January 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were required to (1) include professional, amateur or collegiate/university athletes with COVID-19; (2) present data on acute/postacute COVID-19 symptoms and (3) have an observational design. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. RESULTS: 43 studies with 11 518 athletes were included. For acute presentation, the pooled event rates for asymptomatic and severe COVID-19 were 25.5% (95% CI: 21.1% to 30.5%) and 1.3% (95% CI: 0.7% to 2.3%), respectively. For postacute presentations, the pooled estimate of persistent symptoms was 8.3% (95% CI: 3.8% to 17.0%). Pooled estimate for myocardial involvement was 5.0% (95% CI: 2.5% to 9.8%) in athletes undergoing any cardiac testing, and 2.5% (95% CI: 1.0% to 5.8%) in athletes undergoing MRI, although clinical symptoms were not characterised. None of the studies with a control group (eg, non-infected athletes) could confirm a causal relationship between COVID-19 and myocardial involvement. CONCLUSION: This broad characterisation of COVID-19 presentations in athletes indicates that ~94% exhibited mild or no acute symptoms. The available evidence did not confirm a causal relationship between COVID-19 and myocardial involvement. A small proportion of athletes experienced persistent symptoms while recovering from infection, which were mostly mild in nature, but could affect return-to-play decisions and timing.

Skeletal muscle histidine-containing dipeptide contents are increased in freshwater turtles (C. picta bellii) with cold-acclimation.

Freshwater turtles found in higher latitudes can experience extreme challenges to acid-base homeostasis while overwintering, due to a combination of cold temperatures along with the potential for environmental hypoxia. Histidine-containing dipeptides (HCDs; carnosine, anserine and balenine) may facilitate pH regulation in response to these challenges, through their role as pH buffers. We measured the HCD content of three tissues (liver, cardiac and skeletal muscle) from the anoxia-tolerant painted turtle (C. picta bellii) acclimated to either 3 or 20 °C. HCDs were detected in all tissues, with the highest content shown in the skeletal muscle. Turtles acclimated to 3 °C had more HCD in their skeletal muscle than those acclimated to 20 °C (carnosine = 20.8 ± 4.5 vs 12.5 ± 5.9 mmol·kg DM-1; ES = 1.59 (95%CI: 0.16-3.00), P = 0.013). The higher HCD content shown in the skeletal muscle of the cold-acclimated turtles suggests a role in acid-base regulation in response to physiological challenges associated with living in the cold, with the increase possibly related to the temperature sensitivity of carnosine's dissociation constant.

Individual Participant Data Meta-Analysis Provides No Evidence of Intervention Response Variation in Individuals Supplementing With Beta-Alanine.

Currently, little is known about the extent of interindividual variability in response to beta-alanine (BA) supplementation, nor what proportion of said variability can be attributed to external factors or to the intervention itself (intervention response). To investigate this, individual participant data on the effect of BA supplementation on a high-intensity cycling capacity test (CCT110%) were meta-analyzed. Changes in time to exhaustion (TTE) and muscle carnosine were the primary and secondary outcomes. Multilevel distributional Bayesian models were used to estimate the mean and SD of BA and placebo group change scores. The relative sizes of group SDs were used to infer whether observed variation in change scores were due to intervention or non-intervention-related effects. Six eligible studies were identified, and individual data were obtained from four of these. Analyses showed a group effect of BA supplementation on TTE (7.7, 95% credible interval [CrI] [1.3, 14.3] s) and muscle carnosine (18.1, 95% CrI [14.5, 21.9] mmol/kg DM). A large intervention response variation was identified for muscle carnosine (σIR = 5.8, 95% CrI [4.2, 7.4] mmol/kg DM) while equivalent change score SDs were shown for TTE in both the placebo (16.1, 95% CrI [13.0, 21.3] s) and BA (15.9, 95% CrI [13.0, 20.0] s) conditions, with the probability that SD was greater in placebo being 0.64. In conclusion, the similarity in observed change score SDs between groups for TTE indicates the source of variation is common to both groups, and therefore unrelated to the supplement itself, likely originating instead from external factors such as nutritional intake, sleep patterns, or training status.

The Bone Metabolic Response to Exercise and Nutrition.

Bone (re)modeling markers can help determine how the bone responds to different types, intensities, and durations of exercise. They also might help predict those at risk of bone injury. We synthesized evidence on the acute and chronic bone metabolic responses to exercise, along with how nutritional factors can moderate this response. Recommendations to optimize future research efforts are made.

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.

Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid-base regulation of skeletal muscle.

Histidine containing dipeptides (HCDs: carnosine, anserine and balenine) have numerous therapeutic and ergogenic properties, but there is a lack of consensus on the mechanistic pathways through which they function. Potential roles include intracellular buffering, neutralisation of reactive species, and calcium regulation. Comparative investigations of the HCD content of various species provide unique insight into their most likely mechanisms of action. This review chronologically describes how the comparative physiology studies, conducted since the beginning of the 20th century, have shaped our understanding of the physiological roles of HCDs. The investigation of a wide range of physiologically distinct species indicates that those species with a strong reliance on non-oxidative forms of energy production are abundant in HCDs. These include: whales who experience long periods of hypoxia while diving; racehorses and greyhound dogs who have highly developed sprint abilities, and chickens and turkeys whose limited capacity for flight is largely fuelled by their white, glycolytic, muscle. Additionally, a higher HCD content in the Type 2 muscle fibres of various species (which have greater capacity for non-oxidative metabolism) was consistently observed. The pKa of the HCDs render them ideally suited to act as intracellular physicochemical buffers within the pH transit range of the skeletal muscle. As such, their abundance in species which show a greater reliance on non-oxidative forms of energy metabolism, and which experience regular challenges to acid-base homeostasis, provides strong evidence that intracellular proton buffering is an important function of the HCDs in skeletal muscle.

Insulin-like growth factor-1 (IGF-1) poly (lactic-co-glycolic acid) (PLGA) microparticles - development, characterisation, and in vitro assessment of bioactivity for cardiac applications.

Aim: The aim of this study was to evaluate the formulation of a synthetic IGF-1 (pIGF-1) in PLGA microparticles (MP). Methods: Poly (lactic-co-glycolic acid) (PLGA) MPs loaded with pIGF-1 were prepared, characterised and evaluated using double emulsion solvent evaporation method. Results: Spherical MPs showed an average particle size of 2 µm, encapsulation efficiency (EE) of 67% and 50% degradation over 15 days. With a view to enhancing retention in the myocardium, the MP formulation was encapsulated in a cross-linked hyaluronic acid hydrogel. pIGF-1 released from MPs and from MPs suspended in hyaluronic acid hydrogel remained bioactive, determined by a significant increase in cellular proliferation of c-kit+ cells. Conclusion: This formulation has potential for loco-regional delivery to damaged myocardium to promote the survival of cardiomyocytes.

Reduced energy availability: implications for bone health in physically active populations.

PURPOSE: The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals. METHODS: We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals. RESULTS: Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries. CONCLUSIONS: Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

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.

Physiological responses to prolonged saturation diving: a field-based pilot study.

This study aimed to assess the effect of extreme environmental exposure during an operational saturation dive on airway inflammation (exhaled nitric oxide (FeNo)), components of fitness (flexibility and aerobic capacity) and blood hematological variables. Six saturation divers, who undertook a 26±0.5 day operational saturation dive were recruited to take part in this study. Participants completed a field-based repeated measure test battery on three occasions (pre-dive, post-dive and 24 hours after saturation dive). Hemoglobin concentration was significantly (P⟨0.001) reduced from pre- (15.3±0.8 g/dL) to post-saturation (14.25±1.2 g/dL) dive but recovered toward baseline values within 24 hours (15.13±1.03 g/dL; P=0.04). Similarly, a reduction in plasma volume was observed in all participants from pre- to post-saturation dive trials. Airway inflammation response was non-significant, although a large inter-individual response was evident. Hip flexion, assessed by the sit and reach test did not change following the saturation dive. Data on aerobic capacity was collected in one participant only, due to practical difficulties in participant access. In summary, this is the first investigation to conduct a multiple-component field-based study on operational saturation divers. The findings for this exploratory study present interesting groundings for further investigation.

Brief communication: Self-reported health and activity habits and attitudes in saturation divers.

INTRODUCTION: Exposure to the confined hyperbaric, hyperoxic environment of the saturation chamber poses a number of unique physiological challenges to divers. Appropriately tailored training, nutrition and health programs may help support the body to cope with and overcome these challenges. AIM: To describe the self-reported habits and attitudes of saturation divers toward issues related to health, lifestyle, nutrition and physical activity. METHODS: A questionnaire was developed to elicit information related to four key areas: 1) respondent demographics; 2) physical activity habits and attitudes; 3) nutritional attitudes; and 4) general lifestyle and health information. RESULTS: Respondents (n = 89/45%) reported a generally healthy lifestyle, including high physical activity levels while onshore, low tobacco use and alcohol intakes within U.K.-recommended guidelines. Responses to in-chamber items demonstrated reduced physical activity, disrupted sleep and distorted taste and smell perception. In addition, lethargy, headaches and musculoskeletal stiffness/soreness were reported as frequent symptoms following a period of time spent in saturation. CONCLUSIONS: Results of this study provide an in-sight into the self-reported practices and attitudes of saturation divers and appear to indicate a generally healthy lifestyle in the respondents. Some themes emerged which may impact on diver health and performance while in saturation. The results of this report may help provide a platform to generate hypotheses for further research and facilitate development of appropriately tailored nutrition and training-based strategies for saturation divers.

The impact of making-weight on cognitive performance in apprentice jockeys.

Jockeys regularly engage in rapid weight-loss practices in preparation for competition. These practices are thought to impair cognitive function, although the evidence in support of this theory remains inconclusive. The purpose of this study was to examine the effects of making-weight on cognitive function in apprentice jockeys in a simulated and competitive environment. Apprentice jockeys (n = 12) reduced their body mass by 4% in 48 h in a simulated environment using weight-loss methods typically adopted in preparation for racing. Simple and choice reaction time, attention, learning and memory were assessed before and after the weight loss. A further 10 apprentice jockeys performed the cognitive function assessment in a competitive racing environment at both a self-reported "normal" and "light" body mass. Hydration status and body mass were assessed in all trials. In the simulated environment, body mass was reduced by 4.2 ± 0.3%, yet no change in cognitive function was observed. Cognitive function also remained unchanged in the competitive environment after a body mass loss of 5.7 ± 1.9%. Typical reductions in body mass in preparation for racing have no effect on cognitive function in apprentice jockeys in a simulated and competitive environment. Further research is required to investigate the physiological mechanisms preventing the adverse effects of making-weight on cognitive function in jockeys.

How bone tissue and cells experience elevated temperatures during orthopaedic cutting: an experimental and computational investigation.

During orthopaedic surgery elevated temperatures due to cutting can result in bone injury, contributing to implant failure or delayed healing. However, how resulting temperatures are experienced throughout bone tissue and cells is unknown. This study uses a combination of experiments (forward-looking infrared (FLIR)) and multiscale computational models to predict thermal elevations in bone tissue and cells. Using multiple regression analysis, analytical expressions are derived allowing a priori prediction of temperature distribution throughout bone with respect to blade geometry, feed-rate, distance from surface, and cooling time. This study offers an insight into bone thermal behavior, informing innovative cutting techniques that reduce cellular thermal damage.

Intermittent actuation attenuates fibrotic behaviour of myofibroblasts.

The foreign body response (FBR) to implanted materials culminates in the deposition of a hypo-permeable, collagen rich fibrotic capsule by myofibroblast cells at the implant site. The fibrotic capsule can be deleterious to the function of some medical implants as it can isolate the implant from the host environment. Modulation of fibrotic capsule formation has been achieved using intermittent actuation of drug delivery implants, however the mechanisms underlying this response are not well understood. Here, we use analytical, computational, and in vitro models to understand the response of human myofibroblasts (WPMY-1 stromal cell line) to intermittent actuation using soft robotics and investigate how actuation can alter the secretion of collagen and pro/anti-inflammatory cytokines by these cells. Our findings suggest that there is a mechanical loading threshold that can modulate the fibrotic behaviour of myofibroblasts, by reducing the secretion of soluble collagen, transforming growth factor beta-1 and interleukin 1-beta, and upregulating the anti-inflammatory interleukin-10. By improving our understanding of how cells involved in the FBR respond to mechanical actuation, we can harness this technology to improve functional outcomes for a wide range of implanted medical device applications including drug delivery and cell encapsulation platforms. STATEMENT OF SIGNIFICANCE: A major barrier to the successful clinical translation of many implantable medical devices is the foreign body response (FBR) and resultant deposition of a hypo-permeable fibrotic capsule (FC) around the implant. Perturbation of the implant site using intermittent actuation (IA) of soft-robotic implants has previously been shown to modulate the FBR and reduce FC thickness. However, the mechanisms of action underlying this response were largely unknown. Here, we investigate how IA can alter the activity of myofibroblast cells, and ultimately suggest that there is a mechanical loading threshold within which their fibrotic behaviour can be modulated. These findings can be harnessed to improve functional outcomes for a wide range of medical implants, particularly drug delivery and cell encapsulation devices.