Carnosine is an abundant histidine-containing dipeptide in human skeletal muscle and formed by beta-alanine and L-histidine. It performs various physiological roles during exercise and has attracted strong interest in recent years with numerous investigations focused on increasing its intramuscular content to optimize its potential ergogenic benefits. Oral beta-alanine ingestion increases muscle carnosine content although large variation in response to supplementation exists and the amount of ingested beta-alanine converted into muscle carnosine appears to be low. Understanding of carnosine and beta-alanine metabolism and the factors that influence muscle carnosine synthesis with supplementation may provide insight into how beta-alanine supplementation may be optimized. Herein we discuss modifiable factors that may further enhance the increase of muscle carnosine in response to beta-alanine supplementation including, (i) dose; (ii) duration; (iii) beta-alanine formulation; (iv) dietary influences; (v) exercise; and (vi) co-supplementation with other substances. The aim of this narrative review is to outline the processes involved in muscle carnosine metabolism, discuss theoretical and mechanistic modifiable factors which may optimize the muscle carnosine response to beta-alanine supplementation and to make recommendations to guide future research.

Introduction: Placebos are used as a control treatment that is meant to be indistinguishable from the active intervention. However, where substantive placebo effects may occur, studies that do not include a non-placebo control arm may underestimate the overall effect of the intervention (active plus placebo components). This study aimed to determine the relative magnitude of the placebo effect associated with nutritional supplements (caffeine and extracellular buffers) by metaanalysing data from studies containing both placebo and non-placebo control sessions. Methods:Bayesian multilevel meta-analysis models were used to estimate pooled effects and express the placebo effect as a percentage of the overall intervention effect. Results: Thirty-four studies were included, with the median pooled effect size (ES0.5) indicating a very small (ES0.5=0.09 [95%CrI:0.01 to 0.17]) improvement in performance of placebo compared to control. There was no moderating effect of exercise type (capacity or performance), exercise duration or training status. The comparison between active intervention and control indicated a small to medium effect (ES0.5=0.37 [95%CrI:0.20 to 0.56]). Expressed in relative terms, the placebo effect was equivalent to 25% [75%CrI:16 to 35%] and 59% [75%CrI:34 to 94%] of the total intervention effect for buffers and caffeine. Conclusion: These results demonstrate a very small, but potentially important placebo effect with nutritional supplementation studies. A substantive proportion of supplement effects may be due to placebo effects, with the relative proportion influenced by the magnitude of the overall ergogenic effect. Where feasible, intervention studies should employ nonplacebo control-arm comparators to identify the proportion of the effect estimated to come from placebo effects and avoid underestimating the overall benefits that the physiological plus psychobiological aspects associated with an intervention provide in the real world.

Objective To investigate if a cloth facemask could affect physiological and perceptual responses to exercise at distinct exercise intensities in healthy young individuals. Methods Nine participants (sex, female/male: 6/3; age: 13±1 years; VO2peak: 44.5±5.5 mL/kg/min) underwent a progressive square-wave test at four intensities: (1) 80% of ventilatory anaerobic threshold (VAT), (2) VAT, and (3) 40% between VAT and V˙O2peak wearing a triple-layered cloth facemask or not. Participants then completed a final stage to exhaustion at a running speed equivalent to the maximum achieved during the cardio-respiratory exercise test (Peak). Physiological, metabolic, and perceptual measures were measured. Results Mask did not affect spirometry (forced vital capacity, peak expiratory flow, forced expiratory volume; all p≥0.27), respiratory (inspiratory capacity, end-expiratory volume [EELV] to functional vital capacity ratio, EELV, respiratory frequency [Rf], tidal volume [VT], Rf/VT, end-tidal carbo dioxide pressure, ventilatory equivalent to carbon dioxide ratio; all p≥0.196), hemodynamic (heart rate, systolic and diastolic blood pressure; all p>0.41), ratings of perceived exertion (p = 0.04) or metabolic measures (lactate; p = 0.78) at rest or at any exercise intensity. Conclusions This study shows that performing moderate to severe activity is safe and tolerable for healthy youth while wearing a cloth facemask. Trial registration ClinicalTrials.gov: NCT04887714.

Purpose: Investigate whether a cloth facemask could affect physiological and perceptual responses to exercise at distinct exercise intensities in untrained individuals. Methods: Healthy participants (n = 35; 17 men, age 30 [4] y, and 18 women, age 28 [5] y) underwent a progressive square wave test at 4 intensities: (1) 80% of ventilatory anaerobic threshold; (2) ventilatory anaerobic threshold; (3) respiratory compensation point; and (4) exercise peak (Peak) to exhaustion, 5-minute stages, with or without a triple-layered cloth facemask (Mask or No-Mask). Several physiological and perceptual measures were analyzed. Results: Mask reduced inspiratory capacity at all exercise intensities (P < .0001). Mask reduced respiratory frequency (P = .001) at Peak (−8.3 breaths·min−1; 95% confidence interval [CI], −5.8 to −10.8), respiratory compensation point (−6.9 breaths·min−1; 95% CI, −4.6 to −9.2), and ventilatory anaerobic threshold (−6.5 breaths·min−1; 95% CI, −4.1 to −8.8), but not at Baseline or 80% of ventilatory anaerobic threshold. Mask reduced tidal volume (P < .0001) only at respiratory compensation point (−0.5 L; 95% CI, −0.3 to −0.6) and Peak (−0.8 L; 95% CI, −0.6 to −0.9). Shallow breathing index was increased with Mask only at Peak (11.3; 95% CI, 7.5 to 15.1). Mask did not change HR, lactate, ratings of perceived exertion, blood pressure, or oxygen saturation. Conclusions: A cloth facemask reduced time to exhaustion but had no major impact on cardiorespiratory parameters and had a slight but clinically meaningless impact on respiratory variables at higher intensities. Moderate to heavy activity is safe and tolerable for healthy individuals while wearing a cloth facemask. ClinicalTrials.gov: NCT04887714.

Bitter solutions may not be effective in improving functional performance in older adults. Lack of significant findings could be due to 1) inappropriately low dosages of caffeine to produce an ergogenic effect 2) caffeine is not as effective quinine in stimulating oral receptors in the mouth 3) decreased chemosensitivity and oral receptor function due to age related changes. Further research is needed to assess the effects of bitter solution mouthwashes in older adults as a way to effect acutely change performance measures. PURPOSE: Cannabidiol (CBD) may exert physiological and psychological effects that benefit athletes (e.g. protect against neurological damage; reduce inflammation, anxiety and pain) (McCartney et al. 2020). This pilot study investigated the effects of CBD on physiological responses to exercise to determine its practical utility within the sporting context. METHODS: On two occasions, nine endurance-trained males (VO2max: 57.4±4.0 mL•min -1 •kg -1 ) ran for 60 mins at a fixed, moderate-intensity (70% VO2max) (RUN 1) before completing an incremental run to exhaustion (RUN 2) on an indoor treadmill (21.4±0.4°C). Participants received an oral dose of CBD (300 mg) or placebo 1.5 hrs prior to exercise in a randomised, doubleblind, crossover design. Respiratory gases were sampled continuously between 24-32, 37-45 and 50-58 mins of submaximal exercise; heart rate (HR), ratings of perceived exertion (RPEs), ratings of pleasure-displeasure, blood glucose (BG) and lactate (BL) concentrations were measured at 20-min intervals. Blood was drawn at baseline, pre-and post-RUN 1, post-RUN 2 and 1 hr post-RUN 2. RESULTS: CBD tended to increase submaximal oxygen consumption (+24±13 mL•min -1 , p=0.094). No differences in HR, RPE, BG, BL, or respiratory exchange ratio were observed during submaximal exercise (p's>0.10); VO2max (CBD: 3987±462; Placebo: 3868±577 mL•min -1 ; p=0.121) and time to exhaustion (CBD: 1286±150; Placebo: 1246±197 sec; p=0.204) were also similar during the incremental run. CBD tended to increase ratings of pleasure at 20-(p=0.050) and 40-mins (p=0.065) of submaximal exercise. Serum interleukin (IL)-6, IL-1β, tumor necrosis factor-α, lipopolysaccharide and myoglobin concentrations increased from baseline with exercise (i.e., post-RUN 1, post-RUN 2 and/or 1 hr post-RUN 2, p's<0.05); however, the change was too small to reliably evaluate the effect of CBD. Plasma CBD concentrations were 0±0, 3±2, 77±18, 164±35 and 99±26 ng.mL -1 at each respective time point. CONCLUSIONS: These preliminary findings suggest that CBD has potential to alter physiological responses during exercise. Further research involving a larger participant sample is required to confirm and better understand these effects.