Blood alkalosis, as indicated by an increased blood bicarbonate concentration and pH, has been shown to be beneficial for exercise performance. Sodium bicarbonate, sodium citrate, and sodium or calcium lactate, can all result in increased circulating bicarbonate and have all independently been shown to improve exercise capacity and performance under various circumstances. Although there is considerable evidence demonstrating the efficacy of these supplements in several sports-specific situations, it is commonly acknowledged that their efficacy is equivocal, due to contrasting evidence. Herein, we discuss the physiological and environmental factors that may modify the effectiveness of these supplements including, (i) absolute changes in circulating bicarbonate; (ii) supplement timing, (iii) the exercise task performed, (iv) monocarboxylate transporter (MCT) activity; (v) training status, and (vi) associated side-effects. The aim of this narrative review is to highlight the factors which may modify the response to these supplements, so that individuals can use this information to attempt to optimize supplementation and allow the greatest possibility of an ergogenic effect.

This study investigated the effect of open-placebo on cycling time-trial (TT) performance. Twenty-eight trained female cyclists completed a 1-km cycling TT following a control session or an open-placebo intervention. The intervention consisted of an individual presentation, provided by a medic, in which the concept of open-placebo was explained to the participant, before she ingested two red and white capsules containing flour; 15 min later, they performed the TT. In the control session, the participant sat quietly for 20 min. Heart rate and ratings of perceived exertion (RPE) were monitored throughout exercise, while blood lactate was determined pre- and post-exercise. Post-exercise questionnaires were employed to gain insight into the perceived influence of the supplement on performance. Open-placebo improved time-to-completion (P = 0.039, 103.6±5.0 vs. 104.4±5.1 s, -0.7±1.8 s, -0.7±1.7%) and mean power output (P = 0.01, 244.8±34.7 vs. 239.7±33.2, +5.1±9.5 W) during the TT. Individual data analysis showed that 11 individuals improved, 13 remained unchanged and 4 worsened their performance with open-placebo. Heart rate, RPE and blood lactate were not different between sessions (all P>0.05). Positive expectation did not appear necessary to induce performance improvements, suggesting unconscious processes occurred, although a lack of an improvement appeared to be associated with a lack of belief. Open-placebo improved 1-km cycling TT performance in trained female cyclists. Although the intervention was successful for some individuals, individual variation was high, and some athletes did not respond or even performed worse. Thus, open-placebo interventions should be carefully considered by coaches and practitioners, while further studies are warranted.

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.

Creatine has been considered an effective ergogenic aid for several decades; it can help athletes engaged in a variety of sports and obtain performance gains. Creatine supplementation increases muscle creatine stores; several factors have been identified that may modify the intramuscular increase and subsequent performance benefits, including baseline muscle Cr content, type II muscle fibre content and size, habitual dietary intake of Cr, aging, and exercise. Timing of creatine supplementation in relation to exercise has recently been proposed as an important consideration to optimise muscle loading and performance gains, although current consensus is lacking regarding the ideal ingestion time. Research has shifted towards comparing creatine supplementation strategies pre-, during-, or post-exercise. Emerging evidence suggests greater benefits when creatine is consumed after exercise compared to pre-exercise, although methodological limitations currently preclude solid conclusions. Furthermore, physiological and mechanistic data are lacking, in regard to claims that the timing of creatine supplementation around exercise moderates gains in muscle creatine and exercise performance. This review discusses novel scientific evidence on the timing of creatine intake, the possible mechanisms that may be involved, and whether the timing of creatine supplementation around exercise is truly a real concern.

Supplementation with β-alanine (BA) increases muscle carnosine content, although the amount of BA used for muscle carnosine loading has been suggested to be low. However, methodological issues may have underestimated the amount of BA used. The aim of this study was to determine the estimated amount of BA converted to muscle carnosine, using a retrospective analysis from a 4-week randomized controlled trial investigating the effects of BA supplementation on muscle carnosine content of the m. vastus lateralis. Twenty-five males (age 27±5 years, height 1.74±0.09 m, body mass 77.4±11.5 kg) were supplemented with 6.4 g·day-1 of BA (N=17) or placebo (PL; N=8) for 28 days. Pre- and postsupplementation participants provided a muscle biopsy subsequently analysed for carnosine content using HPLC. Data were analysed using mixed-models and Pearson’s correlations. Muscle carnosine content increased by +11.0±6.7 mmol·kg-1dm (P<0.0001) in BA, with no change in PL (P=0.99). The estimated amount of BA converted to muscle carnosine was 2.1±1.2% (Range: 0.5 to 4.5%) of the total dose ingested. Pearson’s correlations showed that pre-supplementation carnosine was correlated to post-supplementation carnosine in the BA group (r=0.65, r2=0.38, P=0.009), but not the absolute change in carnosine (r=-0.28, r2=0.08, P=0.28) or the amount of BA used (r=-0.31, r2=0.10, P=0.22). The estimated amount of ingested BA used for carnosine synthesis was extremely low following 4 weeks of BA supplementation at 6.4 g·day-1. Data suggest that very little of the BA ingested is used for muscle carnosine synthesis and highlights the potential for further work to optimise BA supplementation in humans.

This study investigated the effect of beta-alanine supplementation on short-duration sprints and final 4-km simulated uphill cycling time-trial performance during a comprehensive and novel exercise protocol representative of the demands of road-race cycling, and determined if changes were related to increases in muscle carnosine content. Seventeen cyclists (age 38±9 y, height 1.76±0.07 m, body mass 71.4±8.8 kg, V ̇O2max 52.4±8.3 ml•kg -1 •min -1 ) participated in this placebo-controlled, double-blind study. Cyclists undertook a prolonged intermittent cycling protocol lasting 125 minutes, with a 10-s sprint every 20 minutes, finishing with a 4km time-trial at 5% simulated incline. Participants completed two familiarization and two main sessions pre-supplementation, and one post-supplementation session following 28 days of 6.4 g•day -1 of beta-alanine (N=11) or placebo (N=6; maltodextrin). Muscle biopsies obtained preand post-supplementation were analysed for muscle carnosine content. There were no main effects on sprint performance throughout the intermittent cycling test (all P>0.05). There was no group (P=0.69), time (P=0.50) or group x time interaction (P=0.26) on time-to-complete the 4-km time-trial. Time-to-completion did not change from pre-to post-supplementation for BA (-19.2±45.6 s, P=0.43) or PL (+2.8±31.6 s, P=0.99). Beta-alanine did not influence blood lactate values or ratings of perceived exertion during the prolonged cycling test. Beta-alanine supplementation increased muscle carnosine content from pre-to post-supplementation (+9.4±4.0 mmol•kg -1 dm; P<0.0001) but was not related to performance changes. Chronic betaalanine supplementation increased muscle carnosine content but did not improve short-duration sprint performance throughout simulated road race cycling, nor 4-km uphill time-trial performance conducted at the end of this cycling test.

Supplementation with β-alanine (BA) increases muscle carnosine content, although the amount of BA used for muscle carnosine loading has been suggested to be low. However, methodological issues may have underestimated the amount of BA used. The aim of this study was to determine the estimated amount of BA converted to muscle carnosine, using a retrospective analysis from a 4-week randomized controlled trial investigating the effects of BA supplementation on muscle carnosine content of the m. vastus lateralis. Twenty-five males (age 27±5 years, height 1.74±0.09 m, body mass 77.4±11.5 kg) were supplemented with 6.4 g·day-1 of BA (N=17) or placebo (PL; N=8) for 28 days. Pre- and postsupplementation participants provided a muscle biopsy subsequently analysed for carnosine content using HPLC. Data were analysed using mixed-models and Pearson’s correlations. Muscle carnosine content increased by +11.0±6.7 mmol·kg-1dm (P<0.0001) in BA, with no change in PL (P=0.99). The estimated amount of BA converted to muscle carnosine was 2.1±1.2% (Range: 0.5 to 4.5%) of the total dose ingested. Pearson’s correlations showed that pre-supplementation carnosine was correlated to post-supplementation carnosine in the BA group (r=0.65, r2=0.38, P=0.009), but not the absolute change in carnosine (r=-0.28, r2=0.08, P=0.28) or the amount of BA used (r=-0.31, r2=0.10, P=0.22). The estimated amount of ingested BA used for carnosine synthesis was extremely low following 4 weeks of BA supplementation at 6.4 g·day-1. Data suggest that very little of the BA ingested is used for muscle carnosine synthesis and highlights the potential for further work to optimise BA supplementation in humans.

No abstract