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Purpose: To determine the association between estimated muscle fiber typology and the start and turn phases of elite swimmers during competition. Methods: International and national competition racing performance was analyzed from 21 female (FINA points = 894 ± 39: 104.5 ± 1.8% world record ratio [WRR]) and 25 male (FINA points = 885 ± 54: 104.8 ± 2.1% WRR) elite swimmers. The start, turn, and turn out times were determined from each of the swimmers’ career best performance times (FINA points = 889 ± 48: 104.7 ± 2.0% WRR). Muscle carnosine concentration was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and was expressed as a carnosine aggregate z score relative to an age- and gender-matched nonathlete control group to estimate muscle fiber typology. Linear mixed models were employed to determine the association between muscle fiber typology and the start and turn times. Results: While there was no significant influence of carnosine aggregate z score on the start and turn times when all strokes and distance events were entered into the model, the swimmers with a higher carnosine aggregate z score (ie, faster muscle typology) had a significantly faster start time in 100-m events compared with the swimmers with a lower carnosine aggregate z score (P = .02, F = 5.825). The start and turn times were significantly faster in the male compared with the female swimmers in the 100-m events compared with other distances, and between the 4 different swimming strokes (P Conclusion: This study suggests that start times in sprint events are partly determined (and limited) by muscle fiber typology, which is highly relevant when ∼12% of the overall performance time is determined from the start time.

Supplementation with β-alanine (BA) increases muscle carnosine content, although the amount of BAused for muscle carnosine loading has been suggested to be low. However, methodological issues mayhave underestimated the amount of BA used. The aim of this study was to determine the estimatedamount of BA converted to muscle carnosine, using a retrospective analysis from a 4-week randomizedcontrolled 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 contentusing HPLC. Data were analysed using mixed-models and Pearson’s correlations. Muscle carnosinecontent increased by +11.0±6.7 mmol·kg-1dm (P

To examine the role of chronic (in)activity on muscle carnosine (MCarn) and how chronic (in)activity affects MCarn responses to β-alanine supplementation in spinal cord-injured athletes, 16 male athletes with paraplegia were randomized (2:1 ratio) to receive β-alanine ( n = 11) or placebo (PL, n = 5). They consumed 6.4 g/day of β-alanine or PL for 28 days. Muscle biopsies of the active deltoid and the inactive vastus lateralis (VL) were taken before and after supplementation. MCarn in the VL was also compared with the VL of a group of individuals without paraplegia ( n = 15). MCarn was quantified in whole muscle and in pools of individual fibers by high-performance liquid chromatography. MCarn was higher in chronically inactive VL vs. well-trained deltoid (32.0 ± 12.0 vs. 20.5 ± 6.1 mmol/kg DM; P = 0.018). MCarn was higher in inactive vs. active VL (32.0 ± 12.0 vs. 21.2 ± 7.5 mmol/kg DM; P = 0.011). In type-I fibers, MCarn was significantly higher in the inactive VL than in the active deltoid (38.3 ± 4.7 vs. 27.3 ± 11.8 mmol/kg DM, P = 0.014). MCarn increased similarly between inactive VL and active deltoid in the β-alanine group (VL: 68.9 ± 55.1%, P = 0.0002; deltoid: 90.5 ± 51.4%, P < 0.0001), with no changes in the PL group. MCarn content was higher in the inactive VL than in the active deltoid and the active VL, but this is probably a consequence of fiber type shift (type I to type II) that occurs with chronic inactivity. Chronically inactive muscle showed an increase in MCarn after BA supplementation equally to the active muscle, suggesting that carnosine accretion following β-alanine supplementation is not influenced by muscle inactivity.

Supplemental digital content is available in the text., Purpose This study aimed to describe the kinetics of carnosine washout in human skeletal muscle over 16 wk. Methods Carnosine washout kinetics were studied in 15 young, physically active omnivorous men randomly assigned to take 6.4 g·d−1 of β-alanine (n = 11) or placebo (n = 4) for 8 wk. Muscle carnosine content (M-Carn) was determined before (PRE), immediately after (POST), and 4, 8, 12, and 16 wk after supplementation. High-intensity exercise tests were performed at these same time points. Linear and exponential models were fitted to the washout data, and the leave-one-out method was used to select the model with the best fit for M-Carn decay data. Repeated-measures correlation analysis was used to assess the association between changes in M-Carn and changes in performance. Results M-Carn increased from PRE to POST in the β-alanine group only (+91.1% ± 29.1%; placebo, +0.04% ± 10.1%; P < 0.0001). M-Carn started to decrease after cessation of β-alanine supplementation and continued to decrease until week 16 (POST4, +59% ± 40%; POST8, +35% ± 39%; POST12, +18% ± 32%; POST16, −3% ± 24% of PRE M-Carn). From week 12 onward, M-Carn was no longer statistically different from PRE. Both linear and exponential models displayed very similar fit and could be used to describe carnosine washout, although the linear model presented a slightly better fit. The decay in M-Carn was mirrored by a similar decay in high-intensity exercise tolerance; M-Carn was moderately and significantly correlated with total mechanical work done (r = 0.505; P = 0.032) and time to exhaustion (r = 0.72; P < 0.001). Conclusions Carnosine washout takes 12–16 wk to complete, and it can be described either by linear or exponential curves. Changes in M-Carn seem to be mirrored by changes in high-intensity exercise tolerance. This information can be used to optimize β-alanine supplementation strategies.

Purpose: To determine the influence of muscle fiber typology (MFT) on the pacing strategy of elite swimmers competing in the 200-m freestyle event. Method: The top 3 career-best performances from 25 elite 200-m freestyle swimmers were analyzed—12 women (1:58.0 [0:01.3] min:s) and 13 men (1:48.4 [0:02.5]). Muscle carnosine concentration was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus muscles and expressed as a carnosine aggregate z score (CAZ score) relative to an age- and gender-matched nonathlete control group to estimate MFT. Linear regression models were employed to examine the influence of MFT on the percentage of overall race time spent in each 50-m lap. Results: Swimmers with a higher CAZ score spent a greater percentage of race time in lap 3 compared with swimmers with a lower CAZ score (0.1%, 0.0% to 0.2%; mean, 90% confidence interval, P = .02). For every 1% increase in the percentage of race time spent in lap 1, the percentage of race time spent in lap 3 decreased by 0.4% for swimmers with a higher CAZ score (0.2% to −0.5%, P = .00, r = −.51), but not for swimmers with a lower CAZ score (−0.1%, −0.3% to 0.1%, P = .28, r = −.18). The percentage of race time spent in lap 4 decreased by 0.8% for higher-CAZ-score swimmers (−0.5% to −1.0%, P = .00, r = −.66) and by 0.9% for lower-CAZ-score swimmers (−0.6% to −1.3%, P = .00, r = −.65) when lap 1 percentage increased by 1%. Conclusion: MFT may influence the pacing strategy of swimmers in the 200-m freestyle event, which provides an avenue for maximizing individualized pacing strategies of elite swimmers.

Beta-alanine (BA) supplementation increases muscle carnosine content (MCarn), and has many proven, and purported, ergogenic and therapeutic benefits. Currently, many questions on the nature of the MCarn response to supplementation are open, and the response to these has considerable potential to enhance the efficacy and application of this supplementation strategy. To address these questions, we conducted a systematic review with Bayesian-based meta-analysis of all published aggregate data using a dose response (Emax) model. Meta-regression was used to consider the influence of potential moderators (including dose, sex, age, baseline MCarn and analysis method used) on the primary outcome. The protocol was designed according to PRISMA guidelines and a three-step screening strategy was undertaken to identify studies that measured the MCarn response to BA supplementation. Additionally, we conducted an original analysis of all available individual data on the MCarn response to BA supplementation from studies conducted within our lab (n = 99). The Emax model indicated that human skeletal muscle has large capacity for non-linear MCarn accumulation, and that commonly used BA supplementation protocols may not come close to saturating muscle carnosine content. Neither baseline values, nor sex, appeared to influence subsequent response to supplementation. Analysis of individual data indicated that MCarn is relatively stable in the absence of intervention, and effectually all participants respond to BA supplementation (99.3% response [95%CrI: 96.2 – 100]).

Muscle Fibre Composition (MFC) and resting carnosine levels are both important characteristics of skeletal muscle which contribute towards performance and fatigue during high-intensity exercise. It’s well documented that type II fibres are fast contracting, fast fatiguing, and are characterised by a high metabolic capacity for anaerobic metabolism. Despite the ability to produce higher forces, individuals with a relatively high proportion of type II muscle fibres are likely to experience more acidosis within the muscle. At the cellular level, type II fibers also have higher resting levels of carnosine. Carnosine, a buffer of hydrogen ions, is therefore important in delaying the rate of fatigue during high-intensity exercise. Higher levels of muscle carnosine found in some athletic individuals has largely been attributed to genetic factors such as type II fibres, however few studies have examined this relationship. Therefore, the main purpose of this thesis was to examine potential relationships between MFC, resting carnosine levels, and multiple sprint (Wingate) performance.Twenty-six healthy males (25 ± 4 years) were recruited for this study. Each participant had a muscle biopsy taken from the Vastus Lateralis (VL) to determine Muscle Fibre Composition (MFC) and resting muscle carnosine levels. After sufficient recovery from the biopsy procedure, participants completed 3 x 30second sprints (Wingate bouts) on a cycle ergometer; each separated by 4 minutes of rest. Mean Power (MP), anaerobic capacity (AC), peak power (PP), total work (TW) and a fatigue index (FI) was calculated for each Wingate. The statistical analysis included descriptive statistics, Pearson correlation and linear regressions.Resting muscle carnosine levels were not related to percentage of type II fibres (r= 0.056; p= 0.77), percentage area of type II fibres (p= 0.83; r= 0.048) or relative fibre area (p= 0.77; r= 0.065). In addition, resting carnosine levels were not related to any performance or fatigue measures in the repeated Wingate protocol. Significant relationships were found between both percentage area of type II fibres (p =0.043; r = 0.04) and percentage of type II fibres (p =0.0432; r = 0.4075) with fatigue index during the third Wingate bout. There were no significant relationships between MFC and fatigue in the first Wingate, however percentage of type II fibres was significantly related to the fatigue profile during the last 15 seconds of the 2nd (r=-0.42; p= 0.036) and 3rd (r= -0.44; p= 0.028) Wingate sprints.In summary, resting carnosine levels were not related to MFC nor any performance measure from the repeated Wingate protocol. This study did show however that individuals with a higher percentage of type II fibres may show greater levels of fatigue and decreased performance in the latter stages of maximal anaerobic exercise.

Cross-sectional studies suggest that training can increase muscle carnosine (MCarn), although longitudinal studies have failed to confirm this. A lack of control for dietary β-alanine intake or muscle fiber type shifting may have hampered their conclusions. The purpose of the present study was to investigate the effects of high-intensity interval training (HIIT) on MCarn.Twenty vegetarian men were randomly assigned to a control (CON) (n = 10) or HIIT (n = 10) group. High-intensity interval training was performed on a cycle ergometer for 12 wk, with progressive volume (6-12 series) and intensity (140%-170% lactate threshold [LT]). Muscle carnosine was quantified in whole-muscle and individual fibers; expression of selected genes (CARNS, CNDP2, ABAT, TauT, and PAT1) and muscle buffering capacity in vitro (βmin vitro) were also determined. Exercise tests were performed to evaluate total work done, V˙O2max, ventilatory thresholds (VT) and LT.Total work done, VT, LT, V˙O2max, and βmin vitro were improved in the HIIT group (all P0.05), but not in CON (P0.05). MCarn (in mmol·kg dry muscle) increased in the HIIT (15.8 ± 5.7 to 20.6 ± 5.3; P = 0.012) but not the CON group (14.3 ± 5.3 to 15.0 ± 4.9; P = 0.99). In type I fibers, MCarn increased in the HIIT (from 14.4 ± 5.9 to 16.8 ± 7.6; P = 0.047) but not the CON group (from 14.0 ± 5.5 to 14.9 ± 5.4; P = 0.99). In type IIa fibers, MCarn increased in the HIIT group (from 18.8 ± 6.1 to 20.5 ± 6.4; P = 0.067) but not the CON group (from 19.7 ± 4.5 to 18.8 ± 4.4; P = 0.37). No changes in gene expression were shown.In the absence of any dietary intake of β-alanine, HIIT increased MCarn content. The contribution of increased MCarn to the total increase in βmin vitro appears to be small.

β-alanine (BA) is a nonproteogenic amino acid that combines with histidine to form carnosine. The amount taken orally in individual doses, however, is limited due to symptoms of paresthesia that are associated with higher doses. The use of a sustained-release formulation has been reported to reduce the symptoms of paresthesia, suggesting that a greater daily dose may be possible. The purpose of the present study was to determine whether increasing the daily dose of BA can result in a similar increase in muscle carnosine in a reduced time.Eighteen men and twelve women were randomized into either a placebo (PLC), 6-g BA (6G), or 12-g BA (12G) groups. PLC and 6G were supplemented for 4 weeks, while 12G was supplemented for 2 weeks. A resting blood draw and muscle biopsy were obtained prior to (PRE) and following (POST) supplementation. Plasma and muscle metabolites were measured by high-performance liquid chromatography. The loss in peak torque (ΔPT) was calculated from maximal isometric contractions before and after 250 isokinetic kicks at 180°·secBoth 12G (p = 0.026) and 6G (p = 0.004) increased muscle carnosine compared to PLC. Plasma histidine was decreased from PRE to POST in 12G compared to PLC (p = 0.002) and 6G (p = 0.001), but no group x time interaction (p = 0.662) was observed for muscle histidine. No differences were observed for any hematological measure (e.g., complete blood counts) or in symptoms of paresthesia among the groups. Although no interaction was noted in ΔPT, a trend (p = 0.073) was observed.Results of this investigation indicate that a BA supplementation protocol of 12 g/d

Beta-alanine (BA) supplementation increases muscle carnosine content (MCarn), and is ergogenic in many situations. Currently, many questions on the nature of the Mcarn response to supplementation are open, and the response to these has considerable potential to enhance the efficacy and applications of this supplementation strategy.ObjectiveTo conduct a Bayesian analysis of available data on the Mcarn response to BA supplementation.MethodsA systematic review with meta-analysis of individual and published aggregate data using a dose response (Emax) model was conducted. The protocol was designed according to PRISMA guidelines. A three-step screening strategy was undertaken to identify studies that measured the Mcarn response to BA supplementation. In addition, individual data from 5 separate studies conducted in the authors’ laboratory were analysed. Data were extracted from all controlled and uncontrolled supplementation studies conducted on healthy humans. Meta-regression was used to consider the influence of potential moderators (including dose, sex, age, baseline Mcarn and analysis method used) on the primary outcome.Results and ConclusionThe Emax model indicated that human skeletal muscle has large capacity for non-linear Mcarn accumulation, and that commonly used BA supplementation protocols may not come close to saturating muscle carnosine content. Neither baseline values, nor sex, appear to influence subsequent response to supplementation. Analysis of individual data indicated that Mcarn is relatively stable in the absence of intervention, and effectually all participants respond to BA supplementation (99.3% response [95%CrI: 96.2 – 100]).

Made available in DSpace on 2020-12-10T19:45:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) The study investigated the influence of beta-alanine supplementation during a high-intensity interval training (HIIT) program on repeated sprint ability (RSA) performance. This study was randomized, double-blinded, and placebo controlled. Eighteen men performed an incremental running test until exhaustion (T-INC) at baseline and followed by 4-wk HIIT (10 x 1min runs 90% maximal T-INC velocity [1-min recovery]). Then, participants were randomized into two groups and performed a 6-wk HIIT associated with supplementation of 6.4 g/day of beta-alanine (G beta) or dextrose (placebo group; GP). Pre- and post-6-wk HIIT + supplementation, participants performed the following tests: 1) T-INC; 2) supramaximal running test; and 3) 2 x 6 x 35-m sprints (RSA). Before and immediately after RSA, neuromuscular function was assessed by vertical jumps, maximal isometric voluntary contractions of knee extension, and neuromuscular electrical stimulations. Muscle biopsies were performed to determine muscle carnosine content, muscle buffering capacity in vitro (beta m(in) (vitro)), and content of phos-phofructokinase (PFK), monocarboxylate transporter 4 (MCT4), and hypoxia-inducible factor-1 alpha (HIF-1 alpha). Both groups showed a significant time effect for maximal oxygen uptake (G beta: 6.2 +/- 3.6% and GP: 6.5 +/- 4.2%; P > 0.01); only G beta showed a time effect for total (-3.0 +/- 2.0%; P > 0.001) and best (-3.3 +/- 3.0%; P = 0.03) RSA times. A group-by-time interaction was shown after HIIT + Supplementation for muscle carnosine (G beta: 34.4 +/- 2.3 mmol.kg(-1).dm(-1) and GP: 20.7 +/- 3.0 mmol.kg(-1) dm(-1); P = 0.003) and neuromuscular voluntary activation after RSA (G beta: 87.2 +/- 3.3% and GP: 78.9 +/- 12.4%; P = 0.02). No time effect or group-by-time interaction was shown for supramaximal running test performance, beta m, and content of PFK, MCT4, and HIF-1 alpha. In summary, beta-alanine supplementation during HIIT increased muscle carnosine and attenuated neuromuscular fatigue, which may contribute to an enhancement of RSA performance. NEW & NOTEWORTHY beta-Alanine supplementation during a high-intensity interval training program increased repeated sprint performance. The improvement of muscle carnosine content induced by beta-alanine supplementation may have contributed to an attenuation of central fatigue during repeated sprint. Overall, beta-alanine supplementation may be a useful dietary intervention to prevent fatigue. Sao Paulo State Univ, Lab Physiol & Human Performance, Post Grad Program Human Movement Sci, Bauru, SP, Brazil Univ Sao Paulo, Fac Med, Sch Phys Educ & Sport, Rheumatol Div,Appl Physiol & Nutr Res Grp, Sao Paulo, SP, Brazil Univ Sao Paulo, Fac Med, Inst Orthopaed & Traumatol, Ribeirao Preto, SP, Brazil Univ Sao Paulo, Sch Phys Educ & Sports Ribeirao Preto, Ribeirao Preto, SP, Brazil Mato Grosso do Sul Fed Univ, Lab Resp Pathophysiol, Sao Paulo, SP, Brazil Sao Paulo State Univ, Fac Sci, Dept Phys Educ, Bauru, SP, Brazil Sao Paulo State Univ, Lab Physiol & Human Performance, Post Grad Program Human Movement Sci, Bauru, SP, Brazil Sao Paulo State Univ, Fac Sci, Dept Phys Educ, Bauru, SP, Brazil FAPESP: 2016/02683-6 FAPESP: 2016/11076-6 FAPESP: 2016/17836-2 FAPESP: 2016/50438-0 CNPq: 307719/2016-2 CAPES: 001

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.

Carnosine (β-alanyl-L-histidine) is an abundant compound in skeletal muscle, suggesting it plays an important role during exercise, with a key physiological role considered to be intracellular pH regulation.1 Chronic β-alanine supplementation can increase muscle carnosine content when taken for several weeks,2 and studies have shown that supplementation between 4 and 24 weeks can improve high-intensity exercise capacity, with the gains in exercise associated with the increase in muscle carnosine content.3 4 Although several studies have demonstrated the efficacy of β-alanine supplementation as an ergogenic aid, there are a number of confounding factors that may modify its effect, including exercise …

Beta-alanine is widely considered an effective ergogenic aid and is recognized by the International Olympic Committee as one of five sports supplements that have sufficient evidence to support its use. An expanding literature base attesting to its ergogenic potential in a variety of high-intensity sports underpins its worldwide popularity as an ergogenic aid. Beta-alanine supplementation, and a subsequent increase in intramuscular carnosine, may augment the ability of the body to resist exercise-induced changes in muscle pH, improving high-intensity exercise performance. A few studies have explored the influence of beta-alanine supplementation on health-related parameters in older adults and overall positive results have been reported. The efficiency of beta-alanine supplementation to increase muscle carnosine appears to be low, with only approximately 2-6% of beta-alanine consumed being incorporated into muscle carnosine, with the remainder routed towards oxidation or transamination. The greatest modifier of the ergogenic efficacy of beta-alanine supplementation appears to be the duration of the exercise task performed.

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, V̇O2max 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 4-km time-trial at 5% simulated incline. Participants completed two familiarization sessions, and two main sessions, one pre-supplementation and one post-supplementation following 28 days of 6.4 g·day-1 of beta-alanine (N=11) or placebo (N=6; maltodextrin). Muscle biopsies obtained pre- and 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-1dm; P

β-Alanine is a nonproteogenic amino acid that combines with histidine to form a dipeptide molecule known as carnosine. Carnosine is an H+ buffer that is especially useful in preventing the decline in muscle pH during high-intensity exercise. β-Alanine has been shown to be the rate-limiting precursor of carnosine formation, and therefore supplementation with β-alanine increases muscle carnosine. β-Alanine supplementation has ergogenic effects on exercise performance, specifically in high-intensity events for 1–4 min. However, carnosine has been suggested to have various other roles in the body, including acting as an antioxidant, antiglycating agent, and ion chelator, which may have significant effects on aging and other health benefits. Besides β-alanine supplementation, carnosine content is dependent on various other factors, such as diet, gender, and training status. This chapter aims to review the ergogenic effects of β-alanine supplementation on exercise performance and highlight the beneficial effects of carnosine content on health.

Purpose: To investigate the influence of β-alanine (BA) supplementation on muscle carnosine content, muscle pH and the power-duration relationship (i.e., critical power and W′).Methods: In a double-blind, randomized, placebo-controlled study, 20 recreationally-active males (22 ± 3 y, V°O2peak 3.73 ± 0.44 L·min−1) ingested either BA (6.4 g/d for 28 d) or placebo (PL) (6.4 g/d) for 28 d. Subjects completed an incremental test and two 3-min all-out tests separated by 1-min on a cycle ergometer pre- and post-supplementation. Muscle pH was assessed using 31P-magnetic resonance spectroscopy (MRS) during incremental (INC KEE) and intermittent knee-extension exercise (INT KEE). Muscle carnosine content was determined using 1H-MRS.Results: There were no differences in the change in muscle carnosine content from pre- to post-intervention (PL: 1 ± 16% vs. BA: −4 ± 25%) or in muscle pH during INC KEE or INT KEE (P > 0.05) between PL and BA, but blood pH (PL: −0.06 ± 0.10 vs. BA: 0.09 ± 0.13) during the incremental test was elevated post-supplementation in the BA group only (P < 0.05). The changes from pre- to post-supplementation in critical power (PL: −8 ± 18 W vs. BA: −6 ± 17 W) and W′ (PL: 1.8 ± 3.3 kJ vs. BA: 1.5 ± 1.7 kJ) were not different between groups. No relationships were detected between muscle carnosine content and indices of exercise performance.Conclusions: BA supplementation had no significant effect on muscle carnosine content and no influence on intramuscular pH during incremental or high-intensity intermittent knee-extension exercise. The small increase in blood pH following BA supplementation was not sufficient to significantly alter the power-duration relationship or exercise performance.

Carnosinase 1 (CN1) has been postulated to be a susceptibility factor for developing diabetic nephropathy (DN). Although its major substrate, carnosine, is beneficial in rodent models of DN, translation of these findings to humans has been hampered by high CN1 activity in human serum resulting in rapid degradation of carnosine. To overcome this hurdle, we screened a protease-directed small-molecule library for inhibitors of human recombinant CN1. We identified SAN9812 as a potent and highly selective inhibitor of CN1 activity with a K-i of 11nM. It also inhibited CN1 activity in human serum and serum of transgenic mice-overexpressing human CN1. Subcutaneous administration of 30mg/kg SAN9812 led to a sustained reduction in circulating CN1 activity in human CN1 transgenic (TG) mice. Simultaneous administration of carnosine and SAN9812 increased carnosine levels in plasma and kidney by up to 100-fold compared to treatment-naive CN1-overexpressing mice. To our knowledge, this is the first study reporting on a potent and selective CN1 inhibitor with in vivo activity. SAN9812, also called carnostatine, may be used to increase renal carnosine concentration as a potential therapeutic modality for renal diseases linked to glycoxidative conditions.

Background: Muscle carnosine is related to contractile function (Ca+ + handling) and buffering of exercise-induced acidosis. As these muscular functions are altered in Multiple Sclerosis (MS) it is relevant to understand muscle carnosine levels in MS. Methods: Tibialis anterior muscle carnosine was measured in an animal MS model (EAE, experimental autoimmune encephalomyelitis, n = 40) and controls (CONEX, n = 40) before and after exercise training (EAE(EX), CONEX, 10d, 1 h/d, 24 m/min treadmill running) or sedentary conditions (EAE(SED), CONSED). Human m. vastus lateralis carnosine of healthy controls (HC, n = 22) and MS patients (n = 24) was measured. Results: EAE muscle carnosine levels were decreased (p < .0001) by similar to 40% to similar to 64% at 10d and 17d following EAE induction (respectively) regardless of exercise (p = .823). Similarly, human MS muscle carnosine levels were decreased (- 25%, p = .03). Conclusion: Muscle carnosine concentrations in an animal MS model and MS patients are substantially reduced. In EAE exercise therapy does not restore this.

β-Alanine is one of the more popular sport supplements used by strength/power athletes today. The popularity of β-alanine stems from its ability to enhance intracellular muscle-buffering capacity thereby delaying fatigue during high-intensity exercise by increasing muscle carnosine content. Recent evidence also suggests that elevated carnosine levels may enhance cognitive performance and increase resiliency to stress. These benefits are thought to result from carnosine's potential role as an antioxidant. This review will discuss these new findings including recent investigations examining β-alanine supplementation and increased resiliency to posttraumatic stress and mild traumatic brain injury. This review will focus on the physiology of carnosine, the effect of β-alanine ingestion on carnosine elevations, and the potential ergogenic benefits it has for competitive and tactical athletes.

β-Alanine (BA) supplementation results in elevated intramuscular carnosine content, enhancing buffering capacity during intense exercise. Although men have greater muscle carnosine content than women, elevations still appear to occur despite high baseline levels. Recent research has suggested that BA supplementation may also reduce muscle l-histidine. Thus, the purpose of this investigation was to compare 28 days of BA (6 g·d-1) supplementation in men and women on performance and muscle carnosine, l-histidine, and BA. We hypothesized that supplementation would result in similar elevations in carnosine and performance between sexes and decrease l-histidine. Twenty-six men and women were assigned either BA or placebo (PLA). At baseline, a trend toward greater carnosine (P = .069) was observed in men, and intramuscular BA content was significantly (P ≤ .05) greater in men. Statistical analysis was performed using magnitude-based inferences. Changes in muscle carnosine were likely and very likely greater after BA supplementation compared with PLA in men and women, respectively, but changes were unclear between sexes (mean sex difference: 2.50 ± 4.30 mmol·kg-1 ww). The attenuation of exercise fatigue was likely greater in BA compared with PLA, but the change was unclear between sexes (mean sex difference: 14.0 ± 39.0 Nm). Changes in muscle BA following supplementation was unclear in men, likely elevated in women, but unclear between sexes (mean sex difference: 0.03 ± 0.42 mmol·kg-1 ww). Changes in muscle l-histidine were unclear in men and women, and unclear between sexes (mean sex difference: 0.09 ± 0.13 mmol·kg-1 ww). In conclusion, BA supplementation increased muscle carnosine and attenuated fatigue in men and women similarly but did not reduce muscle l-histidine.

Introduction: Skeletal muscle carnosine content can be increased through [beta]-alanine supplementation, but the maximum increase achievable with supplementation is unknown. No study has investigated the effects of prolonged supplementation on carnosine-related genes or exercise capacity.\ud Purpose: To investigate the effects of 24-weeks of [beta]-alanine supplementation on muscle carnosine content, gene expression and high-intensity cycling capacity (CCT110%).\ud Methods: Twenty-five active males were supplemented with 6.4 g[middle dot]day-1 of sustained release [beta]-alanine (BA) or placebo (PL) over a 24-week period. Every 4 weeks participants provided a muscle biopsy and performed the CCT110%. Biopsies were analysed for muscle carnosine content and gene expression (CARNS, TauT, ABAT, CNDP2, PHT1, PEPT2 and PAT1).\ud Results: Carnosine content was increased from baseline at every time point in BA (all P

The purpose of this study was to examine the effect of β-alanine (BA) ingestion on tissue carnosine levels and the impact such changes would have on combat specific activity. Eighteen soldiers (19.9 ± 0.8 year) from an elite combat unit were randomly assigned to either a BA or placebo (PL) group. Before and following a 30-day supplementation period carnosine content of the gastrocnemius muscle and brain was determined by proton magnetic resonance spectroscopy. During each testing session, participants performed military relevant tasks that included a 2.5 km run, a 1-min sprint, 50-m casualty carry, repeated 30-m sprints with target shooting, and a 2-min serial subtraction test (SST) to assess cognitive function under stressful conditions. A significant elevation (p = 0.048) in muscle carnosine content was noted in BA compared to PL. Changes in muscle carnosine content was correlated to changes in fatigue rate (r = 0.633, p = 0.06). No changes (p = 0.607) were observed in brain carnosine content. Following supplementation, no differences were noted in 2.5 km run, 1-min sprint, repeated sprint, or marksmanship performance, but participants in BA significantly (p = 0.044) improved their time for the 50-m casualty carry and increased their performance (p = 0.022) in the SST compared to PL. In summary, 30-days of BA ingestion can increase muscle carnosine content and improve aspects of military specific performance. Although cognitive performance was significantly greater in participants consuming BA compared to placebo, current study methods were unable to detect any change in brain carnosine levels, thus, the precise mechanism underlying these effects remains elusive.

Carnosine occurs in high concentrations in human skeletal muscle and assists working capacity during high-intensity exercise. Chronic beta-alanine (BA) supplementation has consistently been shown to augment muscle carnosine concentration, but the effect of training on the carnosine loading efficiency is poorly understood. The aim of the present study was to compare muscle carnosine loading between trained and untrained arm and leg muscles. In a first study ( n = 17), reliability of carnosine quantification by proton magnetic resonance spectroscopy (1H-MRS) was evaluated in deltoid and triceps brachii muscles. In a second study, participants ( n = 35; 10 nonathletes, 10 cyclists, 10 swimmers, and 5 kayakers) were supplemented with 6.4 g/day of slow-release BA for 23 days. Carnosine content was evaluated in soleus, gastrocnemius medialis, and deltoid muscles by 1H-MRS. All the results are reported as arbitrary units. In the nonathletes, BA supplementation increased carnosine content by 47% in the arm and 33% in the leg muscles (not significant). In kayakers, the increase was more pronounced in arm (deltoid) vs. leg (soleus + gastrocnemius) muscles (0.089 vs. 0.049), whereas the reverse pattern was observed in cyclists (0.065 vs. 0.084). Swimmers had significantly higher increase in carnosine in both deltoid (0.107 vs. 0.065) and gastrocnemius muscle (0.082 vs. 0.051) compared with nonathletes. We showed that 1) carnosine content can be reliably measured by 1H-MRS in deltoid muscle, 2) carnosine loading is equally effective in arm vs. leg muscles of nonathletes, and 3) carnosine loading is more pronounced in trained vs. untrained muscles.

The objective of this study was to assess the effects of constant high ambient temperatures on meat quality, antioxidant capacity, and carnosine expression in longissimus dorsi muscle of finishing pigs. Castrated 24 male DLY (crossbreeds between Landrace×Yorkshire sows and Duroc boars) pigs were allocated to one of three treatments: constant ambient temperature at 22°C and ad libitum feeding (CON, n = 8); constant high ambient temperature at 30°C and ad libitum feeding (H30, n = 8); and constant ambient temperature at 22°C and pair-fed with H30 (PF, n = 8). Meat quality, malondialdehyde (MDA) content, antioxidant capacity, carnosine content, and carnosine synthetase (CARNS1) mRNA expression in longissimus dorsi muscle were measured after three weeks. The results revealed that H30 had lower pH24 h, redness at 45 min, and yellowness at 24 h post-mortem (p

Muscle carnosine has pH-buffering, antioxidant and carbonyl scavenging properties, which may affect pork quality attributes. Study objectives were to: (1) compare muscle carnosine content and carnosine-related gene mRNA abundance in purebred pigs (n=282), (2) study the effect of muscle carnosine content on pork quality attributes and gene expression across breeds, and (3) study transcript abundance of carnosine-related genes in various tissues. Pigs were raised under similar conditions and slaughtered at 120±4.5kg. Longissimus thoracis muscles were sampled on the dressing line for gene expression and at 24h for meat quality measurements. Muscle carnosine content and carnosine-related gene mRNA abundance were modulated according to pig breeds. Greater pH24h, better water holding capacity and improved meat color values were found in pigs with high muscle carnosine content. Data suggest that high muscle carnosine is associated with improved pork meat quality attributes. The pig genetic background may be a key determinant for muscle carnosine content regulation.

This study evaluated the effects of carnosine supplementation on carnosine concentration in muscles and blood biochem-ical indices of rats. Thirty-two eight-week-old Sprague-Dawley male rats were randomly divided into a control group(CON) as well as three carnosine-treated groups. The carnosine-treated groups included groups fed diets composed of0.01% carnosine (LC), 0.1% carnosine (MC), and 1.0% carnosine (HC). Body weight gain, food intake, feed efficacy rate,protein efficacy rate, and organ weights were not significantly different among the groups. In all groups, the mean carnosinelevels in gastrocnemius muscles were higher than the mean carnosine levels in soleus muscles. Carnosine concentrations insoleus muscles and gastrocnemius muscles were significantly higher in the HC group compared to all other groups ( p

In the historical city center of Ghent in Belgium, an international group of scientists gathered for a 3-day meeting dedicated to carnosine research. The meeting took place in July 2011, which is more than 10 years following the previous congress of this kind, organized by Alexander Boldyrev in Moscow in the year 2000. The Moscow meeting was held on the occasion of the centenary of Gulewitch and Amiradzhibi’s discovery of the dipeptide carnosine in meat extract. A special issue with contributions from the invited participants was published in Biochemistry (Moscow) in 2000, entitled: ‘‘Biological role of carnosine in the functioning of excitable tissues’’ (Guest editor: A. A. Boldyrev; Original Russian text). The Ghent meeting was therefore considered the Second International Meeting on Carnosine. The souvenir medals that were created to mark the occasion of both meetings are displayed in Fig. 1. A thorough understanding of the biological role of carnosine and its methylated analogues anserine and ophidine/ balenine, is still hampered by the relatively low frequency of scientific discoveries on this topic. However, in the 11-year period separating both meetings there has been an exponential increase in the number of publications and citations on carnosine (see Fig. 2). Indeed, significant progress was made in the fields of both biochemistry and medicine, as well as in sport science. The genes for carnosine synthase and carnosinase, the principal enzymes responsible for carnosine synthesis and degradation, were molecularly identified and cloned in 2003 and 2010, respectively. A polymorphism in the gene for the carnosine-degrading enzyme carnosinase was defined as an important genetic risk factor for diabetic nephropathy. The evidence for a therapeutic role of carnosine in aging and neurologic diseases has expanded and new target diseases, such as diabetes/metabolic syndrome, liver and kidney disease and cancer, have been successfully explored in animal experiments. Carnosinase-resistant analogues of carnosine are developed in the pharmaceutical industry for increased therapeutic potential and stability. Finally, the content of muscle carnosine appears to influence athletic performance and can be augmented by oral beta-alanine supplementation, making beta-alanine increasingly popular in the athletic community. Thus, a new meeting was timely and needed. The current special issue in Amino Acids provides a selection of contributions presented at the Ghent meeting, containing original papers, review articles and a new perspective. Carnosine was originally discovered in skeletal muscle, where it has a far greater concentration compared to all other tissues. The regulation of the carnosine content in muscle is still incompletely understood, but the current knowledge is elegantly summarized in this special issue by Harris et al. (2012, this issue). A recent development of a non-invasive magnetic resonance spectroscopy (MRS) based method to quantify muscle carnosine in humans has further facilitated the research on this topic. Accordingly, a study based on over 260 male and female healthy humans aged 9–83 years (Baguet et al. 2012, this issue) indicates This is the introduction paper to the Special Issue of Amino Acids, entitled ‘Carnosine in Exercise and Disease’ and edited by Craig Sale and Wim Derave.

Due to the well-defined role of β-alanine as a substrate of carnosine (a major contributor to H+ buffering during high-intensity exercise), β-alanine is fast becoming a popular ergogenic aid to sports performance. There have been several recent qualitative review articles published on the topic, and here we present a preliminary quantitative review of the literature through a meta-analysis. A comprehensive search of the literature was employed to identify all studies suitable for inclusion in the analysis; strict exclusion criteria were also applied. Fifteen published manuscripts were included in the analysis, which reported the results of 57 measures within 23 exercise tests, using 18 supplementation regimes and a total of 360 participants [174, β-alanine supplementation group (BA) and 186, placebo supplementation group (Pla)]. BA improved (P = 0.002) the outcome of exercise measures to a greater extent than Pla [median effect size (IQR): BA 0.374 (0.140–0.747), Pla 0.108 (−0.019 to 0.487)]. Some of that effect might be explained by the improvement (P = 0.013) in exercise capacity with BA compared to Pla; no improvement was seen for exercise performance (P = 0.204). In line with the purported mechanisms for an ergogenic effect of β-alanine supplementation, exercise lasting 60–240 s was improved (P = 0.001) in BA compared to Pla, as was exercise of >240 s (P = 0.046). In contrast, there was no benefit of β-alanine on exercise lasting

Carnosine (β-alanyl-L-histidine) is found in high concentrations in skeletal muscle and chronic β-alanine (BA) supplementation can increase carnosine content. This placebo-controlled, double-blind study compared two different 8-week BA dosing regimens on the time course of muscle carnosine loading and 8-week washout, leading to a BA dose-response study with serial muscle carnosine assessments throughout. Thirty-one young males were randomized into three BA dosing groups: (1) high-low: 3.2 g BA/day for 4 weeks, followed by 1.6 g BA/day for 4 weeks; (2) low-low: 1.6 g BA/day for 8 weeks; and (3) placebo. Muscle carnosine in tibialis-anterior (TA) and gastrocnemius (GA) muscles was measured by 1H-MRS at weeks 0, 2, 4, 8, 12 and 16. Flushing symptoms and blood clinical chemistry were trivial in all three groups and there were no muscle carnosine changes in the placebo group. During the first 4 weeks, the increase for high-low (TA 2.04 mmol/kgww, GA 1.75 mmol/kgww) was ~twofold greater than low-low (TA 1.12 mmol/kgww, GA 0.80 mmol/kgww). 1.6 g BA/day significantly increased muscle carnosine within 2 weeks and induced continual rises in already augmented muscle carnosine stores (week 4-8, high-low regime). The dose-response showed a carnosine increase of 2.01 mmol/kgww per 100 g of consumed BA, which was only dependent upon the total accumulated BA consumed (within a daily intake range of 1.6-3.2 g BA/day). Washout rates were gradual (0.18 mmol/kgww and 0.43 mmol/kgww/week; ~2%/week). In summary, the absolute increase in muscle carnosine is only dependent upon the total BA consumed and is not dependent upon baseline muscle carnosine, the muscle type, or the daily amount of supplemented BA.

The role of the presence of carnosine (β-alanyl-l-histidine) in millimolar concentrations in human skeletal muscle is poorly understood. Chronic oral β-alanine supplementation is shown to elevate muscle carnosine content and improve anaerobic exercise performance during some laboratory tests, mainly in the untrained. It remains to be determined whether carnosine loading can improve single competition-like events in elite athletes. The aims of the present study were to investigate if performance is related to the muscle carnosine content and if β-alanine supplementation improves performance in highly trained rowers. Eighteen Belgian elite rowers were supplemented for 7 wk with either placebo or β-alanine (5 g/day). Before and following supplementation, muscle carnosine content in soleus and gastrocnemius medialis was measured by proton magnetic resonance spectroscopy (1H-MRS) and the performance was evaluated in a 2,000-m ergometer test. At baseline, there was a strong positive correlation between 100-, 500-, 2,000-, and 6,000-m speed and muscle carnosine content. After β-alanine supplementation, the carnosine content increased by 45.3% in soleus and 28.2% in gastrocnemius. Following supplementation, the β-alanine group was 4.3 s faster than the placebo group, whereas before supplementation they were 0.3 s slower ( P = 0.07). Muscle carnosine elevation was positively correlated to 2,000-m performance enhancement ( P = 0.042 and r = 0.498). It can be concluded that the positive correlation between baseline muscle carnosine levels and rowing performance and the positive correlation between changes in muscle carnosine and performance improvement suggest that muscle carnosine is a new determinant of rowing performance.

Carnosine (β-alanyl-l-histidine) is present in high concentrations in human skeletal muscles. The oral ingestion of β-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content both in trained and untrained humans. Little human data exist about the dynamics of the muscle carnosine content, its metabolic regulation, and its dependence on muscle fiber type. The present study aimed to investigate in three skeletal muscle types the supplementation-induced amplitude of carnosine synthesis and its subsequent elimination on cessation of supplementation (washout). Fifteen untrained males participated in a placebo-controlled double-blind study. They were supplemented for 5–6 wk with either 4.8 g/day β-alanine or placebo. Muscle carnosine was quantified in soleus, tibialis anterior, and medial head of the gastrocnemius by proton magnetic resonance spectroscopy (MRS), before and after supplementation and 3 and 9 wk into washout. The β-alanine supplementation significantly increased the carnosine content in soleus by 39%, in tibialis by 27%, and in gastrocnemius by 23% and declined postsupplementation at a rate of 2–4%/wk. Average muscle carnosine remained increased compared with baseline at 3 wk of washout (only one-third of the supplementation-induced increase had disappeared) and returned to baseline values within 9 wk at group level. Following subdivision into high responders (+55%) and low responders (+15%), washout period was 15 and 6 wk, respectively. In the placebo group, carnosine remained relatively constant with variation coefficients of 9–15% over a 3-mo period. It can be concluded that carnosine is a stable compound in human skeletal muscle, confirming the absence of carnosinase in myocytes. The present study shows that washout periods for crossover designs in supplementation studies for muscle metabolites may sometimes require months rather than weeks.

The carnosine and taurine contents of the vastus lateralis of two diverse groups of Korean male subjects (elderly and impaired glucose-tolerant (IGT) subjects and young elite swimmers at a national sport university) having a similar national diet, were examined. Despite marked differences in age, fitness and clinical status the two groups showed almost identical muscle carnosine and taurine contents. In the case of carnosine, the results suggest a similar contribution to intracellular buffering capacity in the two groups of subjects, with no evidence of a reduction of this in elderly IGT subjects. In addition, both groups showed the same inverse relationship between the muscle carnosine and taurine contents; the spread of values between subjects, within-groups, most likely reflect variations in the type I (low carnosine, high taurine) or type II (high carnosine, low taurine) composition of the vastus lateralis. The relationship is consistent with a role of taurine in osmoregulation, compensating for variations between fibre types in the carnosine content.

Purpose. Beta-alanine (BA) supplementation has been shown to augment muscle carnosine concentration, thereby promoting high-intensity exercise performance. Trained muscles of athletes have a higher increase in carnosine concentration after BA supplementation compared to untrained muscles, but it remains to be determined whether this is due to an accumulation of acute exercise effects or to chronic adaptations from prior training. The aim of the present study was to investigate whether high-volume (HV) and/or high-intensity (HI) exercise can improve BA-induced carnosine loading in untrained subjects. Methods. All participants (n=28) were supplemented with 6.4 g/day of BA for 23 days. The subjects were allocated to a control group, HV or HI training group. During the BA supplementation period, the training groups performed 9 exercise sessions consisting of either 75–90 min continuous cycling at 35–45% Wmax (HV) or 3 to 5 repeats of 30s cycling at 165% Wmax with 4 min recovery (HI). Carnosine content was measured in soleus and gastrocnemius medialis by proton magnetic resonance spectroscopy. Results. There was no difference in absolute increase in carnosine content between the groups in soleus and gastrocnemius muscle. For the average muscle carnosine content, a higher absolute increase was found in HV (+ 2.95 mM; P = 0.046) and HI (+ 3.26 mM; P = 0.028) group compared to the control group (+ 1.91 mM). However, there was no additional difference between the HV and HI training group. Conclusions. HV and HI exercise training showed no significant difference on BA-induced muscle carnosine loading in soleus and gastrocnemius muscle. It can be suggested that there can be a small cumulative effect of exercise on BA supplementation efficiency, although differences did not reach significance on individual muscle level.

It has been suggested that histidine-containing dipeptide carnosine (β-alanyl-L-histidine), which is believed to act as a cytosolic buffering agent, is present predominantly in skeletal muscle. The purpose of this study was to investigate the effects of sprint training (30-s maximal cycle ergometer sprinting) on muscle carnosine concentration. Six untrained males trained 2 days per week for 8 weeks on an electronic-braked cycle ergometer. Muscle biopsy samples were taken from the vastus lateralis before and two days after the last training session and were analyzed for carnosine concentration by the use of an amino acid autoanalyzer. The carnosine concentration was significantly increased after sprint training (P < 0.05). The mean power during 30-s maximal cycle ergometer sprinting was significantly increased following training. When dividing the 30-s sprinting into 6 phases (0-5, 6-10, 11-15, 16-20, 21-25, 26-30 s), the magnitude of increase in mean power was significantly larger for the last 2 phases than the first phase (P < 0.05). These results suggest that the increases in skeletal muscle carnosine concentration following sprint training may be associated with the increase in sustainability of high power during 30-s maximal cycle ergometer sprinting.