24-Week ß-alanine ingestion does not affect muscle taurine or clinical blood parameters in healthy males.

PURPOSE: To investigate the effects of chronic beta-alanine (BA) supplementation on muscle taurine content, blood clinical markers and sensory side-effects. METHODS: Twenty-five healthy male participants (age 27 ± 4 years, height 1.75 ± 0.09 m, body mass 78.9 ± 11.7 kg) were supplemented with 6.4 g day-1 of sustained-release BA (N = 16; CarnoSyn™, NAI, USA) or placebo (PL; N = 9; maltodextrin) for 24 weeks. Resting muscle biopsies of the m. vastus lateralis were taken at 0, 12 and 24 weeks and analysed for taurine content (BA, N = 12; PL, N = 6) using high-performance liquid chromatography. Resting venous blood samples were taken every 4 weeks and analysed for markers of renal, hepatic and muscle function (BA, N = 15; PL, N = 8; aspartate transaminase; alanine aminotransferase; alkaline phosphatase; lactate dehydrogenase; albumin; globulin; creatinine; estimated glomerular filtration rate and creatine kinase). RESULTS: There was a significant main effect of group (p = 0.04) on muscle taurine, with overall lower values in PL, although there was no main effect of time or interaction effect (both p > 0.05) and no differences between specific timepoints (week 0, BA: 33.67 ± 8.18 mmol kg-1 dm, PL: 27.75 ± 4.86 mmol kg-1 dm; week 12, BA: 35.93 ± 8.79 mmol kg-1 dm, PL: 27.67 ± 4.75 mmol kg-1 dm; week 24, BA: 35.42 ± 6.16 mmol kg-1 dm, PL: 31.99 ± 5.60 mmol kg-1 dm). There was no effect of treatment, time or any interaction effects on any blood marker (all p > 0.05) and no self-reported side-effects in these participants throughout the study. CONCLUSIONS: The current study showed that 24 weeks of BA supplementation at 6.4 g day-1 did not significantly affect muscle taurine content, clinical markers of renal, hepatic and muscle function, nor did it result in chronic sensory side-effects, in healthy individuals. Since athletes are likely to engage in chronic supplementation, these data provide important evidence to suggest that supplementation with BA at these doses for up to 24 weeks is safe for healthy individuals.

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.

A kinetic model of carnosine synthesis in human skeletal muscle.

Drawing on previously published data, a mathematical model is proposed to describe the synthesis of carnosine in muscle using a slow release ß-alanine supplement (SR-CarnoSyn®). The model pre-supposes that the rate of synthesis for any given dose of ß-alanine (within the range 1.6-6.4 g day-1) is constant with time, but is first order with respect to daily ß-alanine dose. Simultaneously with synthesis, decay in carnosine is also assumed to be occurring, the rate in this case being a function of the concentration of carnosine. Decay in carnosine appears describable by first-order kinetics. By integration of the two rate reactions, a single mathematical equation was derived to describe the synthesis of carnosine and which closely fitted the experimental data over 56 days. The model, if validated by additional studies, could be used to compliment empirical observations of the changes in carnosine in muscle with supplementation, and allow objective examination of a number of possible influences affecting the rate constants of synthesis and decay.

High-Intensity Interval Training Augments Muscle Carnosine in the Absence of Dietary Beta-alanine Intake.

PURPOSE: 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 ß-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. METHODS: 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 (ßmin vitro) were also determined. Exercise tests were performed to evaluate total work done, V˙O2max, ventilatory thresholds (VT) and LT. RESULTS: Total work done, VT, LT, V˙O2max, and ßmin vitro were improved in the HIIT group (all P < 0.05), but not in CON (P > 0.05). 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. CONCLUSIONS: In the absence of any dietary intake of ß-alanine, HIIT increased MCarn content. The contribution of increased MCarn to the total increase in ßmin vitro appears to be small.

Twenty-four Weeks of ß-Alanine Supplementation on Carnosine Content, Related Genes, and Exercise.

INTRODUCTION: Skeletal muscle carnosine content can be increased through ß-alanine (BA) 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. PURPOSE: This study aimed to investigate the effects of 24 wk of BA supplementation on muscle carnosine content, gene expression, and high-intensity cycling capacity (CCT110%). METHODS: Twenty-five active males were supplemented with 6.4 g·d of sustained release BA or placebo for a 24 wk period. Every 4 wk participants provided a muscle biopsy and performed the CCT110%. Biopsies were analyzed for muscle carnosine content and gene expression (CARNS, TauT, ABAT, CNDP2, PHT1, PEPT2, and PAT1). RESULTS: Carnosine content was increased from baseline at every time point in BA (all P < 0.0001; week 4 = +11.37 ± 7.03 mmol·kg dm, week 8 = +13.88 ± 7.84 mmol·kg dm, week 12 = +16.95 ± 8.54 mmol·kg dm, week 16 = +17.63 ± 8.42 mmol·kg dm, week 20 = +21.20 ± 7.86 mmol·kg dm, and week 24 = +20.15 ± 7.63 mmol·kg dm) but not placebo (all P > 0.05). Maximal increases were +25.66 ± 7.63 mmol·kg dm (range = +17.13 to +41.32 mmol·kg dm), and absolute maximal content was 48.03 ± 8.97 mmol·kg dm (range = 31.79 to 63.92 mmol·kg dm). There was an effect of supplement (P = 0.002) on TauT; no further differences in gene expression were shown. Exercise capacity was improved in BA (P = 0.05) with possible to almost certain improvements across all weeks. CONCLUSIONS: Twenty-four weeks of BA supplementation increased muscle carnosine content and improved high-intensity cycling capacity. The downregulation of TauT suggests it plays an important role in muscle carnosine accumulation with BA supplementation, whereas the variability in changes in muscle carnosine content between individuals suggests that other determinants other than the availability of BA may also bear a major influence on muscle carnosine content.

ß-Alanine supplementation enhances human skeletal muscle relaxation speed but not force production capacity.

ß-Alanine (BA) supplementation improves human exercise performance. One possible explanation for this is an enhancement of muscle contractile properties, occurring via elevated intramuscular carnosine resulting in improved calcium sensitivity and handling. This study investigated the effect of BA supplementation on in vivo contractile properties and voluntary neuromuscular performance. Twenty-three men completed two experimental sessions, pre- and post-28 days supplementation with 6.4 g/day of BA (n = 12) or placebo (PLA; n = 11). During each session, force was recorded during a series of knee extensor contractions: resting and potentiated twitches and octet (8 pulses, 300 Hz) contractions elicited via femoral nerve stimulation; tetanic contractions (1 s, 1-100 Hz) via superficial muscle stimulation; and maximum and explosive voluntary contractions. BA supplementation had no effect on the force-frequency relationship, or the force responses (force at 25 and 50 ms from onset, peak force) of resting or potentiated twitches, and octet contractions (P > 0.05). Resting and potentiated twitch electromechanical delay and time-to-peak tension were unaffected by BA supplementation (P > 0.05), although half-relaxation time declined by 7-12% (P < 0.05). Maximum and explosive voluntary forces were unchanged after BA supplementation. BA supplementation had no effect on evoked force responses, implying that altered calcium sensitivity and/or release are not the mechanisms by which BA supplementation influences exercise performance. The reduced half-relaxation time with BA supplementation might, however, be explained by enhanced reuptake of calcium, which has implications for the efficiency of muscle contraction following BA supplementation.

Effect of ß-alanine supplementation on 20 km cycling time trial performance

The effects of ß-alanine supplementation on high-intensity cycling performance and capacity have been evaluated, although the effects on longer duration cycling performance are unclear. Nineteen UK category 1 male cyclists completed four 20 km cycling time trials, two before and two after supplementation with either 6.4 g•d-1 ß-alanine (n = 10; BA) or a matched placebo (n = 9; P). Performance time for the 20 km time trial and 1 km split times were recorded. There was no significant effect of ß-alanine supplementation on 20 km time trial performance (BA-pre 1943 ± 129 s; BA-post 1950 ± 147 s; P-pre 1989 ± 106 s; P-post 1986 ± 115 s) or on the performance of each 1 km split. The effect of ß-alanine on 20 km time trial performance was deemed unclear as determined by magnitude based inferences. Supplementation with 6.4 g•d-1 of ß-alanine for 4 weeks did not affect 20 km cycling time trial performance in well trained male cyclists

Influence of training status on high-intensity intermittent performance in response to ß-alanine supplementation.

Recent investigations have suggested that highly trained athletes may be less responsive to the ergogenic effects of ß-alanine (BA) supplementation than recreationally active individuals due to their elevated muscle buffering capacity. We investigated whether training status influences the effect of BA on repeated Wingate performance. Forty young males were divided into two groups according to their training status (trained: T, and non-trained: NT cyclists) and were randomly allocated to BA and a dextrose-based placebo (PL) groups, providing four experimental conditions: NTPL, NTBA, TPL, TBA. BA (6.4 g day(-1)) or PL was ingested for 4 weeks, with participants completing four 30-s lower-body Wingate bouts, separated by 3 min, before and after supplementation. Total work done was significantly increased following supplementation in both NTBA (p = 0.03) and TBA (p = 0.002), and it was significantly reduced in NTPL (p = 0.03) with no difference for TPL (p = 0.73). BA supplementation increased mean power output (MPO) in bout 4 for the NTBA group (p = 0.0004) and in bouts 1, 2 and 4 for the TBA group (p ≤ 0.05). No differences were observed in MPO for NTPL and TPL. BA supplementation was effective at improving repeated high-intensity cycling performance in both trained and non-trained individuals, highlighting the efficacy of BA as an ergogenic aid for high-intensity exercise regardless of the training status of the individual.

The ergogenic effect of beta-alanine combined with sodium bicarbonate on high-intensity swimming performance.

We investigated the effect of beta-alanine (BA) alone (study A) and in combination with sodium bicarbonate (SB) (study B) on 100- and 200-m swimming performance. In study A, 16 swimmers were assigned to receive either BA (3.2 g·day(-1) for 1 week and 6.4 g·day(-1) for 4 weeks) or placebo (PL; dextrose). At baseline and after 5 weeks of supplementation, 100- and 200-m races were completed. In study B, 14 were assigned to receive either BA (3.2 g·day(-1) for 1 week and 6.4 g·day(-1) for 3 weeks) or PL. Time trials were performed once before and twice after supplementation (with PL and SB), in a crossover fashion, providing 4 conditions: PL-PL, PL-SB, BA-PL, and BA-SB. In study A, BA supplementation improved 100- and 200-m time-trial performance by 2.1% (p = 0.029) and 2.0% (p = 0.0008), respectively. In study B, 200-m time-trial performance improved in all conditions, compared with presupplementation, except the PL-PL condition (PL-SB, +2.3%; BA-PL, +1.5%; BA-SB, +2.13% (p < 0.05)). BA-SB was not different from BA-PL (p = 0.21), but the probability of a positive effect was 78.5%. In the 100-m time-trial, only a within-group effect for SB was observed in the PL-SB (p = 0.022) and BA-SB (p = 0.051) conditions. However, 6 of 7 athletes swam faster after BA supplementation. The probability of BA having a positive effect was 65.2%; when SB was added to BA, the probability was 71.8%. BA and SB supplementation improved 100- and 200-m swimming performance. The coingestion of BA and SB induced a further nonsignificant improvement in performance.

The effect of 4 weeks beta-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres.

Seven male students were supplemented with beta-alanine (beta-ALG) for 4 weeks (6.4 g day(-1)) and seven with a matching placebo (PLG). Subjects undertook 4 weeks of isokinetic training with the right leg (T) whilst the left leg was untrained (UT), serving as a control. Each training session consisted of 10 x 10 maximal 90 degrees extension and flexion contractions at 180 degrees /s using a Kin-Com isokinetic dynamometer, with 1 min rest between bouts. Muscle biopsies were taken from the vastus lateralis immediately before and at the end of the supplementation period. Following freeze drying muscle fibres were dissected and characterised by their MHC profile, as type I, IIa, IIx, or as hybrids of these. Carnosine was measured by HPLC. There was a significant increase in carnosine in both T and UT legs of the beta-ALG (9.63 +/- 3.92 mmol kg(-1) dry muscle and 6.55 +/- 2.36 mmol kg(-1) dry muscle respectively). There was a significant increase in the carnosine content of all fibre phentotypes, with no significant difference between types. There were no significant differences in the changes in muscle or in fibres between the T and UT legs. In contrast there was no significant change in the carnosine content in either the T or UT legs with placebo. The results indicate that 4 weeks training has no effect on the muscle carnosine content. Whilst an increase was seen with beta-alanine supplementation, this was not further influenced by training. These findings suggest that beta-alanine availability is the main factor regulating muscle carnosine synthesis.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial.

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.