The role of chronic muscle (in)activity on carnosine homeostasis: a study with spinal cord-injured athletes.

To examine the role of chronic (in)activity on muscle carnosine (MCarn) and how chronic (in)activity affects MCarn responses to ß-alanine supplementation in spinal cord-injured athletes, 16 male athletes with paraplegia were randomized (2:1 ratio) to receive ß-alanine (n = 11) or placebo (PL, n = 5). They consumed 6.4 g/day of ß-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 ß-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 ß-alanine supplementation is not influenced by muscle inactivity.

Insulin does not stimulate ß-alanine transport into human skeletal muscle.

To test whether high circulating insulin concentrations influence the transport of ß-alanine into skeletal muscle at either saturating or subsaturating ß-alanine concentrations, we conducted two experiments whereby ß-alanine and insulin concentrations were controlled. In experiment 1, 12 men received supraphysiological amounts of ß-alanine intravenously (0.11 g·kg-1·min-1 for 150 min), with or without insulin infusion. ß-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and ß-alanine analyses. ß-Alanine content in 24-h urine was assessed. In experiment 2, six men ingested typical doses of ß-alanine (10 mg/kg) before insulin infusion or no infusion. ß-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1, no differences between conditions were shown for plasma ß-alanine, muscle ß-alanine, muscle carnosine and urinary ß-alanine concentrations (all P > 0.05). In experiment 2, no differences between conditions were shown for plasma ß-alanine or muscle ß-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase ß-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the Vmax of ß-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize ß-alanine transport into muscle following ß-alanine intake.

Kinetics of Muscle Carnosine Decay after ß-Alanine Supplementation: A 16-wk Washout Study.

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 ß-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 ß-alanine group only (+91.1% ± 29.1%; placebo, +0.04% ± 10.1%; P < 0.0001). M-Carn started to decrease after cessation of ß-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 ß-alanine supplementation strategies.

The Muscle Carnosine Response to Beta-Alanine Supplementation: A Systematic Review With Bayesian Individual and Aggregate Data E-Max Model and Meta-Analysis.

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]).

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.

Beta-alanine supplementation enhances judo-related performance in highly-trained athletes.

OBJECTIVES: In official judo competitions, athletes usually engage in 5-7 matches in the same day, performing numerous high-intensity efforts interspersed by short recovery intervals. Thus, glycolytic demand in judo is high and acidosis may limit performance. Carnosine is a relevant intracellular acid buffer whose content is increased with beta-alanine supplementation. Thus, we hypothesized that beta-alanine supplementation could attenuate acidosis and improve judo performance. DESIGN: Twenty-three highly-trained judo athletes were randomly assigned to receive either beta-alanine (6.4gday-1) or placebo (dextrose, same dosage) for 4 weeks. METHODS: Performance was assessed before (PRE) and after (POST) supplementation through a 5-min simulated fight (randori) followed by 3 bouts of the Special Judo Fitness Test (SJFT). Blood samples were collected for blood pH, bicarbonate (HCO3-) and lactate determination. RESULTS: Beta-alanine supplementation improved the number of throws per set and the total number of throws (both p<0.05). Placebo did not change these variables (both p>0.05). Blood pH and HCO3- reduced after exercise (all p<0.001), with no between-group differences (all p>0.05). However, the lactate response to exercise increased in the beta-alanine group as compared to placebo (p<0.05). CONCLUSIONS: In conclusion, 4 weeks of beta-alanine supplementation effectively enhance judo-related performance in highly-trained athletes.

Effect of Creatine Loading on Oxygen Uptake during a 1-km Cycling Time Trial.

PURPOSE: For the first time, we investigated the effects of altering cellular metabolic capacitance, via a 5-d creatine (Cr) loading protocol (20 g·d⁻¹), on oxygen uptake (VO2), accumulated oxygen deficit, muscle recruitment, and performance during a 1-km cycling time trial. METHODS: In a double-blind, randomized, placebo-controlled design, 19 amateur cyclists were allocated to a Cr (n = 10, VO2peak = 56.0 ± 7.8 mL·kg⁻¹·min⁻¹) or placebo (n = 9, VO2peak = 56.0 ± 8.4 mL·kg⁻¹·min⁻¹) group, and performed a 1-km cycling time trial before and after the supplementation period. RESULTS: Body mass was significantly increased in the Cr group (P < 0.05), but not in the placebo group. Participants adopted an "all-out" pacing strategy in both groups. However, Cr loading reduced VO2 immediately after the beginning (12th to 23th seconds), and this was accompanied by a reduced aerobic and increased anaerobic contribution. The VO2 mean response time was slower (pre: 17.2 ± 5.6 s vs post: 19.9 ± 4.6 s), the total O2 uptake was reduced (pre: 4.64 ± 0.59 L vs post: 4.47 ± 0.53 L), and the oxygen deficit was increased (pre: 0.82 ± 0.27 L vs post: 0.98 ± 0.25 L) after Cr loading. No differences were observed in the placebo group for these variables. Plasma lactate and integrated electromyography were not altered in either group, nor was the time to complete the trial (Cr group: pre: 89.1 ± 6.7 s vs post 89.1 ± 6.2 s and placebo group: pre 85.9 ± 4.9 s vs post 87.0 ± 5.4 s). CONCLUSION: Cr loading slows the V˙O2 response and increases the anaerobic contribution during a 1-km cycling time trial.

Suplementação d creatina e seus efeitos sobre desempenho em exercícios contíínuos e intermitentes de alta intensiddde / Creatinesupplemeentation and its effectson performance in continous andd intermittent high intensity exercise

RESUMOA presente revisão teve como objetivo verificar os efeitos da suplementação de Creatina (Cr) sobre o desempenho em exercícios contínuos e intermitentes de curta duração e alta intensidade, relatando resultados de estudos publicados desde 1993. Na maioria dos estudos, os resultados demonstram a eficácia da suplementação de Cr em aumentar a capacidade e desempenho em exercícios de predominância anaeróbia. Resultados controversos podem ser atribuídos a questões como o ganho de massa corporal, protocolo de suplementação insuficiente para promover aumento significativo das reservas intramusculares de Cr e possível presença de indivíduos não respondentes. A extrapolação desses resultados para o "mundo real" dos esportes ainda precisa ser melhor analisada através de pesquisas, visando esclarecer a real vantagem do uso deste suplemento por atletas e praticantes de diversas modalidades esportivas.

ABSTRACTThis review aimed to verify the effects of creatine supplementation on performance during short-term, high-intensity continuous and intermittent exercises, considering studies results published since 1993. In the majority of these studies, improvements on anaerobic capacity and performance in predominantly anaerobic exercise were evident. Controversial results may be attributed to some issues, such as body mass gain, no significant increase on muscle Cr content due to inadequate supplementation protocol, and influence of non-responders participants. Extrapolation of these results to the sports "real world" should be further analyzed to clarify the real advantages of Cr using as a supplement for athletes and Sports Enthusiast.