Exercise training and beta-alanine-induced muscle carnosine loading

PURPOSE: Beta-alanine (BA) supplementation has been shown to augment muscle carnosine concentration, thereby promoting high-intensity (HI) 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 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 nine exercise sessions, consisting of either 75-90 min continuous cycling at 35-45% Wmax (HV) or 3 to 5 repeats of 30 s 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. CONCLUSION: 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

Exercise alters and beta-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscle

Title on article: Exercise alters and β-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscl

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Muscle carnosine loading by beta-alanine supplementation is more pronounced in trained vs. untrained muscles

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

Effect of 10 Week Beta-Alanine Supplementation on Competition and Training Performance in Elite Swimmers

Although some laboratory-based studies show an ergogenic effect with beta-alanine supplementation, there is a lack of field-based research in training and competition settings. Elite/Sub-elite swimmers (n = 23 males and 18 females, age = 21.7 ± 2.8 years; mean ± SD) were supplemented with either beta-alanine (4 weeks loading phase of 4.8 g/day and 3.2 g/day thereafter) or placebo for 10 weeks. Competition performance times were log-transformed, then evaluated before (National Championships) and after (international or national selection meet) supplementation. Swimmers also completed three standardized training sets at baseline, 4 and 10 weeks of supplementation. Capillary blood was analyzed for pH, bicarbonate and lactate concentration in both competition and training. There was an unclear effect (0.4%; ±0.8%, mean, ±90% confidence limits) of beta-alanine on competition performance compared to placebo with no meaningful changes in blood chemistry. While there was a transient improvement on training performance after 4 weeks with beta-alanine (−1.3%; ±1.0%), there was an unclear effect at ten weeks (−0.2%; ±1.5%) and no meaningful changes in blood chemistry. Beta-alanine supplementation appears to have minimal effect on swimming performance in non-laboratory controlled real-world training and competition settings

Inhibiting beta-alanine transamination : a way to promote muscle histidine-containing dipeptide loading in mice?

Purpose. Of the orally supplied beta-alanine (BA), only 2-3% is excreted in the urine and only 1-6% is converted to muscle carnosine during a long-term supplementation protocol1. Moreover, it was already shown in the ‘50s that more than 90% of the injected C14-labeled BA in rats was recovered in the expired CO2 in 5 hours². We now hypothesize that BA can be transaminated into malonate semi-aldehyde by the enzymes ‘beta-alanine - 2-oxoglutarate transaminase’ (ABAT) and ‘beta-alanine-pyruvate transaminase’ (AGXT2). Vigabatrin (VG) is a specific inhibitor of ABAT, while aminooxyacetic acid (AOA) inhibits all pyridoxal-5’-phosphate (PLP) - dependent enzymes, including ABAT and AGXT2. The aim of the present study was to elucidate the effect of specific (VG) and non-specific (AOA) BA transaminase inhibitors on BA-induced muscle HCD loading in mice. Methods. A total of 66 male C57BL/6 mice (10 weeks old) were used in this study. Mice were randomly divided in 6 groups and underwent different treatments, which differed in the amount of BA in the drinking water (0%, 0.1%, 0.6%, 1.2%) and in the subcutaneous injection of VG, AOA or saline (every 72h or 24h). After 2 weeks, muscles and organs were dissected and blood was collected. Serum BA levels were analysed by means of HPLC. Brain ABAT activity was determined by the fluorometric quantification of NADH formation following addition of GABA to a brain homogenate. Muscle and organ HCD levels were analysed by means of LC-MS/MS and qPCR analysis was used to measure the expression of carnosine-related enzymes and transporters. Results. Taurine transporter and carnosine synthesis enzyme are mainly expressed in muscles and brain. In contrast, the BA transaminating enzymes show highest expression in liver and kidney and very low expression in muscles. Brain ABAT activity is significantly decreased when VG or AOA is administered (-82.2% and -87.8%, respectively; p < 0.001). Serum BA levels are not affected by the supplementation of 0.1% BA alone or in combination with VG administration, but significant increases are found when this low amount of BA is combined with AOA (p = 0.007 vs 0.1%BA – SAL for serum). Subsequently, this leads to significantly higher HCD loading in the different muscles and highest effects are found in soleus and heart (p < 0.001 for 0.1%BA – AOA vs 0.1%BA – SAL). The more glycolytic muscles also show higher HCD loading with AOA administration (p < 0.001 and p = 0.024 vs 0%BA – SAL for tibialis anterior and gastrocnemius, respectively), but effects are absent in kidney and brain. Furthermore, no effects of specific inhibition (VG) were found in any of these tissues. Conclusion. Non-specific inhibition of BA transamination has positive effects on BA-induced HCD loading in both muscles and organs, suggesting that muscle HCD synthesis is dependent on the amount of beta-alanine transamination in mice. References: [1] Stegen S., Blancquaert L., Everaert I., et al. Med Sci Sports Exc. 2013, 45 (8): 1478-85. [2] Pihl and Fritzson. J Biol Chem. 1955, 215: 345-51

Exercise alters and β-alanine combined with exercise augments histidyl dipeptide levels and scavenges lipid peroxidation products in human skeletal muscle

Carnosine and anserine are dipeptides synthesized from histidine and β-alanine by carnosine synthase (ATPGD1). These dipeptides, present in high concentration in the skeletal muscle, form conjugates with lipid peroxidation products such as 4-hydroxy trans-2-nonenal (HNE). Although skeletal muscle levels of these dipeptides could be elevated by feeding β-alanine, it is unclear how these dipeptides and their conjugates are affected by exercise training with or without β-alanine supplementation. We recruited twenty physically active men, who were allocated to either β-alanine or placebo-feeding group matched for VO2 peak, lactate threshold, and maximal power (Wmax). Participants completed 2 weeks of conditioning phase followed by 1 week of exercise testing (CPET) and a single session followed by 6 weeks of high intensity interval training (HIIT). Analysis of muscle biopsies showed that the levels of carnosine and ATPGD1 expression were increased after CPET and decreased following a single session and 6 weeks of HIIT. Expression of ATPGD1 and levels of carnosine were increased upon β-alanine-feeding after CPET, while ATPGD1 expression decreased following a single session of HIIT. The expression of fiber type markers myosin heavy chain (MHC) I and IIa remained unchanged after CPET. Levels of carnosine, anserine, carnosine-HNE, carnosine-propanal and carnosine-propanol were further increased after 9 weeks of β-alanine supplementation and exercise training, but remained unchanged in the placebo-fed group. These results suggest that carnosine levels and ATPGD1 expression fluctuates with different phases of training. Enhancing carnosine levels by β-alanine feeding could facilitate the detoxification of lipid peroxidation products in the human skeletal muscle