Muscle carnosine metabolism and β-alanine supplementation in relation to exercise and training

Carnosine is a dipeptide with a high concentration in mammalian skeletal muscle. It is synthesized by carnosine synthase from the amino acids L-histidine and beta-alanine, of which the latter is the rate-limiting precursor, and degraded by carnosinase. Recent studies have shown that the chronic oral ingestion of beta-alanine can substantially elevate (up to 80%) the carnosine content of human skeletal muscle. Interestingly, muscle carnosine loading leads to improved performance in high-intensity exercise in both untrained and trained individuals. Although carnosine is not involved in the classic adenosine triphosphate-generating metabolic pathways, this suggests an important role of the dipeptide in the homeostasis of contracting muscle cells, especially during high rates of anaerobic energy delivery. Carnosine may attenuate acidosis by acting as a pH buffer, but improved contractile performance may also be obtained by improved excitation-contraction coupling and defence against reactive oxygen species. High carnosine concentrations are found in individuals with a high proportion of fast-twitch fibres, because these fibres are enriched with the dipeptide. Muscle carnosine content is lower in women, declines with age and is probably lower in vegetarians, whose diets are deprived of beta-alanine. Sprint-trained athletes display markedly high muscular carnosine, but the acute effect of several weeks of training on muscle carnosine is limited. High carnosine levels in elite sprinters are therefore either an important genetically determined talent selection criterion or a result of slow adaptation to years of training. beta-Alanine is rapidly developing as a popular ergogenic nutritional supplement for athletes worldwide, and the currently available scientific literature suggests that its use is evidence based. However, many aspects of the supplement, such as the potential side effects and the mechanism of action, require additional and thorough investigation by the sports science community

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

A New Method for Non-Invasive Estimation of Human Muscle Fiber Type Composition

Background: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT) or type-II fibers and slow-twitch (ST) or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative.status: publishe

beta-Alanine supplementation reduces acidosis but not oxygen uptake response during high-intensity cycling exercise

The oral ingestion of beta-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content. Carnosine is thought to act as a physiologically relevant pH buffer during exercise but direct evidence is lacking. Acidosis has been hypothesised to influence oxygen uptake kinetics during high-intensity exercise. The present study aimed to investigate whether oral beta-alanine supplementation could reduce acidosis during high-intensity cycling and thereby affect oxygen uptake kinetics. 14 male physical education students participated in this placebo-controlled, double-blind study. Subjects were supplemented orally for 4 weeks with 4.8 g/day placebo or beta-alanine. Before and after supplementation, subjects performed a 6-min cycling exercise bout at an intensity of 50% of the difference between ventilatory threshold (VT) and (V) over dotO(2peak). Capillary blood samples were taken for determination of pH, lactate, bicarbonate and base excess, and pulmonary oxygen uptake kinetics were determined with a bi-exponential model fitted to the averaged breath-by-breath data of three repetitions. Exercise-induced acidosis was significantly reduced following beta-alanine supplementation compared to placebo, without affecting blood lactate and bicarbonate concentrations. The time delay of the fast component (Td(1)) of the oxygen uptake kinetics was significantly reduced following beta-alanine supplementation compared to placebo, although this did not reduce oxygen deficit. The parameters of the slow component did not differ between groups. These results indicate that chronic beta-alanine supplementation, which presumably increased muscle carnosine content, can attenuate the fall in blood pH during high-intensity exercise. This may contribute to the ergogenic effect of the supplement found in some exercise modes

Effect of beta-alanine and histidine supplementation on muscle carnosine loading

Carnosine (β-alanyl-L-histidine) occurs in high concentrations in human skeletal muscle where it works as a proton buffer (Derave et al, 2010). Studies on different animal species reported that beta-alanine and/or L-histidine supplementation are able to increase muscle carnosine and/or anserine content (Tamaki et al., 1977; Dunnett and Harris (1999) and Park et al., 2013). In humans, Harris et al (2006) showed that chronic oral beta-alanine supplementation can elevate muscle carnosine content. However, the effect of L-histidine was never established. Therefore, the aims of this study were to investigate the effect of beta-alanine and L-histidine supplementation, alone and combined, on human muscle carnosine loading. 15 male and 15 female participants (age: 20.0 ± 2.4 yr, body weight: 66.0 ± 10.6 kg) were divided in three groups (n=10). Each group was supplemented with either pure beta-alanine (BA) (6g/day), L-histidine hydrochloride monohydrate (HIS) (4.7g/day) or both amino acids (BA+HIS). Before and after 23 days of supplementation, carnosine content was evaluated in soleus and gastrocnemius medialis muscles by 1H-MRS. Both BA and BA+HIS groups showed significantly increased carnosine concentrations after 23 days of supplementation (BA: soleus p<0.001 (+57.2%), gastrocnemius p=0.002 (+34.6%). BA+HIS: soleus p<0.001 (+54.0%), gastrocnemius p=0.004 (+33.1%)), in contrast to the HIS group of which the carnosine concentration remained constant during the supplementation period (soleus p=0.894 (+5.0%), gastrocnemius p=0.528 (+4.0%)). This is the first study to investigate the effect of L-histidine supplementation on muscle carnosine content. In contrast to the animal data, histidine supplementation does not induce carnosine loading in human muscles. Furthermore, combined supplementation with beta-alanine and L-histidine has no additional effect compared to beta-alanine supplementation alone. Collectively, these data confirm that beta-alanine is the rate-limiting factor for carnosine synthesis in humans. References Derave W et al (2010). Sports medicine 40: 247–63. Tamaki N et al (1977). Journal of Nutritional Science and Vitaminology 23: 331-340. Dunnett and Harris (1999). Equine Vet J (Suppl.) 30: 499-504 Park SW et al (2013). Japan Poultry Science 50: 251-256. Harris RC et al (2006). Amino Acids 30(3): 279–289

beta-Alanine supplementation reduces acidosis but not oxygen uptake response during high-intensity cycling exercise

The oral ingestion of beta-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content. Carnosine is thought to act as a physiologically relevant pH buffer during exercise but direct evidence is lacking. Acidosis has been hypothesised to influence oxygen uptake kinetics during high-intensity exercise. The present study aimed to investigate whether oral beta-alanine supplementation could reduce acidosis during high-intensity cycling and thereby affect oxygen uptake kinetics. 14 male physical education students participated in this placebo-controlled, double-blind study. Subjects were supplemented orally for 4 weeks with 4.8 g/day placebo or beta-alanine. Before and after supplementation, subjects performed a 6-min cycling exercise bout at an intensity of 50% of the difference between ventilatory threshold (VT) and VO(2peak). Capillary blood samples were taken for determination of pH, lactate, bicarbonate and base excess, and pulmonary oxygen uptake kinetics were determined with a bi-exponential model fitted to the averaged breath-by-breath data of three repetitions. Exercise-induced acidosis was significantly reduced following beta-alanine supplementation compared to placebo, without affecting blood lactate and bicarbonate concentrations. The time delay of the fast component (Td(1)) of the oxygen uptake kinetics was significantly reduced following beta-alanine supplementation compared to placebo, although this did not reduce oxygen deficit. The parameters of the slow component did not differ between groups. These results indicate that chronic beta-alanine supplementation, which presumably increased muscle carnosine content, can attenuate the fall in blood pH during high-intensity exercise. This may contribute to the ergogenic effect of the supplement found in some exercise modes.status: publishe

The influence of sex, age and heritability on human skeletal muscle carnosine content

The dipeptide carnosine is found in high concentrations in human skeletal muscle and shows large interindividual differences. Sex and age are determining factors, however, systematic studies investigating the sex effects on muscle carnosine content throughout the human lifespan are lacking. Despite the large inter-individual variation, the intra-individual variation is limited. The question may be asked whether the carnosine content is a muscle characteristic which may be largely genetically determined. A total of 263 healthy male and female subjects of 9–83 years were divided into five different age groups: prepubertal children (PC), adolescents (A), young adults (YA), middle adults (MA) and elderly (E). We included 25 monozygotic and 22 dizygotic twin pairs among the entire study population to study the heritability. The carnosine content was measured non-invasively in the gastrocnemius medialis and soleus by proton magnetic resonance spectroscopy (1H-MRS). In boys, carnosine content was significantly higher (gastrocnemius 22.9%; soleus 44.6%) in A compared to PC, while it did not differ in girls. A decrease (*16%) was observed both in males and females from YA to MA. However, elderly did not have lower carnosine levels in comparison with MA. Higher correlations were found in monozygotic (r = 0.86) compared to dizygotic (r = 0.51) twins, in soleus muscle, but not in gastrocnemius. In conclusion, this study found an effect of puberty on muscle carnosine content in males, but not in females. Muscle carnosine decreased mainly during early adulthood and hardly from adulthood to elderly. High intra-twin correlations were observed, but muscle-dependent differences preclude clear conclusions toward heritability

Important role of muscle carnosine in rowing performance

The role of the presence of carnosine (beta-alanyl-L-histidine) in millimolar concentrations in human skeletal muscle is poorly understood. Chronic oral beta-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 beta-alanine supplementation improves performance in highly-trained rowers. Eighteen Belgian elite rowers were supplemented for 7 weeks with either placebo or beta-alanine (5 g/day). Before and following supplementation, muscle carnosine content in soleus and gastrocnemius medialis was measured by proton magnetic resonance spectroscopy ((1)H-MRS) and the performance was evaluated in a 2000 m ergometer test. At baseline, there was a strong positive correlation between 100 m, 500 m, 2000 m and 6000 m speed and muscle carnosine content. After beta-alanine supplementation, the carnosine content increased by 45.3 % in soleus and 28.2 % in gastrocnemius. Following supplementation, the beta-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 2000 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