ArticlePDF Available

Effect of slow-release β-Alanine tablets on absorption kinetics and paresthesia

Authors:
  • Retired from Nestlé

Abstract

Oral β-alanine (βA) doses larger than 800 mg commonly result in unpleasant sensory symptoms (paresthesia). However, the association of form (pure vs. slow-release) with side-effects has not been fully described. The aim of this single-blinded, randomized three-arm clinical trial was to compare plasma kinetics and symptoms following βA bolus administration in solution or in slow-release tablet form. Eleven healthy adults ingested 1.6 g of a pure βA reference solution (REF), 1.6 g in slow-release βA tablets (TAB) or a placebo (PLA) after an overnight fast. During the next 6 h, urinary and plasma βA concentrations were measured and questionnaires about intensity, nature (pins and needles, itching, flushing, irritation, numbness, soreness), and spatial distribution of unusual sensations were filled in. TAB resulted in a smaller peak plasma concentration than REF (82 vs. 248 μmol L(-1), p<0.001), delayed time to peak (1.0 vs. 0.5 h, p<0.01) no difference in area under the curve, reduced loss in urine (202 vs. 663 μmol, p<0.0001), and improved retention (98.9 vs. 96.3%, p<0.001). Symptoms described as "pins and needles" were perceived rapidly on the skin of the arms and trunk after REF (Tmax=15 min) and their time course nearly mimicked plasma concentrations. Maximum intensity scores were weaker with TAB ("very low") than with REF ("low", p<0.001), while TAB and PLA did not differ with respect to side-effects. In summary, ingesting 1.6 g βA in slow-release tablets rather than pure in solution results in slower absorption kinetics, improved whole body retention and sensory side-effects that cannot be differentiated from PLA.
ERRATUM
Erratum to: Effect of slow-release b-alanine tablets
on absorption kinetics and paresthesia
Jacques De
´combaz Maurice Beaumont
Jacques Vuichoud Florilene Bouisset
Trent Stellingwerff
ÓSpringer-Verlag Wien 2013
Erratum to: Amino Acids (2012) 43:67–76
DOI 10.1007/s00726-011-1169-7
In the original publication of Table 1, the last two entries
of the first column have been published with incorrect
units. The corrected Table 1is produced below:
The online version of the original article can be found under
doi:10.1007/s00726-011-1169-7.
J. De
´combaz (&)M. Beaumont J. Vuichoud F. Bouisset
T. Stellingwerff
Nestle
´Research Center, Lausanne, Switzerland
e-mail: decombaz.jac@bluewin.ch
Present Address:
T. Stellingwerff
Canadian Sports Centre-Pacific, Victoria, Canada
Table 1 b-Alanine pharmacokinetic analysis
TAB
a
REF
b
P
C
max
(lmol L
-1
) 81.9 ±27.5 248.2 ±112.7 0.0002
T
max
(min) 60.0 ±16.2 29.4 ±7.2 0.0015
AUC (lmol L
-1
h) 229.4 ±83.7 253.4 ±81.1 0.5504
K
a
(h
-1
) 3.55 ±2.69 11.98 ±7.21 0.0007
T
lag
(min) 17.4 ±9.6 14.4 ±4.2 0.6606
T
1/2
(min) 80.4 ±64.2 37.2 ±21.6 0.0485
Mean ±SD
C
max
peak concentration, T
max
time to peak, AUC area under the
curve, K
a
absorption rate constant, T
lag
time until first appearance in
plasma, T
1/2
half-time of disappearance
a
bA slow-release tablets
b
bA reference aqueous solution
123
Amino Acids
DOI 10.1007/s00726-013-1557-2
... A limited number of investigations have reported that nutritional supplements are capable of inducing the perception of pain including niacin (increased dental pain) [40], and glyceryltrinitrate (migraine and cluster headache) [41]. While the exact mechanism of paresthesia from B-ALA supplementation is unknown [42] it has been suggested to excite nociceptive sensory receptors located on the dorsal root ganglion [43]. It should be noted that in the current study, B-ALA increased the perception of total pain, and this was independent of the effect of exercise in nature. ...
... Since one common side effect of B-ALA consumption is paresthesia [23], it is not surprising that supplementation increased perception of the sensory component of pain in the current study. One other study has utilized β-alanine supplementation and the McGill Pain Questionnaire sensory dimension [42]. Décombaz et al. studied the effect of a slow-release B-ALA tablet compared to delivery in an aqueous solution, and while no difference in the sensory perception of pain was observed between treatments, an increase in pain intensity measured by other pain scales was reported [42]. ...
... One other study has utilized β-alanine supplementation and the McGill Pain Questionnaire sensory dimension [42]. Décombaz et al. studied the effect of a slow-release B-ALA tablet compared to delivery in an aqueous solution, and while no difference in the sensory perception of pain was observed between treatments, an increase in pain intensity measured by other pain scales was reported [42]. Other nutritional supplements have been associated with sensory characteristics of pain including Vitamin B6 (sensory neuronal pain) [44], and folate (high intake being associated with peripheral neuropathy in individuals with a specific gene variant) [45]. ...
Article
Full-text available
This double-blinded, placebo-controlled, crossover study examined the effect of induced painful sensation (via acute Beta Alanine (B-ALA) ingestion) on Love and Care of Nature (LCN), heart rate (HR), rating of perceived exertion (RPE), and McGill Pain Questionnaire (MPQ) during outdoor exercise. Twenty participants volunteered on consecutive days to complete a 0.8 km (0.5 mi) up-hill hike after consuming either B-ALA (6.4 g) or placebo. Immediately after consumption participants answered LCN, RPE, and MPQ questionnaires, immersed in a natural environment for 45 min, and then completed a hike as quickly as possible without running. No difference in HR (p = 0.846), or RPE (p = 0.606) were observed between treatments. Total MPQ scores increased with consumption of B-ALA (p = 0.001). An increased LCN score was observed following exercise regardless of condition (p = 0.035). The results demonstrate that acute B-ALA supplementation is effective in increasing perceived pain sensations. The results also demonstrate an increase in LCN in the presence of increased perceptions of pain sensations during exercise.
... This was mainly solved through a sustained-release tablet that increased the daily dose without enhancing the intensity of paresthesia [31], but to date, no other galenic formulation has been developed to enable larger acute doses which would permit adherence to shorter supplementation protocols with higher daily amounts. Amino acids in sports nutrition supplements are usually in powder form, providing several grams of active ingredients in a single dose, with the practical advantage of avoiding ingestion of several tablets [32,33]. ...
... Amino acids in sports nutrition supplements are usually in powder form, providing several grams of active ingredients in a single dose, with the practical advantage of avoiding ingestion of several tablets [32,33]. The main problem with β-alanine in pure powder form is that it elicits paresthesia even at low doses due to high peak consequence of its fast absorption [26,31], Thus, a modified-release formulation might represent an alternative to avoid its fast absorption preventing the appearance of the high peak and may allow the administration of larger daily amounts. Galenic modification of powder sport supplements represent a novelty which applies pharmaceutical technology advances to potentially improve some characteristics. ...
... Paresthesia was assessed concomitantly after each blood sample collection using perceptual ratings questionnaires [31] presented always in the same sequence without allowing the subjects to browse back for revision. Paresthesia intensity was assessed with two scale types. ...
Article
Full-text available
Background: β-Alanine is a sport supplement with increasing popularity due to its consistent ability to improve physical performance, with the downside of requiring several weeks of supplementation as imposed to the maximum daily and single dose tolerated without side effects (i.e., paresthesia). To date, the only alternative to overcome this problem has been use of a sustained-release tablet, while powders are the most commonly used format to deliver several grams of amino acids in a single dose. In this study we assessed the bioavailability, pharmacokinetics and paresthesia effect of β-alanine after administration in a novel controlled-released powder blend (test) versus a sustained-release tablet (reference). Methods: Twelve subjects (25.6 ± 3.2 y, 50% female) participated in a randomized, single-blind, crossover study. Each participant was administered orally the test (β-alanine 8 g, l-histidine 300 mg, carnosine 100 mg) or the reference product (10 tablets to reach β-alanine 8 g, Zinc 20 mg) with a 1-week washout period. β-Alanine plasma concentrations (0-8 h) were determined by LC-MS/MS and model-independent pharmacokinetic analysis was carried out. Paresthesia intensity was evaluated using a Visual Analog Score (VAS) and the categorical Intensity Sensory Score (ISS). Results: The CMAX and AUC0→∞ increased 1.6- and 2.1-fold (both p < 0.001) in the test product, respectively, which yielded 2.1-fold higher bioavailability; Ka decreased in the test (0.0199 ± 0.0107 min-1) versus the reference (0.0299 ± 0.0121 min-1) product (p = 0.0834) as well as V/F and Cl/F (both p < 0.001); MRT0→last increased in the test (143 ± 19 min) versus reference (128 ± 16 min) formulation (p = 0.0449); t1/2 remained similar (test: 63.5 ± 8.7 min, reference: 68.9 ± 9.8 min). Paresthesia EMAX increased 1.7-fold using the VAS (p = 0.086) and the ISS (p = 0.009). AUEC increased 1.9-fold with the VAS (p = 0.107) and the ISS (p = 0.019) reflecting scale intrinsic differences. Pharmacokinetic-pharmacodynamic analysis showed a clockwise hysteresis loop without prediction ability between CMAX, AUC0→∞ and EMAX or AUEC. No side effects were reported (except paresthesia). Conclusions: The novel controlled-release powder blend shows 100% higher bioavailability of β-alanine, opening a new paradigm that shifts from chronic to short or mid-term supplementation strategies to increase carnosine stores in sports nutrition.
... In this context, a study that was carried out by Dolu and co-workers suggested that high-dose carnosine produced anxiety-like effects in rats [245]. In line with these findings, different clinical trials have shown that the administration of β-alanine is linked to paresthesia [246] or an increased perception of pain [247]. ...
Article
Full-text available
Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway is a primary event in the pathophysiology of drug-induced cardiotoxicity and neurotoxicity. The Nrf2 pathway regulates the expression of different genes whose products are involved in antioxidant and inflammatory responses and the detoxification of toxic species. Cardiotoxic drugs, such as the anthracycline doxorubicin, or neurotoxic drugs, such as paclitaxel, suppress or impair the Nrf2 pathway, whereas the rescue of this pathway counteracts both the oxidative stress and inflammation that are related to drug-induced cardiotoxicity and neurotoxicity. Therefore Nrf2 represents a novel pharmacological target to develop new antidotes in the field of clinical toxicology. Interestingly, carnosine (β-alanyl-l-histidine), an endogenous dipeptide that is characterized by strong antioxidant, anti-inflammatory, and neuroprotective properties is able to rescue/activate the Nrf2 pathway, as demonstrated by different preclinical studies and preliminary clinical evidence. Starting from these new data, in the present review, we examined the evidence on the therapeutic potential of carnosine as an endogenous antidote that is able to rescue the Nrf2 pathway and then counteract drug-induced cardiotoxicity and neurotoxicity.
... Decrease the amount of urinary losses of beta-alanine as well as decrease the paraesthesia side-effects of beta-alanine as a nutrition ergogenic aid Décombaz et al., 2012 Sport science/equipment integration Ergometer power meters Ability to more accurately estimate exercise energy expenditure to better project energetic nutrition requirements Haakonssen et al., 2013 Basic integrated activity monitors (HR, GPS, and accelerometry) ...
Article
Full-text available
Sports nutrition is a relatively new discipline; with ~100 published papers/year in the 1990s to ~3,500+ papers/year today. Historically, sports nutrition research was primarily initiated by university-based exercise physiologists who developed new methodologies that could be impacted by nutrition interventions (e.g., carbohydrate/fat oxidation by whole body calorimetry and muscle glycogen by muscle biopsies). Application of these methods in seminal studies helped develop current sports nutrition guidelines as compiled in several expert consensus statements. Despite this wealth of knowledge, a limitation of the current evidence is the lack of appropriate intervention studies (e.g., randomized controlled clinical trials) in elite athlete populations that are ecologically valid (e.g., in real-life training and competition settings). Over the last decade, there has been an explosion of sports science technologies, methodologies, and innovations. Some of these recent advances are field-based, thus, providing the opportunity to accelerate the application of ecologically valid personalized sports nutrition interventions. Conversely, the acceleration of novel technologies and commercial solutions, especially in the field of biotechnology and software/app development, has far outstripped the scientific communities' ability to validate the effectiveness and utility of the vast majority of these new commercial technologies. This mini-review will highlight historical and present innovations with particular focus on technological innovations in sports nutrition that are expected to advance the field into the future. Indeed, the development and sharing of more “big data,” integrating field-based measurements, resulting in more ecologically valid evidence for efficacy and personalized prescriptions, are all future key opportunities to further advance the field of sports nutrition.
... Finally, our interest in investigating the effects of acute BA supplementation protocols in aerobic-anaerobic transition zones is based on establishing a safe dose of BA to improve performance during training and competition. Likewise, this supplementation format avoids exposure to weeks of prolonged BA use, thus decreasing the risk of exposure to paresthesia symptoms generated at each intake (36). ...
Article
Full-text available
To determine the acute effect of low and high-dose BA trials on maximal aerobic speed (MAS) in endurance athletes. We hypothesized that high doses of BA have a greater effect than low doses, both compared to baseline. Twelve male endurance athletes volunteered for the study (age = 21.8 ± 2.37 years, weight = 69.8 ± 4.36 kg, height = 174 ± 5.45 cm, maximal oxygen uptake = 59.6 ± 3.77 mLO2·kg-1·min-1). The experimental design applied was randomized cross-over, double-blind. Treatment included three 6-minute run tests (6-MRT), the first as a baseline, then randomized 6-MRT with low (30 mg·kg-1) and high (45 mg·kg-1) dose BA trials. The 6-MRTs were separated by 72 hours. The main variable of the study was the distance (m) performed in the 6-MRT. Differences between tests were established through ANOVA and Tukey's multiple comparison tests (p < 0.05). The analysis showed significant differences between baseline and both doses (p < 0.001). No significant differences were observed between low and high-dose BA trials (p > 0.05). Both 30 and 45 mg·kg-1 of BA increased physical performance at maximal aerobic speed in endurance athletes. The acute intake formats described in the present investigation may be helpful for endurance athletes training and competing in aerobic-anaerobic transition zones.
... Supplementation with β-A has been shown to influence cycle capacity [4], ventilatory threshold, and fatigue time in humans [5]. However, with the supplementation higher than 800 mg, it can cause abnormalities in the host body [6]. Therefore, it is essential to select the appropriate dose for β-A supplementation to impart desired benefits. ...
Article
Full-text available
With an aim to explore the effects of β -alanine ( β -A) on spatial memory and fatigue resistance, Kunming mice were treated with different concentrations of β-A (418, 836, and 2090 mg·kg<sup> -1</sup>·day<sup> -1</sup>). After gavage feeding with β -A for 10 weeks, results of the maze and MWM tests showed that β -A can enhance spatial learning and memory in mice. After evaluating the fatigue resistance, biochemical parameters (LG, GG, BUN, SOD, and MDA) showed significant differences in the low concentration treatment group compared to control group. Our data demonstrated that the appropriate dose of β -A can alleviate the oxidative stress and muscle fatigue in mice. Subsequently, expression of mRNA of key genes involved in cAMP-PKA pathway (PDE4A, MAPK1, adcy1, cAMP and CREB) was up regulated. Also, expression levels of apoptotic pathway genes were significantly affected as confirmed by qPCR and Western blotting. Our results demonstrated that β -A can enhance spatial learning and memory in mice via regulation of cAMP-PKA and apoptotic pathway.
... We should of course mention that both supplements can cause mild side-effects. β-A may produce paresthesia if taken as a single high dose, an effect that disappears about an hour after ingestion (Artioli et al. 2010) and can be easily avoided by taking lower doses (400-500 mg) or slow-release capsules of β-A (Décombaz et al. 2012). SB SUP may cause gastrointestinal symptoms such as nausea, stomach pain, diarrhea and vomiting. ...
Article
Muscle acidification is one of the main factors causing fatigue during exercise, thus compromising performance. The sport supplements beta alanine (β-A) and sodium bicarbonate (SB) are thought to enhance the effects of the body’s buffer systems by reducing H+ concentrations. The aim of this systematic review was to analyze the effects of β-A and SB co-supplementation on the organism’s buffering capacity and sport performance. The databases PubMed, Web of Science, Medline, CINAHL and SPORTDiscus were searched until November 2021 following PRISMA guidelines. Randomized controlled trials, at least single-blind, performed in athletes of any age were considered. Nine studies including a total of 221 athletes were identified for review. Athletes were supplemented with β-A and SB while they performed exercise tests to assess physical performance and buffer capacity. Five of the nine studies indicated there was some additional improvement in buffering capacity and performance with co-supplementation, while one study concluded that the effect was comparable to the added effects of the individual supplements. According to the results of the studies reviewed, we would recommend β-A and SB co-supplementation during high intensity exercises lasting between 30 s and 10 min.
... Diaries were maintained to ensure adherence to the supplementation protocol, with a high level of adherence in both groups (Table 1). A questionnaire was applied following the final session to extract information regarding supplementation including, (i) what supplement they believe they had ingested ("beta-alanine", "placebo", "don't know"), (ii) any side-effects experienced and details thereof (Decombaz, Beaumont, Vuichoud, Bouisset, & Stellingwerff, 2012), and (iii) whether they thought supplementation had improved their training. ...
Article
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<0.0001) but was not related to performance changes (r=0.320, P=0.37). Chronic beta-alanine supplementation increased muscle carnosine content but did not improve short-duration sprint performance throughout simulated road race cycling, nor 4-km uphill time-trial performance conducted at the end of this cycling test.
Article
Background Allergic contact dermatitis (ACD) is a common skin condition characterized by contact hypersensitivity to allergens, accompanied with skin inflammation and a mixed itch and pain sensation. The itch and pain dramatically affects patients’ quality of life. However, still little is known about the mechanisms triggering pain and itch sensations in ACD. Methods We established a mouse model of ACD by sensitization and repetitive challenge with the hapten oxazolone. Skin pathological analysis, transcriptome RNA sequencing (RNA-seq), qPCR, Ca ²⁺ imaging, immunostaining, and behavioral assay were used for identifying gene expression changes in dorsal root ganglion innervating the inflamed skin of ACD model mice and for further functional validations. Results The model mice developed typical ACD symptoms, including skin dryness, erythema, excoriation, edema, epidermal hyperplasia, inflammatory cell infiltration, and scratching behavior, accompanied with development of eczematous lesions. Transcriptome RNA-seq revealed a number of differentially expressed genes (DEGs), including 1436-DEG mRNAs and 374-DEG-long noncoding RNAs (lncRNAs). We identified a number of DEGs specifically related to sensory neuron signal transduction, pain, itch, and neuroinflammation. Comparison of our dataset with another published dataset of atopic dermatitis mouse model identified a core set of genes in peripheral sensory neurons that are exclusively affected by local skin inflammation. We further found that the expression of the pain and itch receptor MrgprD was functionally upregulated in dorsal root ganglia (DRG) neurons innervating the inflamed skin of ACD model mice. MrgprD activation induced by its agonist β-alanine resulted in exaggerated scratching responses in ACD model mice compared with naïve mice. Conclusions We identified the molecular changes and cellular pathways in peripheral sensory ganglia during ACD that might participate in neurogenic inflammation, pain, and itch. We further revealed that the pain and itch receptor MrgprD is functionally upregulated in DRG neurons, which might contribute to peripheral pain and itch sensitization during ACD. Thus, targeting MrgprD may be an effective method for alleviating itch and pain in ACD.
Article
Full-text available
Muscle carnosine synthesis is limited by the availability of β-alanine. Thirteen male subjects were supplemented with β-alanine (CarnoSyn™) for 4 wks, 8 of these for 10 wks. A biopsy of the vastus lateralis was obtained from 6 of the 8 at 0, 4 and 10 wks. Subjects undertook a cycle capacity test to determine total work done (TWD) at 110% (CCT110%) of their maximum power (Wmax). Twelve matched subjects received a placebo. Eleven of these completed the CCT110% at 0 and 4 wks, and 8, 10 wks. Muscle biopsies were obtained from 5 of the 8 and one additional subject. Muscle carnosine was significantly increased by +58.8% and +80.1% after 4 and 10 wks β-alanine supplementation. Carnosine, initially 1.71 times higher in type IIa fibres, increased equally in both type I and IIa fibres. No increase was seen in control subjects. Taurine was unchanged by 10 wks of supplementation. 4 wks β-alanine supplementation resulted in a significant increase in TWD (+13.0%); with a further +3.2% increase at 10 wks. TWD was unchanged at 4 and 10 wks in the control subjects. The increase in TWD with supplementation followed the increase in muscle carnosine.
Article
Full-text available
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 ((1)H-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.
Article
Full-text available
This review discusses the role of beta-alanine as a neurotransmitter. Beta-alanine is structurally intermediate between alpha-amino acid (glycine, glutamate) and gamma-amino acid (GABA) neurotransmitters. In general, beta-alanine satisfies a number of the prerequisite classical criteria for being a neurotransmitter: beta-alanine occurs naturally in the CNS, is released by electrical stimulation through a Ca(2+) dependent process, has binding sites, and inhibits neuronal excitability. beta-Alanine has 5 recognized receptor sites: glycine co-agonist site on the NMDA complex (strychnine-insensitive); glycine receptor site (strychnine sensitive); GABA-A receptor; GABA-C receptor; and blockade of GAT protein-mediated glial GABA uptake. Although beta-alanine binding has been identified throughout the hippocampus, limbic structures, and neocortex, unique beta-alaninergic neurons with no GABAergic properties remain unidentified, and it is impossible to discriminate between beta-alaninergic and GABAergic properties in the CNS. Nevertheless, a variety of data suggest that beta-alanine should be considered as a small molecule neurotransmitter and should join the ranks of the other amino acid neurotransmitters. These realizations open the door for a more comprehensive evaluation of beta-alanine's neurochemistry and for its exploitation as a platform for drug design.
Article
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.
Article
Four different French versions of the McGill Pain Questionnaire (MPQ) have been published: 3 are MPQ translations in Canadian French and 1 (QDSA) is an MPQ reconstruction in (France) French. The aim of our work was to study the validity of these available questionnaires for use in France. The validity was evaluated by 44 French physicians. Various validity criteria were studied: item, dimension, subclass and pain descriptor intensity. A new French MPQ was also developed. Significant validity differences emerged between the different MPQ versions. This study confirms the satisfactory validity of the QDSA. The validity of the newly developed French MPQ was equal but not better than the QDSA. A 15-item short MPQ-QDSA version was also developed. For studies with patients from France, it is recommended that the QDSA or the short MPQ-QDSA versions be used.
Article
Seven male students were supplemented with β-alanine (β-ALG) for 4weeks (6.4gday−1) and seven with a matching placebo (PLG). Subjects undertook 4weeks of isokinetic training with the right leg (T) whilst the left leg was untrained (UT), serving as a control. Each training session consisted of 10×10 maximal 90° extension and flexion contractions at 180°/s using a Kin-Com isokinetic dynamometer, with 1min 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 β-ALG (9.63±3.92mmolkg−1 dry muscle and 6.55±2.36mmolkg−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 4weeks training has no effect on the muscle carnosine content. Whilst an increase was seen with β-alanine supplementation, this was not further influenced by training. These findings suggest that β-alanine availability is the main factor regulating muscle carnosine synthesis.
Article
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.
Article
We examined the effect of β-alanine supplementation plus sodium bicarbonate on high-intensity cycling capacity. Twenty males (age = 25 ± 5 yr, height = 1.79 ± 0.06 m, body mass = 80.0 ± 10.3 kg) were assigned to either a placebo (P) or a β-alanine (BA; 6.4 g·d(-1) for 4 wk) group based on power max, completing four cycling capacity tests at 110% of power max (CCT110%) to determine time to exhaustion (TTE) and total work done. A CCT(110%) was performed twice (habituation and baseline) before supplementation (with maltodextrin [MD]) and twice after supplementation (with MD and with sodium bicarbonate [SB]), using a crossover design with 2 d of rest between trials, creating four study conditions (PMD, PSB, BAMD, and BASB). Blood pH, Lactate, bicarbonate and base excess were determined at baseline, before exercise, immediately after exercise, and 5 min after exercise. Data were analyzed using repeated-measures ANOVA. TTE was increased in all conditions after supplementation (+1.6% PMD, +6.5% PSB, +12.1% BAMD, and +16.2% BASB). Both BAMD and BASB resulted in significantly improved TTE compared with that before supplementation (P ≤ 0.01). Although further increases in TTE (4.1%) were shown in BASB compared with BAMD, these differences were not significant (P = 0.74). Differences in total work done were similar to those of TTE. Blood bicarbonate concentrations were significantly (P ≤ 0.001) elevated before exercise in PSB and BASB but not in PMD or BAMD. Blood lactate concentrations were significantly elevated after exercise, remaining elevated after 5 min of recovery (P ≤ 0.001) and were highest in PSB and BASB. Results show that BA improved high-intensity cycling capacity. However, despite a 6-s (∼4%) increase in TTE with the addition of SB, this did not reach statistical significance, but magnitude-based inferences suggested a ∼70% probability of a meaningful positive difference.
Article
In this narrative review, we present and discuss the current knowledge available on carnosine and beta-alanine metabolism as well as the effects of beta-alanine supplementation on exercise performance. Intramuscular acidosis has been attributed to be one of the main causes of fatigue during intense exercise. Carnosine has been shown to play a significant role in muscle pH regulation. Carnosine is synthesized in skeletal muscle from the amino acids l-histidine and beta-alanine. The rate-limiting factor of carnosine synthesis is beta-alanine availability. Supplementation with beta-alanine has been shown to increase muscle carnosine content and therefore total muscle buffer capacity, with the potential to elicit improvements in physical performance during high-intensity exercise. Studies on beta-alanine supplementation and exercise performance have demonstrated improvements in performance during multiple bouts of high-intensity exercise and in single bouts of exercise lasting more than 60 s. Similarly, beta-alanine supplementation has been shown to delay the onset of neuromuscular fatigue. Although beta-alanine does not improve maximal strength or VO2max, some aspects of endurance performance, such as anaerobic threshold and time to exhaustion, can be enhanced. Symptoms of paresthesia may be observed if a single dose higher than 800 mg is ingested. The symptoms, however, are transient and related to the increase in plasma concentration. They can be prevented by using controlled release capsules and smaller dosing strategies. No important side effect was related to the use of this amino acid so far. In conclusion, beta-alanine supplementation seems to be a safe nutritional strategy capable of improving high-intensity anaerobic performance.