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The Beta-Alanine Dose for Maintaining Moderately Elevated Muscle Carnosine Levels.
Abstract
Chronic beta-alanine (BA) supplementation is an increasingly popular nutritional strategy, because it can elevate muscle carnosine content and thereby enhance high-intensity exercise performance. The current study investigates 1) whether sex and body mass are determinants of BA induced muscle carnosine loading, and 2) the optimal maintenance dose for ensuring constantly elevated muscle carnosine stores.
During the loading phase, 34 participants (men and women) were supplemented with 3.2g (4×800 mg) BA/day for 46 days (slightly different loading strategies were applied concerning the effect of meal-timing and supplementation form). Thereafter, 19 participants (men and women) continued taking free-powder BA for 6 more weeks (maintenance phase). The participants were matched and re-divided into three groups respectively receiving 0.4g BA/day, 0.8g BA/day and 1.2g BA/day. Muscle carnosine content was measured in m. soleus and m. gastrocnemius using H-MRS.
Body mass and sex had only minimal effect on the absolute increase in muscle carnosine. Given the lower baseline values of women, the relative increase for women was higher, indicating that women require less BA for the same relative increase. In addition, a significant negative correlation was observed between body mass and the relative increase in muscle carnosine (r=-0.45, p=0.007). A maintenance dose of ∼1.2 g BA/day, was most effective to keep muscle carnosine content elevated at post-supplementation level.
Sex and body mass do not markedly affect the absolute increase during muscle carnosine loading, although they are determinants for the relative increase. Additionally, we established for the first time an effective maintenance dose of ∼1.2g BA/day to keep muscle carnosine content elevated at 30-50% above baseline for a prolonged period.
... Results in the present study showed a mean increase in muscle carnosine levels of 35.3 ± 45% following BA supplementation and 42.5 ± 99% following BAC supplementation with average doses of 6.1 ± 0.7 g/day of β-ALA. While these mean changes in muscle carnosine levels following β-ALA supplementation are consistent with values reported in other studies [3,10,[37][38][39][40] and we found some group effects with large effect sizes, no statistically significant interactions were observed among groups in muscle carnosine levels. The lack of statistical significance was apparently due to the large variability in muscle carnosine levels observed in response to β-ALA supplementation, Individual group and time data are presented as means ± SD while time and group effects are presented as means ± SEM. ...
... In this regard, most studies on creatine and β-ALA supplementation have been conducted on males and there is some evidence that females may respond differently to creatine and/or β-ALA supplementation. For example, Fosberg and colleagues [42] reported that females had greater total creatine amounts relative to tissue weight; however, other studies show there is no difference between males and females [40,43]. There are also some data suggesting that men may have greater muscle carnosine levels than women [4,44]; however, a recent study showed sex did not have an effect on increasing carnosine levels with supplementation [40]. ...
... For example, Fosberg and colleagues [42] reported that females had greater total creatine amounts relative to tissue weight; however, other studies show there is no difference between males and females [40,43]. There are also some data suggesting that men may have greater muscle carnosine levels than women [4,44]; however, a recent study showed sex did not have an effect on increasing carnosine levels with supplementation [40]. Additionally, Bex and coworkers [45] reported that carnosine loading is more pronounced in trained versus untrained individuals. ...
The purpose of this study was to examine the short-term and chronic effects of β-ALA supplementation with and without creatine monohydrate on body composition, aerobic and anaerobic exercise performance, and muscle carnosine and creatine levels in college-aged recreationally active females.
Thirty-two females were randomized in a double-blind, placebo-controlled manner into one of four supplementation groups: β-ALA only (BA, n = 8), creatine only (CRE, n = 8), β-ALA and creatine combined (BAC, n = 9) and placebo (PLA, n = 7). Participants supplemented for four weeks included a loading phase for the creatine for week 1 of 0.3 g/kg of body weight and a maintenance phase for weeks 2-4 of 0.1 g/kg of body weight, with or without a continuous dose of β-ALA of 0.1 g/kg of body weight with doses rounded to the nearest 800 mg capsule providing an average of 6.1 ± 0.7 g/day of β-ALA. Participants reported for testing at baseline, day 7 and day 28. Testing sessions consisted of obtaining a resting muscle biopsy of the vastus lateralis, body composition measurements, performing a graded exercise test on the cycle ergometer for VO2peak with lactate threshold determination, and multiple Wingate anaerobic capacity tests.
Although mean changes were consistent with prior studies and large effect sizes were noted, no significant differences were observed among groups in changes in muscle carnosine levels (BA 35.3 ± 45; BAC 42.5 ± 99; CRE 0.72 ± 27; PLA 13.9 ± 44%, p = 0.59). Similarly, although changes in muscle phosphagen levels after one week of supplementation were consistent with prior reports and large effect sizes were seen, no statistically significant effects were observed among groups in changes in muscle phosphagen levels and the impact of CRE supplementation appeared to diminish during the maintenance phase. Additionally, significant time × group × Wingate interactions were observed among groups for repeated sprint peak power normalized to bodyweight (p = 0.02) and rate of fatigue (p = 0.04).
Results of the present study did not reveal any consistent additive benefits of BA and CRE supplementation in recreationally active women.
... Previous rowing studies however have looked into male rowers, not female rowers or a sex difference for the effect of beta-alanine supplementation. In a previous study Stegen et al. in 2014 looked into sex and body mass for determinants of β-alanine induced carnosine loading, and the appropriate dosage for maintaining elevated carnosine levels 29 . They found that body mass and sex are determinants of the relative increase in carnosine levels from β-alanine supplementation 29 . ...
... In a previous study Stegen et al. in 2014 looked into sex and body mass for determinants of β-alanine induced carnosine loading, and the appropriate dosage for maintaining elevated carnosine levels 29 . They found that body mass and sex are determinants of the relative increase in carnosine levels from β-alanine supplementation 29 . For females, given the lower baseline of carnosine, it was found that their relative increases in intramuscular carnosine levels were greater, likely indicating that females needed less β-alanine for the same relative increase as men 29 . ...
... They found that body mass and sex are determinants of the relative increase in carnosine levels from β-alanine supplementation 29 . For females, given the lower baseline of carnosine, it was found that their relative increases in intramuscular carnosine levels were greater, likely indicating that females needed less β-alanine for the same relative increase as men 29 . ...
Introduction: Carnosine is an intramuscular buffer, and β-Alanine is the limiting reagent in carnosine synthesis. Thus, β-Alanine supplementation which increases carnosine concentrations, has been shown to have an ergogenic effect. Past studies found improvements in body composition and 2km time trial performance in elite rowers, but there is limited research examining the effects of β-Alanine in collegiate rowers and if sex differences may exist. Methods: Using a double-blind, placebo-controlled randomized design, the effects of four weeks of 3.2 g/d of β-Alanine, or placebo, on body composition and 2km time were tested in male and female collegiate rowers. Performance was taken one and three weeks into supplementation as well as post-supplementation. Body composition was measured using air displacement plethysmography before and after supplementation. Results: Body composition and rowing performance were improved over time. However, change in body composition-1.5 ± 1.9 vs-2.7 ± 2.9 %fat, lean mass 2.3 ± 1.3 vs. 1.4 ± 1.8 kg, and 2km time-2.1 ± 7.9 v-4.2 ± 6.5s, were not different between placebo and β-Alanine groups, respectively (p>0.05), though improvement in 2km tended to be ~50% better with β-Alanine (effect size = 0.29). There were no apparent sex differences over time or with supplementation. Conclusions: β-Alanine supplementation did not have a significant effect on 2km rowing time, although the β-Alanine group tended to improve more than placebo, perhaps as a result of improved buffering capacity. However, further work is needed in this population, specifically using longer and higher β-alanine dosing schemes.
... Carnosine (β-alanyl-L-histidine) is a cytoplasmic dipeptide found in high concentrations within skeletal muscle (Harris et al., 2006), which, due to the pKa of its imidazole side-chain (6.83), is a potent buffer for intramuscular H + accumulation during contractions (Bate-Smith, 1938). β-alanine (BA) has been identified as the rate-limiting substrate in carnosine synthesis (Dunnet and Harris, 1999;Harris et al., 2006) and its ingestion has been shown to increase intramuscular carnosine content (Harris et al., 2006;Baguet et al., 2009;Stellingwerff et al., 2012;Stegen et al., 2013Stegen et al., , 2014Bex et al., 2014) which would presumably improve intramuscular buffering capacity. Some investigations have reported improved high-intensity exercise tolerance and performance following BA supplementation (Hobson et al., 2012;Quesnele et al., 2014;Saunders et al., 2017). ...
... The findings of the current study indicate that muscle carnosine content was not increased following 4 and 6 weeks of BA ingestion (6.4 g·d −1 ). This is in contrast to previous studies that have assessed muscle carnosine content using 1 H-MRS and have shown that BA supplementation results in increased carnosine content in muscles of the calf (Baguet et al., 2009(Baguet et al., , 2010del Favero et al., 2012;Stegen et al., 2013Stegen et al., , 2014Bex et al., 2014;Danaher et al., 2014;Hoffman et al., 2015), thigh (Harris et al., 2006), and upper arm and shoulder . Whilst these studies employed a variety of different supplementation strategies, and although baseline muscle carnosine content and loading rates appear to be muscle specific (Baguet et al., 2009(Baguet et al., , 2010Stegen et al., 2013Stegen et al., , 2014Bex et al., 2014;Danaher et al., 2014), they have consistently reported ∼45% increase in muscle carnosine following a total BA dose of ∼181 g during the supplementation period. ...
... This is in contrast to previous studies that have assessed muscle carnosine content using 1 H-MRS and have shown that BA supplementation results in increased carnosine content in muscles of the calf (Baguet et al., 2009(Baguet et al., , 2010del Favero et al., 2012;Stegen et al., 2013Stegen et al., , 2014Bex et al., 2014;Danaher et al., 2014;Hoffman et al., 2015), thigh (Harris et al., 2006), and upper arm and shoulder . Whilst these studies employed a variety of different supplementation strategies, and although baseline muscle carnosine content and loading rates appear to be muscle specific (Baguet et al., 2009(Baguet et al., , 2010Stegen et al., 2013Stegen et al., , 2014Bex et al., 2014;Danaher et al., 2014), they have consistently reported ∼45% increase in muscle carnosine following a total BA dose of ∼181 g during the supplementation period. In the present study, subjects had ingested a total of 179 g BA after 4 weeks and 269 g BA after 6 weeks. ...
Purpose: To investigate the influence of β-alanine (BA) supplementation on muscle carnosine content, muscle pH and the power-duration relationship (i.e., critical power and W′).
Methods: In a double-blind, randomized, placebo-controlled study, 20 recreationally-active males (22 ± 3 y, V°O2peak 3.73 ± 0.44 L·min⁻¹) ingested either BA (6.4 g/d for 28 d) or placebo (PL) (6.4 g/d) for 28 d. Subjects completed an incremental test and two 3-min all-out tests separated by 1-min on a cycle ergometer pre- and post-supplementation. Muscle pH was assessed using ³¹P-magnetic resonance spectroscopy (MRS) during incremental (INC KEE) and intermittent knee-extension exercise (INT KEE). Muscle carnosine content was determined using ¹H-MRS.
Results: There were no differences in the change in muscle carnosine content from pre- to post-intervention (PL: 1 ± 16% vs. BA: −4 ± 25%) or in muscle pH during INC KEE or INT KEE (P > 0.05) between PL and BA, but blood pH (PL: −0.06 ± 0.10 vs. BA: 0.09 ± 0.13) during the incremental test was elevated post-supplementation in the BA group only (P < 0.05). The changes from pre- to post-supplementation in critical power (PL: −8 ± 18 W vs. BA: −6 ± 17 W) and W′ (PL: 1.8 ± 3.3 kJ vs. BA: 1.5 ± 1.7 kJ) were not different between groups. No relationships were detected between muscle carnosine content and indices of exercise performance.
Conclusions: BA supplementation had no significant effect on muscle carnosine content and no influence on intramuscular pH during incremental or high-intensity intermittent knee-extension exercise. The small increase in blood pH following BA supplementation was not sufficient to significantly alter the power-duration relationship or exercise performance.
... Results in the present study showed a mean increase in muscle carnosine levels of 35.3 ± 45% following BA supplementation and 42.5 ± 99% following BAC supplementation with average doses of 6.1 ± 0.7 g/day of β-ALA. While these mean changes in muscle carnosine levels following β-ALA supplementation are consistent with values reported in other studies [3,10,[37][38][39][40] and we found some group effects with large effect sizes, no statistically significant interactions were observed among groups in muscle carnosine levels. The lack of statistical significance was apparently due to the large variability in muscle carnosine levels observed in response to β-ALA supplementation, Individual group and time data are presented as means ± SD while time and group effects are presented as means ± SEM. ...
... In this regard, most studies on creatine and β-ALA supplementation have been conducted on males and there is some evidence that females may respond differently to creatine and/or β-ALA supplementation. For example, Fosberg and colleagues [42] reported that females had greater total creatine amounts relative to tissue weight; however, other studies show there is no difference between males and females [40,43]. There are also some data suggesting that men may have greater muscle carnosine levels than women [4,44]; however, a recent study showed sex did not have an effect on increasing carnosine levels with supplementation [40]. ...
... For example, Fosberg and colleagues [42] reported that females had greater total creatine amounts relative to tissue weight; however, other studies show there is no difference between males and females [40,43]. There are also some data suggesting that men may have greater muscle carnosine levels than women [4,44]; however, a recent study showed sex did not have an effect on increasing carnosine levels with supplementation [40]. Additionally, Bex and coworkers [45] reported that carnosine loading is more pronounced in trained versus untrained individuals. ...
Background: The purpose of this study was to examine the short-term and chronic effects of β-ALA supplementation with and without creatine monohydrate on body composition, aerobic and anaerobic exercise performance, and muscle carnosine and creatine levels in college-aged recreationally active females. Methods: Thirty-two females were randomized in a double-blind, placebo-controlled manner into one of four supplementation groups: β-ALA only (BA, n = 8), creatine only (CRE, n = 8), β-ALA and creatine combined (BAC, n = 9) and placebo (PLA, n = 7). Participants supplemented for four weeks included a loading phase for the creatine for week 1 of 0.3 g/kg of body weight and a maintenance phase for weeks 2-4 of 0.1 g/kg of body weight, with or without a continuous dose of β-ALA of 0.1 g/kg of body weight with doses rounded to the nearest 800 mg capsule providing an average of 6.1 ± 0.7 g/day of β-ALA. Participants reported for testing at baseline, day 7 and day 28. Testing sessions consisted of obtaining a resting muscle biopsy of the vastus lateralis, body composition measurements, performing a graded exercise test on the cycle ergometer for VO2peak with lactate threshold determination, and multiple Wingate anaerobic capacity tests. Results: Although mean changes were consistent with prior studies and large effect sizes were noted, no significant differences were observed among groups in changes in muscle carnosine levels (BA 35.3 ± 45; BAC 42.5 ± 99; CRE 0.72 ± 27; PLA 13.9 ± 44%, p = 0.59). Similarly, although changes in muscle phosphagen levels after one week of supplementation were consistent with prior reports and large effect sizes were seen, no statistically significant effects were observed among groups in changes in muscle phosphagen levels and the impact of CRE supplementation appeared to diminish during the maintenance phase. Additionally, significant time × group × Wingate interactions were observed among groups for repeated sprint peak power normalized to bodyweight (p = 0.02) and rate of fatigue (p = 0.04). Conclusions: Results of the present study did not reveal any consistent additive benefits of BA and CRE supplementation in recreationally active women.
... Most investigations examining the effects of BA supplementation on carnosine content have been completed in men using dosing regimens ranging between 1.6 and 6.4 g·d −1 [4,8,10,11,[26][27][28]. One study examining the effects of BA supplementation and sex on carnosine content used a dosing regimen of 3.2 g·d −1 of BA for 6 weeks [29]. These researchers reported similar absolute increases in muscle carnosine in the gastrocnemius and soleus muscles in both men and women despite significant differences in baseline carnosine content. ...
... However, this did not affect the absolute increase in carnosine content, although relative increases in carnosine were greater for women compared with men because of the lower baseline content. The investigators also suggested that the absolute increase in muscle carnosine content was not dependent upon sex or baseline carnosine but more on the absolute amount of BA administered [29]. These findings are in agreement with others showing that a dose-response relationship exists between BA supplementation and the resultant increase in carnosine content, where the extent of the change in carnosine seems to be related to the amount of BA administered rather than baseline carnosine content [30]. ...
... In regard to sex comparisons, the change in muscle carnosine levels in both men and women supplementing with BA was similar. This was also consistent with the results of Stegen et al [29], who also reported no difference in muscle carnosine elevations between men and women following a protocol of 3.2 g·d −1 BA supplement for 6 weeks. These findings suggest that similar increases in carnosine content can be found in both men and women regardless of the lower baseline carnosine content in women. ...
... When comparing baseline intramuscular carnosine levels, females have between 12-72% lower levels compared to males. In addition, females often require lower levels of BA supplementation to obtain similar relative increases in carnosine compared to males (Stegen et al., 2014). BA supplementation can delay the onset of muscular fatigue and improve recovery during repeated bouts of high intensity exercise (Saunders et al., 2017). ...
... The evidence in female football players is inconclusive but there is a strong scientific rationale to supplement with BA. Based on current research female football players should use a loading dose for 4 weeks and a maintenance dose based off their weight (Stegen et al., 2014). It is recommended that players weighing 56kg dose with 2.5g·d -1 , 64kg with 3.4g·d -1 and heavier (>70kg) 5.5g·d -1 . ...
... It is recommended that players weighing 56kg dose with 2.5g·d -1 , 64kg with 3.4g·d -1 and heavier (>70kg) 5.5g·d -1 . A maintenance dose of 18mg·kg -1 BW per day is recommended due to the correlation between weight and maintaining muscle carnosine levels (Stegen et al., 2014). To help limit the chance of the player suffering with paraesthesia, it is recommended that the dose is split into 0.8-1.6g ...
The physical demands of professional female football have intensified in recent years. Supplements are only advised in addition to a healthy, balanced diet, but may warrant a greater prevalence in the professional game to support well-being, recovery, and performance. Supplements used by players should be safe, legal, and scientifically proven to be effective. An individual approach should be taken to using supplements dependant on the needs and goals of the player. Female players should aim to improve the frequency of protein intake throughout the day, whilst tailoring doses to individual body mass. Vitamin D supplementation is vital throughout the winter months in countries with limited sun exposure, however doses should be administered based on individual blood test results. Iron is likely to be important to the well-being of female athletes throughout the season, in particular during the menses. Omega-3 and collagen may be of greater benefit to female than male athletes during recovery from soft tissue injury, whilst probiotics and creatine are beneficial throughout the season for reducing risk of illness and optimising recovery, respectively. Ergogenic supplements for football include beta-alanine, nitrate and caffeine. Caution should be taken with caffeine use due to the varying tolerance of difference athletes and sleep impairments that can follow.
... When comparing intramuscular carnosine levels between males and females, a 3.5–1.0 ratio is observed, respectively, (Everaert et al. 2011) and females require lower levels of BA supplementation to obtain the same relative carnosine increases compared to males (Stegen et al. 2014). In females, 28 days of BA supplementation is documented to increase time to exhaustion (TTE; Stout et al. 2006b) and decrease feelings of perceived exertion (Smith et al. 2012); however, these findings have only been evaluated in younger women and cannot be extrapolated to older, female populations. ...
... At least 28 days of BA supplementation is documented to increase high-intensity exercise performance in younger males (Hoffman et al. 2008) and females (Smith et al. 2012), along with untrained older adults (del Favero et al. 2012; McCormack et al. 2013; Stout et al. 2008). With regard to carnosine increases, trained muscle responds more efficiently to BA supplementation (Bex et al. 2014) and females experience greater relative increases compared to males (Stegen et al. 2014). Combined with the fact that carnosine levels naturally decrease with advancing age (Everaert et al. 2011), trained, master-level females may have an unparalleled physiological advantage when it comes to the benefits from exogenous BA supplementation and positive results may be observed sooner than the traditional 28-day loading period (Stout et al. 2006b). ...
Within the aging population, there exists a subset of individuals termed masters athletes (MA). As masters-level competition increases in popularity, MA must find methods to enhance individual athletic performance. Longitudinal beta-alanine (BA) supplementation is suggested to enhance physical capability during exercise; however, these effects have not been evaluated in MA. To examine the longitudinal effects of BA on time to exhaustion (TTE), total work completed (TWC), and lactate clearance in female MA cyclists. Twenty-two female MA (age = 53.3 ± 1.0) participated in this double-blind design. Subjects were randomly assigned to BA (n = 11; 800 mg BA + 8 g dextrose) or placebo (PLA; n = 11; 8 g dextrose) groups and supplemented 4 doses/day over 28 days. Every 7 days, subjects completed a cycling TTE at 120 % VO2max, and TWC was calculated. Blood lactate was measured at baseline, immediate post, and 20-min post each TTE. No significant differences existed between groups for any variable at baseline (p > 0.05). After 28 days supplementation, BA had greater TTE (23 vs 1 % change) and TWC (21 vs 2 % change) than PLA (p < 0.05). Following the 20-min TTE recovery, lactate was 24 % lower in BA compared to PLA (4.35 vs. 5.76 mmol/L, respectively). No differences existed for variables during intermittent weeks. 28 days of BA supplementation increased cycling performance via an enhanced time to exhaustion and total work completed with associated lactate clearance during passive rest in female MA.
... Durante el ejercicio, la pKa de 6,83 hace que la carnosina capte H + (protones) en situaciones de acidosis por contracción muscular. Como hallazgo importante, se han descrito mayores concentraciones de carnosina en las fibras musculares tipo II (12,13) . ...
... Mejora la regulación ácido-base bajo su efecto de buffer el pH intracelular. Mejor desempeño durante el ejercicio vigoroso, de corta duración (2 -6 minutos), además de reducción de la fatiga muscular (12,13,18) Carga: 4,8 -6,4 g/día (80 mg/ kg/día), 4 tomas/día, por 4 -10 semanas. Mantenimiento: 1,2 g/día (4 tomas/día) (18) Parestesias (18) Bicarbonato de sodio Mejora en la regulación ácido-base. ...
... Evidence shows that poultry, beef, and fish are products with a large BA content [9]. BA has been consistently shown to increase levels of carnosine (CA) in human skeletal muscle [9][10][11][12]. This last substance is synthesized by CA synthase when bonding BA with L-histidine [13]; CA is found in the muscular tissue and acts as a buffer of hydrogen protons (H + ) in high-intensity physical exercises of short duration [11,14]. ...
... On the other hand, other studies have shown that CA and L-histidine supplementation do not increase the bioavailability of intramuscular CA [5,14]. For this reason, and considering BA as a precursor in CA formation, several studies have shown an increase between 40-80% of intramuscular CA post BA supplementation [1,[9][10][11]16]. In this regard, the acute effect of BA supplementation has been tested in doses of 30 mg·kg −1 of body mass and prolonged supplementation with doses ranging from 2.0 to 6.4 g/day for periods of time between 4 and 10 weeks [12,17]. ...
Beta-alanine supplementation (BA) has a positive impact on physical performance. However, evidence showing a benefit of this amino acid in aerobic-anaerobic transition zones is scarce and the results controversial. The aim of this systematic review and meta-analysis is to analyze the effects of BA supplementation on physical performance in aerobic-anaerobic transition zones. At the same time, the effect of different dosages and durations of BA supplementation were identified. The search was designed in accordance with the PRISMA ® guidelines for systematic reviews and meta-analyses and performed in Web of Science (WOS), Scopus, SPORTDiscus, PubMed, and MEDLINE between 2010 and 2020. The methodological quality and risk of bias were evaluated with the Cochrane Collaboration tool. The main variables were the Time Trial Test (TTT) and Time to Exhaustion (TTE) tests, the latter separated into the Limited Time Test (LTT) and Limited Distance Test (LDT). The analysis was carried out with a pooled standardized mean difference (SMD) through Hedges' g test (95% CI). Nineteen studies were included in the systematic review and meta-analysis, revealing a small effect for time in the TTT (SMD, −0.36; 95% CI, −0.87-0.16; I 2 = 59%; p = 0.010), a small effect for LTT (SMD, 0.25; 95% CI, −0.01-0.51; I 2 = 0%; p = 0.53), and a large effect for LDT (SMD, 4.27; 95% CI, −0.25-8.79; I 2 = 94%; p = 0.00001). BA supplementation showed small effects on physical performance in aerobic-anaerobic transition zones. Evidence on acute supplementation is scarce (one study); therefore, exploration of acute supplementation with different dosages and formats on physical performance in aerobic-anaerobic transition zones is needed.
... During the post-supplementation testing period, subjects continued to ingest a maintenance dose of βalanine (1.2 g·d −1 ). Recent evidence has suggested that a maintenance dose of ∼1.2 g·d −1 is adequate to maintain already elevated muscle carnosine content (Stegen et al., 2014). ...
The varying results reported in response to β-alanine supplementation may be related to the duration and nature of the exercise protocol employed. We investigated the effects of β-alanine supplementation on a wide range of cycling performance tests in order to produce a clear concise set of criteria for its efficacy. Fourteen trained cyclists (Age = 24.8 ± 6.7 years; VO2max = 65.4 ± 10.2 mL·kg·min−1) participated in this placebo-controlled, double-blind study. Prior to supplementation, subjects completed two (familiarization and baseline) supramaximal cycling bouts until exhaustion (120% pre-supplementation VO2max) and two 1-, 4- and 10-km cycling time trial (TT). Subjects then supplemented orally for 4 weeks with 6.4 g/d placebo or β-alanine and repeated the battery of performance tests. Blood lactate was measured pre-exercise, post-exercise and 5 min post-exercise. β-alanine supplementation elicited significant increases in time to exhaustion (TTE) (17.6 ± 11.5 s; p = 0.013, effect compared with placebo) and was likely to be beneficial to 4-km TT performance time (−7.8 ± 8.1 s; 94% likelihood), despite not being statistically different (p = 0.060). Performance times in the 1- and 10-km TT were not affected by treatment. For the highly trained cyclists in the current study, β-alanine supplementation significantly extended supramaximal cycling TTE and may have provided a worthwhile improvement to 4-km TT performance. However, 1- and 10-km cycling TT performance appears to be unaffected by β-alanine supplementation.
... 6-10 subjects/group. Adapted from Stegen et al. (2014). ...
Carnosine, but not anserine, is present in relatively high concentrations in human skeletal muscle. Young, male subjects with a high proportion of fast-twitch muscle fibers have the highest carnosine concentration within in a healthy population. Human muscle carnosine stores can be markedly enhanced by long-term supplementation of β-alanine (3-6 g for at least 4 weeks), the rate-limiting amino acid for carnosine synthesis. Elevated muscle carnosine levels have been shown to be ergogenic for some high-intensity exercises that last at least 1 min. Although more in vivo human research is needed concerning the underlying ergogenic mechanism, in vitro data suggest that both an enhanced intramyocellular pH buffering and calcium handling could explain (partly) the ergogenic effect of elevated carnosine stores. This chapter further discusses the possible release of carnosine from skeletal muscle into the circulation and its function to act as a depot for the histidine-histamine pathway.
... Esto justifica que se estudie si la suplementación con β-alanina puede mejorar los niveles de carnosina y, con ello, el control de la acidosis inducida por el ejercicio. De hecho, algunos estudios han observado que esta suplementación puede incrementar hasta un 40-80% los niveles de carnosina (44)(45)(46), aunque la variabilidad interindividual es muy grande, y depende de la absorción de cada individuo, del peso, o de su masa magra, siendo la retención mayor a mayor masa muscular (42). Resulta intrigante que solo un 2,5 % de la β-alanina contribuya a la producción de carnosina, eliminándose un 1-2 % de la ingesta en orina, por lo que no se sabe qué ocurre con aproximadamente el 95 % de la β-alanina consumida (47). ...
Introduction: Very few nutritional supplements have scientifically demonstrated their effectiveness as an ergogenic aid. This review will examine creatine monohydrate (MC), the β-hydroxy-β-methylbutyrate (HMB), sodium bicarbonate (BS), the β-alanine and caffeine. Objectives: To analyze the efficacy, mechanisms of action, dose, side effects and some sports that can benefit from their consumption. Methods: Searching in PubMed bibliographic database reviews from the last 15 years and original articles from the last 5 years of the studied substances. Results: Doses of 20 mg/day for 4-7 days are effective in improving strength and muscular power and performance in short and repeated sprints. HMB at doses of 3 g/day for at least 2 weeks contributes to increased lean mass and fat-free mass. The intake of 0.3 g/kg of BS improves performance on tests of 400-1,500 meters in athletics and intermittent sprints. Meanwhile, doses of 80 mg/kg/day of β-alanine for 4-10 weeks may improve performance in high-intensity intermittent exercise. Finally, caffeine at doses of 2 mg/kg improves responsiveness and 3-6 mg/kg improves performance in endurance tests. Conclusions: The revised supplements have shown their efficacy in physical performance, but it is needed to keep in mind that most studies have been conducted with recreational-level athletes. Generally, the better the individual's fitness level is the less improvement in physical performance the supplement shows. However, an increase of only 1% may sometimes allow the athlete to advance several positions in a final. Finally, we should draw attention to the importance of optimizing nutrition before considering the introduction of sports supplements, especially in children and youth. All analyzed substances have scientific basis supporting its ergogenic effect. All of them can be found in the market with Certificate of Quality and Purity.
... A recent study by Bex et al. [21] suggests that increases in whole muscle carnosine concentrations may be slightly higher in trained athletes compared to non-athletes supplementing with betaalanine, but more research is needed to replicate this finding and account for potential differences in single muscle fiber concentrations. Much of the research evaluating increases in muscle carnosine has been performed in young males, but evidence also suggests that beta-alanine supplementation is effective in females [22,23] and the elderly [24]. ...
Position statement
The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of beta-alanine supplementation. Based on the current available literature, the conclusions of the ISSN are as follows: 1) Four weeks of beta-alanine supplementation (4–6 g daily) significantly augments muscle carnosine concentrations, thereby acting as an intracellular pH buffer; 2) Beta-alanine supplementation currently appears to be safe in healthy populations at recommended doses; 3) The only reported side effect is paraesthesia (tingling), but studies indicate this can be attenuated by using divided lower doses (1.6 g) or using a sustained-release formula; 4) Daily supplementation with 4 to 6 g of beta-alanine for at least 2 to 4 weeks has been shown to improve exercise performance, with more pronounced effects in open end-point tasks/time trials lasting 1 to 4 min in duration; 5) Beta-alanine attenuates neuromuscular fatigue, particularly in older subjects, and preliminary evidence indicates that beta-alanine may improve tactical performance; 6) Combining beta-alanine with other single or multi-ingredient supplements may be advantageous when supplementation of beta-alanine is high enough (4–6 g daily) and long enough (minimum 4 weeks); 7) More research is needed to determine the effects of beta-alanine on strength, endurance performance beyond 25 min in duration, and other health-related benefits associated with carnosine.
... The optimal loading protocol is unknown but intakes of 3-6 g/d for [4][5][6][7][8][9][10][11][12] weeks increase this intracellular buffer by 50-85% [136]. To date, no threshold for carnosine concentrations has been found, but a daily intake of ~ 1.2 g appears to maintain muscle carnosine elevations and a return to baseline may require 6-20 weeks of supplement withdrawal [137]. Dietary beta-alanine includes meat from animals that are highly anaerobic (e.g. ...
Despite over 50 years of research, the field of sports nutrition continues to grow at a rapid rate. Whilst the traditional research focus was one that centred on strategies to maximize competition performance, emerging data in the last decade has demonstrated how both macronutrient and micronutrient availability can play a prominent role in regulating those cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training. Nonetheless, in the context of exercise performance, it is clear that carbohydrate (but not fat) still remains king and that carefully chosen ergogenic aids (e.g. caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can all promote performance in the correct exercise setting. In relation to exercise training, however, it is now thought that strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations whereas high carbohydrate availability and antioxidant supplementation may actually attenuate training adaptation. Emerging evidence also suggests that vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise. Finally, novel compounds (albeit largely examined in rodent models) such as epicatechins, nicotinamide riboside, resveratrol, β-hydroxy β-methylbutyrate, phosphatidic acid and ursolic acid may also promote or attenuate skeletal muscle adaptations to endurance and strength training. When taken together, it is clear that sports nutrition is very much at the heart of the Olympic motto, Citius, Altius, Fortius (faster, higher, stronger).
... A recent work (103) showed that women supplemented with b-alanine (4 3 800 mg/d for 46 days) had similar increases in muscle carnosine to men. However, women experienced higher relative increases in muscle carnosine after supplementation, as baseline carnosine levels were lower than those found in men. ...
ATHLETES ARE CONSTANTLY SEARCHING FOR METHODS WITH WHICH TO INCREASE ATHLETIC PERFORMANCE. THE USE OF ERGOGENIC AIDS IS POPULAR AMONG ATHLETES; HOWEVER, MOST RESEARCH IS COLLECTED IN MALE SUBJECTS. BASED ON PHYSIOLOGICAL AND MORPHOLOGICAL DIFFERENCES BETWEEN GENDERS, IT CANNOT BE ASSUMED WOMEN WILL DEMONSTRATE SIMILAR RESPONSES AS MEN. SIXTY-FIVE PERCENT OF FEMALE ATHLETES REPORT USE OF ERGOGENIC AIDS AND IT IS IMPERATIVE TO EVALUATE FEMALE-SPECIFIC BENEFITS. THIS REVIEW PRESENTS THE CURRENT LITERATURE EVALUATING EFFECTS OF ERGOGENIC AIDS ON ANAEROBIC PERFORMANCE IN WOMEN AND RECOMMENDATIONS FOR USE. FOR A VIDEO ABSTRACT OF THIS ARTICLE SEE SUPPLEMENTAL DIGITAL CONTENT 1, http://links.lww.com/SCJ/A180.
... Oral supplementation of carnosine in the drinking water of mice with DN results in accumulation of carnosine in muscular tissues and kidneys, reduction of proteinuria, and increased biosynthesis of insulin [25]. In humans, taking oral supplements of slow-release betaalanine tablets drives to de novo biosynthesis of carnosine, leading to increased carnosine storage in tissues [46][47][48][49][50]. Carnosines, which are secreted into the circulation by skeletal muscle cells during physical exercise, show similar beneficial effects as physical exercise on diabetic complications [14,51]. ...
... Carnosine elevation of up to 160% has been shown in mice by 1.2% β-alanine or 1.8% carnosine in drinking water for a period of 8-12 weeks with improved fatigue resistance in soleus muscle (Everaert et al., 2013a). In humans, β-alanine intake for 4-12 weeks increased concentration of muscle carnosine by 15-85% (Stegen et al., 2014). The increased carnosine content may benefit in an improvement in high-intensity exercise performance (Harris et al., 2006). ...
Muscle carnosine is an intracellular buffer. The intake of β-alanine, combined with carbohydrate and protein, enhanced carnosine loading in human muscle. The aim of the present study was to examine if muscle carnosine loading was enhanced by β-alanine intake and co-ingestion of glucose in male rats. Thirty-six male rats were divided into three groups and supplemented for four weeks: β-alanine (βA group, 1.8% β-alanine in drinking water), β-alanine and glucose (βAGL group, 1.8% β-alanine and 5% glucose in drinking water), and control (C group, drinking water). During the supplementation period, ratswere exercised (20 m·min−1, 10 min·day−1, 4 days·week−1 for 4 weeks). Muscle carnosine concentration was quantified in soleus (n = 12) and rectus femoris (n = 6) muscles using high-performance liquid chromatography. In soleus muscle, carnosine concentration was 2.24 ± 1.10, 6.12 ± 1.08, and 6.93 ± 2.56 mmol/kg dw for control, βA, and βAGL, respectively. In rectus femoris, carnosine concentration was 2.26 ± 1.31, 7.90 ± 1.66, and 8.59 ± 2.33 mmol/kg dw for control, βA, and βAGL respectively. In each muscle, βA and βAGL resulted in similar carnosine increases compared to the control. In conclusion, β-alanine intake for four weeks, either alone or with glucose co-ingestion, equally increased muscle carnosine content. It appears that the potential insulin response to fluid glucose intake does not affect muscle carnosine loading in male rats.
... Muscle carnosine storage and serum carnosinase (the enzyme that hydrolyses carnosine) is respectively lower and higher in women than in men [41,42]. However, determinants of muscle carnosine storage (such as age and fiber type) and muscle carnosine loading (by beta-alanine supplementation) are gender independent [34,43]. In addition, a 70% high-fat diet increased muscle carnosine in female mice. ...
Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes.
Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats), 60% high-fat feeding (male rats), cafeteria feeding (male rats), 70% high-fat feeding (female mice). Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients) and muscle carnosine and gene expression of muscle fiber type markers were measured.
Diet interventions in rodents (cafeteria and 70% high-fat feeding) induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1), +30% (p<0.05) and +39% (p<0.05), respectively). The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05) and tended to increase in the diabetic men (1.6-fold, p = 0.07), compared to healthy lean subjects.
Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional). In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional). Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.
... During prolonged competition, it is of importance for athletes to effectively maintain muscle carnosine concentrations at elevated levels. Stegen et al. (2014) demonstrated that a dose of 1.2g/day is optimal to keep muscle carnosine content elevated at 30-50% above baseline after a loading phase. ...
In the past decades, dietary supplements have gained in popularity worldwide. Athletes are a specific population that constantly search for strategies to improve performance. In this population, supplements can support the body during and after the hard periods of training and thereby increase exercise performance. However, the efficacy of only a few supplements is supported by well substantiated evidence, and one such supplement is beta-alanine. Beta-alanine is able to increase intramuscular carnosine concentrations. This carnosine loading may thereby augment fatigue threshold and improve high-intensity exercise performance, as several physiological roles are ascribed to the dipeptide (pH-buffering, calcium regulation, antioxidant capacities). Because of the range of functions carnosine exerts, it is also a promising dipeptide for some health-related issues. Carnosine is a naturally occurring dipeptide with a high concentration in mammalian skeletal muscle. It is synthesized by carnosine synthase from the amino acids L-histidine and beta-alanine. Muscle carnosine concentrations are shown to be highly stable over time, suggesting that carnosine is subject to a strong homeostatic regulation keeping carnosine levels within a certain normal range. However, as mentioned, one condition in which muscle carnosine homeostasis is greatly disrupted is beta-alanine supplementation. Several studies demonstrated that chronic oral ingestion of beta-alanine can substantially elevate the carnosine content by 40-80%, which subsequently leads to improved performance in high intensity exercise in both trained and untrained individuals. Because of the popularity of beta-alanine as a supplement and the beneficial effects of high muscle carnosine levels, it is important to have a full understanding of the carnosine metabolism and the regulation of muscle carnosine homeostasis. Although beta-alanine is a frequently used dietary supplement, it was recently demonstrated that only 2-3% of the total ingested amount of beta-alanine is actually incorporated into muscle carnosine. This indicates that the major part of ingested beta-alanine has an unknown metabolic fate, signifying that the beta-alanine and carnosine metabolism are not yet fully unraveled and may include a complex regulation of a set of enzymes and transporters. Study 1 of this thesis mainly focused on the role of beta-alanine transaminases in the regulation of muscle carnosine levels upon beta-alanine supplementation. Because most chronically ingested beta-alanine has an unknown metabolic fate, a possible pathway is transamination by GABA-T and AGXT2 in either liver and/or kidney or inside myocytes. GABA-T and AGXT2 were shown to be mainly expressed in kidney and liver and to a much smaller extent in myocytes, suggesting that beta-alanine transamination mainly takes place in these organs. By inactivating the beta-alanine transaminase pathways, both higher circulating beta-alanine levels and higher muscle carnosine loading could be evoked. Thus, muscle carnosine homeostasis is shown to be dependent on the circulating availability of beta-alanine, which is in turn dependent on the degradation of beta-alanine in liver and kidney. These findings partly explain the low efficiency of chronically ingested beta-alanine because beta-alanine is primarily routed toward oxidation. Only upon saturation of this pathway, beta-alanine is incorporated in muscle carnosine. In study 2, focus was shifted to the other amino acid involved in carnosine synthesis. As the efficiency of beta-alanine supplementation is low, it can be questioned whether beta-alanine is indeed the one and only rate-limiting factor for carnosine synthesis and whether carnosine loading efficiency can be enhanced by L-histidine supplementation (alone or combined with beta-alanine). The results indicated that muscle carnosine is not enhanced by L-histidine supplementation, confirming the rate-limiting role of beta-alanine in the carnosine synthesis process. However, chronic beta-alanine supplementation was shown to reduce plasma and muscle histidine levels, demonstrating that, although not rate-limiting, L-histidine availability is not unlimited either. The decline is body histidine levels could be prevented by co-supplementing L-histidine alongside beta-alanine. Further research on the effect of the depletion of histidine levels by beta-alanine supplementation on physiological processes such as carnosine loading of longer duration or protein synthesis in an anabolic state is necessary. To investigate whether muscle carnosine homeostasis is equally disrupted by the absence of any dietary beta-alanine, study 3 was performed. Because meat and fish are the main exogenous source of carnosine, the effect of a 6-month vegetarian diet in previous omnivorous subjects on the carnosine homeostasis was examined. Next to carnosine, creatine and carnitine were also monitored in this study. It was demonstrated that body creatine, but not carnosine and carnitine homeostasis was affected by the 6-month vegetarian diet. These findings suggest that carnosine and carnitine homeostasis can be effectively maintained by endogenous synthesis of these compounds or their precursors. Lastly, study 4 explored the transcriptional events of carnosine-related enzymes and transporters in human skeletal muscles in response to beta-alanine supplementation in order to further elucidate how muscle carnosine homeostasis is disturbed. We found that both beta-alanine transporters and carnosine synthase were greatly upregulated, indicating that the mRNA expression of these effectors is enhanced by increased circulating beta-alanine levels. Thus, increased transsarcolemmal beta-alanine uptake and muscle carnosine synthesis can be seen as a way to maintain plasma beta-alanine homeostasis, thereby disturbing muscle carnosine homeostasis. Altogether, this thesis provided more insights in the regulation of plasma beta-alanine and muscle carnosine homeostasis. As beta-alanine is a popular dietary supplement, a better understanding of its metabolism can lead to clearer guidelines for supplementation.
... To replicate the increase in intracellular carnosine concentration reported in the literature, 4-10 weeks of beta-alanine supplementation (4-6 g/day) is recommended (Hill et al., 2007), while 1.2 g/day appears to maintain elevated muscle carnosine levels (Stegan et al., 2014). Athletes may decide to divide this into several smaller doses to minimize the likelihood of paraesthesia, a common side effect. ...
Bouldering competitions are held up to International level and governed by the International Federation of Sport Climbing. Bouldering has been selected to feature at the 2020 Olympic Games in Tokyo, however, physiological qualities and nutritional requirements to optimise performance remain inadequately defined due to large gaps in the literature. The primary goals of training include optimising the capacity of the anaerobic energy systems and developing sport-specific strength, with emphasis on the isometric function of the forearm flexors responsible for grip. Bouldering athletes typically possess a lean physique, similar to the characteristics of sport climbers with reported body fat values of 6-12%. Athletes strive for a low body weight to improve power to weight ratio and limit the load on the extremities. Specialised nutritional support is uncommon and poor nutritional practices such as chronic carbohydrate restriction are prevalent, compromising the health of the athletes. The high intensity nature of bouldering demands a focus on adequate carbohydrate availability. Protein intake and timing should be structured to maximise muscle protein synthesis and recovery, with the literature suggesting 0.25-0.3 g/kg in 3-4 hour intervals. Supplementing with creatine and β-alanine may provide some benefit by augmenting the capacity of the anaerobic systems. Boulderers are encouraged to seek advice from nutrition experts to enhance performance, particularly important when weight loss is the desired outcome. Further research is warranted across all nutritional aspects of bouldering which is summarised in this review.
... By decreasing muscular acidity (maintaining the balance of muscle pH), carnosine causes increasing the ability and performance of muscle in long and severe activities and muscular fibers, which have the highest amount of carnosine, can generate the most power for longer time periods (18). A plenty of carnosine exists in skeletal muscles texture (especially fast twitch type muscular fibers) but its levels are limited by the betaalanine that is available for muscles (16). The most prominent method of increasing beta-alanine for body muscles is using beta-alanine supplement. ...
... Las publicaciones que obtienen beneficios por la suplementación, coinciden en que las dosis necesarias para producir un efecto ergogénico en el rendimiento neuromuscular se encuentran entre los 4 y los 6,4 gramos al día durante un período aproximado de 4 semanas en los hombres (Van Thienen et al., 2009;Sale et al., 2012;Derave et al., 2007;Carpentier et al., 2015;Tobias et al., 2013;Howe et al., 2013). Los cambios en las concentraciones de carnosina por la suplementación parecen ser más sensibles en las mujeres con respecto a los hombres ( Stegen et al., 2014), por lo que, cantidades comprendidas entre 800 mg y 2,4 gramos al día durante un periodo aproximado de 4 semanas podría ser suficiente para obtener beneficios relevantes en el sexo femenino ( Rodríguez et al., 2014;Glenn et al., 2016). Suplementación de beta- alanina y su relación con ejercicios de fuerza y de carácter cíclico anaeróbico (<60 segundos) BA: beta-alanina; PLA: placebo; NC: no calculable; CMJ: counter-movement jump; SJ: squat jump; TE: tamaño del efecto; SB: bicarbonato sódico; Cr: creatina; MVIC: máxima contracción voluntaria isométrica; BM: masa corporal; WR: luchadores; FB: futbolistas; RM: repetición máxima; p: variable estadística (p<0,05= estadísticamente significativo). ...
The aim of this review is to analyze the ergogenic effects of beta-alanine supplementation on neuromuscular performance. The material used includes those researches of the effects of beta-alanine on strength and on cyclic anaerobic exercises (duration < 60 seconds) (years: 2007-2016). The result of this research is a broad analysis of the subject, which provides basic knowledge needed on this specific area. A critical review of the literature shows that the effects of beta-alanine on neuromuscular performance are not very clear in relation to the different strength exercises, the different Wingate tests and the specific anaerobic performance tests in real situations of competition (i.e., 30-second time trial, 200 yards (yd), 300 yd, and 400-meter straight). The data analyzed do not reveal differences depending on whether they are trained individuals or not. Therefore, the ergogenic effects of this supplement need more confirmation when it comes to high intensity exercises that require high levels of muscle strength /power. However, in repeated sprint exercises (sprint duration < 7 seconds), beta-alanine and the combination of beta-alanine and sodium bicarbonate do not appear to improve performance because the improvement in buffer capacity does not dictate this type of evidence. There is some ambiguity regarding the combination of creatinine and beta-alanine supplementation, as well as limitations on its additive effect in relation to beta-alanine supplementation alone. There is no benefit from supplementation in the physiological parameters of body composition.
... (33) basaron su investigación en una suplementación con 6,4 g·día -1 de BA con dosis de ocho tomas de 800 mg cada 1,5-3 horas de diferencia de ingesta entre tomas por cinco semanas, y aunque los autores expusieron una mejora significativa en la potencia promedio (mayor carga de entrenamiento logrado y más kilogramos levantados) en el grupo suplementado con BA, la mayor limitante reportada por los autores fue llevar a la práctica un protocolo de dosificación donde los deportistas se comprometan con cumplir estrictamente las ingestas señaladas por varias semanas(33).Por último, en las respuestas individuales existe una variabilidad intersujeto posterior a la suplementación de BA (34), mientras que la variación en la síntesis de carnosina muscular en respuesta a la ingesta de BA es alta(9,14). En algunos estudios se ha descrito que las mujeres requieren menores niveles de suplementación de BA para obtener aumentos relativos similares en carnosina en comparación con los hombres(35). De hecho, según Stout y cols.(17), ...
Introducción: la beta-alanina (BA) es una de las ayudas ergogénicas más utilizadas actualmente por deportistas, pero la mayoría de los estudios centran su investigación en la suplementación prolongada. Objetivos: determinar el efecto agudo de la suplementación con BA sobre una prueba de tiempo límite (PTL) a velocidad aeróbica máxima (VAM) en atletas de resistencia. Material y método: once atletas de resistencia (VO2máx 61,6 ± 9,5 mLO2•kg-1•min-1) fueron parte del estudio. El diseño fue doble ciego, cruzado intrasujeto, y la suplementación de BA fue de 30 mg•kg-1 o placebo (PL) 60 minutos antes de completar una PTL. Las variables fueron: tiempo y distancia en la PTL y concentraciones de lactato ([La]) postesfuerzo en los minutos 1, 3, 5, 7 y 9. Para el análisis se utilizó una prueba t de Student y el tamaño del efecto (TE) se realizó mediante la prueba d de Cohen. Resultados: el tiempo en la PTL evidenció diferencias significativas entre la BA y PL (p = 0,047; TE = 0,48). No se observaron diferencias significativas en distancia entre ambos grupos (p = 0,071; TE = 0,48) y las [La] evidenciaron diferencias significativas entre ambos grupos en los minutos 3, 5 y 7, respectivamente (p < 0,05). Conclusión: la suplementación aguda con BA evidenció aumentos significativos en el tiempo de ejecución en la PTL a intensidades correspondientes a VAM. Por lo anterior, la suplementación aguda con BA es una ayuda ergogénica que podría ser considerada por los atletas de resistencia para aumentar el rendimiento deportivo.
Palabras Clave:
Beta-alanina. Ayuda ergogénica. Prueba de ejercicios.
... 67 Other work using a single dose of carnosine at the time of cecal ligation and puncture demonstrated that carnosine supplementation decreased serum and tissue malondialdehyde levels compared with control animals. 66 Chronic b-alanine supplementation can significantly augment muscle carnosine concentrations, 72,73 presenting a viable therapeutic approach. The role of decreased b-alanine in the current model has not been tested directly with skeletal muscle function; direct supplementation of these metabolites will offer valuable information in future studies. ...
Sepsis is a multiorgan disease affecting the ileum and jejunum (small intestine), liver, skeletal muscle, and lung clinically. The specific metabolic changes in the ileum, jejunum, liver, skeletal muscle, and lung have not previously been investigated. Live Pseudomonas aeruginosa, isolated from a patient, was given via i.v. catheter to pigs to induce severe sepsis. Eighteen hours later, ileum, jejunum, medial gastrocnemius skeletal muscle, liver, and lung were analyzed by nontargeted metabolomics analysis using gas chromatography/mass spectrometry. The ileum and the liver demonstrated significant changes in metabolites involved in linoleic acid metabolism: the ileum and lung had significant changes in the metabolism of valine/leucine/isoleucine; the jejunum, skeletal muscle, and liver had significant changes in arginine/proline metabolism; and the skeletal muscle and lung had significant changes in aminoacyl-tRNA biosynthesis, as analyzed by pathway analysis. Pathway analysis also identified changes in metabolic pathways unique for different tissues, including changes in the citric acid cycle (jejunum), β-alanine metabolism (skeletal muscle), and purine metabolism (liver). These findings demonstrate both overlapping metabolic pathways affected in different tissues and those that are unique to others and provide insight into the metabolic changes in sepsis leading to organ dysfunction. This may allow therapeutic interventions that focus on multiple tissues or single tissues once the relationship of the altered metabolites/metabolism to the underlying pathogenesis of sepsis is determined.
... However, when body weight is taken into account, it can be hypothesized that, following chronic fixed dosing, light subjects are also favoured. Indeed, a negative correlation between body weight and the change in carnosine following chronic fixed dose β-alanine supplementation has already been observed in the gastrocnemius muscle of male subjects [26]. In practice, commercial β-alanine is available in a wide variety of single dosages of 0.5 g up to 1.35 g, but it can also be acquired as powder. ...
Personalised dosing of performance-enhancing food supplements is a hot topic. β-alanine is currently dosed using a fixed dose; however, evidence suggests that this might favour light compared to heavy subjects. A weight-relative dose seems to reverse this problem. In the present study, a novel dosing strategy was tested. A fragmented dose, composed of a fixed fragment of 800 mg and a weight-relative fragment of 10 mg/kg body weight, was compared to a fixed dose of 1600 mg and a weight-relative dose of 20 mg/kg body weight in a cohort of 20 subjects with a body weight ranging 48–139 kg (79.9 ± 24.4 kg). The results show that, following a fragmented dose, the influence of body weight on the pharmacokinetic response (iAUC) over a 210 min period was absent (r = −0.168; p = 0.478), in contrast to the fixed or weight-relative dose. The pharmacokinetic response also seemed more homogenous (CV% = 26%) following a fragmented dose compared to the fixed (33%) and the weight-relative dose (31%). The primary advantage of the easy-to-calculate fragmented dosing strategy is that it does not systematically favour or impair a certain weight group. Thorough dosage studies are lacking in the current field of sports and food supplements, therefore similar considerations can be made towards other (ergogenic) food supplements.
... Esto justifica que se estudie si la suplementación con β-alanina puede mejorar los niveles de carnosina y, con ello, el control de la acidosis inducida por el ejercicio. De hecho, algunos estudios han observado que esta suplementación puede incrementar hasta un 40-80% los niveles de carnosina (44)(45)(46), aunque la variabilidad interindividual es muy grande, y depende de la absorción de cada individuo, del peso, o de su masa magra, siendo la retención mayor a mayor masa muscular (42). Resulta intrigante que solo un 2,5 % de la β-alanina contribuya a la producción de carnosina, eliminándose un 1-2 % de la ingesta en orina, por lo que no se sabe qué ocurre con aproximadamente el 95 % de la β-alanina consumida (47). ...
INTRODUCTION
Very few nutritional supplements have scientifically demonstrated their effectiveness as an ergogenic aid. This review will examine creatine monohydrate (MC), the β-hydroxy-β-methylbutyrate (HMB), sodium bicarbonate (BS), the β-alanine and caffeine.
OBJECTIVES
To analyze the effi cacy, mechanisms of action, dose, side effects and some sports that can benefit from their consumption.
METHODS
Searching in PubMed bibliographic database reviews from the last 15 years and original articles from the last 5 years of the studied substances.
RESULTS
Doses of 20 mg/day for 4-7 days are effective in improving strength and muscular power and performance in short and repeated sprints. HMB at doses of 3 g/day for at least 2 weeks contributes to increased lean mass and fat-free mass. The intake of 0.3 g/kg of BS improves performance on tests of 400-1,500 meters in athletics and intermittent sprints. Meanwhile, doses of 80 mg/kg/day of β-alanine for 4-10 weeks may improve performance in high-intensity intermittent exercise. Finally, caffeine at doses of 2 mg/kg improves responsiveness and 3-6 mg/kg improves performance in endurance tests.
CONCLUSIONS
The revised supplements have shown their efficacy in physical performance, but it is needed to keep in mind that most studies have been conducted with recreational-level athletes. Generally, the better the individual´s fitness level is the less improvement in physical performance the supplement shows. However, an increase of only 1% may sometimes allow the athlete to advance several positions in a final. Finally, we should draw attention to the importance of optimizing nutrition before considering the introduction of sports supplements, especially in children and youth. All analyzed substances have scientific basis supporting its ergogenic effect. All of them can be found in the market with Certificate of Quality and Purit.
... Increasing muscle carnosine has resulted in improvements in exercise performance lasting primarily 2-4 min [129]. While the majority of data with beta-alanine supplementation is in males, women have reported lower initial muscle carnosine levels, suggesting they could potentially see greater benefits compared to men [130]. Varanoske et al. [131] reported 28 days of beta-alanine supplementation was more effective for women, than men, for increasing muscle carnosine, although fatigue attenuation was similar for both men and women [131]. ...
Although there is a plethora of information available regarding the impact of nutrition on exercise performance, many recommendations are based on male needs due to the dominance of male participation in the nutrition and exercise science literature. Female participation in sport and exercise is prevalent, making it vital for guidelines to address the sex-specific nutritional needs. Female hormonal levels, such as estrogen and progesterone, fluctuate throughout the mensural cycle and lifecycle requiring more attention for effective nutritional considerations. Sex-specific nutritional recommendations and guidelines for the active female and female athlete have been lacking to date and warrant further consideration. This review provides a practical overview of key physiological and nutritional considerations for the active female. Available literature regarding sex-specific nutrition and dietary supplement guidelines for women has been synthesized, offering evidenced-based practical information that can be incorporated into the daily lives of women to improve performance, body composition, and overall health.
... In animal husbandry, β-alanine can improve the utilization rate of feed by livestock and poultry, improve the growth performance, increase the content of active peptides and antioxidant capacity of muscles, as well as improve meat quality (Qi et al. 2016). In the food industry, β-alanine can be used not only to synthesize condiments such as sweeteners, but also as a potential sports nutrition supplement for higher endurance by increasing the concentration of carnosine in muscles (Painelli et al. 2018;Stegen et al. 2014). In environmental applications, it can be directly used to synthesize poly-β-alanine (Lee et al. 2012), which plays an important role in water purification. ...
β-Alanine (3-aminopropionic acid) is the only naturally occurring β-type amino acid. Although it is not incorporated into proteins, it has important physiological functions in the metabolism of animals, plants and microorganisms. Furthermore, it has attracted great interest due to its wide usage as a precursor of many significant industrial chemicals for medicine, feed, food, environmental applications and other fields. With the depletion of fossil fuels and concerns regarding environmental issues, biological production of β-alanine has attracted more attention relative to chemical methods. In this review, we first summarize the pathways through which natural microorganisms synthesize β-alanine. Then, the current research progress in the biological synthesis of β-alanine is also elaborated. Finally, we discuss the main problems and challenges in optimizing the biological pathways, offering perspectives on promising new biological approaches.
This chapter presents two essential premises to abolish the classic bilateral relationship between nutrition and strength: the relationship of strength production with hypertrophy, focusing in the mechanical and physiological mechanisms involved on strength production (i); and, the relationship between sport, strength and nutrition, avoiding using the term strength sport modalities that present an old wrong conceptualization, in as much as strength training is not only specific for the strength sport modalities (ii). This chapter will focus on those type of sport supplements that provide ergogenic effects for enhancing muscular strength production, following the two premises previously described. The ergogenic effects of the sport supplements is dependent on the mechanical and metabolic demands of each modality of exercise. Therefore, in the present chapter, it has been reviewed the sport supplements with possible ergogenic aids to increase muscle strength, including the mechanism of action related to increased muscle force production, including a correct guidelines with the optimal dosage and timing to administer these supplements. We selected caffeine, creatine, β-alanine, Sodium bicarbonate and Nitrate as the five top sports supplements with the most evidence-based use in the sports nutrition, improving neuromuscular function through various metabolic pathways that directly/indirectly lead to muscle strength gain.
It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, including an increase in cancer incidence, wrinkling and diminished skin elasticity, atherosclerosis, osteoporosis, weight loss, age-related cataract, glaucoma and others. Shorter telomere length in leukocytes was associated cross-sectionally with cardiovascular disorders and its risk factors, including pulse pressure and vascular aging, obesity, vascular dementia, diabetes, coronary artery disease, myocardial infarction (although not in all studies), cellular turnover and exposure to oxidative and inflammatory damage in chronic obstructive pulmonary disease . It has been proposed that telomere length may not be a strong biomarker of survival in older individuals, but it may be an informative biomarker of healthy aging. The data reveal that telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state and in this article these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. In particular, the presence of highly specific correlations and early causal relationships between telomere loss in the absence of telomerase activity and replicative senescence or crisis, and from the other side, telomerase reactivation and cell immortality, point to a new and important treatment strategies or the therapeutic manipulation during treatment of age related disorders and cancer. Once better controls and therapeutic treatments for aging and age-related disorders are achieved, cellular rejuvenation by manipulating telomeres and enzyme telomerase activity may reduce some of the physiological declines that accompany aging. In this work we raise and support a therapeutic concept of using non-hydrolized forms of naturally occurring imidazole-dipeptide based compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur with the demonstrated evidence of telomere shortening appeared to be a hallmark of oxidative stress and disease. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival and an advanced oral nutritional support with non-hydrolized carnosine (or carcinine and patented compositions thereof) is a useful therapeutic tool of a critical telomere length maintenance that may fundamentally be applied in the treatment of age-related sight-threatenting eye disorders, prolong life expectancy, increase survival and chronological age of an organism in health control, smoking behavior and disease.
The use of dietary supplements in sports is widespread as athletes are continuously searching for strategies to increase performance at the highest level. Beta-alanine is such a supplement that became increasingly popular during the past years. This review examines the available evidence regarding the optimization of supplementation, the link between beta-alanine and exercise performance and the underlying ergogenic mechanism.
It has been repeatedly demonstrated that chronic beta-alanine supplementation can augment intramuscular carnosine content. Yet, the factors that determine the loading process, as well as the mechanism by which this has an ergogenic effect, are still debated. On the basis of its biochemical properties, several functions are ascribed to carnosine, of which intramuscular pH buffer and calcium regulator are the most cited ones. In addition, carnosine has antiglycation and antioxidant properties, suggesting it could have a therapeutic potential.
On the basis of the millimolar presence of carnosine in mammalian muscles, it must play a critical role in skeletal muscle physiology. The recent number of studies shows that this is related to an improved exercise homeostasis and excitation-contraction coupling. Recent developments have led to the optimization of the beta-alanine supplementation strategies to elevate muscle carnosine content, which are helpful in its application in sports and to potential future therapeutic applications.
Functional dietary supplements are now regarded as an important factor to keep physical health, maintain exercise status and improve athletic performance. More and more sports industries are focusing on such supplements, which makes the industry develop rapidly and pay more and more attention to the research and development of different products, functions and the efficacy of health care. In this paper, the functional dietary supplements were classified and summarized, and energy supply supplements were discussed in detail: glucose and Adenosine Triphosphate; Exercise protection supplements: chondroitin sulphate, glucosamine, collagen, vitamin D and calcium; Endurance supplements: strength supplements such as protein, creatine, β-alanine, epicatechin, and taurine. The existing problems of functional dietary supplements were analysed and summarized, and the future development prospects were prospected, hoping to provide references for the development and research of new products of functional dietary supplements.
Longitudinal beta-alanine (BA) supplementation can improve exercise performance in males through increases in carnosine; however, females experience greater relative increases in carnosine compared to males. This potentially allows females to benefit from acute BA doses; however, effects of an acute BA dose on performance in females remain unknown. The purpose of this investigation was to evaluate how an acute dose of 1.6 g BA affects anaerobic performance in female cyclists. Twelve females (age=26.6±1.3 y) volunteered to participate in this randomized, double-blind study. All participants completed two supplement trials: 1) Placebo=34 g dextrose and 2) BA=1.6 g BA + 34 g dextrose. Thirty-minutes after supplementation, participants performed three repeated Wingate cycling tests with 2 min of active rest after each. Fatigue index, mean power, and peak power were measured during each Wingate. Lactate, heart rate, and rating of perceived exertion (RPE) were measured at rest, immediately after each Wingate, and after each active rest period. RPE significantly decreased (p<0.001) immediately following Wingates 1 and 2 and after each 2-min rest period for the BA trials; however, no differences were observed immediately after Wingate 3 (p>0.05). No significant supplementation effect was observed for any performance or physiological variable (p>0.05 for all variables). Findings suggest that an acute dose of BA (1.6 g) decreases RPE during anaerobic power activities in trained female cyclists.
Beta-alanine (BA) supplementation increases exercise performance due to increases in the intramuscular lactate buffer, carnosine. Females are more sensitive to these increases and results are further pronounced in trained individuals. Baseline intramuscular carnosine levels also naturally decrease with age; therefore, trained older females may experience augmented benefits from BA supplementation. However, the ability of BA to increase lower-body isokinetic strength (ISO) in female masters athletes (MA) is unknown. The purpose of this study was to examine the longitudinal effects of BA supplementation on ISO, hand-grip strength (HG), and body composition in female MA cyclists. Twenty-two subjects participated in this double-blind, randomized study. Subjects were randomized into two groups (PLA=8 g dextrose; BA=800 mg+8 g dextrose) and supplemented four times/day for 28 days. ISO, HG, and body composition were evaluated at baseline and at the same day/time each week over the 28 day intervention. No differences existed between groups at baseline or at the 7, 14, and 21 day time points for any variables (p>0.05). When evaluating ISO after 28 days, total work performed during the final 3 of the assessment (24.0% vs -16.8% change) in flexion and average peak torque (5.4% vs. 2.9% change) in extension were significantly increased from baseline in BA compared to PLA (p<0.05). No differences existed for HG or body composition after supplementation. Twenty-eight days of BA supplementation increased peak torque and work completed, indicating BA improves lower-body exercise performance in female MA.
Beta-alanine (BA) supplementation has been shown to be effective in improving physical performance by increasing carnosine concentration. However, it is still necessary to know the effect of a maintenance dose on performance. Thus, this study aimed to investigate the effects of a maintenance dose of BA supplementation on performance. Forty-four anaerobically trained men with 23.9 ± 3.8 years of age, 176.0 ± 0.05 cm height, 81.2 ± 7.5 kg body mass, and 15.5 ± 2.9% of body fat performed a cycle ergometer test consisting of 4 sprints of 30 s with 4 minutes of active recovery. The study comprised 3 phases: (a) presupplementation, (b) supplementation with 6.4 g·d BA or placebo, and (c) postsupplementation with a maintenance dose of 1.2 g·d of BA or interruption of supplementation. Data were analyzed using generalized estimated equations with a priori 0.05 level of significance. The placebo group and interruption group presented a lower power (7.28 ± 0.66 and 7.71 ± 0.42 W·kg vs. 8.04 ± 0.84 and 9.25 ± 1.18 W·kg, respectively; p < 0.05) during the third sprint in postsupplementation, whereas the maintenance group maintained the required power (7.47 ± 1.03 vs. 8.74 ± 1.07 W·kg; p > 0.05). The placebo group also presented higher percentage of fatigue (44.5% ± 12.3 and 44.8% ± 7.7 vs. 37.6 ± 7.2%; p = 0.021) and higher subjective perception of exertion (8.92 ± 0.90 vs. 8.00 ± 1.60; p = 0.028). Therefore, the maintenance dose of 1.2 g·d BA was effective in maintaining performance, whereas a reduction in performance was observed after supplementation interruption.
[Purpose] The aim of the present narrative review was to consider the evidence on the timing, optimal dose and intake duration of the main dietary supplements in sports nutrition, i.e. β-alanine, nitrate, caffeine, creatine, sodium bicarbonate, carbohydrate and protein. [Methods] This review article focuses on timing, optimal dose and intake duration of main dietary supptlements in sports nutrition. [Results] This paper reviewed the evidence to determine the optimal time, efficacy doses and intake duration for sports supplements verified by scientific evidence that report a performance enhancing effect in both situation of laboratory and training settings[Conclusion] Consumption of the supplements are usually suggested into 5 specific times, such as pre-exercise (nitrate, caffeine, sodium bicarbonate, carbohydrate and protein),
during exercise (carbohydrate), post-exercise (creatine, carbohydrate, protein), meal time (β-alanine, creatine, sodium bicarbonate, nitrate, carbohydrate and protein), and before sleep (protein). In addition, the recommended dosing protocol for the supplements nitrate and β-alanine are fixed amounts irrespective of body weight, while dosing protocol for sodium bicarbonate, caffeine and creatine supplements are related to corrected body weight (mg/kg bw). Also, intake duration is suggested for creatine and β-alanine, being effective in chronic daily time < 2 weeks while caffeine, sodium bicarbonate are effective in acute daily time (1-3 hours). Plus, ingestion of nitrate supplement is required in both chronic daily time < 28 days and acute daily time (2-2.5 h) prior exercise.
[Key words] Sports nutrition, Dietary supplements, Timing, Dose, Intake duration
Ergogenic nutritional supplements are a type of sports food. Sodium bicarbonate and b-alanine are two of the most popular and legally permitted ergogenic dietary supplements. These two chemicals have a comparable ergogenic effect because they help to neutralize hydrogen cations created during anaerobic glycolysis during exercise. The hydrogen ions will exit the trained muscles faster if the extracellular regulatory capacity of the organism is increased by strengthening the stores of bicarbonate ions. And before the acidification within the muscle cells becomes a limiting factor of athletic performance, more hydrogen ions and lactic acid will be produced. The goal of this review is to go over the two most common dietary supplements, sodium bicarbonate and b-alanine, that have been shown to improve athletic performance by neutralizing hydrogen cations created during anaerobic glycolysis during exercise. Sodium bicarbonate and b-alanine are legal ergogenic aids that are inexpensive and simple to make, and they have been used by athletes for decades. The extracellular mechanism of "neutralization" of hydrogen ions that build in the exercised muscle is aided by sodium bicarbonate consumption, which increases bicarbonate concentrations in the blood. The ideal dose is between 0.3 and 0.5 grams per kilogram of body weight, and it should be consumed 150-180 minutes before exercise to minimize or lessen gastrointestinal problems. B-alanine supplementation can also improve anaerobic exercise performance, with a more apparent effect in trials lasting 1 to 4 minutes at high intensity, whereas its ergogenic effect appears to be minimal to moderate in exercises lasting up to 25 minutes. Furthermore, it improves the volume of resistance training; yet, increasing strength has no added advantage. Carnosine reserves in muscle are greatly increased after 4 weeks of administration (4-6 gr/day), operating as an intramuscular mechanism for controlling H+ concentration. Furthermore, a loading dose of 4-6 grams per day in doses of 2 grams or fewer is necessary for a least of 2 weeks, with a larger benefit after 4 weeks. Paraesthesia is the sole negative effect at the prescribed levels (tingling).
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We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly ( P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body ( P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained ∼50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.
Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal-ion chelation, and antioxidant capacity as well as the capacity to protect against formation of advanced glycation and lipoxidation end-products. For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress are involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide. This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds. However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule.
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.
Carnosine was first discovered in skeletal muscle, where its concentration is higher than in any other tissue. This, along with an understanding of its role as an intracellular pH buffer has made it a dipeptide of interest for the athletic population with its potential to increase high-intensity exercise performance and capacity. The ability to increase muscle carnosine levels via β-alanine supplementation has spawned a new area of research into its use as an ergogenic aid. The current evidence base relating to the use of β-alanine as an ergogenic aid is reviewed here, alongside our current thoughts on the potential mechanism(s) to support any effect. There is also some emerging evidence for a potential therapeutic role for carnosine, with this potential being, at least theoretically, shown in ageing, neurological diseases, diabetes and cancer. The currently available evidence to support this potential therapeutic role is also reviewed here, as are the potential limitations of its use for these purposes, which mainly focusses on issues surrounding carnosine bioavailability.
Chronic oral beta-alanine supplementation can elevate muscle carnosine (beta-alanyl-L-histidine) content and improve high-intensity exercise performance. However, the regulation of muscle carnosine levels is poorly understood. The uptake of the rate-limiting precursor beta-alanine and the enzyme catalyzing the dipeptide synthesis are thought to be key steps. The aims of this study were to investigate the expression of possible carnosine-related enzymes and transporters in both human and mouse skeletal muscle in response to carnosine-altering stimuli. Human gastrocnemius lateralis and mouse tibialis anterior muscle samples were subjected to HPLC and qPCR analysis. Mice were subjected to chronic oral supplementation of beta-alanine and carnosine or to orchidectomy (7 and 30 days, with or without testosterone replacement), stimuli known to, respectively, increase and decrease muscle carnosine and anserine. The following carnosine-related enzymes and transporters were expressed in human and/or mouse muscles: carnosine synthase (CARNS), carnosinase-2 (CNDP2), the carnosine/histidine transporters PHT1 and PHT2, the beta-alanine transporters TauT and PAT1, beta-alanine transaminase (ABAT) and histidine decarboxylase (HDC). Six of these genes showed altered expression in the investigated interventions. Orchidectomy led to decreased muscle carnosine content, which was paralleled with decreased TauT expression, whereas CARNS expression was surprisingly increased. Beta-alanine supplementation increased both muscle carnosine content and TauT, CARNS and ABAT expression, suggesting that muscles increase beta-alanine utilization through both dipeptide synthesis (CARNS) and deamination (ABAT) and further oxidation, in conditions of excess availability. Collectively, these data show that muscle carnosine homeostasis is regulated by nutritional and hormonal stimuli in a complex interplay between related transporters and enzymes.
Due to the well-defined role of β-alanine as a substrate of carnosine (a major contributor to H+ buffering during high-intensity exercise), β-alanine is fast becoming a popular ergogenic aid to sports performance. There have been several recent qualitative review articles published on the topic, and here we present a preliminary quantitative review of the literature through a meta-analysis. A comprehensive search of the literature was employed to identify all studies suitable for inclusion in the analysis; strict exclusion criteria were also applied. Fifteen published manuscripts were included in the analysis, which reported the results of 57 measures within 23 exercise tests, using 18 supplementation regimes and a total of 360 participants [174, β-alanine supplementation group (BA) and 186, placebo supplementation group (Pla)]. BA improved (P=0.002) the outcome of exercise measures to a greater extent than Pla [median effect size (IQR): BA 0.374 (0.140-0.747), Pla 0.108 (-0.019 to 0.487)]. Some of that effect might be explained by the improvement (P=0.013) in exercise capacity with BA compared to Pla; no improvement was seen for exercise performance (P=0.204). In line with the purported mechanisms for an ergogenic effect of β-alanine supplementation, exercise lasting 60-240 s was improved (P=0.001) in BA compared to Pla, as was exercise of >240 s (P=0.046). In contrast, there was no benefit of β-alanine on exercise lasting <60 s (P=0.312). The median effect of β-alanine supplementation is a 2.85% (-0.37 to 10.49%) improvement in the outcome of an exercise measure, when a median total of 179 g of β-alanine is supplemented.
There is considerable interest in potential ergogenic and therapeutic effects of increasing skeletal muscle carnosine content, although its effects on excitation-contraction (EC) coupling in human muscle have not been defined. Consequently, we sought to characterize what effects carnosine, at levels attained by supplementation, has on human muscle fiber function, using a preparation with all key EC coupling proteins in their in situ positions. Fiber segments, obtained from vastus lateralis muscle of human subjects by needle biopsy, were mechanically skinned, and their Ca(2+) release and contractile apparatus properties were characterized. Ca(2+) sensitivity of the contractile apparatus was significantly increased by 8 and 16 mM carnosine (increase in pCa(50) of 0.073 ± 0.007 and 0.116 ± 0.006 pCa units, respectively, in six type I fibers, and 0.063 ± 0.018 and 0.103 ± 0.013 pCa units, respectively, in five type II fibers). Caffeine-induced force responses were potentiated by 8 mM carnosine in both type I and II fibers, with the potentiation in type II fibers being entirely explicable by the increase in Ca(2+) sensitivity of the contractile apparatus caused by carnosine. However, the potentiation of caffeine-induced responses caused by carnosine in type I fibers was beyond that expected from the associated increase in Ca(2+) sensitivity of the contractile apparatus and suggestive of increased Ca(2+)-induced Ca(2+) release. Thus increasing muscle carnosine content likely confers benefits to muscle performance in both fiber types by increasing the Ca(2+) sensitivity of the contractile apparatus and possibly also by aiding Ca(2+) release in type I fibers, helping to lessen or slow the decline in muscle performance during fatiguing stimulation.
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.
The aim of this study was to investigate the effects of beta-alanine supplementation on exercise capacity and the muscle carnosine content in elderly subjects. Eighteen healthy elderly subjects (60-80 years, 10 female and 4 male) were randomly assigned to receive either beta-alanine (BA, n=12) or placebo (PL, n=6) for 12 weeks. The BA group received 3.2 g of beta-alanine per day (2×800 mg sustained-release Carnosyn™ tablets, given 2 times per day). The PL group received 2× (2×800 mg) of a matched placebo. At baseline (PRE) and after 12 weeks (POST-12) of supplementation, assessments were made of the muscle carnosine content, anaerobic exercise capacity, muscle function, quality of life, physical activity and food intake. A significant increase in the muscle carnosine content of the gastrocnemius muscle was shown in the BA group (+85.4%) when compared with the PL group (+7.2%) (p=0.004; ES: 1.21). The time-to-exhaustion in the constant-load submaximal test (i.e., TLIM) was significantly improved (p=0.05; ES: 1.71) in the BA group (+36.5%) versus the PL group (+8.6%). Similarly, time-to-exhaustion in the incremental test was also significantly increased (p=0.04; ES 1.03) following beta-alanine supplementation (+12.2%) when compared with placebo (+0.1%). Significant positive correlations were also shown between the relative change in the muscle carnosine content and the relative change in the time-to-exhaustion in the TLIM test (r=0.62; p=0.01) and in the incremental test (r=0.48; p=0.02). In summary, the current data indicate for the first time, that beta-alanine supplementation is effective in increasing the muscle carnosine content in healthy elderly subjects, with subsequent improvement in their exercise capacity.
Carnosine is present in high concentrations in skeletal muscle where it contributes to acid buffering and functions also as a natural protector against oxidative and carbonyl stress. Animal studies have shown an anti-diabetic effect of carnosine supplementation. High carnosinase activity, the carnosine degrading enzyme in serum, is a risk factor for diabetic complications in humans. The aim of the present study was to compare the muscle carnosine concentration in diabetic subjects to the level in non-diabetics. Type 1 and 2 diabetic patients and matched healthy controls (total n=58) were included in the study. Muscle carnosine content was evaluated by proton magnetic resonance spectroscopy (3 Tesla) in soleus and gastrocnemius. Significantly lower carnosine content (-45%) in gastrocnemius muscle, but not in soleus, was shown in type 2 diabetic patients compared with controls. No differences were observed in type 1 diabetic patients. Type II diabetic patients display a reduced muscular carnosine content. A reduction in muscle carnosine concentration may be partially associated with defective mechanisms against oxidative, glycative and carbonyl stress in muscle.
Carnosine is an abundant dipeptide in human skeletal muscle with proton buffering capacity. There is controversy as to whether training can increase muscle carnosine and thereby provide a mechanism for increased buffering capacity. This study investigated the effects of 5 weeks sprint training combined with a vegetarian or mixed diet on muscle carnosine, carnosine synthase mRNA expression and muscle buffering capacity. Twenty omnivorous subjects participated in a 5 week sprint training intervention (2-3 times per week). They were randomized into a vegetarian and mixed diet group. Measurements (before and after the intervention period) included carnosine content in soleus, gastrocnemius lateralis and tibialis anterior by proton magnetic resonance spectroscopy ((1)H-MRS), true-cut biopsy of the gastrocnemius lateralis to determine in vitro non-bicarbonate muscle buffering capacity, carnosine content (HPLC method) and carnosine synthase (CARNS) mRNA expression and 6 × 6 s repeated sprint ability (RSA) test. There was a significant diet × training interaction in soleus carnosine content, which was non-significantly increased (+11%) with mixed diet and non-significantly decreased (-9%) with vegetarian diet. Carnosine content in other muscles and gastrocnemius buffer capacity were not influenced by training. CARNS mRNA expression was independent of training, but decreased significantly in the vegetarian group. The performance during the RSA test improved by training, without difference between groups. We found a positive correlation (r = 0.517; p = 0.002) between an invasive and non-invasive method for muscle carnosine quantification. In conclusion, this study shows that 5 weeks sprint training has no effect on the muscle carnosine content and carnosine synthase mRNA.
Carnosine is found in high concentrations in skeletal muscles, where it is involved in several physiological functions. The muscle carnosine content measured within a population can vary by a factor 4. The aim of this study was to further characterize suggested determinants of the muscle carnosine content (diet, gender and age) and to identify new determinants (plasma carnosinase activity and testosterone). We investigated a group of 149 healthy subjects, which consisted of 94 men (12 vegetarians) and 55 women. Muscle carnosine was quantified in M. soleus, gastrocnemius and tibialis anterior using magnetic resonance proton spectroscopy and blood samples were collected to determine CNDP1 genotype, plasma carnosinase activity and testosterone concentrations. Compared to women, men have 36, 28 and 82% higher carnosine concentrations in M. soleus, gastrocnemius and tibialis anterior muscle, respectively, whereas circulating testosterone concentrations were unrelated to muscle carnosine levels in healthy men. The carnosine content of the M. soleus is negatively related to the subjects' age. Vegetarians have a lower carnosine content of 26% in gastrocnemius compared to omnivores. In contrast, there is no difference in muscle carnosine content between omnivores with a high or low ingestion of β-alanine. Muscle carnosine levels are not related to the polymorphism of the CNDP1 gene or to the enzymatic activity of the plasma carnosinase. In conclusion, neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content, whereas vegetarianism, female gender and increasing age are the factors associated with reduced muscle carnosine stores.
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.
Carnosine (beta-alanyl-L-histidine) is present in high concentrations in human skeletal muscles. The oral ingestion of beta-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content both in trained and untrained humans. Little human data exist about the dynamics of the muscle carnosine content, its metabolic regulation, and its dependence on muscle fiber type. The present study aimed to investigate in three skeletal muscle types the supplementation-induced amplitude of carnosine synthesis and its subsequent elimination on cessation of supplementation (washout). Fifteen untrained males participated in a placebo-controlled double-blind study. They were supplemented for 5-6 wk with either 4.8 g/day beta-alanine or placebo. Muscle carnosine was quantified in soleus, tibialis anterior, and medial head of the gastrocnemius by proton magnetic resonance spectroscopy (MRS), before and after supplementation and 3 and 9 wk into washout. The beta-alanine supplementation significantly increased the carnosine content in soleus by 39%, in tibialis by 27%, and in gastrocnemius by 23% and declined post-supplementation at a rate of 2-4%/wk. Average muscle carnosine remained increased compared with baseline at 3 wk of washout (only one-third of the supplementation-induced increase had disappeared) and returned to baseline values within 9 wk at group level. Following subdivision into high responders (+55%) and low responders (+15%), washout period was 15 and 6 wk, respectively. In the placebo group, carnosine remained relatively constant with variation coefficients of 9-15% over a 3-mo period. It can be concluded that carnosine is a stable compound in human skeletal muscle, confirming the absence of carnosinase in myocytes. The present study shows that washout periods for crossover designs in supplementation studies for muscle metabolites may sometimes require months rather than weeks.
Ageing is associated with a significant reduction in skeletal muscle carnosine which has been linked with a reduction in the buffering capacity of muscle and in theory, may increase the rate of fatigue during exercise. Supplementing beta-alanine has been shown to significantly increase skeletal muscle carnosine. The purpose of this study, therefore, was to examine the effects of ninety days of beta-alanine supplementation on the physical working capacity at the fatigue threshold (PWCFT) in elderly men and women.
Using a double-blind placebo controlled design, twenty-six men (n = 9) and women (n = 17) (age +/- SD = 72.8 +/- 11.1 yrs) were randomly assigned to either beta-alanine (BA: 800 mg x 3 per day; n = 12; CarnoSyntrade mark) or Placebo (PL; n = 14) group. Before (pre) and after (post) the supplementation period, participants performed a discontinuous cycle ergometry test to determine the PWCFT.
Significant increases in PWCFT (28.6%) from pre- to post-supplementation were found for the BA treatment group (p < 0.05), but no change was observed with PL treatment. These findings suggest that ninety days of BA supplementation may increase physical working capacity by delaying the onset of neuromuscular fatigue in elderly men and women.
We suggest that BA supplementation, by improving intracellular pH control, improves muscle endurance in the elderly. This, we believe, could have importance in the prevention of falls, and the maintenance of health and independent living in elderly men and women.
The effect of dietary creatine and supplementation on skeletal muscle creatine accumulation and subsequent degradation and on urinary creatinine excretion was investigated in 31 male subjects who ingested creatine in different quantities over varying time periods. Muscle total creatine concentration increased by approximately 20% after 6 days of creatine supplementation at a rate of 20 g/day. This elevated concentration was maintained when supplementation was continued at a rate of 2 g/day for a further 30 days. In the absence of 2 g/day supplementation, total creatine concentration gradually declined, such that 30 days after the cessation of supplementation the concentration was no different from the presupplementation value. During this period, urinary creatinine excretion was correspondingly increased. A similar, but more gradual, 20% increase in muscle total creatine concentration was observed over a period of 28 days when supplementation was undertaken at a rate of 3 g/day. In conclusion, a rapid way to "creatine load" human skeletal muscle is to ingest 20 g of creatine for 6 days. This elevated tissue concentration can then be maintained by ingestion of 2 g/day thereafter. The ingestion of 3 g creatine/day is in the long term likely to be as effective at raising tissue levels as this higher dose.
We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly (P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body (P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained approximately 50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.
The measurement of body composition is of value in the nutritional assessment of patients with chronic obstructive pulmonary disease (COPD). The purpose of the present study was to compare two bedside methods for the measurement of body composition using dual energy X-ray absorptiometry (DEXA) as a reference method. Fat-free mass (FFM) was measured using DEXA, bioelectric impedance analysis (BIA) and skinfold anthropometry (SFA) in a cohort of 85 COPD patients accepted for pulmonary rehabilitation. Patients whose body mass index was >30 were excluded. Relative to DEXA, BIA underestimated FFM, whereas it was overestimated by SFA. There was a systematic increase in bias with mean FFM for both DEXA versus BIA and DEXA versus SFA, but this was almost eliminated when results were expressed as FFM index. Significant sex differences in the bias of BIA and SFA measurements of FFM were found. Forty-two (49.4%) patients were identified as nutritionally depleted using DEXA. Compared to DEXA, the sensitivity for detecting nutritional depletion was 86 and 74% for BIA and SFA, respectively, and the specificity 88 and 98%, respectively. There are significant intermethod differences in the measurement of body composition in chronic obstructive pulmonary disease patients. The choice of measurement method will have implications for nutritional assessment in chronic obstructive pulmonary disease.
Pulmonary embolism (PE) is more often diagnosed post mortem by pathologists than in vivo by clinicians. The identification of practical diagnostic algorithms could reduce the rate of diagnoses first made at autopsy. The literature was reviewed for evidence-based approaches to PE diagnosis. Since the PE mortality rate greatly exceeds that of deep vein thrombosis (DVT), more emphasis was given to reports specifically dealing with PE diagnosis by objective pulmonary vascular imaging techniques than to those aimed at DVT detection. Several studies have shown that standardized clinical estimates can be effectively used to give a pretest probability to calculate, after appropriate objective testing, the post-test probability of PE. A prospective trial has shown that perfusion scanning, rather than ventilation/perfusion scanning, should be the imaging technique of first choice for the management of patients suspected of having PE. The clinical usefulness of spiral computed tomography has not as yet been firmly established. However, ongoing technological developments would probably render the technique accurate enough to replace conventional angiography. The authors propose a noninvasive diagnostic algorithm with high predictive accuracy (positive predictive value 96%; negative predictive value 98%) starting with a standardized assessment of clinical likelihood, followed by a perfusion scan and, eventually, spiral computed tomography in only a minority of patients (< 20%) with discordant clinical and scintigraphic findings.
Beta-alanine in blood-plasma when administered as A) histidine dipeptides (equivalent to 40 mg . kg(-1) bwt of beta-alanine) in chicken broth, or B) 10, C) 20 and D) 40 mg . kg(-1) bwt beta-alanine (CarnoSyn, NAI, USA), peaked at 428 +/- SE 66, 47 +/- 13, 374 +/- 68 and 833 +/- 43 microM. Concentrations regained baseline at 2 h. Carnosine was not detected in plasma with A) although traces of this and anserine were found in urine. Loss of beta-alanine in urine with B) to D) was <5%. Plasma taurine was increased by beta-alanine ingestion but this did not result in any increased loss via urine. Pharmacodynamics were further investigated with 3 x B) per day given for 15 d. Dietary supplementation with I) 3.2 and II) 6.4 g . d(-1) beta-alanine (as multiple doses of 400 or 800 mg) or III) L-carnosine (isomolar to II) for 4 w resulted in significant increases in muscle carnosine estimated at 42.1, 64.2 and 65.8%.
This study examined the effects of 28 days of beta-alanine supplementation on the physical working capacity at fatigue threshold (PWCFT), ventilatory threshold (VT), maximal oxygen consumption (VO2-MAX), and time-to-exhaustion (TTE) in women. Twenty-two women (age+/-SD 27.4+/-6.1 yrs) participated and were randomly assigned to either the beta-alanine (CarnoSyn) or Placebo (PL) group. Before (pre) and after (post) the supplementation period, participants performed a continuous, incremental cycle ergometry test to exhaustion to determine the PWCFT, VT, VO2-MAX, and TTE. There was a 13.9, 12.6 and 2.5% increase (p<0.05) in VT, PWCFT, and TTE, respectively, for the beta-alanine group, with no changes in the PL (p>0.05). There were no changes for VO2-MAX (p>0.05) in either group. Results of this study indicate that beta-alanine supplementation delays the onset of neuromuscular fatigue (PWCFT) and the ventilatory threshold (VT) at submaximal workloads, and increase in TTE during maximal cycle ergometry performance. However, beta-alanine supplementation did not affect maximal aerobic power (VO2-MAX). In conclusion, beta-alanine supplementation appears to improve submaximal cycle ergometry performance and TTE in young women, perhaps as a result of an increased buffering capacity due to elevated muscle carnosine concentrations.
Carnosine (beta-alanyl-l-histidine) is present in high concentrations in human skeletal muscle. The ingestion of beta-alanine, the rate-limiting precursor of carnosine, has been shown to elevate the muscle carnosine content. We aimed to investigate, using proton magnetic resonance spectroscopy (proton MRS), whether oral supplementation with beta-alanine during 4 wk would elevate the calf muscle carnosine content and affect exercise performance in 400-m sprint-trained competitive athletes. Fifteen male athletes participated in a placebo-controlled, double-blind study and were supplemented orally for 4 wk with either 4.8 g/day beta-alanine or placebo. Muscle carnosine concentration was quantified in soleus and gastrocnemius by proton MRS. Performance was evaluated by isokinetic testing during five bouts of 30 maximal voluntary knee extensions, by endurance during isometric contraction at 45% maximal voluntary contraction, and by the indoor 400-m running time. beta-Alanine supplementation significantly increased the carnosine content in both the soleus (+47%) and gastrocnemius (+37%). In placebo, carnosine remained stable in soleus, while a small and significant increase of +16% occurred in gastrocnemius. Dynamic knee extension torque during the fourth and fifth bout was significantly improved with beta-alanine but not with placebo. Isometric endurance and 400-m race time were not affected by treatment. In conclusion, 1) proton MRS can be used to noninvasively quantify human muscle carnosine content; 2) muscle carnosine is increased by oral beta-alanine supplementation in sprint-trained athletes; 3) carnosine loading slightly but significantly attenuated fatigue in repeated bouts of exhaustive dynamic contractions; and 4) the increase in muscle carnosine did not improve isometric endurance or 400-m race time.
Introduction:
Beta-alanine (BA) is a popular ergogenic supplement because it can induce muscle carnosine loading. We hypothesize that, by analogy with creatine supplementation, 1) an inverse relationship between urinary excretion and muscle loading is present, and 2) the latter is stimulated by carbohydrate- and protein-induced insulin action.
Methods:
In study A, the effect of a 5-wk slow-release BA (SRBA) supplementation (4.8 g · d(-1)) on whole body BA retention was determined in seven men. We further determined whether the coingestion of carbohydrates and proteins with SRBA would improve retention. In study B (34 subjects), we explored the effect of meal timing on muscle carnosine loading (3.2 g · d(-1) during 6-7 wk). One group received pure BA (PBA) in between the meals; the other received PBA at the start of the meals, to explore the effect of meal-induced insulin release. Further, we compared with a third group receiving SRBA at the start of the meals.
Results and conclusion:
Orally ingested SRBA has a very high whole body retention (97%-98%) that is not declining throughout the 5-wk supplementation period, nor is it influenced by the coingestion of macronutrients. Thus, a very small portion (1%-2%) is lost through urinary excretion, and equally only a small portion is incorporated into muscle carnosine (≈ 3%), indicating that most ingested BA is metabolized (possibly through oxidation). Second, in soleus muscles, the efficiency of carnosine loading is significantly higher when PBA is coingested with a meal (+64%) compared with in between the meals (+41%), suggesting that insulin stimulates muscle carnosine loading. Finally, the chronic supplementation of SRBA versus PBA seems equally effective.
Purpose:
Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice.
Methods:
Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography.
Results:
Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces).
Conclusion:
Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.
In this review, the development of understanding of the biological functions of carnosine is briefly discussed. Carnosine was first described as a component of meat in 1900 by V. S. Gulevitch. Changes in the concepts of the role of carnosine in metabolism are followed starting from the early suggestion that it is the end product of protein degradation to the modern ideas based on demonstrating its specific involvement in intracellular signaling regulation in excitable tissue cells. The discovery of the ability of carnosine to regulate expression of early response genes broadens the concept about carnosine as a cellular peptide regulator. The first attempts for application of carnosine in sport and medical practice are described.
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.
1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated.
2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak.
3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%.
4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content.
5. No side effects of creatine supplementation were noted.
6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
The in vitro deproteinized vastus lateralis muscle buffer capacity, carnosine, and histidine levels were examined in 20 men from 4 distinct populations (5 sprinters, 800-m runners; 5 rowers; 5 marathoners; 5 untrained). Needle biopsies were obtained at rest from the vastus lateralis muscle. The buffer capacity was determined in deproteinized homogenates by repeatedly titrating supernatant extracts over the pH range of 7.0-6.0 with 0.01 N HCl. Carnosine and histidine levels were determined on an amino acid AutoAnalyzer. Fast-twitch fiber percentage was determined by staining intensity of myosin adenosinetriphosphatase. High-intensity running performance was assessed on an inclined treadmill run to fatigue (20% incline; 3.5 m X s-1). Significantly (P less than 0.01) elevated buffer capacities, carnosine levels, and high-intensity running performances were demonstrated by the sprinters and rowers, but no significant differences existed between these variables for the marathoners vs. untrained subjects. Low but significant (P less than 0.05) interrelationships were demonstrated between buffer capacity, carnosine levels, and fast-twitch fiber composition. These findings indicate that the sprinters and rowers possess elevated buffering capabilities and carnosine levels compared with marathon runners and untrained subjects.
The aminoacyl-imidazole dipeptides carnosine (beta-alanyl-L-histidine) and anserine (beta-alanyl-1-methyl-histidine) are present in relatively high concentrations in excitable tissues, such as muscle and nervous tissue. In the present study we describe the existence of a marked sexual dimorphism of carnosine and anserine in skeletal muscles of CD1 mice. In adult animals the concentrations of anserine were higher than those of carnosine in all skeletal muscles studied, and the content of aminoacyl-imidazole dipeptides was remarkably higher in males than in females. Postnatal ontogenic studies and hormonal manipulations indicated that carnosine synthesis was up-regulated by testosterone whereas anserine synthesis increased with age. Regional variations in the concentrations of the dipeptides were observed in both sexes, skeletal muscles from hind legs having higher amounts of carnosine and anserine than those present in fore legs or in the pectoral region. The concentration of L-lysine in skeletal muscles also showed regional variations and a sexual dimorphic pattern with females having higher levels than males in all muscles studied. The results suggest that these differences may be related with the anabolic action of androgens on skeletal muscle.
This study was undertaken as part of a larger investigation into carnosine metabolism and function in the Thoroughbred horse. More specifically, we wished to evaluate plasma carnosine concentration as a potential indicator of muscle carnosine status. In contrast to man, carnosine is present in equine plasma where its presence is consistent with the absence of plasma carnosinase. A significant effect of age on plasma carnosine concentration in resting Thoroughbred horses was observed. Values in horses age 3 years and older were 113-14.1 micromol/l, whereas concentrations in foals and yearlings were 3.9-8.7 micromol/l (P<0.001). Lower values in young horses may reflect lower skeletal muscle carnosine concentrations. There was no significant within-day variation in plasma carnosine concentration in fed and fasted horses (P>0.05). Intense exercise resulted in a small significant increase (P<0.05) in plasma carnosine concentration (pre-exercise, 10.3 +/- 1.0 micromol/l; postexercise, 12.4 +/- 4.4 micromol/l). Greater increases were observed (57.6-702.3 micromol/l) following onset of exercise-induced rhadomyolysis (ERS). An apparent relationship was observed between elevated plasma carnosine and increased plasma creatine kinase (CK) and aspartate transaminase (AST) activities. Plasma carnosine concentrations did not reflect the severity of the condition as determined by clinical examination. In conclusion, elevated plasma carnosine levels are observed following exercise induced muscle damage, with the greatest elevations occurring during episodes of external rhabdomylosis syndrome. Plasma carnosine measurements could provide an alternative clinical indicator of muscle damage; and in conjunction with plasma taurine measurements may be indicative of selective type 1 or type 2 muscle fibre damage. However, given the complexity of the analytical technique, its applications would probably be confined to specialist referral or research centres.
Ingestion of sodium bicarbonate is known to enhance sprint performance, probably via increased buffering of intracellular acidity. The goal was to compare the effect of ingestion of sodium bicarbonate with that of other potential buffering agents (sodium citrate and sodium lactate) and of a placebo (sodium chloride) on sprinting.
In a double-blind randomized crossover trial, 15 competitive male endurance runners performed a run to exhaustion 90 min after ingestion of each of the agents in the same osmolar dose relative to body mass (3.6 mosmol x kg) on separate days. The agents were packed in gelatin capsules and ingested with 750 mL of water over 90 min. During each treatment we assayed serial finger-prick blood samples for lactate and bicarbonate. A familiarization trial was used to set a treadmill speed for each runner's set of runs. We converted changes in run time between treatments into changes in a time trial of similar duration using the critical-power model, and we estimated likelihood of practical benefit using 0.5% as the smallest worthwhile change in time-trial performance.
The mean run times to exhaustion for each treatment were: bicarbonate 82.3 s, lactate 80.2 s, citrate 78.2 s, and chloride 77.4 s. Relative to bicarbonate, the effects on equivalent time-trial time were lactate 1.0%, citrate 2.2%, and chloride 2.7% (90% likely limits +/- 2.1%). Ingested lactate and citrate both appeared to be converted to bicarbonate before the run. There were no substantial differences in gut discomfort between the buffer treatments.
Bicarbonate is possibly more beneficial to sprint performance than lactate and probably more beneficial than citrate or chloride. We recommend ingestion of sodium bicarbonate to enhance sprint performance.
Carnosine (beta-alanyl-L-histidine) and related peptides such as homocarnosine (gamma-amino-butyryl-histidine), balenine beta-alanyl-L-3-methylhistidine) and anserine beta-alanyl-L-1-methylhistidine) are histidine-containing dipeptides (HD) particularly abundant in excitable tissues such as nervous system and skeletal muscle. Although their biochemical role is still unknown, several evidences indicate that these endogenous compounds act as quenchers of reactive and cytotoxic carbonyl species. In this presentation we will review the structural evidences and ex vivo data supporting this hypothesis. We first elucidated the reaction mechanism of carnosine as quencher of alpha, beta-unsaturated aldehydes such as 4-hydroxy-trans-2,3-nonenal (HNE) and acrolein (ACR) and then demonstrated the efficacy of carnosine and related peptides as detoxifying agents of HNE in spontaneously oxidized rat skeletal muscle, by detecting the corresponding HNE-Michael adducts in the crude biological matrix by liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Finally, we set-up and validated a sensitive, selective and specific LC-ESI-MS/MS method for the determination of HD and of the corresponding HNE-Michael adducts to monitor their profile in physiological (aging) and pathological conditions (diabetes, atherosclerosis) characterized by a carbonyl-mediated degenerative overload. The results obtained, beside to give a contribution to the understanding of the biochemical role of histidine-dipeptides, provide a strong rational to the design of novel derivatives, active as exogenous agents able to detoxify carbonyl compounds.
Beta-alanine supplementation and high intensity exercise performance. Thesis for the degree of Doctor of Philosophy. (Dissertation)
- C A Hill
Hill CA. Beta-alanine supplementation and high intensity exercise performance. Thesis for the degree
of Doctor of Philosophy. (Dissertation). University of Chichester, 2007a.