REVIEW

URRENT
C
OPINION

Beta-alanine supplementation, muscle carnosine

and exercise performance
Laura Blancquaert, Inge Everaert, and Wim Derave

Purpose of review
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.
Recent findings
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.
Summary
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.
Keywords
dietary supplement, high-intensity exercise performance, L-carnosine, pH buffering

INTRODUCTION
Beta-alanine has become a popular dietary supplement among competitive athletes participating in
a range of sports. The rationale for this is based on
well substantiated evidence that beta-alanine
supplementation is able to increase intramuscular
L-carnosine (beta-alanyl-L-histidine) concentrations. This carnosine loading may thereby augment
fatigue threshold and improve high-intensity
exercise performance. Carnosine is a cytoplasmic
dipeptide combining the proteinogenic amino acid
L-histidine with the nonproteinogenic beta-amino
acid beta-alanine and occurs in high concentrations
in human skeletal muscle (58 mmol/l wet weight)
that makes carnosine one of the most abundant
intramuscular molecular compounds. Almost a
decade ago, Harris et al. [1] were the first to demonstrate that chronic beta-alanine supplementation is
able to increase muscle carnosine concentration,
suggesting that beta-alanine is the rate-limiting
factor for the dipeptide synthesis. Shortly after this

finding, it has been reported that enhanced muscle

carnosine levels are able to increase performance in
various high-intensity exercise models [2]. Together,
these findings formed the keystone for a new interesting research field, with a growing interest for
beta-alanine as a nutritional supplement, mainly
for athletic populations. From then on, numerous
studies assessed the effect of oral beta-alanine supplementation on both muscle carnosine levels and
different types of exercise, leading to divergent results
and somewhat inconsistent conclusions. This review
will update, summarize and discuss the most recent
findings associated with beta-alanine supplementation and exercise performance. First, the metabolic
Department of Movement and Sports Sciences, Ghent University, Ghent,
Belgium
Correspondence to Wim Derave, Watersportlaan 2, B-9000 Ghent,
Belgium. E-mail: wim.derave@ugent.be
Curr Opin Clin Nutr Metab Care 2015, 18:6370
DOI:10.1097/MCO.0000000000000127

1363-1950 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

www.co-clinicalnutrition.com

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Protein, amino acid metabolism and therapy

KEY POINTS
 Chronic beta-alanine supplementation increases muscle
carnosine concentration, subsequently leading to an
improved performance in high-intensity exercises.
 Exercise training and meal coingestion can improve
efficiency of oral beta-alanine supplementation toward
muscle carnosine loading.
 The ergogenic effect of beta-alanine supplementation is
equally effective in trained and untrained individuals.
 The carnosine shuttle hypothesis implies that carnosine
can work as a Ca2/H exchanger by improving
calcium delivery to and proton removal from the
sarcomere site.

fate of ingested beta-alanine will be discussed

together with strategies to improve the amount of
muscle carnosine loading provoked by beta-alanine
intake. Second, the link between beta-alanine and
exercise performance will be elucidated, followed by
a closer look at the ergogenic mechanism of the
popular supplement. Finally, the potential benefits
of beta-alanine and carnosine toward health and
clinical pathologies will be shortly elucidated.

HOW TO OPTIMIZE CARNOSINE LOADING

BY BETA-ALANINE SUPPLEMENTATION?
Even though beta-alanine is increasingly popular
as a supplement, less is known about the factors
that control the uptake, storage and metabolism in
skeletal muscle. It was already shown that oral ingestion of 46 g beta-alanine/day during 410 weeks
increases carnosine concentrations by 4080%.
Moreover, Stellingwerff et al. [3] identified a linear

doseresponse relationship between beta-alanine

intake and carnosine loading, suggesting that the
total amount of consumed beta-alanine during a
certain period, which determines the intramyocellular availability of beta-alanine, is an important determinant of the degree of muscle carnosine loading.
Taking into account the high baseline muscle
carnosine levels, an increase of 4080% is a considerable amount of loading (e.g., 2435 mmol/kg
dry weight in vastus lateralis muscle after 4 weeks of
supplementation [1]). However, the current supplementation protocol used by a lot of athletes requires
us to take a large dose of beta-alanine each day
during several weeks, divided in multiple little
dosages throughout the day, as doses larger than

800 mg (10 mg/kg body weight) can provoke
moderate-to-severe paresthesia symptoms [1]. To
circumvent these symptoms, a slow-release betaalanine tablet form has become commercially available and was shown to result in slower absorption
kinetics, and therefore minimized sensory sideeffects [4]. Beta-alanine supplementation efficiency
can be calculated by dividing the molar increase in
muscle carnosine by the total ingested molar amount
of beta-alanine. Surprisingly, this efficiency is very
low (2.8% when assuming that 40% of body mass is
muscle mass [5 ]), indicating that only a minor part of
ingested beta-alanine is actually incorporated into
muscle carnosine (Table 1). Furthermore, Stegen et al.
[5 ] showed that urinary beta-alanine excretion is
low (12%) and not increasing during a chronic
supplementation period. Together, these findings
indicate that approximately 95% of ingested betaalanine has an unknown metabolic fate, which is
possibly attributable to oxidation of beta-alanine.
Given the fact that beta-alanine is gaining popularity
in athletic populations and in order to establish
appropriate supplementation protocols, it is priority
&

&

Table 1. Summary of the efficiency of beta-alanine supplementation for different supplementation studies, showing that meal
co-ingestion, exercise training and high daily intakes during a limited period lead to highest efficiency of beta-alanine-induced
carnosine loading
Study

Dose

Meal

Training

Stegen et al. [5 ]

3.2 g/day, 46 day

Pure

2.39

Stegen et al. [5 ]

3.2 g/day, 46 day

Slow-release

2.76

Stegen et al. [5 ]

3.2 g/day, 46 day

Pure

2.99

Bex et al. [6 ]

6.4 g/day, 23 day

Slow-release

3.49

Chung et al. [20 ]

6.4 g/day, 42 day

Slow-release

5.65

Bex et al. [6 ]

6.4 g/day, 23 day

Slow-release

5.82

&

&

&

&

&

&

Beta-alanine form

Efficiency (%)

&

All studies measured carnosine in both soleus and gastrocnemius muscles, and efficiency was calculated as the average of both muscle types. Stegen et al. [5 ]
&
used physically active students, Bex et al. [6 ] used nonathletes and kayakers (untrained muscles), cyclists and swimmers (trained muscles) and Chung et al.
&
[20 ] used well trained cyclists/triathletes. Beta-alanine efficiency is calculated by dividing the total molar increase in muscle carnosine (40% of body
weight  D[muscle carnosine]) by the total ingested molar amount of beta-alanine.

64

www.co-clinicalnutrition.com

Volume 18  Number 1  January 2015

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Beta-alanine, muscle carnosine and exercise Blancquaert et al.

to gain better insight into the metabolism of this

uncommon amino acid.
In this context, a few studies recently revealed
some determinants of carnosine loading (Table 1).
First, Stegen et al. [5 ] showed that meal coingestion
is able to enhance the efficiency of beta-alanine
supplementation, suggesting that insulin could play
a stimulating role in one or more crucial steps of the
muscle carnosine synthesis process. In addition,
training and/or training status appears to be another
potent determinant of muscle carnosine loading. A
recent study [6 ] demonstrated that, both within
athletes and between athletes participating in different sports, trained muscles had approximately twofold higher carnosine loading compared with
untrained muscles for the same oral beta-alanine
dose and duration. When comparing the efficiency
of beta-alanine in the leg muscles (soleus and gastrocnemius) between the different athlete groups, this
ranged from 3.49% (nonathletes and kayakers, who
do not train their legs) up to 5.82% (swimmers and
cyclists, who do train their legs). This was a surprising discovery because it was previously proposed
that training had no effect on loading efficiency [7],
even though there was a lack of clear and extensive
research on this topic. As the study of Bex et al. [6 ]
was observational more than interventional, the
underlying mechanisms are not yet clear. In
addition to improving the beta-alanine supplementation protocol, effectively maintaining the carnosine concentrations at elevated levels is another
important challenge, especially when aiming to
pursue benefit for a prolonged period of time
(e.g., in the case of prolonged competition periods
or in the potential use of chronic diseases). It is
known that upon cessation of supplementation,
muscle carnosine gradually returns to presupplementation levels in a slow washout process that
takes 620 weeks [8]. Only recently a few studies
focused on establishing a suitable maintenance
dose for beta-alanine, in order to ensure constantly
elevated muscle carnosine stores after a loading
phase. A first attempt was published by Stellingwerff
et al. [3], demonstrating that 1.6 g beta-alanine/day
during 4 weeks is still able to provoke a further
30% increase in muscle carnosine (following a
4-week loading protocol of 3.2 g beta-alanine/day).
Hereafter, Stegen et al. [9 ] investigated three intermediate doses (0.4, 0.8 and 1.2 g/day), concluding
that an average dose of 1.2 g/day is considered
optimal to keep muscle carnosine content elevated
at 3050% above baseline for a prolonged period
of time.
Although already a few strategies were discovered to increase the efficiency of the beta-alanine
supplementation protocol, the acquired knowledge
&

&

&

&

is still incomplete and more research is needed to

result in clearer guidelines for athletes. Furthermore, there are large interindividual differences
in carnosine loading effectiveness that are hardly
understood at present. Thus, not only the betaalanine metabolism needs to be further unraveled
but also the carnosine metabolism is still far from
fully understood. As a matter of fact, research on
carnosine metabolism is only recently gaining the
necessary fundamental knowledge with the investigation of the expression profiles of carnosinerelated enzymes and transporters in human skeletal
muscle [10]. The molecular identification of carnosine synthase [11], carnosine N-methyltransferase
in chicken [12], b-alanyl-lysine dipeptidase [13 ]
and the disclosure of the role of aldose reductase
in the carnosineacrolein conjugates metabolism
[14] are just a few examples of recent biochemical
discoveries that are essential to make progress in
this field.
&

WHAT TYPE OF EXERCISE PROTOCOLS

BENEFEIT MOST FROM BETA-ALANINE
SUPPLEMENTATION?
In recent years, many studies further investigated
beta-alanine as an ergogenic aid, extending on the
findings by Hill et al. [2]. This study [2] demonstrated that the capacity to cycle at 110% of
maximal power was improved by 13 and 16%
following, respectively, 4 and 10 weeks of chronic
beta-alanine supplementation in healthy untrained
volunteers. Yet, not all studies have been able to
demonstrate beneficial effects of carnosine loading
on exercise performance. Multiple factors may
underlie these equivocal findings, such as the individual variability in carnosine loading and the
different types of exercise or performance protocols that were employed. Therefore, a meta-analysis
recently summarized the available literature on
beta-alanine and exercise performance [15], concluding that beta-alanine is beneficial in exercise
types lasting 14 min (P 0.001), whereas the effect
is absent in shorter (P 0.312) and less pronounced
in longer (P 0.046) duration exercises. However,
for the latter category, the amount of studies was
still limited at the time of meta-analysis and they
mostly reported results of exercise capacity tests
with a maximal duration of 25 min. Only two
studies [16,17] investigated the effect on exercise
performance tests: one demonstrating a positive
effect on 2000 m rowing performance with a
maximal duration of 7 min [16], and a second showing no effect on 10 min time trial performance at the
final stage of a simulated endurance cycling event
[17]. Two more studies [18,19] could confirm the

1363-1950 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

www.co-clinicalnutrition.com

65

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Protein, amino acid metabolism and therapy

likely positive effect of beta-alanine on 2000 m

rowing performance.
As there was a lack of evidence concerning the
effect of beta-alanine supplementation on endurance performance, Chung et al. [20 ] recently investigated the effect on a 1-h time-trial performance in
well trained cyclists. Although beta-alanine induced
a remarkable doubling of muscle carnosine content,
this did not affect 1-h time-trial performance under
laboratory conditions, which is in agreement with
the less pronounced effect of beta-alanine in longer
duration exercises.
Furthermore, of the 15 experimental studies
included in the meta-analysis [15], none of them
deals with the performance in aquatic sports.
Recently, the use of beta-alanine supplementation
gained growing interest in swimming performance.
Chung et al. [21] found no clear effect of 10 weeks
of beta-alanine supplementation on performance
in elite and sub-elite swimmers, but it should be
noted that both sprint, middle-distance and
distance swimmers were included. In contrast, De
Salles Painelli et al. [22] reported significant
improvements in 200 m swimming performance
and a trend toward an improvement in a 100 m
swim after 5 weeks of beta-alanine supplementation.
In addition, another recent study [23] investigating
the effect on maximal sprint swimming did not find
beneficial effects on 100 m swim performance. In
general, these results are in accordance with the
conclusion formulated by Hobson et al. [15] as
100 m swim performance times were around 1 min
of duration in the studies of De Salles Painelli et al.
[22] and Mero et al. [23]. For 200 m, performance
times are around 2 min, which is within the most
effective time window. Additionally, several studies
[2426] reported that beta-alanine is not able to
improve repeated sprint performance and intermittent activities, suggesting that beta-alanine is
unlikely to be beneficial in team sports, such as
football, hockey and rugby.
&

IS BETA-ALANINE EFFECTIVE TOWARD

PERFORMANCE IN ELITE ATHELETES?
As carnosine loading by beta-alanine supplementation has the potential to increase exercise performance, elite athletes are most interested in this
nutritional supplement. However, the majority of
beta-alanine supplementation studies that have
shown a positive effect used recreationally active
participants and several recent investigations have
shown no improvements or only marginal effects of
beta-alanine in trained athletes [16,18,19,20 ,27].
Anyhow, it should be noted that most of these
studies used an exercise protocol that does not lie
&

66

www.co-clinicalnutrition.com

within the 110 min time window. All together,

these studies could impeach whether beta-alanine
can be equally beneficial for highly trained individuals.
This potentially confounding effect of training
status on ergogenic potential could be in accordance
with another popular nutritional ergogenic supplement, namely nitrate. Even though this supplement
was shown to reduce the oxygen cost of exercise
and improve exercise performance in recreationally
active individuals and sub-elite athletes, several
recent studies [28,29] reported no ergogenic effect
of acute or short-term nitrate supplementation on
exercise performance in highly trained endurance
athletes.
In the case of beta-alanine, Bex et al. [6 ] revealed
that athletes are more responsive to beta-alanineinduced carnosine loading compared to nonathletes.
Moreover, a recent study [30 ] directly compared
whether athletes respond differently to beta-alanine
supplementation in comparison to nontrained
recreationally active individuals. It was concluded
that beta-alanine supplementation improves performance of four 30-s lower body Wingate bouts to a
similar extent in both trained and untrained participants, highlighting the efficacy of beta-alanine as an
ergogenic aid for high-intensity exercise regardless of
the training status of the individuals. Thus, highly
trained athletes can benefit from beta-alanine supplementation, which supports the use of this popular
dietary supplement in athletic populations.
&

&

DOES COMBINED BETA-ALANINE AND

NAHCO3 SUPPLEMENTATION HAVE
ADDITIVE EFFECTS?
In order to seek strategies to maximally improve
performance, combination of beta-alanine with
another ergogenic supplement, namely sodium
bicarbonate, recently became a new popular research
topic. As beta-alanine and bicarbonate have intracellular and extracellular buffering capacity, respectively, there are grounds to believe that cosupplementation of these substances may have an
additive or even synergistic effect on exercise
capacity and performance.
Sale et al. [31] were the first to investigate this
combined supplementation, reporting a further
nonsignificant 4.1% improvement in time to exhaustion (TTE) in a cycling capacity test (CCT110%) with
co-supplementation compared to beta-alanine
supplementation alone. Although not significant,
magnitude-based inferences suggest a
70% probability of a meaningful positive difference. Same
conclusions were drawn from subsequent studies,
reporting a minimal additive effect in a 4-min cycling
Volume 18  Number 1  January 2015

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Beta-alanine, muscle carnosine and exercise Blancquaert et al.

time trial [32], a further nonsignificant improvement

in 100 and 200 m swim performance [22] and a nonsignificant but increased TTE in a CCT110% [33],
all comparing combined supplementation with
beta-alanine alone. Taking into account the slow
washout process of beta-alanine, the 6-week
crossover design used in the latter study [33] may
confound these results. Similarly to these studies,
Hobson et al. [19] reported a small (1.1  5.6 s) but
possibly beneficial additional effect on 2000-m
rowing performance. Surprisingly, one study [34]
did find a significantly greater performance improvement after the co-ingestion of beta-alanine and
NaHCO3 (14%) compared with beta-alanine
(7%) or NaHCO3 alone (8%), employing an
intermittent exercise protocol involving four 30-s
upper body Wingate tests. To date, this is the first
study demonstrating a significant additive ergogenic
benefit from co-supplementation of beta-alanine
and NaHCO3, which may be attributed to two main
methodological differences, being the chronic
NaHCO3 loading protocol (0.5 g/kg body weight for
7 days vs. 0.3 g/kg body weight as an acute dose in
other studies) and the type of exercise that was
employed (intermittent protocol instead of a single
bout TTE or continuous fixed duration/distance exercise protocols). In contrast, Ducker et al. [25] reported
slower sprint times with co-ingestion compared to
NaHCO3 ingestion alone, suggesting reverse effects of
co-supplementation on repeated sprint exercise.
However, with only six participants per condition,
these results cannot directly be generalized. Moreover, two recent studies reported no ergogenic effect
of co-supplementation on repeated sprints (5  6 s)
performed in hypoxia [35] and maximal sprint swimming [23], but participants were not blinded in the
latter study. In general, the majority of the studies
did find a small but nonsignificant additive effect of
co-supplementation of beta-alanine and NaHCO3,
which may be meaningful in performance terms to
elite athletes in a real-world setting.

WHAT MECHANISMS UNDERLIE THE

ERGOGENIC EFFECT OF BETA-ALANINE
AND CARNOSINE?
Although intracellular pH buffering was originally
proposed to be the raison detre of muscle carnosine,
several other functions have subsequently been
ascribed to this dipeptide [36 ]. Carnosines effects
on excitationcontraction coupling by improved
calcium handling and the defense against reactive
oxygen species are properties with relevance to
muscle function [36 ]. Some in-vivo studies in
humans could [37] and others could not [38]
demonstrate improved acid-base balance during
&

&

high-intensity exercise, following beta-alanine

supplementation. The mechanisms underlying
ergogenic effects of beta-alanine supplementation
may therefore be more complex than previously
thought. Below we will sketch our current opinion.
Release of calcium from the sarcoplasmic reticulum and binding of calcium to troponin are key
steps to induce contraction of muscle cells. Carnosine has been suggested to be involved in one or
several steps of this process. Dutka et al. [39] demonstrated that raised cytoplasmic carnosine concentrations increase Ca2 sensitivity of the contractile
apparatus in both type I and type II human fibers in
a concentration-dependent manner. This increase
in Ca2 sensitivity equates a substantial increase in
the submaximal force output for a given cytoplasmic-free Ca2 concentration. Additionally, the
force potentiation in response to elevated muscle
carnosine levels was also confirmed in whole incubated skeletal muscles of mice [40]. The authors
reported a marked leftward shift of the force
frequency relationship in extensor digitorum
longus muscle following supplementation with
1.2% beta-alanine in the drinking water. Up to
now, improved calcium handling by carnosine loading could only be demonstrated in vitro. Studies
using in-vivo models are necessary to confirm the
possible role of enhanced carnosine levels for
increasing calcium sensitivity in muscle fibers.
Recently, an intriguing link between the pH
buffering capacity and the calcium-handling role
of carnosine was elucidated in cardiac myocytes.
Both calcium ions and protons can competitively
bind to proteins and dipeptides, such as carnosine.
In contrast to proteins, which are fixed buffers,
carnosine is a mobile buffer, freely dissolved in
the myoplasm. Based on this, a novel hypothesis
was put forward by Swietach et al. [41 ,42] stating
that the carnosine can act as a diffusible Ca2/H
exchanger. Sarcomere contraction requires Ca2 for
cross-bridge formation and ATP as an energy source.
On the one hand, ATP, produced from anaerobic
glycolysis, generates H accumulation at the sarcomere site that needs to be transported to the sarcolemma. On the other hand, Ca2 needs to diffuse
from the sarcoplasmic reticulum to the sarcomeres.
As both Ca2 and H can bind to carnosine,
increased H generation at the sarcomere site can
induce unloading of Ca2, which will in turn
increase both cross-bridge formation and force.
At the sarcoplasmic reticulum site, unloading of
H from carnosine is enhanced by Ca2 release
from the sarcoplasmic reticulum, thereby promoting the subsarcolemmal H concentration, driving
trans-sarcolemmal H export. It can be suggested
that this mechanism, which could be termed the

1363-1950 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

&&

www.co-clinicalnutrition.com

67

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Protein, amino acid metabolism and therapy

H+

Muscle fiber
SR
Ca++

Ca++
H+
Ca++

O
Ca++ -carn

HO
O

Carnosine
shuttle
Ca++ -carn

H+ -carn
H+

Glucose

H
N

H+ -carn

Ca++

NH
NH2

Cross-bridges

ATP

FIGURE 1. Current hypothesis on the ergogenic mechanism of carnosine in skeletal muscle, based on the findings of Swietach
et al. [41 ] in cardiac myocytes. It poses that carnosine can act as a shuttle by transporting both H and Ca2 between the
sarcomere region and the subsarcolemmal/T-tubular region. This would improve calcium delivery to and proton removal from
the sarcomere site. Inset shows molecular structure of carnosine with indication (arrow) of competitive binding site of H and
Ca2. SR, sarcoplasmic reticulum.
&&

carnosine shuttle, would explain much of the ergogenic effects of muscle carnosine loading (Fig. 1).

WHAT IS THE HEALTH-RELATING

POTENTIAL OF CARNOSINE?
As carnosine has a wide spectrum of bioactive properties, one could assume that carnosine is not only
able to fulfill benefits toward exercise performance
in athletes, but may also have therapeutic effects
toward certain disorders in which muscle function is
a key component [36 ]. In this respect, two studies
[43,44] investigated the effect of beta-alanine
supplementation on muscle carnosine content
and exercise capacity in elderly individuals, as this
is a continuously growing population in which
improving skeletal muscle function could contribute to maintaining independence and exercise
tolerance. The first study [43] indicates that betaalanine supplementation is effective in increasing
muscle carnosine content in healthy elderly individuals (aged 6080 years), paralleled by an
improvement in physical capacity (TTE during a
constant workload and incremental treadmill test).
Subsequently, a second study [44], using relatively
low doses of beta-alanine, fortified these findings,
showing increased physical working capacity after a
&

68

www.co-clinicalnutrition.com

12-week supplementation period, although carnosine contents were not measured in this study. On
the basis of these studies, beta-alanine supplementation possibly represents one of the few evidencebased dietary interventions that may delay the
decrease in exercise capacity with aging.
Because of the health-protective functions that
carnosine possesses [36 ], it could be believed that
next to the presence of carnosine in muscle, also the
presence in plasma could have therapeutic benefits.
However, in humans, circulating carnosine is
readily degraded by the highly active serum carnosinase enzyme (CN1), mostly resulting in a low or
even nonmeasurable plasma carnosine concentrations after supplementation or dietary ingestion.
Though, Everaert et al. [45] found that people with
low CN1 activity and content show measurable
increases in carnosinemia following carnosine
ingestion in a dose (60 mg/kg body weight) far
exceeding the normal dietary intake [36 ]. Thereupon, the relevance of low serum CN1 activity
toward athletic populations was demonstrated, as
it was shown that explosive athletes at an elite level
have lower serum CN1 activity and content,
possibly resulting from genetic selection [46 ]. However, regarding the therapeutic potential of plasma
carnosine, most studies are conducted in animal
&

&

&

Volume 18  Number 1  January 2015

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Beta-alanine, muscle carnosine and exercise Blancquaert et al.

models (mostly rodents) of human diseases [47], but

it should be noted that rodents have very low levels
of serum carnosinase activity, in contrast to high
levels in humans. Due to this difference, therapeutic
effects of carnosine in animal models cannot
directly be transferred to humans as it is believed
that a part of the beneficial effects of carnosine
administration is related to plasma carnosine levels.

CONCLUSION
Although carnosine has been discovered more than
a century ago, many aspects still need to be elucidated in order to get a complete understanding of
this multipotent dipeptide. Currently, beta-alanine
is already taken by a lot of athletes, but the metabolic fate of ingested beta-alanine is still mainly
unknown. The majority of the available evidence
supports the ergogenic potential of beta-alanine
supplementation for certain types of exercise, with
more work still required in applied sport-specific
settings. Clearly, the mechanisms by which
enhanced muscle carnosine concentrations result
in improved exercise performance need to be refined
in detail, with particular focus that it most likely
involves a complex interaction between pH buffering, Ca2-handling or other accessory functions.
Compared to the ergogenic potential, research on
the therapeutic potential of carnosine is still in its
infancy, with the need to further discover which
populations have reduced muscle carnosine concentrations and which ones benefit from increasing
plasma and/or muscle carnosine content.
Acknowledgements
The studies on beta-alanine and carnosine from our
research groups were financially supported by grants
from the Research Foundation, Flanders (FWO
G.0243.11 and G.0352.13N).
Conflicts of interest
There are no conflicts of interest.

REFERENCES AND RECOMMENDED

READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
&
of special interest
&& of outstanding interest
1. Harris RC, Tallon MJ, Dunnett M, et al. The absorption of orally supplied betaalanine and its effect on muscle carnosine synthesis in human vastus lateralis.
Amino Acids 2006; 30:279289.
2. Hill CA, Harris RC, Kim HJ, et al. Influence of beta-alanine supplementation on
skeletal muscle carnosine concentrations and high intensity cycling capacity.
Amino Acids 2007; 32:225233.
3. Stellingwerff T, Anwander H, Egger A, et al. Effect of two b-alanine dosing
protocols on muscle carnosine synthesis and washout. Amino Acids 2012;
42:24612472.
4. Decombaz J, Beaumont M, Vuichoud J, et al. Effect of slow-release b-alanine
tablets on absorption kinetics and paresthesia. Amino Acids 2012; 43:6776.

5. Stegen S, Blancquaert L, Everaert I, et al. Meal and beta-alanine coingestion

&
enhances muscle carnosine loading. Med Sci Sports Exerc 2013; 45:1478
1485.
This study revealed that meal coingestion enhances carnosine loading by betaalanine supplementation, resulting in practical guidelines regarding timing of betaalanine intakes throughout the day.
6. Bex T, Chung W, Baguet A, et al. Muscle carnosine loading by beta-alanine
&
supplementation is more pronounced in trained vs. untrained muscles. J Appl
Physiol 2014; 116:204209.
This was the first study to show an effect of training on carnosine loading,
suggesting that beta-alanine should be supplemented during a period of substantial training volume.
7. Kendrick IP, Kim HJ, Harris RC, et al. The effect of 4 weeks beta-alanine
supplementation and isokinetic training on carnosine concentrations in type I
and II human skeletal muscle fibres. Eur J Appl Physiol 2009; 106:131138.
8. Baguet A, Reyngoudt H, Pottier A, et al. Carnosine loading and washout in
human skeletal muscles. J Appl Physiol 2009; 106:837842.
9. Stegen S, Bex T, Vervaet C, et al. The beta-alanine dose for maintaining
&
moderately elevated muscle carnosine levels. Med Sci Sports Exerc 2014;
46:14261432.
This study successfully established a maintenance dose for beta-alanine after a
chronic supplementation period, which is of great importance to keep carnosine
levels elevated during a prolonged period of time.
10. Everaert I, De Naeyer H, Taes Y, Derave W. Gene expression of carnosinerelated enzymes and transporters in skeletal muscle. Eur J Appl Physiol 2013;
113:11691179.
11. Drozak J, Veiga-da-Cunha M, Vertommen D, et al. Molecular identification of
carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1).
J Biol Chem 2010; 285:93469356.
12. Drozak J, Chrobok L, Poleszak O, et al. Molecular identification of carnosine
N-methyltransferase as chicken Histamine N-methyltransferase-like Protein
(HNMT-Like). PLoS One 2013; 8:e64805.
13. Veiga-da-Cunha M, Chevalier N, Stroobant V, et al. Metabolite proofreading in
&
carnosine and homocarnosine synthesis: molecular identification of PM20D2
as b-alanyl-lysine dipeptidase. J Biol Chem 2014; 289:1972619736.
This study molecularly identified an enzyme assisting the carnosine synthase
enzyme by degrading all the wrongly synthesized dipeptides to leave only the
physiologically relevant one.
14. Baba SP, Hoetker JD, Merchant M, et al. Role of aldose reductase in the
metabolism and detoxification of carnosine-acrolein conjugates. J Biol Chem
2013; 288:2816328179.
15. Hobson RM, Saunders B, Ball G, et al. Effects of b-alanine supplementation
on exercise performance: a meta-analysis. Amino Acids 2012; 43:2537.
16. Baguet A, Bourgois J, Vanhee L, et al. Important role of muscle carnosine in
rowing performance. J Appl Physiol 2010; 109:10961101.
17. Van Thienen R, Van Proeyen K, Vanden Eynde B, et al. Beta-alanine improves
sprint performance in endurance cycling. Med Sci Sports Exerc 2009;
41:898903.
18. Ducker KJ, Dawson B, Wallman KE. Effect of beta-alanine supplementation on
2000-m rowing-ergometer performance. Int J Sport Nutr Exerc Metab 2013;
23:336343.
19. Hobson RM, Harris RC, Martin D, et al. Effect of beta-alanine with and without
sodium bicarbonate on 2,000-m rowing performance. Int J Sport Nutr Exerc
Metab 2013; 23:480487.
20. Chung W, Baguet A, Bex T, et al. Doubling of muscle carnosine concentration
&
does not improve laboratory 1-h cycling time trial performance. Int J Sport Nutr
Exerc Metab 2014; 24:315324.
As studies on the effect of beta-alanine on longer duration exercises are limited,
this study showed for the first time that beta-alanine is not improving the performance of a 1-h cycling time trial.
21. Chung W, Shaw G, Anderson ME, et al. Effect of 10 week beta-alanine
supplementation on competition and training performance in elite swimmers.
Nutrients 2012; 4:14411453.
22. De Salles Painelli V, Roschel H, de Jesus F, et al. The ergogenic effect of betaalanine combined with sodium bicarbonate on high-intensity swimming performance. Appl Physiol Nutr Metab 2013; 38:525532.
23. Mero AA, Hirvonen P, Saarela J, et al. Effect of sodium bicarbonate and betaalanine supplementation on maximal sprint swimming. J Int Soc Sports Nutr
2013; 10:52.
24. Saunders B, Sale C, Harris RC, Sunderland C. Effect of beta-alanine
supplementation on repeated sprint performance during the Loughborough
Intermittent Shuttle Test. Amino Acids 2012; 43:3947.
25. Ducker KJ, Dawson B, Wallman KE. Effect of beta alanine and sodium
bicarbonate supplementation on repeated-sprint performance. J Strength
Cond Res 2013; 27:34503460.
26. Smith-Ryan AE, Fukuda DH, Stout JR, Kendall KL. High-velocity intermittent
running: effects of beta-alanine supplementation. J Strength Cond Res 2012;
26:27982805.
27. Derave W, Ozdemir MS, Harris RC, et al. Beta-alanine supplementation
augments muscle carnosine content and attenuates fatigue during repeated
isokinetic contraction bouts in trained sprinters. J Appl Physiol 2007;
103:17361743.
28. Jones AM. Dietary nitrate supplementation and exercise performance. Sports
Med 2014; 44:3545.

1363-1950 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

www.co-clinicalnutrition.com

69

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Protein, amino acid metabolism and therapy

29. Hoon MW, Hopkins WG, Jones AM, et al. Nitrate supplementation and highintensity performance in competitive cyclists. Appl Physiol Nutr Metab 2014;
39:10431049.
30. De Salles Painelli V, Saunders B, Sale C, et al. Influence of training status on
&
high-intensity intermittent performance in response to b-alanine supplementation. Amino Acids 2014; 46:12071215.
This study showed that training status has no influence on the ergogenic potential
of beta-alanine by directly comparing its efficacy in trained and nontrained
individuals.
31. Sale C, Saunders B, Hudson S, et al. Effect of b-alanine plus sodium bicarbonate on high-intensity cycling capacity. Med Sci Sports Exerc 2011; 43:1972
1978.
32. Bellinger PM, Howe ST, Shing CM, Fell JW. Effect of combined b-alanine and
sodium bicarbonate supplementation on cycling performance. Med Sci
Sports Exerc 2012; 44:15451551.
33. Danaher J, Gerber T, Wellard RM, Stathis CG. The effect of b-alanine and
NaHCO3 co-ingestion on buffering capacity and exercise performance with
high-intensity exercise in healthy males. Eur J Appl Physiol 2014; 114:1715
1724.
34. Tobias G, Benatti FB, de Salles Painelli V, et al. Additive effects of betaalanine and sodium bicarbonate on upper-body intermittent performance.
Amino Acids 2013; 45:309317.
35. Saunders B, Sale C, Harris RC, et al. Effect of sodium bicarbonate and betaalanine on repeated sprints during intermittent exercise performed in hypoxia.
Int J Sport Nutr Exerc Metab 2014; 24:196205.
36. Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carno&
sine. Physiol Rev 2013; 93:18031845.
This review gives a clear and extensive summary of the physiological, biochemical
and therapeutic knowledge on carnosine and related compounds since its discovery more than a century ago.
37. Baguet A, Everaert I, De Naeyer H, et al. Effects of sprint training combined
with vegetarian or mixed diet on muscle carnosine content and buffering
capacity. Eur J Appl Physiol 2011; 111:25712580.
38. Gross M, Boesch C, Bolliger CS, et al. Effects of beta-alanine supplementation and interval training on physiological determinants of severe exercise
performance. Eur J Appl Physiol 2014; 114:221234.

70

www.co-clinicalnutrition.com

39. Dutka TL, Lamboley CR, McKenna MJ, et al. Effects of carnosine on contractile apparatus Ca2 sensitivity and sarcoplasmic reticulum Ca2 release
in human skeletal muscle fibers. J Appl Physiol (1985) 2012; 112:728
736.
40. Everaert I, Stegen S, Vanheel B, et al. Effect of beta-alanine and carnosine
supplementation on muscle contractility in mice. Med Sci Sports Exerc 2013;
45:4351.
41. Swietach P, Youm J-B, Saegusa N, et al. Coupled Ca2/H transport by
&&
cytoplasmic buffers regulates local Ca2 and H ion signaling. Proc Natl
Acad Sci U S A 2013; 110:E2064E2073.
In this excellent study, the pH buffering role and the Ca2 handling role of
carnosine were shown to interact in cardiomyocytes, and it provides at present
the best available hypothesis on the understanding of the ergogenic mechanism of
carnosine.
42. Swietach P, Leem C-H, Spitzer KW, Vaughan-Jones RD. Pumping Ca2 ions
up H gradients: a cytoplasmic Ca2/H exchanger without a membrane.
J Physiol 2014; 592:31793188.
43. Del Favero S, Roschel H, Solis MY, et al. Beta-alanine (CarnosynTM) supplementation in elderly subjects (60-80 years): effects on muscle carnosine
content and physical capacity. Amino Acids 2012; 43:4956.
44. McCormack WP, Stout JR, Emerson NS, et al. Oral nutritional supplement
fortified with beta-alanine improves physical working capacity in older adults:
a randomized, placebo-controlled study. Exp Gerontol 2013; 48:933
939.
45. Everaert I, Taes Y, De Heer E, et al. Low plasma carnosinase activity promotes
carnosinemia after carnosine ingestion in humans. Am J Physiol Renal Physiol
2012; 302:F1537F1544.
46. Baguet A, Everaert I, Yard B, et al. Does low serum carnosinase activity
&
favor high-intensity exercise capacity? J Appl Physiol 2014; 116:553
559.
The main finding of this study was the low serum carnosinase (CN1) activity and
content in explosive athletes, suggesting a relevance of this enzyme toward
exercise performance.
47. Aldini G, Orioli M, Rossoni G, et al. The carbonyl scavenger carnosine
ameliorates dyslipidaemia and renal function in Zucker obese rats. J Cell
Mol Med 2011; 15:13391354.

Volume 18  Number 1  January 2015

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.