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CREATINE AND beta-ALANINE SUPPLEMENTATION IN STRENGTH/POWER ATHLETES

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Creatine and beta-alanine are two of the most popular sport supplements used by strength/power athletes today. The popularity of creatine has resulted in more than 600 studies examining the physiology, efficacy and safety of its use among various athletic populations. Recently, beta-alanine has become as popular a supplement for the anaerobic athlete due to its unique ability to enhance muscle buffering capacity. This review examine the studies that have been conducted on the efficacy of these supplements. In addition, the physiology that underlies the mechanisms of action behind these supplements will be described and provide an understanding to the potential ergogenic benefits that they hold for strength and power athletes. Finally, discussion will also examine the potential adverse effects associated with each supplement.
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ABSTRACT: Creatine and ß-alanine are two of the most popular
sport supplements used by strength/power athletes today. The
popularity of creatine has resulted in more than 600 studies
examining the physiology, efficacy and safety of its use among
various athletic populations. Recently, ß-alanine has become as
popular a supplement for the anaerobic athlete due to its unique
ability to enhance muscle buffering capacity. This review will
examine the studies that have been conducted on the efficacy of
these supplements. In addition, the physiology that underlies the
mechanisms of action behind these supplements will be described
and provide an understanding to the potential ergogenic benefits
that they hold for strength and power athletes. Finally, discussion
will also examine the potential adverse effects associated with
each supplement.
KEY WORDS: Body Mass Changes, Creatine Side Effects,
Physiology, Skeletal Muscle Adaptation
Corresponding Author: Jay R. Hoffman, Ph.D., FACSM, FNSCA,
Department of Health and Exercise Science, The College of New Jersey,
PO Box 7718, Ewing, New Jersey 08628; Tel: 609-771-2287;
Fax: 609-637-5153; E-mail: hoffmanj@tcnj.edu
INTRODUCTION
For the past 20 years the most popular supplement among
strength/power athletes has been creatine. This is in part
related to the efficacy that has been demonstrated in the
hundreds of studies that have been published to date. In
addition, creatine use has been shown to be quite safe in a
number of studies examining both short and long term effects
in young, healthy athletic populations. β-alanine is a relatively
new supplement that is starting to gain in popularity due to
its ability to enhance the quality of training sessions and its
impact on sport performance by delaying fatigue. This paper
will examine the physiology of both creatine and β-alanine,
their mechanism of action, dosing patterns, effects on
performance, and health issues associated with their use. In
addition, the benefit of combining these two supplements is
also explored.
CREATINE AND β-ALANINE SUPPLEMENTATION IN STRENGTH/POWER ATHLETES
Jay R. Hoffman
The College of New Jersey, Ewing, NJ 08628-0718
[Received December 31, 20089; Accepted February 13, 2010]
CURRENT TOPICS IN NUTRACEUTICAL RESEARCH Vol. 8, No. 1, pp. 19-32, 2010
ISSN 1540-7535 print , Copyright © 2010 by New Century Health Publishers, LLC
www.newcenturyhealthpublishers.com
All rights of reproduction in any form reserved
PHYSIOLOGY OF CREATINE
Creatine is a nitrogenous organic compound that is synthesized
naturally in the body primarily in the liver. It can also be
synthesized in smaller amounts in both the kidneys and pancreas.
The amino acids arginine, glycine and methionine are the
precursors for the synthesis of creatine in those organs. Creatine
can also be consumed in the diet with high concentrations found
in both meat and fish. Approximately 98% of creatine is stored
within skeletal muscle in either its free form (40%) or in its
phosphorylated form (60%) (Heymsfield et al., 1983). It is the
phosphorylated form of creatine, referred to as phosphocreatine
(PCr), that the muscle cell uses to provide energy to fuel high
intensity exercise. Small amounts of creatine are also stored in the
heart, brain and testes. Creatine is transported from its site of
synthesis to the skeletal muscle via the circulation.
Creatine combined with a phosphate group has a critical role in
energy metabolism. It acts as a substrate in the formation of
adenosine triphosphate (ATP) by rephosphorylating adenosine
diphosphate (ADP). This becomes quite important during short
duration, high intensity exercise. The ability to rapidly
rephosphorylate ADP to ATP is dependent upon the enzyme
creatine kinase and the availability of PCr within the muscle. As
PCr concentrations become reduced, the ability to maintain or
produce high intensity exercise will decline. During short duration,
high intensity activity (i.e. 50m - 100m sprint) the energy needed
to perform that activity is derived primarily through the hydrolysis
of PCr (Gaitanos et al., 1993; Hirvonen et al., 1987). As duration
of high intensity exercise increases, the extent that PCr serves as
the primary source of energy is reduced. For example, during a 6-
second bout of maximal exercise (e.g., a set of 6 repetitions in the
squat exercise, or a 50 m sprint) PCr concentrations within the
muscle are reduced between 35 – 57% from resting levels (Gaitanos
et al., 1993, Boobis et al., 1987). As exercise duration increases to
30-seconds (e.g. a 200 m sprint), PCr levels in the muscle are
reduced to 64 – 80% of resting levels (Bogdanis et al., 1996;
Boobis et al., 1987; Cheetham et al., 1986), and during repetitive
high intensity exercise PCr levels in the muscle become almost
completely depleted (McCartney et al., 1986). As muscle PCr
concentrations decrease the ability to perform maximal exercise is
20
Creatine and
β
-alanine supplementation
reduced (Hirvonen et al., 1992). However, if muscle PCr
concentrations are elevated the ability to sustain high intensity
exercise will be maintained. This is the basis behind creatine
supplementation.
Creatine supplementation has been demonstrated to elevate
muscle creatine content by approximately 20% (Febbraio et al.,
1995; Hultman et al., 1996). Interestingly, there does appear to
be a ceiling effect in which once muscle creatine concentrations are
saturated, any further intake will be unable to increase muscle
creatine concentrations. Once creatine concentrations in skeletal
muscle reach 150 – 160 mmol.kg-1 dry weight additional
supplementation does not appear to be able to further increase
muscle creatine concentrations (Balsom et al., 1994; Greenhaff,
1995). This helps coaches, nutritionists and sport scientists assist
athletes by helping develop proper and realistic dosing schemes,
and prevents the ‘if a little is good, then more must be better’
philosophy that is often employed by athletes in the use of
nutritional supplements.
CREATINE DOSING SCHEMES
To maximize the muscle creatine concentrations athletes will
typically use a dosing regimen of 20 – 25 grams daily for 5 days, or
0.3 g.kg-1 body mass if an individual wishes to dose relative to their
body weight (Hultman et al., 1996). This is generally termed the
loading phase. To maintain muscle creatine content a maintenance
dose of 2 -5 g.day-1 or 0.03 - 0.075 g.kg-1day-1 is often used
following the loading phase. However, if athletes supplement with
creatine without an initial loading dose, muscle creatine content can
still reach similar levels that are seen in athletes that initially used a
loading dose. The only difference is that it will take longer to reach
that same muscle creatine concentration ( 30 days versus 5 days).
Muscle creatine levels will remain elevated as long as the maintenance
dose is taken. Once creatine supplementation is stopped muscle
creatine concentrations will return to original baseline levels within
approximately 4-weeks (Febbraio et al., 1995; Hultman et al., 1996).
EFFICACY OF CREATINE SUPPLEMENTATION
Creatine supplementation is one of the most widely studied ergogenic
aids to date. The results of these investigations have been consistent in
showing significant ergogenic benefits (Bemben et al., 2001; Brenner
et al., 2000; Eckerson et al., 2004; Haff et al., 2000; Hoffman et al.,
2006; Kirksey et al., 1999; Lehmkuhl et al., 2003; Pearson et al., 1999;
Volek et al., 1999). Although the efficacy of creatine is primarily seen
during prolonged supplementation, varying durations of dosing
regimens have been studied with varying results. Short-term creatine
supplementation protocols (3 – 6 days) have generally not resulted in
significant performance improvements during a single, acute bout of
explosive exercise (Cooke et al., 1995; Dawson et al., 1995; Mujica et
al., 1996; Odland et al., 1997; Snow et al., 1998). However, one study
did report that a 3-day loading dose (20 g of creatine monohydrate per
day) in NCAA Division I strength/power athletes was able to significantly
improve repeat sprint cycle performance (Ziegenfuss et al., 2002).
Considering that the greatest increases in muscle creatine concentrations
occur within the first 2 – 3 days of a loading phase, it is likely that the
differences between this latter study and the others may be related to the
exercise protocol used. The study that showed a positive effect used a
multiple set high intensity sprint protocol (6 x 10 sec loaded sprints)
with a 60-s rest interval between each sprint. The majority of the other
studies used an isolated bout of exercise or a longer rest interval that
would allow greater muscle phosphagen restoration. Other studies
demonstrating the efficacy of short-term (5-6 days) creatine
supplementation have used a loading dose (20 gd-1) as their supplement
regime (Cottrell et al., 2002; Cox et al., 2002; Mujica et al, 2000; Preen
et al., 2001; Stout et al., 2000) and have used a more appropriate
testing regimen (e.g. repeated or prolonged high intensity exercise).
Only two investigations are known that have shown ergogenic benefits
from a low dose creatine supplementation (Burke et al., 2000; Hoffman
et al., 2005). One study used a dosing scheme of 7.7 gd-1 (0.1 gkg-1)
during 28 days of supplementation (Burke et al., 2000). Although this
was a much longer supplementation period than typically seen during
short-term studies, it was the first study to show efficacy with a low-
dose, relatively short duration supplement regimen. Hoffman and
colleagues (2005) demonstrated that even using a low-dose (6-g·day-1),
short duration (6 days) supplementation regimen in active, college-
aged men changes in fatigue rate may be seen, although no improvements
were demonstrated in maximal power performance.
It is important to note that the typical creatine dosing schedule
for strength/power athletes is generally longer than 3 – 7 days.
Studies examining typical dosing regimens (28 – 84 days) have
consistently demonstrated significant improvements in strength
and power performance (Bemben et al., 2001, Haff et al., 2000;
Hoffman et al., 2006; Kirksey et al., 1999; Pearson et al., 1999;
Volek et al., 1999; Kreider et al, 1998). The magnitude of strength
improvements has been reported to be nearly 2 -3 fold greater in
athletes supplementing with creatine compared to a placebo (see
Figure 1). Clearly, the benefit of creatine supplementation is
expressed by enhancing the quality of workouts. By improving
the quality of each training session the training stimulus to the
muscle will ultimately yield greater physiological adaptation
resulting in improved performance.
40
35
30
25
20
15
10
5
0
Bench Press
Placebo Creatine
Kg
Squat
FIGURE 1. Typical Strength Improvements Resulting from
Creatine Supplementation in Strength/Power Athletes. Adapted
from Hoffman and colleagues (2006).
Creatine and
β
-alanine supplementation 21
THE EFFECT OF CREATINE SUPPLEMENTATION ON
BODY MASS CHANGES
Creatine supplementation has also been generally associated
with increases in body weight. During prolonged
supplementation increases in body mass are primarily seen as
fat free mass. Increases in weight gain appear to occur relatively
quickly as individuals supplement with creatine. This is likely
related to an increase in total body water. As creatine content
within skeletal muscle increases the intracellular osmotic
gradient that results causes water to fill the cell (Volek and
Kraemer, 1996). Increases in lean body mass are likely related
to the enhanced stimulus to the muscle from a higher quality
workout resulting in an increased synthesis of muscle
contractile proteins (Balsom et al., 1993; Bessman and Savabi,
2000).
CREATINE SUPPLEMENTATION AND
SKELETAL MUSCLE ADAPTATION
As discussed earlier, creatine supplementation
is associated with increases in lean body mass,
strength and power. These improvements are
in part related to the physiological adaptations
that occur within skeletal muscle as a result of
the training stimulus, but are also aided by the
creatine intervention. A 12-week examination
of creatine supplementation during a
periodized resistance training program revealed
a significantly greater increase in the cross-
sectional area of Type I, Type IIa and Type IIab
fibers (see Figure 2) in subjects ingesting
creatine compared to a placebo (Volek et al.,
1999). It was suggested that the greater gains
in muscle cross-sectional area could be
attributable to the higher quality workouts
associated with creatine supplementation.
These results were confirmed by another study
examining a 12-week training and dosing
protocol (Willoughby and Rosene, 2001).
Figure 3 depicts the effect that creatine
supplementation in conjunction with a heavy
resistance training program can have on
amplifying the response of myosin heavy chain
protein synthesis (these are the microfilaments
comprising muscle that are involved in muscle
contraction). Again, this is likely due to the
greater training stimulus that is associated with
the higher creatine content within skeletal
muscle. It appears that creatine is effective in
eliciting muscle morphological changes, most
probably as in indirect manner by providing
the athlete the ability to sustain a higher quality
workout that stimulates the greater
physiological response.
In contrast, some investigators have
indicated that creatine may have a direct
40
35
25
20
15
10
5
0
% improvment
Type llab
Type llaType l
Creatine Placebo
***
FIGURE 2. Effect of 12-Weeks of Creatine Supplementation on Increases in Muscle
Cross-Sectional Area. * = p < 0.05. Adapted from Volek and colleagues (1999).
90
80
70
60
50
40
30
20
10
0
mg-ml
-1
CON P CR
*
*,#
*
FIGURE 3. Creatine Supplementation and Change in Myofibrillar Protein Content.
Con = untrained control; P = placebo; Cr = creatine; * = significantly different (p <
0.05) than Con; # = significantly different than P. Adapted from Willoughby and
Rosene (2001).
effect on changing skeletal muscle morphology. Vierck and
colleagues (2003), showed that when creatine is added to a
cell culture of satellite cells it had the potential to increase
satellite cell proliferation and differentiation. Satellite cells
are myogenic stem cells that lie dormant between the basal
lamina of the myofiber and the plasma membrane. When
activated these cells proliferate, differentiate and fuse with
existing myofibers within muscle to permit DNA accretion
and cause muscle hypertrophy. The fusion of the satellite
cells appears to be a necessary occurrence for muscle
differentiation (Dayton and Hathaway, 1989). Thus, it does
appear that creatine may both a direct and indirect role in
stimulating muscle morphological changes during
supplementation.
22
Creatine and
β
-alanine supplementation
CREATINE SUPPLEMENTATION: RESPONDERS VS.
NON-RESPONDERS
For creatine to provide an ergogenic benefit it is believed that
muscle creatine concentrations need to be increased by close to 20
mmol·kg-1 of dry weight (Greenhaff, 1997). If not, then the
benefits of creatine may not be realized. Greenhalf and colleagues
(1994) have suggested that between 20 – 30% of subjects that
ingest creatine may not respond. Non-responders are defined as
subjects that achieve a less than 10 mmol·kg-1 of dry weight increase
in muscle creatine content following 5 days of creatine
supplementation at 20 g·d-1. This has been confirmed by other
investigators as well (Syrotuik and Bell, 2004). Approximately
30% of individuals that supplement with creatine appear to be
non-responders (Greenhaff et al., 1994; Syrotuik and Bell, 2004).
Interestingly, subjects that were deemed non-responders also had
lower strength performance gains compared to responders during
the 5-days supplementation period (Syrotuik and Bell, 2004).
Interestingly, the majority of subjects that supplemented were
labeled as quasi-responders; individuals whose muscle creatine
concentrations increased greater than 10 mmol·kg-1 of dry weight,
but less than 20 mmol·kg-1 of dry weight. These individuals
exhibited greater strength scores than the non-responders, but
slightly less than that seen in the responders.
Whether a strength/power athlete will respond to creatine
supplementation or not appears to be dependent on initial muscle
creatine content (Syrotuik and Bell, 2004; Ekblom, 1996; Harris
et al, 1992). Athletes with low initial muscle creatine or
phosphocreatine concentrations benefit the most from creatine
supplementation, while those athletes with high initial levels benefit
the least. While initial muscle creatine content appears to be the
most important factor determining the effectiveness of creatine
supplementation, muscle fiber composition may also contribute
to the potential ergogenic benefit of creatine supplementation.
Syrotuik and Bell (2004) reported that responders have the greatest
percentage of type II fibers, followed by the quasi-responders and
the non-responders had the lowest percentage of type II fibers. It
appears that individuals who have predominantly fast twitch fibers
with low initial levels of muscle creatine may reap the greatest
benefit from creatine supplementation.
SIDE EFFECTS ASSOCIATED WITH CREATINE
SUPPLEMENTATION
An increase in body mass associated with creatine
supplementation has been suggested to be an unwanted side effect
by some individuals (Schilling et al., 2001). For most athletes
supplementing with creatine, weight gain is often a desired
outcome. Side effects generally refer to potentially debilitating
effects. There have been a host of anecdotal reports regarding
creatine supplementation and gastrointestinal, cardiovascular and
muscular problems. Muscle cramps has been the most frequently
mentioned side-effect associated with creatine ingestion. However,
controlled prospective studies have been unable to document any
significant side effects from creatine supplementation. Even during
prolonged supplementation (10 – 12 weeks), in competitive
athletes or recreationally trained individuals, the frequency of side
effects reported by individuals supplementing with creatine were
no different than those seen in individuals ingesting a placebo
(Hoffman et al., 2006; Volek et al., 1999; Kreider et al., 1998).
Even studies of longer duration supplement protocols appear
to support the notion that creatine is relatively safe. Schilling and
colleagues (2001) retrospectively examined current and former
competitive athletes that had used creatine for up to 4-years in
duration. They reported only occasional gastrointestinal upset
during the loading phase, primarily described as ‘gas’ to mild
diarrhea. Other major concerns during creatine supplementation
include kidney strain due to the high nitrogen content of creatine
and reported increases in creatinine excretion during short-term
ingestion (Harris et al., 1992). However, no renal dysfunction has
been reported in either short- (5 days) or long-term (up to 5 years)
creatine use (Poortsman and Francaux, 1999; Poortsman et al.,
1997).
One of the greatest myths associated with creatine
supplementation is that it can increase the athlete’s risk for heat
illness, especially when it is consumed in hot environments. It has
been suggested that creatine supplementation should be avoided
by athletes during activities being performed in the heat (Terjung
et al., 2000). The basis behind this was that creatine is an
osmotically active substance that will increase the solute content of
skeletal muscle during supplementation (Ziegenfuss et al., 1998).
As the concentration of creatine within skeletal muscle increases it
will increase the osmotic gradient drawing water into the cell through
the process of osmosis. As a result the water content of the muscle
cell increases. It is thought that the osmotic pull of water into
skeletal muscle, due to an increase in creatine content, may
exacerbate the plasma volume loss generally seen during exercise
in the heat (Lopez et al., 2009). However, a number of scientific
studies have actually examined this specific question and have
clearly indicated that creatine supplementation does not increase
the risk for dehydration or reduce the ability of athletes to
thermoregulate (Lopez et al., 2009; Mendel et al., 2005; Vogel et
al., 2000; Watson et al., 2006; Wright et al., 2007).
In one study examining the effect of creatine supplementation
and fluid regulation, a 5 -day creatine loading protocol in subjects
dehydrated to 2.5% and 4.0% of their body weight elicited a ~ -
7% and a ~-9% loss in plasma volume, respectively (Vogel et al.,
2000). Each subject group exercised 75 min on a cycle ergometer.
Results of the study demonstrated that creatine ingestion in
hypohydrated subjects did not negatively impact hydration status.
In addition, no increase in muscle cramping was reported as well.
Additional studies examining the effect of creatine supplementation
on thermoregulation during exercise in the heat, in both
euhydrated and dehydrated subjects, have been consistent in
finding no reduction in the ability of subjects to tolerate both heat
and exercise stresses (Watson et al., 2006; Wright et al., 2007).
Recently a meta-analysis (e.g., a statistical examination of the
scientific literature in a particular subject area) on creatine
supplementation and exercise in the heat concluded that creatine
supplementation neither hinders nor negatively affects the athlete’s
ability to exercise in the heat or body fluid balance (Lopez et al.,
2009).
Creatine and
β
-alanine supplementation 23
WHAT TYPE OF CREATINE IS MOST EFFECTIVE ?
The vast majority of research that has demonstrated the efficacy
of creatine supplementation has used the creatine monohydrate
form. Several laboratories have shown that the intestinal absorption
of creatine when it is supplied in the monohydrate form is nearly
100% (Chanutin, 1926; Deldicque et al., 2008). However, there
are a number of sport nutrition companies that have used various
formulations of creatine with exaggerated claims of greater efficacy.
It has caused some confusion among athletes and coaches alike as
to the best creatine to use. This has generated several investigations
by sport nutrition scientists to compare the effects of these various
creatine formulations. Jäger and colleagues (2007) examined the
change in plasma creatine concentrations and pharmokinetics of
creatine absorption following ingestion of equal concentrations of
creatine monohydrate, tri-creatine citrate and creatine pyruvate.
Their results indicated that these different forms of creatine can
result in slightly altered kinetics of plasma creatine absorption
with the highest plasma concentrations seen from the ingestion of
creatine pyruvate. The researchers though did not believe that
there were any differences in the bioavailability of these different
forms of creatine since the absorption of creatine monohydrate is
practically 100% to begin with. In addition the use of effervescent
powders containing di-creatine citrate has been shown to have
similar bioavailability as creatine monohydrate (Dash and Sawhney,
2002; Ganguly et al., 2003), and is often found in a number of
creatine supplements
Another form of creatine that is being marketed is creatine ethyl
ester. Sport nutrition companies that promote this product often
claim that creatine ethyl ester can enhance creatine absorption,
delay its degradation and simply increase its bioavailability. How
this can be accomplished when creatine monohydrate absorption
is already close to 100% has left many sport biochemists shaking
their heads. The suggested hypothesis is that the esterification of
creatine will decrease its hydrophilicity, and bypass the creatine
transporter due to an enhanced sarcolemmal permeability towards
creatine (Spillane et al., 2009). Although creatine ethyl ester has
been shown to be rapidly degraded to creatinine in the gut due to
the low pH (Child and Tallon, 2007; Mold et al., 1955),
companies continue to make their claims. Spillane and colleagues
(2009) compared 5-days of creatine ethyl ester supplementation
to creatine monohydrate and placebo and found it to be inferior
to both creatine monohydrate and placebo in changes in body
mass and lean body mass (Spillane et al., 2009). The use of
creatine ethyl ester showed no significant increase in serum and
muscle creatine content suggesting that a large portion of that
supplement was degraded within the gut following ingestion.
PHYSIOLOGY OF β-ALANINE
β-alanine is a non-essential, non-proteogenic amino acid that is
synthesized in the liver (Matthews and Traut, 1987). It is also
common in many foods that we eat, such as beef, chicken and
turkey. In the diet β-alanine is consumed as a histidine containing
dipeptide such anserine, balenine and carnosine, however, it is
carnosine that is the principle histidine containing dipeptide found
in human skeletal tissue. The hydrolysis of these dipeptides yields
β-alanine, which is taken up into skeletal muscle for the re-synthesis
of carnosine. By itself, the ergogenic properties of β-alanine are
very limited, and it appears to be only effective as an ergogenic aid
by its involvement in the synthesis of carnosine (Dunnett and
Harris, 1999). Carnosine itself has important ergogenic potential
for strength and power athletes by its ability to act as an intracellular
buffer to high intensity exercise.
Carnosine is comprised of the amino acids â-alanine and
histidine. It is unable to be absorbed from the circulation by
muscle (Bauer and Schulz, 1994), so it needs to be synthesized
within skeletal muscle. Skeletal muscle has a relatively low
concentration of β-alanine (Skaper et al., 1973), but a high
concentration of histidine and carnosine synthetase, the enzyme
responsible for carnosine synthesis. As a result, it is β-alanine that
is the rate limiting step in carnosine synthesis. Supplementing
with β-alanine (4 to 6 grams per day) for 4 weeks has resulted in a
mean increase of 64% in carnosine within skeletal muscle (Harris
et al., 2006).
In humans, carnosine is found primarily in fast-twitch skeletal
muscle, and is estimated to contribute up to 40% of skeletal muscle
buffering capacity of H+ produced during high intensity exercise
(Harris et al., 2006; Hill et al., 2007). Similarly, histidine containing
dipeptides (anserine, balenine and carnosine) is found in great
concentrations in a number of vertebrate species that perform
highly anaerobic activites. Whales, that can spend prolonged time
under water are reported to have concentrations of 400 mmol·kg-
1 of dry muscle, while thoroughbred race horses and greyhound
race dogs have histidine containing dipeptide concentrations of
110 mmol·kg-1 of dry muscle and 90 mmol·kg-1 of dry muscle,
respectively (Abe, 2000; Artioli et al., 2009; Harris et al., 1990)
Interestingly, human sprinters have been reported to have muscle
carnosine concentrations ranging between 17 – 25 mmol·kg-1 of
dry muscle (Harris et al., 1990). As expected, these concentrations
are higher than that typically found in endurance athletes,
untrained individuals, and the elderly (Harris et al., 2006; Suzuki
et al., 2002).
Training does appear to have a profound effect on muscle
carnosine concentrations. One of the primary physiological
adaptations for anaerobic athletes during their training is the
development of an enhanced buffering capacity (Hoffman, 2002).
Parkhouse and colleagues (1985) demonstrated that highly trained
anaerobic athletes have a greater buffering capacity and a
significantly greater skeletal muscle concentration of carnosine than
endurance athletes and untrained subjects. Tallon and colleagues
(2005) compared trained bodybuilders to untrained control
subjects and reported that muscle carnosine concentrations in the
vastus lateralis were significantly greater in the bodybuilders, which
could not be explained by differences in the muscle size between
the groups. The nature of the training program of bodybuilders
does suggest that high intensity resistance training can stimulate
endogenous changes in muscle carnosine concentrations. Other
investigators have examined the relationship between skeletal
muscle carnosine content and high intensity exercise performance
in trained cyclists (Suzuki et al., 2002). A positive relationship
between carnosine concentration and the mean power from a 30
24
Creatine and
β
-alanine supplementation
second maximal sprint on a cycle ergometer was found. Thus,
adding support to the theory that skeletal muscle carnosine levels
have a positive correlation to anaerobic exercise performance due
to the relationship of carnosine and muscle buffering capacity.
These cross-sectional studies though do not provide a clear
understanding of the effects of training on muscle carnosine
concentrations. Although Suzuki and colleagues (2004) were able
to see a 100% elevation in muscle carnosine concentrations following
8-weeks of high intensity training, the majority of longitudinal
training studies (lasting 4 – 16 weeks) investigating high intensity
exercise and muscle carnosine changes have been unable to provide
support (Kendrick et al., 2008; 2009; Kim et al., 2006; Mannion
et al., 1994). Furthermore, the results of Tallon et al., (2005) may
be suspect as the bodybuilders examined in their study did self-
admit to using anabolic steroids. Carnosine synthesis has been
shown to be up-regulated by circulating testosterone concentrations
(Penafiel et al., 2004), however whether exogenous androgens can
elevate muscle carnosine content is not clear. Considering that most
of the available evidence to date indicates that neither short nor long
term high intensity training regimens can elevate muscle carnosine
concentrations, the method that appears to best increase muscle
carnosine content is supplementing with β-alanine.
ββ
ββ
β-ALANINE DOSING SCHEME
Harris and colleagues (2006) examined the effect of three different
dosing regimens (10 mg·kg-1, 20 mg·kg-1 and 40 mg·kg-1 body weight).
The two highest doses yielded the greatest increase in plasma β-
alanine concentrations (see Figure 4), but were also associated with
uncomfortable side effects (e.g. paresthesia; a tingling-like sensation
felt in the skin) that prohibits those dosages from being used. The 10
mg·kg-1 (equivalent to an approximate 800 mg dose) resulted in an
elevation in plasma β-alanine concentrations, albeit significantly lower
than the higher doses but without the associated side effect. The
kinetics of the β-alanine response to the low dosing scheme was a time
to peak in plasma β-alanine
concentration of 30 – 40
minutes following
ingestion, a concentration
half-life (time at which
50% reduction of peak
concentration) of 25
minutes, and a return to
baseline concentration by 3
hours post-ingestion.
According to this kinetic
profile the appropriate
dosing regimen should be
800 mg of β-alanine taken
every three to four hours.
This would provide a daily
dosing regimen of 4.8 g –
6.4 g per day. However,
there is some evidence that
indicates that dosing
should be relative to an
FIGURE 4. Plasma ββ
ββ
β-alanine Concentrations. Adapted from Harris et al., 2006
0
250
500
750
1000
0 60 120 180 240 300 360
Time (min)
10 mg.kg-1 bwt
20 mg.kg-1 bwt
40 mg.kg-1 bwt
Plasma ß-
alanineµmol.l
-1
individual’s body mass (Hoffman et al., 2008a). Maximal performance
benefits appear to occur when daily dosing is between 50 – 80 mg·kg-
1 body mass per day (this would involve multiple feedings).
Hill and colleagues (2007) using a comparable dosing protocol
(4.0 g a day for the first week of supplementation and then 6.4 g
per day for an additional 9 weeks (this was equivalent to the 50 –
80 mg·kg-1 body mass per day) measured muscle carnosine
concentrations at weeks 0, 4, and 10. In addition, subjects
performed a cycling to exhaustion test at 110% of max power.
Muscle carnosine concentrations increased by 58% at week 4 and
an additional 15% at week 10. Additionally, there was a 13% and
16% increase in total work done at weeks 4 and 10, respectively.
Although the majority of studies have found positive results using
this dosing scheme, there is some evidence that suggests that muscle
carnosine concentrations may also be elevated (37%) in untrained
subjects following only two weeks of supplementation (Harris et
al., 2007). In addition, recent studies have examined the use of
time-release capsule technology and have demonstrated that
dosages of 1600 mg per ingestion four times per day can also be
consumed without any side effects and result in a 40% increase in
muscle carnosine concentrations (Derave et al., 2007; Harris et al.,
2009). This latter method appears to be a more practical dosing
pattern that has the same ergogenic potential without any
accompanying side effects.
Based upon the available evidence, it is not clear whether a
ceiling effect exists regarding muscle carnosine content and β-
alanine supplementation. It does appear though that the limits on
supplementation dose may be more related to the side effects
associated with higher dosing regimens. Future investigations will
need to examine whether the use of time-release capsules can result
in greater muscle carnosine content than powder or regular capsule
ingestion. Regarding the time course of muscle carnosine
concentrations returning to baseline concentrations following
cessation of β-alanine supplementation, the information is not clear.
A recent study investigated
subjects consuming 4.8 g
of β-alanine per day for 6
weeks (Baguet et al.,
2009). Following three
weeks of supplement
cessation, muscle carnosine
concentrations decreased
by only 30%. By nine
weeks of cessation muscle
carnosine concentrations
returned to baseline levels.
Additional evaluation of
the data suggested that the
time course to a return to
baseline levels may be
dependent upon the
effectiveness of the
supplementation
program. Those subjects
that were deemed high
Creatine and
β
-alanine supplementation 25
responders (greater accumulation of muscle carnosine content)
required a greater washout time to return to baseline levels (~15
weeks), while low responders saw a return to baseline levels within
6 weeks.
EFFICACY OF β-ALANINE SUPPLEMENTATION
The physiological mechanism described concerning β-alanine
supplementation suggests that it would be most effective in
performances involving high intensity activity. The investigations
that have focused on this aspect of athletic performance have
consistently reported positive results in the ergogenic benefit of β-
alanine supplementation (Derave et al., 2007; Hill et al., 2007;
Hoffman et a., 2006; Hoffman et al., 2008a, b; Stout et al., 2006;
2007; Van Thienen et al. 2009). Stout et al. (2006) examined
the effects of β-alanine supplementation on physical working
capacity at fatigue threshold (PWCFT) in untrained young men.
Subjects consumed either 1.6 g of β-alanine or a placebo four
times per day for six days, then 3.2 grams per day for 22 additional
days. Prior to, and following supplementation, the subjects
performed an incremental cycle ergometry test to determine PWCFT,
which was determined from bipolar surface electromyography
recorded from the vastus lateralis muscle. The PWCFT provides a
measure for the highest exercise intensity a person can maintain
without signs of fatigue and has been highly correlated with
anaerobic threshold measurements (lactate and ventilatory
thresholds). The results of that study demonstrated a significantly
greater increase in PWCFT (9%) in the β–alanine group compared
to no change in the placebo. In a follow-up study, Stout’s research
group examined the effect of 28 days of β-alanine supplementation
in untrained college-age women. They confirmed their previous
results by demonstrating a significantly greater PWCFT (12.6%),
ventilatory threshold (13.9%) and time to exhaustion (2.5%)
during a graded exercise cycle ergometry test than the placebo
supplemented group (Stout et al., 2007). These findings indicated
that 28 days of β-alanine supplementation in untrained subjects
can delay fatigue during intense exercise.
The efficacy of β-alanine supplementation has also been
demonstrated in trained strength/power athletes. Hoffman and
colleagues (2008a) examined the effect of two weeks of
supplementation (4.5 g·day-1) prior to the onset of training camp
in college football players. Supplementation continued for an
additional two weeks during pre-season practices. Performance
testing which occurred following two weeks of supplementation
revealed no ergogenic effect in sprint times or fatigue rates during
performance of repeated line drills (an approximate 30 – 35 second
shuttle run performed three times with 2-min rest between each
sprint). In addition, no significant differences were observed in
peak power, mean power and total work in a 60-sec Wingate
anaerobic power test. However, a trend (p = 0.07) towards a
reduced rate of fatigue was found in the football players consuming
the supplement versus the placebo. Examination of the resistance
training logs (performed during training camp) revealed no
significant difference in the average training intensity in either the
bench press or squat exercises, but did indicate a trend (p = 0.09)
towards a higher (9.2 %) volume of training (both bench press
and squat combined) seen for the athletes supplementing with β-
alanine compared to the placebo. In addition, subjective feelings
of fatigue during camp were significantly lower in athletes using
the supplement compared to the placebo.
The inability to see any effect on repeated sprints of
approximately 30 – 35 seconds but, a trend towards an improved
fatigue rate in a 60-sec maximal intensity bout of exercise provides
support to the effect that β-alanine supplementation has on
improved buffering capacity during prolonged high intensity
exercise. Interestingly, Derave and colleagues (2007) reported
that 4-weeks of β-alanine supplementation in 400-m sprinters
could delay fatigue in repeated isokinetic bouts (5 sets) of exercise,
but not improve 400-m race time. It appears that prolonged high
intensity exercise bouts (~60 sec) benefit the most from improved
buffering capacities brought about by increases in muscle carnosine
concentrations. However, high intensity exercise performed
immediately following a prolonged bout of endurance exercise
may also benefit from β-alanine supplementation. A recent study
demonstrated that trained cyclists supplementing for 8-weeks could
improve 30-second sprint performance following a 110-min time
trial (Van Thienen et al., 2009).
A 4-week training study, employing a double-blind cross-over
design, examined the effect of 4.8 g per day of β-alanine on the
acute endocrine response to a resistance training session in eight
experienced, resistance trained athletes (Hoffman et al., 2008b).
When consuming β-alanine the Δ total number of repetitions
performed in the squat exercise per workout (expressed as the
difference between workouts performed at week 0 and week 4)
was significantly greater than when using a placebo (9.0 ± 4.1 and
0.3 ± 7.8, respectively). In addition, a significant difference
between the groups was also seen in Δ mean power. The greater
volume of training though did not correspond to any significant
change to the acute testosterone or growth hormone response to
the exercise protocol. In addition, no difference was seen in
improvement of squat strength following 4-weeks of
supplementation between subjects supplementing with β-alanine
(5.9 ± 4.3 kg) versus the placebo (3.9 ± 4.1 kg).
The lack of significant strength improvement is consistent with
other studies that have failed to show significant improvements in
strength following β-alanine supplement durations lasting between
4 – 10 weeks (Kendrick et al., 2008; 2009). These results are not
surprising considering the physiological mechanism that is affected
by elevations in muscle carnosine concentrations. An improved
intra-muscular buffering system would have a greater effect on
fatiguing type exercises by extending duration of exercise. As a
result it does not have a direct effect on strength development.
Thus, it is not surprising that in relatively short duration training
protocols no significant improvements in strength are seen in
trained individuals. In contrast, the window of strength
improvements for untrained individuals is so large during the
onset of a resistance training program (Hoffman, 2002), that
supplements are generally not recommended for novice resistance
trained populations. The ability of β-alanine supplementation to
enhance strength performance is likely more effective during
prolonged durations of training. Improvements in muscle
26
Creatine and
β
-alanine supplementation
buffering capacity appears to improve the quality of a resistance
training workout by increasing the number of repetitions that can
be performed at a given intensity of training (Hoffman et al.,
2006; 2008a,b). The greater training volume would potentially
provide a greater stimulus for muscle adaptation, but likely
following a longer duration of training.
THE EFFECT OF ββ
ββ
β-ALANINE SUPPLEMENTATION
AND BODY MASS CHANGES
Several of the training studies examining β-alanine
supplementation have been unable to see any change
in body mass in studies ranging from 4 – 15 weeks
(Hoffman et al., 2006; 2008b). This has been
attributed to the low daily caloric intake of subjects in
those studies. However, the greater volume of training
seen in the resistance training program of trained
strength/power athletes supplementing with β-
alanine appeared to stimulate significant decreases in
fat mass and increases in lean body mass compared to
subjects consuming creatine only or a placebo
(Hoffman et al., 2006). The higher training volume
associated with β-alanine supplementation is typical
of a resistance training program designed to enhance
muscle hypertrophy adaptations, similar to that
performed by bodybuilders. Improvements in lean
muscle mass and decreases in fat mass are desirable
outcomes for individuals whose primary training goals
are improvements in body composition.
SIDE EFFECTS ASSOCIATED WITH β-
ALANINE SUPPLEMENTATION
The only known side effect associated with β-alanine
supplementation is paresthesia. Paresthesia is a sensation of
numbing or tingling in the skin. It appears when high doses of β-
alanine are ingested. It generally disappears within one hour
following ingestion (Harris et al., 2006). Interestingly, when β-
alanine is mixed with a carbohydrate and electrolyte drink the
appearance of this side effect appears negligible (Hoffman et al.,
2006). Studies examining potential side effects from prolonged
(greater than 15 weeks) supplementation durations have not been
performed. However, considering that β-alanine is an amino acid
with an important physiological role in the body, in dosages studied
that are similar to that consumed regularly in the diet, it is likely a
very safe supplement to use (Artioli et al., 2009).
CREATINE AND ββ
ββ
β-ALANINE COMBINATION
Hoffman and colleagues (2006) were the first research team to
examine the combination of both creatine and β-alanine
supplements. The hypothesis was that this combination of
supplements would provide a significant benefit for strength/
power athletes. Results of their study demonstrated that this
combination significantly improved the quality of the workout
more so than creatine alone. Specifically, improvements in training
volume was found (see Figure 5) that was associated with
significantly greater gains in lean body mass and decreases in fat
mass. Interestingly, creatine and creatine + β-alanine resulted in
significantly greater strength gains in 1-RM bench press and 1-
RM squat than the placebo. However, the addition of β-alanine
did not provide any further benefit to strength improvement.
Similarly, Stout et al., (2006) also compared the combination of
creatine and β-alanine to creatine and β-alanine alone. Significant
improvements were seen, but no additive benefits were noted in
physical work capacity in previously untrained men.
SUMMARY
Creatine is the most widely studied ergogenic aid to date.
Evidence is convincing that it is both safe and effective in enhancing
performance in strength/power activities. Significant
improvements in size, strength and power are associated with
creatine supplementation. Similarly, the evidence examining the
efficacy of β-alanine supplementation for athletes participating in
high intensity exercise is also quite convincing. However, the
additive benefits of combining β-alanine to creatine in enhancing
strength performance is not clear, but may become more relevant
for enhancing the quality of the workout. For the experienced
resistance trained athlete this may stimulate greater strength and
power adaptations in training durations greater than that presently
studied. In addition, the benefits may also be more prevalent
during actual athletic performance when athletes will perform
repeated, prolonged duration high intensity exercise.
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32
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Purpose: The purpose of this study was to examine the effect of creatine supplementation in conjunction with resistance training on physiological adaptations including muscle fiber hypertrophy and muscle creatine accumulation. Methods: Nineteen healthy resistance-trained men were matched and then randomly assigned in a double-blind fashion to either a creatine (N = 10) or placebo (N = 9) group. Periodized heavy resistance training was performed for 12 wk. Creatine or placebo capsules were consumed (25 g x d(-1)) for 1 wk followed by a maintenance dose (5 g x d(-1)) for the remainder of the training. Results: After 12 wk, significant (P < or = 0.05) increases in body mass and fat-free mass were greater in creatine (6.3% and 6.3%, respectively) than placebo (3.6% and 3.1%, respectively) subjects. After 12 wk, increases in bench press and squat were greater in creatine (24% and 32%, respectively) than placebo (16% and 24%, respectively) subjects. Compared with placebo subjects, creatine subjects demonstrated significantly greater increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) muscle fiber cross-sectional areas. Muscle total creatine concentrations were unchanged in placebo subjects. Muscle creatine was significantly elevated after 1 wk in creatine subjects (22%), and values remained significantly greater than placebo subjects after 12 wk. Average volume lifted in the bench press during training was significantly greater in creatine subjects during weeks 5-8. No negative side effects to the supplementation were reported. Conclusion: Creatine supplementation enhanced fat-free mass, physical performance, and muscle morphology in response to heavy resistance training, presumably mediated via higher quality training sessions.