Branched chain amino acids supplementation enhance exercise capacity and lipid oxidation during endurance exercise after muscle glycogen depletion

Abstract

It has been demonstrated that branched-chain amino acids (BCAA) transaminase activation occurs simultaneously with exercise-induced muscle glycogen reduction, suggesting that BCAA supplementation might play an energetic role in this condition. This study aimed to test whether BCAA supplementation enhances exercise capacity and lipid oxidation in glycogen-depleted subjects.
Using a double-blind cross-over design, volunteers (N.=7) were randomly assigned to either the BCAA (300 mg . kg . day -1) or the placebo (maltodextrine) for 3 days. On the second day, subjects were submitted to an exercise-induced glycogen depletion protocol. They then performed an exhaustive exercise test on the third day, after which time to exhaustion, respiratory exchange ratio (RER), plasma glucose, free fatty acids (FFA), blood ketones and lactate were determined. BCAA supplementation promoted a greater resistance to fatigue when compared to the placebo (+17.2%). Moreover, subjects supplemented with BCAA showed reduced RER and higher plasma glucose levels during the exhaustive exercise test.
In conclusion, BCAA supplementation increases resistance to fatigue and enhances lipid oxidation during exercise in glycogen-depleted subjects.

Full text

82 THE JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS March 2011
Anno: 2011
Mese: March
Volume: 51
No: 1
Rivista: THE JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS
Cod Rivista: J SPORTS MED PHYS FITNESS
Lavoro: 3005-JSM
titolo breve: Branched-chain amino acids supplementation
primo autore: GUALANO
pagine: 1-2
A. B. GUALANO 1*, T. BOZZA 1*, P. LOPES DE CAMPOS 1, 2, H. ROSCHEL 1, A. DOS SANTOS COSTA 1,
M. LUIZ MARQUEZI 1, 2, F. BENATTI 1, A. HERBERT LANCHA JUNIOR 1
Branched-chain amino acids supplementation
enhances exercise capacity and lipid oxidation during
endurance exercise after muscle glycogen depletion
Acknowledgements.—The authors would like to thank Fundação de
Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho
Nacional de Desenvolvimento Cientíco e Tecnológico (CNPq) for -
nancial support.
Part of this work was presented at the 52nd Annual Meeting of the
American College of Sports Medicine, held in Nashville, TN, USA;
June 3, 2005.
*Both authors have contributed equally to this manuscript.
Received on December 1, 2009.
Accepted on December 10, 2010.
Corresponding author: B. Gualano, Av. Professor Mello Moraes 65,
Butantã 05508-900, São Paulo, SP, Brazil.
E-mail address: gualano@usp.br
1School of Physical Education and Sport
University of Sao Paulo, Sao Paulo, SP, Brazil
2Institute of Biology, University of Campinas
Campinas, SP, Brazil
Aim. It has been demonstrated that branched-chain amino
acids (BCAA) transaminase activation occurs simultaneously
with exercise-induced muscle glycogen reduction, suggesting
that BCAA supplementation might play an energetic role in
this condition. This study aimed to test whether BCAA sup-
plementation enhances exercise capacity and lipid oxidation
in glycogen-depleted subjects.
Methods. Using a double-blind cross-over design, volunteers
(N.=7) were randomly assigned to either the BCAA (300 mg
. kg . day -1) or the placebo (maltodextrine) for 3 days. On the
second day, subjects were submitted to an exercise-induced gly-
cogen depletion protocol. They then performed an exhaustive
exercise test on the third day, after which time to exhaustion,
respiratory exchange ratio (RER), plasma glucose, free fatty
acids (FFA), blood ketones and lactate were determined. BCAA
supplementation promoted a greater resistance to fatigue when
compared to the placebo (+17.2%). Moreover, subjects supple-
mented with BCAA showed reduced RER and higher plasma
glucose levels during the exhaustive exercise test.
Results. No signicant differences appeared in FFA, blood ke-
tones and lactate concentrations.
Conclusion. In conclusion, BCAA supplementation increases
resistance to fatigue and enhances lipid oxidation during ex-
ercise in glycogen-depleted subjects.
K : Amino acids, branched-chain - Exercise - Glyco-
gen - Citric acid cycle.
The tricarboxylic acid cycle (TCA) is the major
common pathway for the oxidation of carbohy-
drates, lipids and some amino acids. The TCA cy-
cle is regulated directly by accessible pools of its
two substrates oxaloacetate and acetyl-CoA, and its
product citrate,1, 2 suggesting that the continuous
production of oxaloacetate can theoretically deter-
mine oxidative metabolic rate.2 However, it is well
established that only muscle and liver glycogen lev-
els cannot support the great oxaloacetate demand
imposed by either fasting or prolonged physical ac-
tivity.2 Hence, one can expect that lipid oxidation
might be partially limited by carbohydrate availabil-
ity.3 Accordingly, muscle fatigue seems to coincide
with depleted glycogen content during prolonged
exercise. Thus it seems plausible to discuss that in
this case, fatigue is related to provision mediated
through a limited supply of substrate (i.e., oxaloa-
cetate) to the TCA cycle and/or limitations in the
TCA ux due to reduced TCA intermediates con-
centration,4 although the latter has been a matter of
intense debate, for details, see the excellent review
by Bowtell et al. 2007.1
The TCA cycle is characterized by a continuous
generation of its intermediates, which releases CO2
BODY COMPOSITION, NUTRITION, SUPPLEMENTATION
ORIGINAL ARTICLES
J SPORTS MED PHYS FITNESS 2011;51:82-8
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Vol. 51 - No. 1 THE JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS 83
and other metabolites, such as citrate and glutamine.
During catabolic conditions (i.e., exhaustive exer-
cise or fasting), a constant loss of carbon skeletons
occurs, commonly referred as “cataplerosis”, which
need to be replenished by specic reactions aimed to
promote TCA expansion, namely “anaplerosis”. For
example, our group has demonstrated that oxaloac-
etate can be generated through aspartate, asparagine
and glutamate transamination.5, 6
Branched-chain amino acids (BCAA) which are
primarily oxidated in skeletal muscle, may contrib-
ute to energy metabolism during exercise as energy
sources and substrates to expand the pool of TCA
intermediates through anaplerosis reactions.7 Isoleu-
cine and valine may increase succinyl-CoA availa-
bility, possibly leading to an increase in oxaloacetate
concentration, which could hypothetically result in
a higher FFA oxidation, especially in a glycogen-
depleted condition (i.e., during fasting or prolonged
physical activity).
Also, it has been demonstrated that BCAA
transaminase activation occurs simultaneously with
exercise-induced muscle glycogen reduction.3, 8, 9 In
light of this, we hypothesized that glycogen deple-
tion might enhance the BCAA contribution to en-
ergy provision, thus delaying the onset of fatigue.
Therefore, the aim of this study was to test whether
BCAA supplementation improves exercise capacity
and FFA oxidation in glycogen-depleted subjects.
Materials and methods
Study population
Seven healthy and physically active male volun-
teers (age: 24±2 years, body mass index: 22.3±2.5
kg m-2, VO2peak: 47.2±3.9 ml kg-1 min-1) were select-
ed to participate in this study.
The study protocol was approved by the Universi-
ty’s Ethics Committee, and all eligible study subjects
gave written, informed consent before their partici-
pation.
Overall design
A double-blind cross-over design was used, in
which each subject completed two experimental
conditions randomly. At baseline, subjects under-
went maximal progressive treadmill exercise for
VO2max and anaerobic threshold determination (T1).
One week after T1, subjects were supplemented with
either BCAA (300 mg kg day -1) or placebo (mal-
todextrine, at the same dose) for three days. On the
second day of supplementation, subjects were sub-
mitted to an exercise-induced glycogen depletion
protocol (T2). On the following day, after a 10-hour
fast, subjects performed an exercise bout at 80% of
their anaerobic threshold until exhaustion (T3 or
T4). During this test, resistance to fatigue, respira-
tory exchange ratio (RER), plasma glucose, plasma
free-fatty acids (FFA) and blood ketones were deter-
mined. After a seven-day washout period, subjects
underwent the aforementioned protocol in a cross-
over fashion. Participants were instructed to main-
tain the same food intake pattern during the trials.
The experimental design is depicted in Figure 1.
VO2peak and anaerobic threshold determination (T1)
Subjects completed a graded, continuous exercise
test on a treadmill. The test commenced at 7 km/h
with incremental increases in speed (1.2 km/h ev-
ery 4 min with a 1 min interval for plasma deter-
minations) until voluntary exhaustion. Gas exchange
measurements (VO2, VCO2 , RER and VO2 peak de-
termination) were obtained continuously through-
out the test by a portable espirometer (K4®). Blood
lactate was analyzed every 4 minutes for anaerobic
threshold determination. Attainment of VO2max was
accepted when two of three criteria were met:
a plateau in VO2, a respiratory exchange ratio
(RER)> 1.1 and volitional exhaustion.
3-d
supplementation
3-d
supplementation
7-d
washout
T1 S1 S2T2 T2T3 T4
d
0 3 13 14 154 5
Figure 1.—Experimental design. Subjects (N.=7) were supple-
mented with either BCAA or placebo (S1) for 3 days. On the sec-
ond day, they were submitted to a glycogen depletion protocol
(T2). Then, they performed an exhaustive exercise test on the 3rd
day (T3). After a 7-day washout period, subjects received BCAA
or placebo in a cross-over fashion (S2) and then repeated T2.
Thereafter, they performed other exhaustive exercise tests (T4).
For further details, see Overall Design. T1 = VO2 max test; T2 =
glycogen depletion protocol; T3 and T4 = exhaustive exercise
tests; S1 and S2 = BCAA or placebo supplementation.
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Glycogen depletion protocol (T2)
On the second day of supplementation in both ex-
perimental conditions, subjects underwent an exer-
cise session aimed at glycogen depletion. This ses-
sion consisted of treadmill running for 45 minutes at
70% VO2 peak, followed by two 10-minute sprints at
90% VO2 peak, with a two-minute interval. After this
exercise the subjects remained fasted (~10 h) until
the experiment the next morning. Similar protocols
including continuous and interval exercise have been
reported to give a reduced muscle glycogen level the
following morning.10, 11
Exhaustive exercise tests (T3 and T4)
Subjects performed an exhaustive exercise test
which consisted of treadmill running at 80% of their
anaerobic threshold at a constant velocity (9.9±0.7
km/h) in glycogen depleted condition. Exhaustion
was determined when the subjects were not able to
maintain their initial speed or when test interruption
was requested. Blood samples were collected before
the test and every ve minutes for plasma glucose
and lactate determinations. Ketone bodies, FFA and
ammonia were measured immediately before and
after the test. RER was also determined at rest and
every ve minutes until exhaustion.
BCAA or placebo supplementation
As mentioned earlier, subjects received either en-
capsulated BCAA (300 mg . kg . day -1) or a placebo
(maltodextrine, at same dose) supplementation in a
randomized, cross-over, double-blind fashion. The
supplementation was given three days prior to T3
and T4, including on the days of tests. The BCAA
and placebo conditions were separated by a 7-day
washout period and for the rst trial (T3) 4 subjects
were randomly submitted to BCAA supplementation
and 3 subjects to placebo. For the second trial (T4),
the opposite distribution was adopted. Adherence to
the supplementation protocol was veried through
personal communication on a daily basis.
Plasma analysis
Blood samples were drawn and immediately cen-
trifuged at 4000 rpm for 15 minutes and stored at -20
°C until further analysis.
Plasma FFAs and ketones were analyzed using
commercial kits (Sigma®, SP, Brazil). Plasma glu-
cose and lactate were determined using automatic
lactimeter/glucosimeter (Yellow Spring 2300®, OH,
US). All analyses were performed in duplicate, and
the mean value was calculated.
Statistical analysis
SAS® proc Mixed Model was used to analyze re-
peated measures, and when applicable, Tukey Post
hoc was used for multiple comparisons. All data
is expressed as mean ± sd. The signicance level
adopted to reject the null hypothesis was P≤0.05.
Results
According to daily personal communication, sub-
jects’ compliance to supplementation protocol was
50
45
40
35
30
25
20
20
24
28
32
36
40
15
Time (min)
BCAA Placebo
A
B
*
Figure 2.—Time to exhaustion (min) in maximal exercise (T3
and T4) after BCAA and placebo supplementation. The subjects’
performance was signicantly greater after BCAA supplementa-
tion when compared to placebo (*P=0.001). A) Mean ± SD; B)
individual data.
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Vol. 51 - No. 1 THE JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS 85
100%. Moreover, no reports were received of any
deleterious effects during the study.
BCAA supplementation promoted a greater time
to exhaustion (+17.2%) when compared to the pla-
cebo (Figure 2). It is important to highlight that all
the subjects showed greater exercise capacity after
BCAA supplementation (Figure 2B).
Moreover, a reduction in RER was observed after
10 (1 vs. 1.08) and 20 (0.96 vs. 1.07) minutes of the
exhaustive exercise test (P<0.05), and a trend toward
a lower RER at 30 minutes (0.95 vs. 1.1) (P=0.08)
was observed following BCAA supplementation
when compared to the placebo (Figure 3). The
pooled RER data during the exhaustive exercise re-
veal that, in fact, BCAA supplementation diminished
RER when compared to the placebo (0.97±0.02 vs.
1.05±0.03, P=0.002), suggesting a shift from carbo-
hydrate to lipid oxidation.
Plasma glucose levels were higher at 20, 25 and 30
minutes (P=0.02, P=0.03 and P=0.06, respectively)
after BCAA supplementation when compared to the
placebo. We observed the same trend when consider-
ing pooled glycemic data during exhaustive exercise
(3.5±0.08 vs. 3.1±0.2, P=0.001) (Figure 4).
There were no signicant differences in plasmatic
FFA (Figure 5), blood ketones (Figure 6) and lactate
1.15
1.1
1.05
1
0.95
0.9
0.85
0.8
Respiratory exchange ratio (RER)
Baseline 10 20 30
Time (min)
Placebo
BCAA *
*
#
*1.1
1.05
1
0.95
0.9
0.85
BCAA Placebo
A B
5
4.5
4
3.5
3
2.5
2
1.5
Glycemia (mmol/L)
Baseline
5 10 15 20 25 30
Rest
Time (min)
Placebo
BCAA
*
#
*
*
4.5
4
3.5
3
2.5
2
BCAA Placebo
A B
Figure 3.—Respiratory exchange ratio (RER) after BCAA and placebo supplementation. A) BCAA led to a signicant reduced RER
after 10 and 20 minutes (*P=0.01) during an exhaustive exercise test (T3 and T4), suggesting an increase in lipid oxidation. Also, a
trend was noted toward an increase in RER after BCAA supplementation at 30 minutes (#P=0.08); B) pooled data only during exhaus-
tive exercise test (10 + 20 + 30 minutes) also indicated lower RER after BCAA supplementation compared to placebo (*P=0.002).
Figure 4.—Glycemic levels during exhaustive exercise test (T3 and T4) after BCAA and placebo supplementation. A) The subjects in
BCAA condition showed greater glucose concentration than in placebo trial at 20, 25 (*P=0.04) and 30 minutes (# trend P=0.06); B)
The pooled data throughout the exhaustive exercise test (5 + 10 + 15 + 20 + 25 + 30 minutes) also showed that BCAA supplementation
prevents the glycemic fall observed in placebo (*P=0.001). To convert mmol/L to mg/dL, multiply by 18.
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(data not shown) concentrations between the BCAA
and placebo conditions.
Discussion
The aim of the present study was to test whether
BCAA supplementation was able to improve exer-
cise capacity and FFA oxidation in glycogen-deplet-
ed subjects.
The main results of the present study demonstrate
that 3-day BCAA supplementation improved exer-
cise capacity, lipid oxidation and plasma glucose
levels during an exhaustive exercise in glycogen-
depleted subjects. On the other hand, BCAA sup-
plementation did not affect plasma ketones, plasma
FFA and lactate concentration.
TCA activity is regulated by the concentration of
its intermediates and by the balance between ana-
plerotic and cataplerotic reactions.1, 12 Theoretically,
during a lower carbohydrate availability condition
(i.e., prolonged fasting and/or glycogen depletion),
carbon skeletons provided by amino acids transami-
nation are the main substrates that replenish TCA
intermediates through anaplerotic reactions and he-
patic gluconeogenesis. However, the studies regard-
ing the contribution of supplementary amino acids
as an energy source during glycogen depletion are
contradictory. In fact, some authors indicate that
BCAA transamination during lower carbohydrate
availability might have zero effect on TCA interme-
diates concentration 13 or even stimulate cataplero-
sis, thus limiting oxidative activity.14, 15 These latter
authors hypothesized that, as a consequence of the
initial BCAA aminotransferase reaction, the oxida-
tion of BCAA places a carbon “drain” on the TCA
cycle, which may lead to a reduction in the muscle
concentration of 2-oxoglutarate or other TCAI. Ac-
cording to this theory, the BCAA-mediated drain of
2-oxoglutarate is normally counteracted by the re-
generation of this intermediate through the alanine
aminotransferase reaction, provided that sufcient
glycogen is available to sustain the rate of pyruvate
production. However, during conditions in which
glycogen availability becomes limited, and particu-
larly if the rate of BCAA oxidation is increased, it
was suggested that the concentrations of 2-oxoglu-
tarate and/or other TCA intermediates will decrease.
These authors have further proposed that this scenar-
io may lead to a “suboptimal concentration” of TCA
intermediates and impair oxidative energy provision
in skeletal muscle by reducing TCA ux. In contrast,
our group did not previously observe any changes in
the performance and TCA intermediates concentra-
tion of glycogen-depleted rats that were submitted
to intensive exercise, supplemented with BCAA or
isoleucine, leucine and valine alone (unpublished
data). Additionally, Wagenmakers theory has also
been refuted 13 demonstrating that BCAA ingestion,
Placebo
BCAA
12
8
6
4
2
0
PRE POST
10
FFA (mmol/L)
Placebo
BCAA
0.2
0.12
0.08
0.04
0
PRE POST
0.16
FFA (mmol/L)
Figure 5.—Free fatty acids (FFA) concentration immediately be-
fore and after the exhaustive exercise test, following BCAA and
placebo supplementation. No signicant differences were noted.
Figure 6.—Beta hydroxybutyrate concentration immediately be-
fore and after the exhaustive exercise test, following BCAA and
placebo supplementation. There were no signicant differences
between the trials.
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during conditions of reduced glycogen availability,
did not affect the concentration of 2-oxoglutarate or
other TCA intermediates in human skeletal muscle
during exercise. However, it is worthwhile to high-
light that subjects were not completely glycogen-
depleted (~200 mmol/kg dry wt).13 In the present
study, we used a severe protocol in order to induce
glycogen depletion (see Glycogen Depletion Pro-
tocol) and despite the fact that we were not able to
assess glycogen muscle content, we may presume
the effectiveness of this maneuver based on previ-
ous studies, which used similar protocol.10, 11 There-
fore, whilst the extent of glycogen depletion could
not be directly determined, it is far unlikely that a
substantial glycogen diminution did not occur. Our
ndings also are in disagreement with hypothesis of
Wagenmakers et al.,15 since we observed a greater
resistance to fatigue as a consequence of BCAA sup-
plementation. Collectively, these studies suggest that
any potential drain of TCA during exercise is likely
to be small and to not signicantly impact the total
concentration of intermediates, even following rigor-
ous glycogen depletion.
It has been suggested that TCA ux is regulated
by the condensation of proper amounts of oxaloac-
etate and citrate.2 Thus, the continuous production
of oxaloacetate can be considered a key step in oxi-
dative metabolism. As glycogen concentration itself
cannot support the oxaloacetate demand imposed by
severe fasting and exhaustive exercise, FFA oxidation
becomes limited by carbohydrate availability.2, 3 As-
suming the veracity of this hypothesis, it was expected
that a possible BCAA supplementation-mediated aug-
mentation in oxaloacetate concentration would lead to
increased lipid oxidation. In spite of no changes in se-
rum FFA concentration, we observed with interest that
BCAA supplementation promoted a decreased RER
when compared to the placebo, suggesting increased
lipid oxidation. Considering again that TCA may be a
limiting factor for lipid oxidation by the skeletal mus-
cle during exhaustive exercise,2 our ndings suggest
that BCAA supplementation may contribute to this
process, possibly expanding TCA ux. Furthermore,
the reduced RER can also reveal a BCAA supplemen-
tation-induced glycogen-sparing effect, which might
explain the greater exercise capacity. In fact, we and
others 16 veried that BCAA supplementation pro-
motes a higher hepatic and muscle glycogen concen-
tration in fasting and after exercise. However, caution
should be exercised because we were not able to per-
form muscle biopsies; therefore, we cannot conclude
if TCA intermediates (i.e., oxaloacetate) and muscle
glycogen concentration are indeed affected by BCAA
supplementation as we previously hypothesized.
Alternatively, we cannot rule out the hypothesis
that the improved glycemia maintenance during ex-
ercise as a result of BCAA supplementation might
also have contributed to a better exercise capacity,
since even a slight reduction of glycemia seems to
be associated with fatigue. Importantly, our nd-
ings suggest that BCAA supplementation appears to
prevent the exercise-induced hypoglycemia, particu-
larly in glycogen depleted subjects. Opposing our
results, Tang 17 observed no plasma glucose changes
in swimmers supplemented with BCAA for 15 days
after a 25-minute crawl stroke session. Nonetheless,
it is important to highlight that these athletes were
not in a glycogen-depleted condition. Calders et
al.18 veried that rats receiving BCAA signicantly
improved their resistance to fatigue compared with
those receiving saline, but not with those supple-
mented with glucose. Furthermore, these authors ob-
served that when glucose is administered before ex-
ercise, the supplementary administration of BCAA
had no additional effect on performance. Overall,
these ndings corroborate the hypothesis that the ef-
fect of BCAA administration on performance could
be related to carbohydrate availability during exer-
cise.
In addition to the hypothesis that BCAA supple-
mentation could enhance lipid oxidation, we specu-
lated that, in glycogen-depleted subjects, this sup-
plement would inhibit or attenuate plasma ketones
production as a result of a greater TCA expansion.
However, no signicant differences were noted in
beta hydroxybutyrate concentration. Moreover, we
cannot prove the hypothesis that BCAA supplemen-
tation-induced RER reduction would occur in par-
allel to lactate concentration decreasing. In contrast
to our ndings, De Palo et al.19 found a decreased
lactate concentration in athletes supplemented with
BCAA for one month. The authors conclude that the
lower lactate level at the end of an intense muscular
exercise may reect an improvement of BCAA use,
due to the chronic supplementation with BCAA. Ap-
parently, the short-term supplementation used in our
study may partially explain this discrepancy. Thus,
blood ketones and lactate concentration did not pro-
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GUALANO BRANCHED-CHAIN AMINO ACIDS SUPPLEMENTATION
88 THE JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS March 2011
vide evidence for explaining the higher exercise ca-
pacity after BCAA supplementation in the present
study.
Of note, the reader should be aware that practical
application of the present ndings has some limita-
tions, since it seems unreasonable to give supple-
mentary amino acids instead carbohydrate to an in-
dividual in glycogen depleted state. In fact, one can
say that of more practical relevance are the previous
ndings that BCAA conferred no further benet to
exercise performance when subjects were also give
glucose prior to exercise. Perhaps most importantly,
however, is the fact that our experimental design al-
lowed us to obtain direct evidence that BCAA in-
gestion do not induce fatigue in glycogen depletion
state, contrasting the previous hypothesis by Wagen-
makers et al.14, 15 Additionally, even though our re-
sults are consistent in all of the subjects, our sample
is rather small, which warrants further investigation.
In summary, BCAA supplementation increases re-
sistance to fatigue and enhances lipid oxidation dur-
ing exercise in glycogen-depleted subjects. These
actions do not seem to be related to changes in plas-
ma FFA, lactate and blood ketones concentration.
Further studies should consider the use of a muscle
biopsy aimed to investigate the mechanisms under-
lying these ndings.
References
1. Bowtell JL, Marwood S, Bruce M, Constantin-Teodosiu D, Green-
haff PL. Tricarboxylic acid cycle intermediate pool size: functional
importance for oxidative metabolism in exercising human skeletal
muscle. Sports Med 2007;37:1071-88.
2. Curi R, Lagranha CJ, Rodrigues JR, Pithon-Curi TC, Lancha Jr AH,
Pellegrinotti IL et al. The Krebs cycle as limiting factor for fatty ac-
ids utilization during aerobic exercise. Arq Bras Endocrinol Metab
2003;47:135-43.
3. Gibala MJ, Young ME, Taegtmeyer H. Anaplerosis of the citric acid
cycle: role in energy metabolism of heart and skeletal muscle. Acta
Physiol Scand 2000;168:657-65.
4. Sahlin K, Tonkonogi M, Soderlund K. Energy supply and muscle
fatigue in humans. Acta Physiol Scand 1998;162:261-6.
5. Lancha Jr AH, Recco MB, Abdalla DS, Curi R. Effect of aspartate,
asparagine, and carnitine supplementation in the diet on metabo-
lism of skeletal muscle during a moderate exercise. Physiol Behav
1995;57:367-71.
6. Marquezi ML, Roschel HS, Costa AS, Sawada LA, Lancha Jr
AH. Effect of aspartate and asparagine supplementation on fatigue
determinants in intense exercise. Int J Sport Nutr Exerc Metab
2003;13:65-75.
7. Shimomura Y, Murakami T, Nakai N, Nagasaki M, Harris RA. Ex-
ercise promotes BCAA catabolism: effects of BCAA supplementa-
tion on skeletal muscle during exercise. J Nutr 2004; 134:1583S-
87S.
8. Van Hall G, Raaymakers JSH, Saris WHM, Wagenmakers AJM.
Ingestion of branched-chain amino acids and tryptophan dur-
ing sustained exercise: failure to affect performance. J Physiol
1995;486:789-94.
9. Van Hall G, McLean DA, Saltin B, Wagenmakers AJM. Mecha-
nisms of activation of muscle branched-chain a-keto acid dehydro-
genase during exercise in man. J Physiol 1996;494:899-905.
10. Van Hall G, van der Vusse GJ, Söderlund K, Wagenmakers AJ.
Deamination of amino acids as a source for ammonia production
in human skeletal muscle during prolonged exercise. J Physiol
1995;489:251-61.
11. Blomstrand E, Saltin B. Effect of muscle glycogen on glucose, lac-
tate and amino acid metabolism during exercise and recovery in hu-
man subjects. J Physiol 1999;1:293-302.
12. Lancha Jr AH, Recco MB, Curi R. Pyruvate carboxylase activity in
the heart and skeletal muscles of the rat. Evidence for a stimulating
effect of exercise. Biochem Mol Biol Int 1994;32:483-9.
13. Gibala MJ, Lozej M, Tarnopolsky MA, McLean C, Graham TE.
Low glycogen and branched-chain amino acid ingestion do not
impair anaplerosis during exercise in humans. J Appl Physiol
2001;87:1662-7.
14. Wagenmakers AJ, Coakley JH, Edwards RH. Metabolism of
branched-chain amino acids and ammonia during exercise: clues
from McArdle’s disease. Int J Sports Med 1990;11(Suppl 2):S101-
13.
15. Wagenmakers AJ, Beckers EJ, Brouns F, Kuipers H, Soeters PB,
Van der Vusse GJ et al. Carbohydrate supplementation, glycogen
depletion, and amino acid metabolism during exercise. Am J Physi-
ol 1991; 260:E883-90.
16. De Araujo JA, Falavigna G, Rogero MM, Pires, ISO, Pedrosa, RG,
Castro IA et al. Effect of chronic supplementation with branched-
chain amino acids on the performance and hepatic and muscle gly-
cogen content in trained rats. Life Sci 2006;79:1343-8.
17. Tang FC. Inuence of branched-chain amino acid supplementation
on urinary protein metabolite concentrations after swimming. J Am
Coll Nutr 2006;25:188-94.
18. Calders P, Matthys D, Derave W, Pannier JL. Effect of branched-
chain amino acids (BCAA), glucose, and glucose plus BCAA on
endurance performance in rats. Med Sci Sports Exer 1999;31:583-
7.
19. De Palo EF, Gatti R, Cappellin E, Schiraldi C, De Palo CB, Spinel-
la P. Plasma lactate, GH and GH-binding protein levels in exer-
cise following BCAA supplementation in athletes. Amino Acids
2001;20:1-11.
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