Group Title: Journal of the International Society of Sports Nutrition 2007, 4:2
Title: The effects of short-term alpha-ketoisocaproic acid supplementation on exercise performance: a randomized controlled trial
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Title: The effects of short-term alpha-ketoisocaproic acid supplementation on exercise performance: a randomized controlled trial
Series Title: Journal of the International Society of Sports Nutrition 2007, 4:2
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Creator: Yarrow JF
Parr JJ
White LJ
Borsa PA
Stevens BR
Publication Date: 39276
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Volume ID: VID00001
Source Institution: University of Florida
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Journal of the International Society

of Sports Nutrition Bioed Centra


Research article C

The effects of short-term alpha-ketoisocaproic acid
supplementation on exercise performance: a randomized
controlled trial
Joshua F Yarrow*1,2, Jeffrey J Parr', Lesley J White', Paul A Borsal and
Bruce R Stevens3


a -;


Address: 'University of Florida, Department of Applied Physiology & Kinesiology, Center for Exercise Science, Gainesville, FL 32611, USA,
2Malcolm Randall VA Medical Center, GRECC, Gainesville, FL 32608, USA and 3University of Florida College of Medicine, Department of
Physiology and Functional Genomics, Gainesville, FL 32610, USA
Email: Joshua F Yarrow* jfyarrow@ufl.edu; Jeffrey J Parr jparr@hhp.ufl.edu; Lesley J White lwhite@hhp.ufl.edu;
Paul A Borsa pborsa@hhp.ufl.edu; Bruce R Stevens stevensb@ufl.edu
* Corresponding author



Published: 13 July 2007 Received: 7 June 2007
journal of the International Society of Sports Nutrition 2007, 4:2 doi:10.1 186/1550-2783-4- Accepted: 13 July 2007
2
This article is available from: http://www.jissn.com/content/4/1/2
2007 Yarrow et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Abstract
Background: This study examined the efficacy of short-term alpha-ketoisocaproic acid (KIC)
monotherapy supplementation immediately prior to moderate- and high-intensity single bout
exercise performance.
Methods: Thirteen resistance trained men (22.8 2.5 years; 81.6 12.6 kg) participated in a
prospective, randomized, double blind, placebo controlled crossover experiment. Each subject
completed one familiarization and four experimental trials with either 1.5 g or 9.0 g of either KIC
or isocaloric placebo control (CONT), following an overnight fast. During the experimental trials,
subjects consumed the supplement regimen and then completed leg and chest press repetitions to
failure and 30 s of repeated maximal vertical jumping (VJ) on a force plate.
Results: In this treatment regimen, no significant differences (p > 0.05) were observed between
dosages or conditions for leg press (low CONT = 19.8 0.4 SEM, low KIC = 21.0 0.5, high
CONT = 20.1 0.3, high KIC = 22.4 0.6) or chest press (low CONT = 18.1 0.2, low KIC =
18.5 0.3, high CONT = 17.8 0.3, high KIC = 18.0 0.3) repetitions to failure. Additionally, no
significant differences were observed for peak or mean VJ performance (low CONT = 34.6 2.2
cm and 28.6 1.8 cm; low KIC = 35.6 2.0 cm and 29.4 1.6 cm; high CONT = 35.7 2.1 cm
and 29.4 1.7 cm; high KIC = 34.8 2.3 cm and 28.3 1.7 cm), respectively.
Conclusion: Based on our results, we conclude that acute KIC ingestion by itself with no other
ergogenic supplement, immediately prior to exercise, did not alter moderate- nor high-intensity
single-bout exercise performance in young resistance-trained males. This study addressed single-
dose single-bout performance events; the efficacy of KIC monotherapy supplementation on
repeated high-intensity exercise bouts and long-term exercise training remains unknown.





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Journal of the International Society of Sports Nutrition 2007, 4:2



Background
More than 70% of athletes report using nutritional sup-
plements to improve health and/or sports performance,
[1] however, few supplements have shown ergogenic
potential under controlled experimental conditions [19].
Alpha-ketoisocaproic acid (KIC), the ketoacid of leucine,
has been shown to enhance high intensity exercise per-
formance when consumed in combination with glycine
and L-arginine (GAKIC) [6,26], and reduce exercise
induced muscle damage and preserve skeletal muscle
force production when ingested with B-hydroxy-p-meth-
ylbutyrate (HMB) [27] However, the possibility that lone
KIC supplementation augments exercise performance has
not been previously explored.

With moderate- and high-intensity exercise, factors such
as total energy supply or local muscle fatigue may limit
maximal anaerobic power [8] through reduced force out-
put in skeletal muscle [9]. Theoretically, supplemental
KIC may enhance exercise performance by 1) promoting
total muscle energy supply, [5,11,28] 2) attenuating NH3
accumulation, [15,21] 3) and/or reducing exercise
induced muscle damage [27]. For example, KIC adminis-
tration is purported to spare glucose utilization by skeletal
muscle, possibly by inhibiting glycogen deposition and/
or the pyruvate dehydrogenase enzyme complex in skele-
tal muscle [5,7]. Further, the liver is capable of converting
KIC to ketone bodies [11,28], thus increasing the poten-
tial energy supply during exercise [2]. Additionally, KIC is
readily aminated to leucine, via leucine dehydrogenase
and/or branched chain amino acid transferase at the
expense of NH3, in a variety of tissues including skeletal
muscle, [14,15,21] which may ultimately decrease fatigue
and preserve skeletal muscle force production during
intense exercise [3].

Although KIC supplementation has the potential to aug-
ment moderate- and high-intensity exercise performance,
an effective dosage of KIC has not been determined. We
have previously reported that serum KIC concentrations
increase 150-300% following ingestion of 1.5 g-9.0 g
KIC [29]. Therefore, the purpose of this study was to test
the efficacy of supplementing both a low (1.5 g) and high
(9.0 g) dosage of KIC immediately prior to single bout
exercise performance. We hypothesized that supplemen-
tal KIC would improve both moderate- and high-intensity
muscle performance, compared to placebo, and that a
higher dose would have more pronounced results than a
lower dose of KIC.

Methods
Subjects
Thirteen males (22.8 2.5 years; 81.6 12.6 kg; 16.7%
body fat) volunteered from the general University popula-
tion. The number of participants exceeded that indicated


http://www.jissn.com/content/4/1/2


by an a priori power analysis (P = 0.80, a = 0.05). To be
included, subjects must have participated in upper and
lower body resistance training a minimum of three days
week-1 for the previous two months and been accus-
tomed to one-repetition maximum (1RM) testing. Sub-
jects were excluded if they were a competitive athlete, had
taken any supplement intended to improve muscle per-
formance during the previous month, or self-reported a
diagnosis of diabetes mellitus, aminoacidurias, maple
syrup urine disease, renal failure, muscle wasting, hyper-
tension, abdominal radiotherapy, intestinal resection, or
acute illness. All study participants signed a written
informed consent, approved by the University Institu-
tional Review Board.

Study Design
The overall design of this study was a prospective, rand-
omized, double blind, placebo controlled, crossover
scheme. Each subject performed a familiarization trial
and four experimental trials. Prior to each experimental
trial, KIC (Pharmaceutical Ingredients Ltd., Dayton, N.J.)
or an isocaloric placebo (sucrose) was orally consumed in
500 mg capsules. Each subject participated in two low
dose sessions and two high dose sessions in a completely
randomized order (Figure 1). During the low dose condi-
tions, the supplement was consumed 25 minutes prior to
exercise testing. Whereas in the high dose conditions the
supplement was consumed in two equal doses (45 min-
utes and 25 minutes prior to testing), in order to offset the
possibility of any intestinal distress that might be associ-
ated with high dose bolus amino acid supplementation.
The dosing schedule and specific dosages selected for this
study (1.5 g and 9.0 g) were chosen based on previous
work from our laboratory indicating that serum KIC con-
centrations increase ~150-300% within 45 minutes of
ingesting 1.5 g, 3.0 g, and 9.0 g KIC [29].

In our study, no more than two trials were performed per
week, with a minimum of 72 hours separating sessions.
Participants were instructed to continue their normal
resistance-training program; however, a minimum of 48
hours layoff from resistance exercise was required prior to
each experimental trial. No additional attempt was made
to control outside activity other than to request they per-
form their normal daily activities. Additionally, each
experimental trial was conducted following a 10-hour
overnight fast to account for the possible influence of
energy intake on exercise performance.

Familiarization Session
During the first laboratory visit, anthropometric measure-
ments (body mass and body composition) were collected.
Body mass was measured on a calibrated medical scale.
Body composition was determined using the 7-site skin-
fold method [12]. Additionally, a 1RM was performed on


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Journal of the International Society of Sports Nutrition 2007, 4:2


ual performance scores and group mean performance
scores + standard error (SE). No significant differences
between conditions (KIC vs. placebo) or dose (high dose
vs. low dose) for number of repetitions performed on
either the 50% 1RM leg press or chest press test were
observed (p > 0.05).

30 s Vertical Jump Test
Results from the 30 s VI test are presented in Figures 4
(Peak and Mean VJ) and 5 (Work Decrement); graphs
depict group mean performance scores + SE. The VJ results
are based on the performance of 10 subjects because data
on three subjects was lost due to equipment failure. The
peak and mean VJ values (cm) + SE for the 30 s VJ test were
34.6 + 2.2 and 28.6 1.8 (low placebo), 35.6 + 2.0 and
29.4 1.6 (low KIC), 35.7 2.1 and 29.4 + 1.7 (high pla-
cebo), and 34.8 + 2.3 and 28.3 1.7 (high KIC), respec-
tively. Work was reduced by ~18-19% similarly across all
groups. The total work values (Joules) SE were 5968 +
360 (low placebo), 6170 410 (low KIC), 6097 + 369
(high placebo), and 6067 365 (high KIC). No signifi-
cant differences between conditions or doses were
observed for peak or mean VJ height, work decrement, or
total work (p > 0.05).

Discussion
We designed our study to determine the efficacy of con-
suming either a low (1.5 g) or high (9.0 g) dose of KIC
immediately prior to moderate- and high-intensity single
bout exercise performance. Contrary to our hypothesis,
KIC ingestion did not improve exercise performance, at
either dose. Although there are no published reports doc-
umenting the efficacy of lone KIC supplementation on
moderate- or high-intensity exercise performance, previ-


24


22

20

18

16

14

12


1.5g Placebo


ous studies have shown that 3.2 g KIC given in combina-
tion with 6.0 g glycine and 2.0 g L-arginine (GAKIC)
enhanced high-intensity exercise performance [6,26].

The inconsistency of our findings with previous GAKIC
studies [6,26] may, be due in-part to the differences in
exercise protocols. For example, Buford and Koch [6]
observed a delay in fatigue between repeated high-inten-
sity 10 s maximal cycling bouts, performed after GAKIC
ingestion. Additionally, Stevens et al. [26] reported that
GAKIC enhanced isokinetic peak torque and total work,
and delayed both intra- and inter-set fatigue during a
repeated 35-repetitions (90 sec-1) maximal isokinetic
knee extension protocol. Further, van Someren et al. [27]
reported that KIC + HMB reduced skeletal muscle damage
following repeated bouts of resistance exercise. In contrast
to previous studies, [6,26,27] we examined the efficacy of
administering lone KIC prior to single bouts of exercise
and observed no alterations in exercise performance
attributable to KIC. Our results suggest that repeated high-
intensity exercise bouts may be necessary for the prospec-
tive ergogenic effects of KIC to become apparent, as KIC
potentially 1) reduces skeletal muscle NH3 concentra-
tions, [21] 2) alters anaerobic energetic, [5,28] and/or 3)
attenuates exercise induced muscle damage [27]. Future
research evaluating the effects of KIC administration prior
to repeated high-intensity exercise bouts may assist in
delineating the ergogenic potential of KIC.

Alternatively, our results may suggest that the previously
reported ergogenic effects of GAKIC are due to the inclu-
sion of glycine and/or L-arginine in the GAKIC formula-
tion. Diets supplemented with 1% glycine and 2% L-
arginine have been shown to increase intramuscular crea-


24


22

20

18

16

14

12

10


1.5g KIC


p p

p p



p


9.0g Placebo


9.0g KIC


Figure 2


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hftp://www.jissn.com/content/4/l/2








Journal of the International Society of Sports Nutrition 2007, 4:2


e


1.5g Placebo


1.5g KIC


9.0g Placebo 9.0g KIC


tine phosphate concentrations in laboratory animals [16],
although, these results have not been verified in humans.
Additionally, orally ingested L-arginine has been shown
to improve exercise performance in cardiovascular disease
patients [17,23], possibly by upregulating nitric oxide
dependent skeletal muscle vasodilation [22]. Schaefer and
Piquard [25] have also reported that a 3 g arginine infu-
sion reduced both blood lactate and NH3 peak concentra-
tions during cardiovascular exercise, suggesting that L-
arginine has the potential to augment exercise perform-
ance in healthy individuals. To our knowledge, no previ-
ous research has compared the metabolic responses to
KIC, glycine, and/or L-arginine supplementation prior to
high-intensity exercise.


38 Peak VJ Height
T D Mean VJ Height


.9 32

30

28

26
Low KIC Low P High KIC High P

Figure 4


Conclusion
In theory, short-term KIC supplementation may acutely
enhance exercise performance through a variety of mech-
anisms. However, our results demonstrate that ingestion
of either a low (1.5 g) or high (9.0 g) dose of mono-
therapy KIC prior to exercise does not alter moderate- or
high-intensity exercise performance. The efficacy of KIC
monotherapy supplementation prior to repeated high-
intensity exercise bouts and long-term exercise training
remains unknown.

Competing interests
The authors (JFY, JJP, LJW, and PAB) declare that they
have no competing interests. BRS serves as a consultant to

1400 Jumps 1-5
0 Last 5 jumps
1300

1200


S1100


Low KIC


Low P


High KIC High P


Figure 5


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Figure 3


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Journal of the International Society of Sports Nutrition 2007, 4:2




lovate Health Sciences Research Inc, and receives royalties
assigned to GAKIC. All the authors in this study independ-
ently collected, analyzed, and interpreted the results,
while lovate had no role in data collection, analysis, inter-
pretation, nor manuscript preparation in any manner.


Authors' contributions
JFY participated in design of the study, collected data, ana-
lyzed statistics, and drafted the manuscript. JJP collected
data and helped to draft the manuscript. LJW and PAB
participated in design of the study and helped to draft the
manuscript. BRS conceived of the study, participated in
design of the study, analyzed statistics, and helped to draft
the manuscript. All authors read and approved the final
manuscript.


Acknowledgements
The authors thank the subjects who participated in this study, which was
funded by the University of Florida.

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