Carbohydrate Availability and Muscle Energy

Metabolism during Intermittent Running

ANDREW FOSKETT1, CLYDE WILLIAMS2, LESLIE BOOBIS3, and KOSTAS TSINTZAS4
1
Institute of Food, Nutrition and Human Health, Massey University, Auckland, NEW ZEALAND; 2School of Sport and
Exercise Sciences, Loughborough University, Loughborough, UNITED KINGDOM; 3Sunderland Royal Hospital,
Sunderland, UNITED KINGDOM; and 4Centre for Integrated Systems Biology and Medicine, School of Biomedical
Sciences, Nottingham University, Nottingham, UNITED KINGDOM

Abstract
FOSKETT, A., C. WILLIAMS, L. BOOBIS, and K. TSINTZAS. Carbohydrate Availability and Muscle Energy Metabolism during
Intermittent Running. Med. Sci. Sports Exerc., Vol. 40, No. 1, pp. 96–103, 2008. Purpose: To examine the influence of ingesting a
carbohydrate–electrolyte (CHO-E) solution on muscle glycogen use and intermittent running capacity after consumption of a
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carbohydrate (CHO)-rich diet. Methods: Six male volunteers (mean T SD: age 22.7 T 3.4 yr; body mass (BM) 75.0 T 4.3 kg; V̇O2max
60.2 T 1.6 mLIkgj1Iminj1) performed two trials separated by 14 d in a randomized, crossover design. Subjects consumed either a 6.4%
CHO-E solution or a placebo (PLA) in a double-blind fashion immediately before each trial (8 mLIkgj1 BM) and at 15-min intervals
(3 mLIkgj1 BM) during intermittent high-intensity running to fatigue performed after CHO loading for 2 d. Muscle biopsy samples
were obtained before exercise, after 90 min of exercise, and at fatigue. Results: Subjects ran longer in the CHO-E trial (158.0 T 28.4
min) compared with the PLA trial (131.0 T 19.7 min; P G 0.05). There were no differences in muscle glycogen use for the first 90 min
of exercise (~2 mmol of glucosyl units per kilogram of dry matter (DM) per minute). However, there was a trend for a greater use in the
PLA trial after 90 min (4.2 T 2.8 mmolIkgj1 DMIminj1) compared with the CHO-E trial (2.5 T 0.7 mmolIkgj1 DMIminj1; P = 0.10).
Plasma glucose concentrations were higher at fatigue in the CHO-E than in the PLA trial (P G 0.001). Conclusions: These results
suggest that CHO-E ingestion improves endurance capacity during intermittent high-intensity running in subjects with high preexercise
muscle glycogen concentrations. The greater endurance capacity cannot be explained solely by differences in muscle glycogen, and it
may actually be a consequence of the higher plasma glucose concentration towards the end of exercise that provided a sustained source
of CHO for muscle metabolism and for the central nervous system. Key Words: INTERMITTENT EXERCISE, FATIGUE,
CARBOHYDRATE–ELECTROLYTE SOLUTION, CARBOHYDRATE LOADING

T
he benefits of consuming a high-carbohydrate
(CHO) diet in preparation for prolonged exercise
have been extensively documented (31). Most of the
studies reported in these reviews used prolonged constant-
intensity cycling or running to examine the efficacy of
consuming carbohydrate before and during exercise.
Although prolonged cycling and running are popular forms
of exercise, both as competitive sports and for recreation,
there is greater participation in sports that involve inter-
mittent exercise, such as football, soccer, rugby, and
hockey, and also in multiple-sprint sports, such as basket-
ball, tennis, and badminton. Participation in these sports
involves a combination of brief periods of high-intensity
Address for correspondence: Andrew Foskett, Ph.D., Institute of Food,
Nutrition and Human Health, Massey University, Private Bag 102 904,
North Shore Mail Centre, Auckland, New Zealand; E-mail: a.foskett@
massey.ac.nz.
Submitted for publication May 2007.
Accepted for publication August 2007.
0195-9131/08/4001-0096/0
MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ
Copyright Ó 2007 by the American College of Sports Medicine
DOI: 10.1249/mss.0b013e3181586b2c
exercise punctuated by periods of low-intensity exercise
such as jogging and walking. The high-intensity periods last
no more than 2 to 5 s but are repeated frequently, often with
short rest periods of only 20–30 s (25). A number of recent
studies have examined the influences of carbohydrate
solutions on performance during intermittent exercise.
These studies are based on a shuttle running protocol that
requires participants to complete repeated periods (often
15 min) that include walking, jogging, running, and
sprinting for a distance of 20 m (21), often to the point of
volitional fatigue. The combination and timing of these
activities are designed to closely resemble those in sports
such as soccer and basketball (21,29).
A number of studies using these intermittent exercise
protocols have shown that ingesting glucose-based carbo-
hydrate solutions immediately before and during exercise
improves endurance capacity (19,29). It has been suggested
that the improved endurance running capacity may be a
consequence of a glycogen-sparing effect. Nicholas and
colleagues (20) report that ingesting a carbohydrate–
electrolyte solution (CHO-E) during 90 min of intermittent
high-intensity shuttle running resulted in less muscle
glycogen use, particularly in the Type II fiber population,
than when a placebo solution was ingested. This was a

96

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similar result to that reported for constant-pace treadmill
running to exhaustion, where glycogen sparing, after the
ingestion of a CHO-E solution, was evident only in Type I
(28). However, those studies were performed on subjects
who did not carbohydrate-load before the trials and who,
therefore, had normal resting muscle glycogen stores.
It is well known that a carbohydrate-rich diet after
prolonged exercise increases muscle and liver glycogen
stores and improves submaximal exercise capacity com-
pared with consuming a normal, mixed diet (2). However,
there is some evidence that the performance benefits of
ingesting a carbohydrate solution during exercise may be
relatively minor when preexercise muscle and liver glyco-
gen stores are high. For example, Widrick and colleagues
(30) found no improvements in performance during 120
min of self-paced cycling when their carbohydrate-loaded
subjects ingested a carbohydrate solution during exercise,
suggesting that endogenous body glycogen stores affect the
efficacy of exogenous CHO provision during exercise.
Therefore, the purpose of this study was to investigate the
effects of ingesting a CHO-E solution on performance and
muscle glycogen use during prolonged intermittent high-
intensity running to fatigue in carbohydrate-loaded men.
We hypothesized that a preexercise increase in the body_s
glycogen stores may reduce the benefits of ingesting a
carbohydrate solution during intermittent high-intensity
running on both performance and muscle glycogen use.
METHODS
Subjects. Six recreationally active male games players
(age 22.7 T 3.4 yr; body mass (BM) 75.0 T 4.3 kg; height
1.8 T 0.1 m; V̇O 2max 60.2 T 1.6 mLIkg j1 Imin j1 )
volunteered, with informed written consent, to participate
in this study, which was approved by the Loughborough
University ethics committee.
FIGURE 1—A schematic diagram of the experimental protocol.
MUSCLE METABOLISM DURING INTERMITTENT RUNNING
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Preliminary measurements. Subjects performed a
multistage fitness test (23) to assess their V̇O2max. Subjects
performed the intermittent shuttle running protocol for
45 min (described in the Experimental protocol section) to
familiarize themselves with the running patterns and
experimental procedures. They were first matched for
V̇O2max values and then, where possible, their sprint
performance. This was undertaken so that the competition
between the paired subjects would increase motivation,
especially during the latter stages of the protocol.
Experimental design. Subjects performed two
experimental trials separated by 14 d, after carbohydrate
loading for 2 d. To eliminate any trial order effect,
treatments were assigned randomly in a crossover design.
On each occasion, subjects consumed either a 6.4%
maltodextrin CHO-E solution (sodium 50.4 mLI100
mLj1; potassium 10.3 mLI100 mLj1; osmolality 115
mOsmIkgj1) (GlaxoSmithKline, UK) or a taste-matched
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placebo (PLA) free of carbohydrate (sodium 2.0 mLI100
mLj1; potassium 11.1 mLI100 mLj1; osmolality 25
mOsmIkgj1). Solutions were administered in a double-
blind fashion immediately before the trials (8 mLIkgj1 BM)
and at subsequent 15-min intervals (3 mLIkgj1 BM) until
cessation of the exercise. Previous unpublished studies from
our laboratory have shown these fluid volumes to be well
tolerated during intermittent high-intensity running.
Ingestion of the preexercise bolus and the smaller volumes
every 15 min provided exogenous CHO delivery of approx-
imately 90 gIhj1 in the CHO-E trial.
Experimental protocol. Subjects performed a
glycogen-reducing trial comprising 90 min of intermittent
shuttle running (21) 48 h before the experimental trials, and
they refrained from strenuous exercise, caffeine, tobacco,
and alcohol during the recovery period (Fig. 1). After the
glycogen-reducing trial, subjects were administered a
carbohydrate-rich diet for 48 h (energy intake $ 55 kcalI
Medicine & Science in Sports & Exercised 97
 kgj1 BMIdj1; carbohydrate $ 10 gIkgj1 BMIdj1 (70% of
energy intake); fat $ 1 gIkgj1 BMIdj1 (15%); protein $ 2
gIkgj1 BMIdj1 (15%)). Subjects reported to the laboratory
for the experimental trial after an overnight fast (Q 10 h),
and they voided before the measurement of nude BM. A
urine sample was collected before exercise and at fatigue
and was analyzed for osmolality, using a cryoscopic
osmometer (Osmomat 030). An indwelling cannula
(Venflon, 16-18G, Ohmeda, Hatfield, Herts, UK) was
inserted into an antecubital vein and kept patent by frequent
flushing with sterile saline. A resting muscle sample was
then obtained from the middle portion of m. vastus lateralis
by needle biopsy. Subjects stood for 15 min before a resting
blood sample was obtained. Resting heart rate was
monitored during a 5-min period. Ten minutes before
commencing the main trial, the subjects consumed the
prescribed solution and completed a standardized warm-up
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and stretching protocol.
On completion of the 90 min of intermittent running, a
second muscle sample was obtained after the subject had
been transferred to an examination couch in the laboratory
adjacent to the sports hall. After this sample, subjects ran to
volitional fatigue or until they were withdrawn by the
investigators, at which point a final muscle sample was
obtained. Subjects were withdrawn by the investigators
if they failed to maintain the desired exercise intensity (as
dictated by the audio signal) or if their sprint performance
declined to G 95% of the mean sprint time for the first
45 min.
Exercise protocol. The intermittent exercise protocol
used in the glycogen-depleting trials and the main
experimental trials was the Loughborough Intermittent
Shuttle-running Test (LIST) (21). The LIST is a free-
running exercise protocol designed to simulate the activity
patterns of a game of soccer (Fig. 1). Subjects ran the LIST
for 90 min in six blocks of 15 min separated by 3-min rest
periods. After 90 min, subjects continued with this pattern
of intermittent shuttle running, this time with no rest breaks,
until fatigue. Fluid was administered during the rest phases
for the first 90 min and then at 15-min intervals during the
walking phases of the continuous protocol.
Heart rate was monitored every 15 s during exercise,
using short-range telemetry (Polar Model 810, Kempele,
Finland), and the mean was recorded for each 15-min
exercise period and the run to fatigue. Subjective ratings of
perceived exertion were recorded, using the Borg scale (4),
during the walk phase of the final cycle of each block.
Blood and muscle analyses. An 11-mL blood
sample was taken at rest, after 30, 60, and 90 min of
exercise, and at fatigue, with 4 mL dispensed into lithium
heparinized tubes. From the venous blood samples,
duplicate 20-KL aliquots were deproteinized with 200 KL
of 2.5% perchloric acid, centrifuged, and frozen at j20-C
for subsequent analysis of blood lactate concentration, using
a method previously described (17). Hemoglobin and
hematocrit concentrations were analyzed in triplicate by
98 Official Journal of the American College of Sports Medicine
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the cyanomethemoglobin method (Boehringer Mannheim
GmbH Diagnostica, Mannheim, Germany) and microcen-
trifugation (Hawksley Ltd., Lancing, UK), respectively, and
the results obtained were used to calculate changes in
plasma volume (9). The remaining whole blood was
centrifuged at 4-C, and the plasma was divided into aliquots
and frozen at j20-C for later analysis of free fatty acids
(FFA) and glucose, using commercially available kits
(NEFA-C test, WAKO, Germany and Roche, R-Biopharm
GmbH, Germany respectively), and glycerol, using a
method described in our earlier study (27). Serum was
obtained by centrifugation for 15 min at 4-C of coagulated
whole blood; this was stored at j70-C for subsequent
analysis of insulin (Coat-A-Count Insulin, Diagnostica
Products Corporation (DPC), Caernarfon, UK) and cortisol
(Coat-A-Count Cortisol, DPC, Caernarfon, UK), using
commercially available radioimmunoassay kits and
an automated gamma counter (Packard, Cobra 5000,
Pangbourne, UK).
Muscle samples were obtained through separate incisions
from the lateral portion of the vastus lateralis muscle, using
the needle biopsy procedure with suction applied (10). All
incisions were made through the skin and muscle fascia
under local anesthetic (2–3 mL of 1% lignocaine) before the
start of exercise while the subjects lay supine on an
examination couch. Each muscle sample was snap-frozen
in liquid nitrogen, and, at a later date, a 15- to 20-mg
fragment of muscle was placed in a freeze-dryer (Pirani 10,
Edwards, UK) for 24 h at j50-C and between j10j1 and
j10j2 mbar. The freeze-dried muscle fragments were then
washed with 1 mL of petroleum ether to remove any excess
lipid before each sample was reduced to a fine powder
using an agate pestle and mortar. The precise quantity of
powder obtained from each fragment was determined using
an electronic balance scale (Mettler AE240, Switzerland),
and these powdered samples of dry matter (DM) were
then stored at j80-C, pending later acid extraction and
metabolite analysis.
The mixed muscle extracts were assayed for progly-
cogen, macroglycogen, phosphocreatine (PCr), free glu-
cose, glucose-6-phosphate (G-6-P), and lactate, using
methods described in our earlier studies (27,28). Muscle
samples were also analyzed for the purine nucleotides ATP,
ADP, and IMP, using a method previously described (12).
Statistical analyses. Statistical comparisons of the
physiological, biochemical, and metabolic parameters were
analyzed using a two-way (treatment  time) analysis of
variance for repeated measures (SPSS 11). Mauchly_s test
for sphericity was used; where asphericity was assumed, the
Greenhouse–Geisser correction was used for epsilon G 0.75;
if not, then the Huyn–Feldt correction was used. Where
significant F values were found, a Holm–Bonferroni
stepwise method was used to determine the location of the
variance (1). When there were only single comparisons, a
Student_s t-test for correlated data was used to determine
whether any differences between treatments existed.
http://www.acsm-msse.org

FIGURE 2—Muscle concentrations of proglycogen and macroglyc-
ogen (mmolIkgj1 DM) for the carbohydrate (CHO-E) and the placebo
(PLA) trials. Data are presented as means for the component
concentrations and SD for the total muscle glycogen concentrations.
Furthermore, a Shapiro–Wilks test for normality was used
DM per minute) compared with the CHO-E trial (2.5 T 0.7
mmol glucosyl units per kilogram DM per minute). It was
not possible to attribute these changes in muscle glycogen
use to the individual components, because there were no
differences in the use of proglycogen and macroglycogen
(Fig. 2). There were modest correlations between muscle
glycogen content and muscle glycogen use for the first
90 min (r = 0.658; P G 0.05) and from 90 min to fatigue
(r = 0.656; P G 0.05). Interestingly, fatigue occurred at
similar muscle glycogen concentrations in both trials (~200
mmol glucosyl units per kilogram DM).
There were no differences between trials in muscle
concentrations of PCr, G-6-P, and lactate. Similarly, there
were no differences between trials in the concentrations of
adenine nucleotides ATP and ADP or for IMP, the product
of total adenine nucleotide deamination (Table 1). It should
be noted, however, that there was a short time delay of 38 s

to test whether differences in data were normally
distributed; if this was found to be significant, then a
nonparametric Wilcoxon signed ranks test was used instead
of the Student_s t-test. Relationships between variables were
determined by Pearson product–moment correlation
coefficients. Null hypotheses were rejected at an alpha level
of P G 0.05. All data are reported as means T standard
deviation (SD).
RESULTS
Running capacity and sprint performance. All
subjects ran longer during the CHO-E trial compared with
the PLA trial. They ran for 158.0 T 28.4 min during
the CHO-E trial and 131.0 T 19.7 min during the PLA trial
(P = 0.028), representing a 21% increase in intermittent
running capacity. The mean 15-m sprint times were similar
between trials (CHO-E 2.61 T 0.08 s vs PLA 2.58 T 0.08 s)
and increased over time, irrespective of treatment (F6,30 =
4.1; P = 0.004).
Muscle metabolites. There were no differences in
preexercise muscle glycogen concentrations between trials.
Neither were there differences between trials for muscle
concentrations of proglycogen and macroglycogen (Fig. 2).
There was a similar rate of muscle glycogen use between
trials from before exercise to 90 min (~2 mmol glucosyl
units per kilogram DM per minute) and a trend (P = 0.1) for
a higher rate of muscle glycogen use from 90 min to fatigue
in the PLA trial (4.2 T 2.8 mmol glucosyl units per kilogram
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(T 7) and 52 s (T 13) between the end of the exercise and the
time of muscle sampling for the 90 min and fatigue biopsy
samples, respectively. Despite the expedient and efficient
sampling procedures, this slight delay was attributable to
the time required for the subject to return to the laboratory,
at the end of the run, from the adjacent gymnasium. This
delay may compound interpretation of some muscle
metabolite data; however, earlier studies from our labora-
tory have shown that muscle glycogen concentrations (both
soluble and insoluble fractions) are unaffected by recovery
periods of up to 6 min (3).
Plasma glucose and serum insulin. Plasma glucose
concentration was maintained within the normal phys-
iological range in both trials, although it was significantly
higher at fatigue in the CHO-E trial compared with the PLA
trial (F4,20 = 9.1; P G 0.001; Fig. 3). Although plasma
glucose concentrations also seemed higher in the CHO-E
trial at 30 min, this failed to reach statistical significance.
Serum insulin concentrations were significantly higher
throughout exercise in the CHO-E trial compared with
PLA (F1,5 = 29.1; P = 0.003; Fig. 4).
Plasma FFA and glycerol. There were main effects of
the treatments on plasma FFA concentrations (F1,5 = 10.3;
P = 0.024; Fig. 4) and glycerol concentrations (F1,5 = 13.8;
P = 0.014; Fig. 4) during exercise, with lower values
occurring in the CHO-E trial. There were also main effects
of time, with concentrations of both of these substrates
increasing with exercise duration (F1.2,6.1 = 26.1; F1.6,7.8 =
35.1; P G 0.001; for FFA and glycerol, respectively).

TABLE 1. Mixed muscle metabolite concentrations (mmolIkgj1 DM) before exercise, at 90 min, and at fatigue; values are means (SD).
Preexercise 90 min Fatigue
CHO-E PLA CHO-E PLA CHO-E PLA
PCr 89 (5) 89 (4) 82 (2) 83 (5) 86 (8) 79 (5)
G-6-P 3.8 (1.6) 3.0 (0.9) 4.1 (0.8) 3.0 (0.8) 2.5 (1.0) 3.6 (0.8)
Lactate 8.3 (1.4) 5.2 (1.4) 11.6 (2.9) 10.0 (2.7) 10.7 (4.8) 9.0 (1.8)
ATP 29.3 (2.7) 26.5 (0.9) 26.2 (2.9) 27.5 (1.2) 27.0 (4.2) 24.9 (4.4)
ADP 3.49 (0.79) 3.30 (0.56) 2.51 (0.33) 2.63 (0.68) 2.75 (0.33) 2.31 (1.14)
IMP 0.09 (0.02) 0.09 (0.02) 0.11 (0.04) 0.19 (0.17) 0.23 (0.17) 0.10 (0.05)

MUSCLE METABOLISM DURING INTERMITTENT RUNNING Medicine & Science in Sports & Exercised 99

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 Serum cortisol. Serum cortisol was analyzed as an
indicator of physical stress during the trials. There was a
main effect of time on serum cortisol concentrations, with
values higher in both trials at fatigue (719 T 133 nM) than at
30 min (437 T 103 nM), 60 min (396 T 122 nM), and 90
min (407 T 115 nM) of exercise (F1.4,7 = 12.5; P = 0.007);
however, there was no main trial effect on this marker of
physical stress.
Blood lactate, heart rate, and rate of perceived
exertion. Blood lactate concentrations increased
significantly with the onset of exercise (F4,20 = 40.5; P G
0.001) from a baseline of about 1 mM to a zenith of about
4 mM; however, there were no differences between
treatments. There were no differences in heart rates between
trials, with mean exercise HR of 167 T 9 and 162 T 7 bpm
for the CHO-E and PLA trials, respectively. There was a
main effect of time, with HR values increasing with
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exercise duration and peaking at fatigue (F7,35 = 485; P G

0.001). Similarly there were no differences between trials
for ratings of perceived exertion (RPE), with mean exercise
values of 13 T 1 arbitrary units for both trials. Again, there
was a main effect of time, with RPE values increasing
significantly with exercise duration towards peak values at
fatigue (F5,25 = 10.8; P G 0.001).
Changes in urine osmolality and BM. There were
no differences in urine osmolality before and after trials in
either condition. Subjects arrived at the laboratory with
urine osmolalities within the range 500–600 mOsmIkgj1,
and these were maintained by the end of the main trials.
There were no reported incidences of gastrointestinal distress
FIGURE 3—Plasma glucose (mM) and serum insulin (KIUImLj1)
concentrations for the carbohydrate (CHO-E) and the placebo (PLA)
trials during LIST to fatigue (means (SD)). † Main effect of treatment
(P = 0.003); * difference between treatment at this time point (P G
0.001).
FIGURE 4—Plasma FFA (mM) and glycerol (mM) concentrations for
the carbohydrate (CHO-E) and the placebo (PLA) trials during LIST
to fatigue (mean (SD)). † Main effect of treatment (P G 0.003); * main
effect of time (P G 0.001).
after the fluid ingestion during exercise. Furthermore, there
were no net BM losses within or between trials.
DISCUSSION
The findings from this study show, for the first time, that
after consumption of a carbohydrate-rich diet, carbohydrate
supplementation (90 gIhj1) in the form of a 6.4% CHO-E
solution during exercise led to an improvement in high-
intensity intermittent running capacity, but it did not affect
muscle glycogen use. Although fatigue occurred at similar
muscle glycogen concentrations in both trials, the subjects
were able to run for approximately 21% longer in the
CHO-E trial (158.0 T 28.4 min) compared with the PLA
trial (131.0 T 19.7 min). This enhanced endurance capacity
was achieved in all subjects and was associated with
higher serum insulin concentrations throughout the CHO-E
trial and higher plasma glucose concentrations during the
latter stages of exercise. These results show clearly that
ingesting a CHO-E solution improves endurance capacity
during intermittent high-intensity shuttle running, even
when participants have high preexercise muscle glycogen
concentrations. Therefore, this does not support our
hypothesis that an antecedent CHO-rich diet may negate
the ergogenic efficacy of CHO-E solutions ingested during
this type of exercise.
The dietary and exercise CHO-loading protocol used in
the present study was effective in increasing muscle
glycogen concentrations to similar values before each trial
(CHO-E, 533 T 77 mmol glucosyl units per kilogram DM

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vs PLA, 512 T 102 mmol glucosyl units per kilogram DM).
These resting values are higher than those obtained in an
earlier study using the same sampling and exercise (LIST)
procedures (350–400 mmol glucosyl units per kilogram
DM) and a similar group of subjects as used in the present
study (20). Interestingly the muscle glycogen concentra-
tions at the end of 90 min of exercise in the present study
are similar to the preexercise values reported for subjects in
the study by Nicholas and colleagues (20). In that study, all
the subjects managed to complete the 90 min of the LIST,
both in the CHO-E and PLA trials (20). Therefore, if
endurance capacity during intermittent high-intensity shuttle
running was dictated solely by preexercise muscle glycogen
concentrations, it would be reasonable to expect the
subjects in the present study to have completed an
additional 90 min of exercise. However, this was clearly
not the case, because in the PLA trial the subjects ran for
only 41 min beyond the 90 min, and in the CHO-E trial
they only achieved an additional 68 min. This, coupled with
the observation that a substantial amount of muscle
glycogen was still present at fatigue, suggests that factors
additional to muscle glycogen concentrations may contrib-
ute to fatigue during this type of exercise.
In contrast to the results from the present study, we
previously have reported a greater net muscle glycogen use
with placebo when compared with the ingestion of a
glucose-based CHO-E solution during 90 min of the LIST,
using subjects who were not CHO loaded before the trials
(20). This muscle glycogen sparing was suggested as one
possible mechanism to explain our earlier finding that the
ingestion of a CHO-E throughout exercise increased
endurance capacity during the LIST (19). Similar improve-
ments in endurance capacity have been reported by other
authors (8,29), who also have suggested that the ingestion
of a mixture of glucose–fructose and sucrose-based sol-
utions throughout prolonged, intermittent, high-intensity
shuttle running was a consequence of glycogen sparing.
However, the results from the present study do not show
glycogen sparing during the first 90 min of the LIST.
Indeed, there were no differences in muscle glycogen
concentrations between trials at 90 min, nor were there
any differences in the rates of muscle glycogen use during
this period (~2 mmol glucosyl units per kilogram DM per
minute). Furthermore, there were no differences in the
concentrations of G-6-P and other muscle metabolites at 90
min of exercise. Therefore, an antecedent, CHO-rich diet
preserves the ergogenic effect of glucose-based CHO
solutions ingested during high-intensity intermittent run-
ning, without affecting muscle glycogen use.
These results seem similar to those of Coyle and
colleagues (7), who also used subjects with high preexercise
muscle glycogen stores. They reported no differences in
muscle glycogen use during prolonged continuous exercise
to exhaustion with or without carbohydrate feeding, in the
form of a glucose polymer, but significant differences in
cycling times (3 h 2 min vs 4 h 2 min for their placebo trial
MUSCLE METABOLISM DURING INTERMITTENT RUNNING
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
and CHO trial, respectively). However, in their study, the
rate of glycogen degradation decreased towards the end of
exercise, whereas in the present study there seemed to be an
increased rate of glycogenolysis in the PLA trial. The rates
of glycogen degradation during the first 90 min of the LIST
were the same in both trials, but between 90 min and
fatigue, the values were 4.2 T 2.8 and 2.5 T 0.7 mmol
glucosyl units per kilogram DM per minute (P = 0.1) for the
PLA and CHO-E trials, respectively. The apparent trend for
a faster rate of glycogenolysis in the PLA trial may be
simply a consequence of the significantly shorter run time
compared with the CHO-E trial and similar glycogen
concentrations at fatigue. The double-blind, randomized
crossover design of this study precluded a comparison of
muscle glycogen concentrations at the point of fatigue in
the PLA trial with those at the same sampling time in the
CHO-E trial. Nevertheless, the fact remains that the
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glycogen concentrations at fatigue were similar (~200
mmol glucosyl units per kilogram DM) in both trials, and
yet the time to fatigue in the CHO-E trial was 21% greater
than in the PLA trial. One possible explanation was that
there may have been different amounts of pro- and macro-
glycogen used in the two trials. However, analysis of the
two pools of muscle glycogen revealed no differences
between trials in their concentrations before, during, and
after exercise (Fig. 2). There was a greater rate of
degradation of proglycogen than macroglycogen in both
trials, which is consistent with the earlier studies of Graham
and colleagues (11).
Another possible explanation for the results in the present
study is a differential use of muscle glycogen between fiber
types. It should be noted that in the study of Nicholas and
colleagues (20), although glycogen sparing was apparent in
both Type I and Type II muscle fibers after ingestion of a
CHO-E solution, reduction of glycogen in the Type II
muscle fibers towards a previously described critical level
(14) ultimately seemed to determine the point of fatigue.
Although no single muscle fiber analysis was performed in
the present study, because of the similarities in exercise
protocol and subject characteristics, it would be pertinent to
suggest that there may have been a glycogen-sparing effect
in the Type II fibers in the CHO-E trial in the present study.
The elevated plasma glucose and serum insulin concen-
trations in the CHO-E trial (especially late in exercise) in
the present study could have contributed to enhanced
glycogen synthesis in these fibers during the low-intensity
(walking, jogging, and resting) components of the exercise
protocol, as has been previously reported (15), and this may
explain the tendency for reduced net muscle glycogen use
in this trial late in exercise.
The plasma glucose concentrations were within the
normal range throughout exercise in both trials. However,
in the CHO-E trial, plasma glucose concentrations were
higher at the point of fatigue, as were serum insulin
concentrations, suggesting a greater availability of glucose
than in the PLA trial. The results from studies on cycling to
Medicine & Science in Sports & Exercised 101
 fatigue, in which subjects had high preexercise muscle
glycogen concentrations, suggest that the provision of
exogenous carbohydrate improves endurance capacity by
preventing decreases in plasma glucose concentrations and
carbohydrate oxidation (5,7). However, even in that
exercise modality, it has been shown that once fatigue is
impending, the delivery of exogenous glucose, either orally
or by infusion, cannot sustain exercise at a high intensity
(9 75% V̇O2max) (6). This suggests that when muscle
glycogen concentrations are reduced to critically low
values, the uptake of glucose from the systemic circulation
cannot occur fast enough to maintain contractile activity at
the required rate (13). Therefore, the metabolic and
performance consequences of a reduction in plasma glucose
concentration during prolonged exercise may be closely
associated with the availability of hepatic and muscle
glycogen stores. For example, a modest reduction in plasma
BASIC SCIENCES
glucose concentration early in exercise, when carbohydrate
stores are adequate or well stocked, may have little impact,
whereas when these stores are running low, the same
reduction in plasma glucose may become a significant
determinant of the onset of fatigue, operating through
changes in cerebral metabolism (22).
It has been postulated by Rauch and colleagues (24) that
chemoreceptors constantly monitor the carbohydrate status
of the muscle during exercise, by what the authors have
termed a glycostat, which continually updates the brain.
When carbohydrate stores are severely reduced during the
latter stages of prolonged exercise, the threat to cerebral
metabolism may be prevented by discontinuing exercise, by
central rather than an entirely peripheral mechanism (22).
This teleoanticipatory approach to the complexities of
fatigue is further expanded by Lambert and colleagues
(16), and it is likely that during exhaustive, high-intensity,
intermittent exercise, volitional fatigue is a multifaceted
consequence of peripheral as well as central mechanisms.
However, the extent to which this mechanism operates
during the performance of the LIST protocol, in which the
subjects are not able to self-pace, remains to be determined.
Another possible contribution to the onset of fatigue may
have been the ‘‘energy balance’’ within the working
muscles towards the end of exercise. McConell and
colleagues (18) exercised participants to volitional exhaus-
tion at 69% V̇O2 max and found that CHO supplementation
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