J Appl Physiol 108: 1520–1529, 2010.
First published March 18, 2010; doi:10.1152/japplphysiol.91394.2008.
Fuel selection and cycling endurance performance with ingestion of
[13C]glucose: evidence for a carbohydrate dose response
JohnEric W. Smith,1 Jeffrey J. Zachwieja,1 François Péronnet,2 Dennis H. Passe,3 Denis Massicotte,4
Carole Lavoie,5 and David D. Pascoe6
1
Gatorade Sports Science Institute, Barrington, Illinois; 2Département de kinésiologie, Université de Montréal, Montreal,
Quebec, Canada; 3Scout Consulting LLC, Hebron, Illinois; 4Département de Kinanthropologie, Université du Québec à
Montréal, Montreal; 5Département des Sciences de l’activité Physique, Université du Québec à Trois-Rivières, Trois-Rivières,
Quebec, Canada; and 6Department of Kinesiology, Auburn University, Auburn, Alabama
Submitted 21 October 2008; accepted in final form 10 March 2010
carbon isotope; time trial; muscle glycogen; plasma glucose; insulin
THE MECHANISMS BY WHICH CARBOHYDRATE (CHO) ingestion increases performance during prolonged exercise (7, 20, 21)
remains a matter of debate (25) . Carter et al. (3), Pottier et al.
(38), and Chambers et al. (5) have shown that a 1-h time trial
performance was improved by merely rinsing the mouth at
regular intervals with a CHO solution. The beneficial effect of
CHO ingested during exercise, thus, could be due at least in
part to the stimulation of CHO receptors in the oral cavity,
which could modulate central motor drive and reduce the rate
of perceived exertion. However, improved performance while
ingesting CHO during exercise could also be due in part to a
better maintenance of plasma glucose level and/or to the
associated changes in fuel selection. Indeed, the increased
availability of blood glucose results in a higher rate of CHO
Address for reprint requests and other correspondence: J. W. Smith, Gatorade Sports Science Institute, 617 W. Main St., Barrington, IL 60074 (e-mail:
[email protected]).
1520
oxidation, particularly late in the exercise period (6, 20). This
is mainly due to exogenous CHO oxidation (20) with few
changes, if any, in muscle glycogen oxidation and with a
reduction in glucose released from the liver (22, 23).
Based on the idea that the beneficial effect of CHO ingestion
on endurance performance is at least in part related to changes
in fuel selection due to exogenous CHO oxidation, it can be
hypothesized that this effect will increase with the amount of
exogenous CHO actually oxidized. In support of this hypothesis, Currell and Jeukendrup (9) have reported that the improvement in performance for an ⬃1-h time trial [following a
2-h ride at 55% peak O2 uptake (V̇O2peak)] was larger with
ingestion of a 2:1 glucose-fructose mixture than with ingestion
of glucose only. Although in this study the oxidation rate of
ingested CHO was not measured, the authors speculated that
this result could be due to the fact that multiple transportable
CHO (such as a glucose-fructose mixture) are oxidized at a
higher rate than glucose or glucose polymers alone (21).
Indeed, in a previous experiment, these authors (19) showed
that compared with glucose ingestion (1.8 g/min), the oxidation
rate of a 2:1 mixture of glucose and fructose also ingested at
1.8 g/min was 53% higher and that although this did not reach
significance, endogenous CHO oxidation was 24% lower (19).
However, the existence of a relationship between the amount
of CHO ingested and the effect on endurance performance, as
well as the optimal dose of CHO to be administered during
exercise, remains a matter of debate (21, 25).
The purpose of the present study was to further investigate
the relationship among the rate of glucose ingestion, fuel
selection, and performance during a 20-km time trial preceded
by a 2-h constant load ride in recreational cyclists. The doses
of glucose administered (15, 30, and 60 g/h) were equal to or
lower than that generally recommended to avoid gastrointestinal discomfort (⬃60 g/h) (4, 43). Fat and CHO oxidation as
well as the oxidation rate of glucose from various sources
(exogenous glucose, plasma glucose, glucose released from the
liver and from muscle glycogen) were computed from indirect
respiratory calorimetry combined with a tracer technique using
13
C labeling of the glucose ingested (14, 49). Based on observations that glucose ingestion at doses ranging from 10 (28) to
⬎100 g/h (10, 11, 20) have been shown to improve endurance
performance, we hypothesized that compared with ingestion of
a placebo, the time needed to complete the 20-km time trial
would be lower with glucose ingestion and that the differences
would be meaningful in terms of performance (17, 18). In
addition, based on the suggestion by Currell and Jeukendrup
(9) that the beneficial effect of CHO ingestion is related to the
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Smith JW, Zachwieja JJ, Péronnet F, Passe DH, Massicotte D,
Lavoie C, Pascoe DD. Fuel selection and cycling endurance performance with ingestion of [13C]glucose: evidence for a carbohydrate
dose response. J Appl Physiol 108: 1520 –1529, 2010. First published
March 18, 2010; doi:10.1152/japplphysiol.91394.2008.—Endurance
performance and fuel selection while ingesting glucose (15, 30, and
60 g/h) was studied in 12 cyclists during a 2-h constant-load ride
[⬃77% peak O2 uptake] followed by a 20-km time trial. Total fat and
carbohydrate (CHO) oxidation and oxidation of exogenous glucose,
plasma glucose, glucose released from the liver, and muscle glycogen
were computed using indirect respiratory calorimetry and tracer techniques. Relative to placebo (210 ⫾ 36 W), glucose ingestion increased
the time trial mean power output (%improvement, 90% confidence
limits: 7.4, 1.4 to 13.4 for 15 g/h; 8.3, 1.4 to 15.2 for 30 g/h; and 10.7,
1.8 to 19.6 for 60 g/h glucose ingested; effect size ⫽ 0.46). With 60
g/h glucose, mean power was 2.3, 0.4 to 4.2% higher, and 3.1, 0.5 to
5.7% higher than with 30 and 15 g/h, respectively, suggesting a
relationship between the dose of glucose ingested and improvements
in endurance performance. Exogenous glucose oxidation increased
with ingestion rate (0.17 ⫾ 0.04, 0.33 ⫾ 0.04, and 0.52 ⫾ 0.09 g/min
for 15, 30, and 60 g/h glucose), but endogenous CHO oxidation was
reduced only with 30 and 60 g/h due to the progressive inhibition of
glucose released from the liver (probably related to higher plasma
insulin concentration) with increasing ingestion rate without evidence
for muscle glycogen sparing. Thus ingestion of glucose at low rates
improved cycling time trial performance in a dose-dependent manner.
This was associated with a small increase in CHO oxidation without
any reduction in muscle glycogen utilization.
LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
amount of exogenous CHO actually oxidized, we hypothesized
that the improvement in performance would increase with the
rate of glucose ingestion and oxidation and with the associated
changes in fuel selection.
METHODS
J Appl Physiol • VOL
possible. Participants were aware of their position on the course, but
no verbal stimuli or other information was given.
During each 2-h ride, participants ingested 2,000 ml of one of four
beverages (250 ml every 15 min, beginning at min 15 and ending at
min 120): a placebo (water with electrolytes: 18 mmol/l Na⫹, 3
mmol/l K⫹, and 11 mmol/l Cl⫺) or a 1.5, 3.0, or 6.0% glucose
solution in water with the electrolytes (15, 30, or 60 g/h glucose). No
fluid was ingested during the 20-km time trial. The four beverages,
which were presented in a balanced order and given in opaque plastic
containers, were formulated to be similar in flavor and sweetness and
were kept at 1°C to minimize differences in taste. Uniformly labeled
[13C]glucose (13C/12C ⬎99%; Isotec, Miamisburg, OH) was added to
the beverages containing glucose (⬃1.75 mg/g) to obtain a final
13
C:12C ratio of glucose close to 145‰ [␦-13C]PDB1 (actual values
measured by mass spectrometry: 136 ⫾ 8‰ [␦-13C]PDB1).
Total CHO and fat oxidation rates were calculated from V̇O2 and
V̇CO2 (both in l/min), neglecting the small contribution of protein
oxidation to the energy yield (24):
CHO 共g/min glucose兲 ⫽ (4.210 ⫻ V̇CO2) ⫺ (2.962 ⫻ V̇O2)
(1)
Fat 共g/min兲 ⫽ (1.695 ⫻ V̇O2) ⫺ (1.701 ⫻ V̇CO2)
(2)
13
12
Plasma glucose C: C was measured as previously described (2).
Briefly, plasma glucose was separated by double-bed ion-exchange
chromatography (AG 50W-X8 H⫹ and AG 1-X8 chloride, 200 – 400
mesh; Bio-Rad, Mississauga, ON, Canada) after deproteinization with
barium hydroxide and zinc sulfate (0.3 N). The eluate was evaporated
to dryness (Virtis Research Equipment, New York, NY) and then
combusted (60 min at 400°C with copper oxide), and the CO2 was
recovered for the isotopic analysis.
Measurement of 13C/12C in expired CO2 (BreathMat Plus; Finnigan MAT, Bremen, Germany) and in CO2 from combustion of plasma
glucose (Prism, Manchester, UK) was performed by mass spectrometry. The isotopic composition of ingested glucose, expired CO2, and
plasma glucose was expressed as ‰ difference by comparison with
the PDB1 Chicago standard: ‰[␦-13C]PDB1 ⫽ [(Rspl/Rstd) ⫺ 1] ⫻
1,000, where Rspl and Rstd are the 13C-to-12C ratio in the sample and
standard (1.1237%), respectively (2).
The oxidation rate of exogenous glucose (in g/min) was computed
as follows (23, 37):
Exogenous glucose 共g/min兲 ⫽ V̇CO2[(Rexp ⫺ Rref) ⁄ (Rexo
⫺ Rref)] ⁄ k (3)
In this equation, V̇CO2 is in liters per minute, Rexp is the observed
isotopic composition of expired CO2, Rref is the isotopic composition
of expired CO2 observed in response to exercise with ingestion of the
placebo, Rexo is the isotopic composition of the exogenous glucose
ingested, and k (0.747 l/g) is the volume of CO2 provided by the
complete oxidation of glucose. In addition, based on the isotopic
composition of plasma glucose (Rglu), the percentage of plasma
glucose derived from exogenous glucose (Eq. 4) and the oxidation rate
of plasma glucose (in g/min, Eq. 5), were computed (14, 49):
Percent from exogenous ⫽ [(Rglu ⫺ Rglu-ref) ⁄ (Rexo
⫺ Rglu-ref)] ⫻ 100 (4)
Plasma glucose 共g/min兲 ⫽ V̇CO2[(Rexp ⫺ Rref) ⁄ (Rglu ⫺ Rref)] ⁄ k
(5)
In Eq. 4, Rglu-ref is the baseline isotopic composition of plasma
glucose. The oxidation rate of muscle glycogen (expressed in g/min),
either directly or through the lactate shuttle (1), was computed as the
difference between the rate of total glucose oxidation (Eq. 1) and the
oxidation rate of plasma glucose (Eq. 4). Finally, the oxidation rate of
glucose released by the liver was estimated as the difference between
the oxidation rate of plasma and exogenous glucose. These computations are based on the observation that during exercise, 13C provided
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Twelve trained, recreational, healthy male cyclists or triathletes
volunteered to participate in this study, which was conducted in
accordance with the guidelines of the Declaration of Helsinki. All
participants read and signed an informed consent approved by a
Human Subject Ethics Committee before beginning the study. Mean
and standard deviation (SD) age, height, body mass, V̇O2peak, and
peak power output were 31.7 ⫾ 3.8 yr, 1.82 ⫾ 0.07 m, 77.6 ⫾ 6.9 kg,
55.3 ⫾ 3.6 ml·kg⫺1·min⫺1 (4.3 ⫾ 0.4 l/min), and 388 ⫾ 41 W,
respectively.
Preliminary testing [V̇O2peak and onset of blood lactate accumulation (OBLA) (34)] and the experimental exercises (2-h ride at 95%
OBLA followed by a simulated 20-km time trial on an undulating
course) were performed in a laboratory maintained at 23 ⫾ 1°C and
35– 40% relative humidity with the participants exercising on their
own bicycle affixed to a bicycle trainer (CompuTrainer Pro; RacerMate, Seattle, WA) calibrated according to the manufacturer’s recommendations. V̇O2peak was determined using an incremental multistage cycling protocol (40): after a 10-min warm-up at 100 W, athletes
cycled at 150 W for 5 min, and then power output was increased by
50 W every 3 min until 250 W, after which power output was
increased by 25 W every minute until volitional exhaustion. V̇O2 and
carbon dioxide production (V̇CO2) were computed from expiratory
gases collected during the last 30 s of each stage in Douglas bags and
then analyzed (Vacumed spirometer, Ventura, CA; Ametek S-3A/I
oxygen analyzer and Ametek CD-3A carbon dioxide analyzer, Pittsburgh, PA). On a second occasion, separated from the measurement of
V̇O2peak by at least 7 days, the subjects exercised for 3.5 min at 55, 60,
65, 70, 75, 80, 85, and 90% V̇O2peak, and 3-ml blood samples were
collected during the final 30 s of each stage for measuring blood
lactate concentration and determining OBLA (34).
Before the experimental trials, participants performed three familiarization rides, with at least 7 days between trials, i.e., familiarization
with the 20-km time trial course, the 2-h ride followed by the 20-km
time trial, and, finally, the entire testing procedure (2-h ride with
ingestion of 2,000 ml of water, collection of expired gases, and blood
sampling followed by the 20-km course). Participants then completed
four exercise trials with at least 7 days between trials. For each trial,
participants reported to the laboratory at 5:00 AM following a 10-h
overnight fast, having abstained from exercise over the preceding 24 h.
After voiding and verification that urine specific gravity was ⱕ1.020,
body mass was recorded and an intravenous catheter (BD Insyte
Autoguard; Becton Dickinson Infusion Therapy Systems, Sandy, UT)
was inserted into an antecubital vein to collect blood samples throughout the trial. After a 10-min warm-up at 100 W, participants began the
2-h constant load ride (average workload ⫽ 228 ⫾ 26 W; 77 ⫾ 5%
V̇O2peak). Gas exchanges and heart rate (Polar Electro, Lake Success,
NY) were measured every 15 min. For measurement of the isotopic
composition (13C/12C) of expired CO2, 10-ml samples of the expired
gases collected were directly transferred to vacutainers (BD Vacutainer, Franklin Lakes, NJ) through a line from the Douglas bag
following thorough mixing. At regular intervals during the 2-h constant load ride, blood samples were collected for the measurement of
plasma glucose, lactate, free fatty acid, insulin concentrations and of
13
C/12C in plasma glucose. Two minutes after completing the 2-h ride,
which allowed for removal of the catheter and heart rate monitor,
participants began the simulated 20-km time trial on an undulating
course (9.04 km of incline at a 2% average slope and 10.96 km of
decline at a ⫺1.95% average slope: ⬃180 m uphill and ⬃213 m
downhill) and were asked to complete the course as quickly as
1521
1522
LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
likely limits of the true value of the effect (Table 1). The effect of each
of the three doses of glucose administered was expressed as percent
change relative to the placebo following back transformation of the mean
of the natural logarithm of power outputs (17). The chances that the true
value of the effect was larger than the smallest meaningful effect on the
20-km time trial were then computed (16), and qualitative terms to these
chances were assigned as suggested: ⬍1%, almost certainly not; ⬍5%,
very unlikely; ⬍25%, unlikely or probably not; ⬍50%, possibly not;
⬎50%, possibly; ⬎75%, likely or probable; ⬎95%, very likely; ⬎99%
almost certain (46). For the other variables (heart rate, V̇O2, substrate
oxidation, and plasma glucose, lactate, free fatty acid, and insulin concentrations) for which the smallest worthwhile change was difficult to
ascertain, statistical comparisons were also made using Cohen’s ES with
threshold values for small, moderate, large, very large, and extremely
large effects as 0.2. 0.6, 1.2, 2.0, and 4.0 (18). Although the discussion is
based on the probabilistic magnitude-based inferential analysis, statistical
comparisons were also made for all the variables using one-way (dose or
time) or two-way (dose ⫻ time) analysis of variance for repeated
measures and Duncan’s post hoc test when needed (Statistica; Statsoft,
Tulsa, OK). For the comparison of performance with ingestion of the
placebo and the three doses of glucose, ANOVA was performed after the
power outputs were log-transformed. Exact P values are reported if they
are ⬍0.100 and are expressed to three decimal places. Values of P less
than 0.000 are reported as P ⬍ 0.001.
RESULTS
Time trial performance. The reduction in body mass over the
exercise period was not different among the four experimental
situations (average pooled value ⫾ SD: 1.6 ⫾ 0.8 kg, n ⫽ 48),
indicating dehydration was not a confounding factor in the
results. Compared with the placebo, glucose ingestion increased the average power output sustained and improved the
20-km time trial performance (Table 1). When 1.2% was used
as the smallest meaningful improvement in performance, the
analysis confirmed that the three doses of glucose were very
likely to increase the chances of completing the 20-km time
trial meaningfully faster and that the true effect of ingesting
glucose was not detrimental (⬍1.6% chance of deterioration in
performance). In addition, although increasing the dose from
15 to 30 g/h was very unlikely to result in further improvement
in performance, compared with the lower doses (15 and 30 g/h)
the chances of obtaining a further beneficial effect were likely
Table 1. Performance and improvement in power output during 20-km time trials
Time Trial Performance
Improvement in Power Output, %
Minutes
Watts
15 g/h Glucose
30 g/h Glucose
60 g/h Glucose
Placebo
36.4 ⫾ 2.9
210 ⫾ 36
7.4, 1.4 to 13.4 (0.46)
95.4%, very likely (12)
P ⫽ 0.014
15 g/h Glucose
35.2 ⫾ 2.8
225 ⫾ 40
8.3, 1.6 to 15.2 (0.52)
95.7%, very likely (11)
P ⫽ 0.009
0.8, 0.1 to 1.5 (0.05)
15.1%, very unlikely (204)
P ⫽ 0.773
30 g/h Glucose
35.0 ⫾ 2.6
227 ⫾ 40
10.7, 2.5 to 18.9 (0.73)
96.2%, very likely (⬍10)
P ⫽ 0.001
3.1, 0.5 to 5.7 (0.21)
89.9%, likely (22)
P ⫽ 0.299
2.3, 0.4 to 4.2 (0.16)
84.4%, likely (15)
P ⫽ 0.413
60 g/h Glucose
34.7 ⫾ 2.1
232 ⫾ 34
Data indicate performance in the 20-km time trials with ingestion of placebo and 15, 30, and 60 g/h glucose (mean performance time and power output ⫾
SD) and %improvement in power output [1st line: %improvement, 90% confidence interval limits, and Cohen’s effect size (ES; in parentheses); 2nd line: chances
(% and qualitative) of meaningful improvement (i.e., ⬎1.2 %) and sample size needed for a magnitude-based inference about the practical significance of the
observed changes in performance for a power of 80% (in parentheses); 3rd line: exact P value from 1-way ANOVA and Duncan’s post hoc test]. The chances
of substantial decline in performance relative to placebo were ⬍1.6% (very unlikely) for the 3 doses of glucose.
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from [13C]glucose is not irreversibly lost in pools of the tricarboxylic
acid cycle intermediates and/or bicarbonate, that 13CO2 recovery in
expired gases is, thus, complete or almost complete (42, 44), and that
the recycling of [13C]glucose is minimal (22). However, the 13C/12C
in expired CO2 only slowly equilibrates with 13C/12C in the CO2
produced in tissues (35). To take into account the delay between
13
CO2 production in tissues and at the mouth, we only computed
exogenous and plasma glucose oxidation, as well as oxidation of
glucose released from the liver and muscle glycogen, during the last
60 min of exercise, thus allowing for a 60-min equilibration period.
Energy expenditure, the amount of energy provided by the oxidation of CHO and fat, and the respective contributions of these
substrates to the energy yield were computed from the amounts
oxidized and their respective energy potential (24).
Blood samples were collected through the catheter inserted into an
antecubital vein before the beginning of exercise. Between samplings,
the catheter was kept patent using a saline lock (Solution-Plus,
Mansfield, MA). After centrifugation, plasma samples were stored at
⫺20°C until analysis. Blood lactate concentration was measured
using a Gem Premier 3000 analyzer (Instrumentation Laboratory,
Lexington, MA). Plasma glucose concentration was measured using a
liquid glucose (hexokinase) reagent set kit (Pointe Scientific, Canton,
MI), plasma insulin concentration was measured using a human
insulin ELISA kit (Millipore, St. Charles, MO), and plasma free fatty
acid concentration was measured using a nonessential fatty acid HR2
series reagent kit (Wako Diagnostics, Richmond, VA). All samples
were analyzed on a multisample spectrophotometer (Synergy HT;
Bio-tek Instruments, Winooski, MA).
The mean value observed in a given situation is presented with the
associated standard deviation (mean ⫾ SD), and the mean difference
between two situations is presented with the associated confidence
limits at the 90% confidence level with Cohen’s effect size [mean
difference, lower limit to upper limit, Cohen’s effect size (ES)] as
recommended by Hopkins et al. (18). A probabilistic magnitude-based
inferential analysis was used to analyze the effect of glucose ingestion
on the average power output sustained over the 20-km time trial in
terms of meaningful enhancement of performance (17, 18). Based on
the coefficient of variation for a 40-min simulated cycling time trial
computed by Hopkins et al. (17) using the data reported by Palmer et
al. (36) (⬃2.4%) and on the smallest worthwhile change in performance
in athletes (⬃0.3– 0.7 ⫻ coefficient of variation) (17), the smallest
meaningful improvement in power output chosen for the analysis of the
effect of glucose ingestion was 1.2% (i.e., 2.4% ⫻ the average value
between 0.3 and 0.7). Uncertainty in the estimate of the effect of glucose
ingestion on the power output was expressed as the 90% confidence or
LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
Table 2. Heart rate and oxygen consumption over the first
and second hour of exercise
First hour
HR, beats/min
V̇O2, l/min
Second hour
HR, beats/min
V̇O2, l/min
Placebo
15 g/h
Glucose
30 g/h
Glucose
60 g/h
Glucose
148 ⫾ 11
3.16 ⫾ 0.28
147 ⫾ 12
3.15 ⫾ 0.31
148 ⫾ 12
3.13 ⫾ 0.36
146 ⫾ 11
3.17 ⫾ 0.32
152 ⫾ 12
3.18 ⫾ 0.27
152 ⫾ 13
3.25 ⫾ 0.30
151 ⫾ 14
3.21 ⫾ 0.35
152 ⫾ 11
3.15 ⫾ 0.32
Data are heart rate (HR) and oxygen consumption (V̇O2) (means ⫾ SD) over
the first and second hours of the 2-h ride with ingestion of the placebo and 15,
30, and 60 g/h glucose. See text for Cohen’s ES and statistical comparisons.
g, ES ⫽ 0.60, P ⬍ 0.001) and 15 (10.6, 7.6 to 13.6 g, ES ⫽ 0.72,
P ⬍ 0.001) and 30 g/h glucose (8.0, 6.3 to 9.7 g, ES ⫽ 0.60, P ⬍
0.001) than with ingestion of 60 g/h glucose (3.9, 1.6 to 6.2 g,
ES ⫽ 0.25, P ⫽ 0.003). In contrast, CHO oxidation decreased
from the first to the second hour of exercise with ingestion of the
placebo (⫺18.2, ⫺24.1 to ⫺12.3 g, ES ⫽ 0.56, P ⬍ 0.001) and
15 (⫺20.5, ⫺27.6 to ⫺13.4 g, ES ⫽ 0.60, P ⬍ 0.001) and 30 g/h
glucose (⫺15.1, ⫺20.2 to ⫺10.0 g, ES ⫽ 0.44, P ⬍ 0.001), but
when 60 g/h glucose were ingested, the reduction of CHO oxidation was much smaller (⫺6.4, ⫺12.4 to ⫺0.4 g, ES ⫽ 0.18,
P ⫽ 0.057).
Compared with the placebo, ingestion of 15 or 30 g/h
glucose had only very small effects on CHO and fat oxidation
over the second hour of exercise (range of ES ⫽ 0.05 to 0.12)
(Table 3). A moderate increase in CHO oxidation and a
concomitant decrease in fat oxidation were only observed with
ingestion of the largest dose of glucose (ES ⫽ 0.44 and 0.40,
respectively, compared with the placebo; range of ES ⫽ 0.38
to 0.50, respectively, compared with the lower doses of glucose) (Table 3). As a consequence, compared with the values
observed with the placebo, the energy yields from CHO and fat
oxidation over the second hour of exercise (67.3 ⫾ 13.0 and
32.7 ⫾ 13.0%, respectively) were not modified when doses of
15 and 30 g/h glucose were ingested (ES ⬍ 0.1, P ⬎ 0.7) but,
respectively, increased and decreased with ingestion of 60 g/h
glucose (6.8, 0.5 to 13.1%, similar with opposite signs for
CHO and fat oxidation, ES ⫽ 0.48, P ⫽ 0.029) (Fig. 1).
13 12
C/ C in expired CO2 and plasma glucose. The isotopic
composition (13C/12C) of expired CO2 (pooled average ⫾ SD:
⫺23.4 ⫾ 1.2‰ [␦-13C] PDB1, n ⫽ 48) and plasma glucose
(⫺21.7 ⫾ 1.3‰ [␦-13C] PDB1, n ⫽ 36; this measurement was
not performed when the placebo was ingested), respectively,
were similar at rest before exercise and ingestion of the first
dose of beverage (Fig. 2). A very large increase in 13C/12C in
expired CO2 was observed in response to the placebo trial (2nd
hour vs. 1st hour of exercise: 2.2, 1.2 to 3.2 ‰ [␦-13C] PDB1,
ES ⫽ 1.6, P ⬍ 0.001). The increase was much higher and
extremely large when [13C]glucose was ingested, the average
value observed over the second hour of exercise increasing
Table 3. Comparisons of total CHO and fat oxidation over the second hour of exercise
Difference in Total Oxidation, g
Total Oxidation, g
CHO
Placebo
15 g/h Glucose
171.0 ⫾ 34.9
173.3 ⫾ 36.4
30 g/h Glucose
169.4 ⫾ 35.3
60 g/h Glucose
186.8 ⫾ 37.2
Fat
Placebo
15 g/h Glucose
32.8 ⫾ 13.2
34.1 ⫾ 15.3
30 g/h Glucose
34.4 ⫾ 14.2
60 g/h Glucose
26.7 ⫾ 16.7
Placebo
15 g/h Glucose
30 g/h Glucose
2.3, ⫺9.6 to 14.1
ES ⫽ 0.07, P ⫽ 0.468
⫺1.6, ⫺10.7 to 7.5
ES ⫽ 0.05, P ⫽ 0.608
15.8, 1.3 to 30.4
ES ⫽ 0.44, P ⬍ 0.001
⫺3.9, ⫺17.9 to 10.2
ES ⫽ 0.11, P ⫽ 0.245
13.5, ⫺3.2 to 30.3
ES ⫽ 0.38, P ⬍ 0.001
17.4, 5.1 to 29.7
ES ⫽ 0.48, P ⬍ 0.001
1.3, ⫺3.1 to 5.8
ES ⫽ 0.09, P ⫽ 0.251
1.6, ⫺2.1 to 5.4
ES ⫽ 0.12, P ⫽ 0.182
⫺6.0; ⫺12.6 to 0.5
ES ⫽ 0.40, P ⬍ 0.001
0.3, ⫺3.6 to 4.2
ES ⫽ 0.02, P ⫽ 0.786
⫺7.4; ⫺13.3 to 1.4
ES ⫽ 0.46, P ⬍ 0.001
⫺7.7; ⫺12.2 to 3.1
ES ⫽ 0.50, P ⬍ 0.001
Data are comparisons of total carbohydrate (CHO) and fat oxidation over the second hour of exercise at 77% peak V̇O2 in the 4 experimental trials (placebo
and ingestion of 15, 30, and 60 g/h glucose) [1st line: means ⫾ SD and differences among the trials with the associated 90% confidence limits; 2nd line: Cohen’s
ES and P values (ANOVA and Duncan’s post hoc test)].
J Appl Physiol • VOL
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to increase with a dose of 60 g/h glucose (15). Post hoc power
analyses using magnitude-based inferences (15) showed the
sample size was too small to confidently conclude there were
no differences in performance among the three doses of glucose ingested, although for the comparison between 30 and 60
g/h glucose ingested, the actual sample size (n ⫽ 12) was only
slightly lower than the required sample size (n ⫽ 15).
Heart rate and calorimetry. From the first to the second hour
of the constant load ride, moderate and small increases in heart
rate and V̇O2 were observed (Table 2) [4.7, 3.8 to 5.6 beats/min
and 0.06, 0.04 to 0.08 l/min, ES ⫽ 0.60 and 0.30, P ⫽ 0.007
and 0.161 (main effect), respectively], but these values were,
respectively, similar in the four trials [ES ranging from 0.00 to
0.18, P ranging from 0.275 to 0.971 (main effect)]. Over the
first hour of exercise, compared with the CHO and fat oxidation values observed with the placebo (189.2 ⫾ 33.5 and 25.4 ⫾
12.1 g, respectively), changes in CHO and fat oxidation were very
small with ingestion of 15 (4.5, ⫺6.7 to 15.7 g and ⫺2.0, ⫺7.0 to
3.0 g, ES ⫽ 0.13 and 0.15, P ⫽ 0.178 and 0.095, respectively), 30
(⫺4.8, ⫺13.7 to 4.1 g and 1.0, ⫺2.4 to 4.4 g, ES ⫽ 0.15 and 0.08,
P ⫽ 0.150 and 0.403, respectively), and 60 g/h glucose (4.0, ⫺9.5
to 17.5 g and ⫺2.6, ⫺8.7 to 3.5 g, ES ⫽ 0.12 and 0.19, P ⫽ 0.207
and 0.035, respectively). Fat oxidation increased from the first to
the second hour of the constant load ride in the four trials, the
increase being larger with ingestion of the placebo (7.3, 5.7 to 8.9
1523
1524
LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
Fig. 1. Respective contributions (energy yield, %) of the oxidation of the
various substrates over the second hour of the ride.
Fig. 2. Changes in 13C/12C in plasma glucose (top) and in expired CO2 over the
2-h ride (bottom) with ingestion of the placebo and 15, 30, and 60 g/h glucose.
The percentage of plasma glucose deriving from exogenous glucose is also
shown (top, right y-axis). Values are means ⫾ SD (see text for statistical
comparisons).
J Appl Physiol • VOL
Fig. 3. Oxidation rate of glucose from various sources over the second hour of
the ride with ingestion of 15, 30, and 60 g/h glucose. Values are means ⫾ SD
(see text and Table 4 for statistical comparisons).
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with the ingestion rate (in ‰ [␦-13C] PDB1: 9.6, 8.6 to 10.6 for
15 g/h glucose; 16.3, 15.0 to 17.7 for 30 g/h glucose; and 23.8,
21.9 to 25.7 for 60 g/h glucose; ES ⫽ 6.2, 8.2, and 9.1,
respectively; P ⬍ 0.001 with the 3 doses). During the second
hour of exercise, based on the average value of 13C/12C
observed in plasma glucose (13.2 ⫾ 7.8, 37.0 ⫾ 9.4, and 57.2 ⫾
10.9‰ [␦-13C] PDB1 with 15, 30, and 60 g/h glucose ingested,
respectively), the percentage of plasma glucose deriving from
exogenous glucose (22.2 ⫾ 5.9% with ingestion of 15 g/h glucose) increased with the glucose ingestion rate (from 15 to 30 g/h
ingested: 14.5, 11.6 to 17.4%, ES ⫽ 2.7, P ⬍ 0.001; from 30 to
60 g/h ingested: 13.4, 10.8 to 15.9%, ES ⫽ 2.1, P ⬍ 0.001)
(Fig. 2).
Sources of glucose oxidized. During the second hour of
exercise, compared with the value observed with ingestion of
15 g/h glucose, the rate of exogenous glucose oxidation markedly increased with the ingestion rate (ES ⬎ 3.0, P ⬍ 0.001,
Fig. 3 and Table 4). For 15, 30, and 60 g/h ingestion rates, the
average oxidation rates were 68, 68, and 53% of the ingestion
rates, respectively, and the peak oxidation rates of exogenous
glucose observed at min 120 were 0.22 ⫾ 0.05, 0.39 ⫾ 0.07,
and 0.65 ⫾ 0.09 g/min (Fig. 3). The energy yield from
exogenous glucose oxidation also increased with the amount
ingested (Fig. 1): average values for 15, 30, and 60 g/h
ingestion rates: 3.9, 7.8 and 12.4%, respectively (ES ⬎ 2.5,
P ⬍ 0.001).
Compared with the placebo trial (endogenous glucose oxidation ⫽ total CHO oxidation ⫽ 171.0 ⫾ 34.9 g; see Table 3),
the reduction of endogenous glucose oxidation over the second
hour of the constant load ride (Table 4) was, respectively,
slight, moderate, and small with ingestion of 15, 30, and 60 g/h
glucose (⫺7.7, ⫺19.6 to 4.0 g, ES ⫽ 0.24, P ⫽ 0.283; ⫺21.3,
⫺30.4 to ⫺12.3 g, ES ⫽ 0.63, P ⫽ 0.009; and ⫺15.4, ⫺28.5
to ⫺2.4 g, ES ⫽ 0.46, P ⫽ 0.047, respectively). A small
reduction of endogenous CHO oxidation was observed when
the dose of glucose ingested increased from 15 to 30 g/h, but
no consistent changes were observed when the dose of glucose
was increased from 15 to 60 g/h and from 30 to 60 g/h
(Table 4).
In the three trials the oxidation rate of plasma glucose and
glucose released from the liver increased with time, whereas
the oxidation rate of glucose released from muscle glycogen
decreased (Fig. 3). Compared with the ingestion of 15 g/h
glucose, moderate and large reductions in the oxidation of
glucose released from the liver were observed, respectively,
with ingestion of 30 and 60 g/h glucose (Table 4). In contrast,
oxidation of glucose from muscle glycogen and of plasma
glucose did not decrease with the dose of glucose ingested
(Table 4). As shown in Fig. 1, compared with the value
observed with ingestion of 15 g/h glucose, the energy yields
from the oxidation of plasma glucose and of glucose released
from muscle glycogen (24.7 ⫾ 6.5 and 42.3 ⫾ 11.5%, respec-
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LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
Table 4. Comparisons of CHO oxidation from various sources over the second hour of exercise
Difference in CHO Oxidation, g
CHO Oxidation, g
Exogenous glucose
15 g/h Glucose
30 g/h Glucose
10 ⫾ 2.6
19.7 ⫾ 2.0
60 g/h Glucose
31.3 ⫾ 5.6
163.2 ⫾ 33.3
149.6 ⫾ 35.7
60 g/h Glucose
155.5 ⫾ 34.5
Muscle glycogen
15 g/h Glucose
30 g/h Glucose
109.4 ⫾ 28.3
104.4 ⫾ 42.3
60 g/h Glucose
117.6 ⫾ 40.4
Glucose from liver
15 g/h Glucose
30 g/h Glucose
53.8 ⫾ 17.0
45.2 ⫾ 16.9
60 g/h Glucose
37.9 ⫾ 12.8
Plasma glucose
15 g/h Glucose
30 g/h Glucose
63.8 ⫾ 17.4
64.9 ⫾ 16.2
60 g/h Glucose
69.1 ⫾ 12.1
30 g/h Glucose
9.7, 8.0 to 11.4
ES ⫽ 4.23, P ⬍ 0.001
21.2, 18.8 to 23.7
ES ⫽ 5.16, P ⬍ 0.001
11.5, 8.8 to 14.2
ES ⫽ 3.02, P ⬍ 0.001
⫺13.5, ⫺27.4 to 0.3
ES ⫽ 0.39, P ⫽ 0.009
⫺7.7, ⫺23.6 to 8.3
ES ⫽ 0.23, P ⫽ 0.290
5.9, ⫺6.1 to 17.9
ES ⫽ 0.17, P ⫽ 0.415
⫺5.0, ⫺22.5 to 12.5
ES ⫽ 0.14, P ⫽ 0.587
8.2, ⫺9.0 to 25.4
ES ⫽ 0.23, P ⫽ 0.376
13.2, ⫺0.8 to 27.2
ES ⫽ 0.32, P ⫽ 0.185
⫺8.9, ⫺16.2 to ⫺0.8
ES ⫽ 0.50, P ⫽ 0.020
⫺15.9, ⫺21.5 to ⫺10.3
ES ⫽ 1.07, P ⬍ 0.001
⫺7.3, ⫺11.9 to ⫺2.7
ES ⫽ 0.49, P ⫽ 0.042
1.1, ⫺7.9 to 10.1
ES ⫽ 0.07, P ⫽ 0.784
5.3, ⫺1.0 to 11.7
ES ⫽ 0.36, P ⫽ 0.224
4.2, ⫺1.9 to 10.3
ES ⫽ 0.30, P ⫽ 0.308
Data are comparisons of CHO oxidation from various sources over the second hour of exercise at 77% V̇O2peak with ingestion of 15, 30, and 60 g/h glucose
[1st line: means ⫾ SD and differences among trials with the associated 90% confidence limits; 2nd line: Cohen’s ES and P values (ANOVA and Duncan’s post
hoc test)].
tively) were only slightly modified when the dose of glucose
increased (e.g., 2.8, 0.4 to 5.2%, ES ⫽ 0.47, P ⫽ 0.120; and
4.1, ⫺2.8 to 10.9%, ES ⫽ 0.30, P ⫽ 0.115, respectively, from
15 to 60 g/h glucose ingested). In contrast, when the rate of
glucose ingestion and oxidation increased, the energy yields
from the oxidation of glucose released from the liver markedly
decreased (Fig. 1; e.g., 20.7 ⫾ 6.3 to 15.1 ⫾ 5.5% when the
ingestion rate increased from 15 to 60 g/h: ⫺5.7, ⫺7.7 to
⫺3.7%, ES ⫽ 1.0, P ⬍ 0.001).
Plasma metabolite and insulin concentrations. Baseline
plasma glucose, insulin, lactate, and free fatty acid concentrations were similar in the four experimental situations (Fig. 4).
Plasma lactate concentration increased in response to exercise
and remained stable, slightly below 3 mmol/l, over the second
hour of exercise with no differences among the four experimental situations. Compared with placebo (3.0 ⫾ 1.7 mmol/l),
the differences were only 0.0, ⫺0.6 to 0.6 mmol/l for 15 g/h
glucose ingested; ⫺0.2, ⫺0.9 to 0.4 mmol/l for 30 g/h glucose;
and 0.1 ⫺0.3 to 0.5 mmol/l for 60 g/h glucose (ES ⫽ 0.02,
0.13, and 0.06; P ⫽ 0.686, 0.097, and 0.560, respectively).
Plasma glucose concentration, which decreased during exercise when the placebo was ingested (rest: 5.2 ⫾ 0.9 mmol/l,
average decrease over the second hour of exercise: ⫺0.4, ⫺0.8
to 0.0 mmol/l, ES ⫽ 0.58, P ⫽ 0.019) slightly increased when
15 g/h glucose were ingested (0.2, ⫺0.2 to 0.7 mmol/l; ES ⫽
J Appl Physiol • VOL
0.32, P ⫽ 0.209) and markedly increased with 30 and 60 g/h
intakes (0.4, ⫺0.2 to 1.0 and 0.6, 0.2 to 1.0 mmol/l, ES ⫽ 0.51
and 0.73, P ⫽ 0.017 and 0.002, respectively). Plasma insulin
concentration decreased in the four trials and, compared with
the placebo trial (average value ⫾ SD over the second hour of
exercise: 1.3 ⫾ 1.7 mU/l), was similar to that with ingestion of
15 g/h glucose (⫺0.1, ⫺0.9 to 0.6 mU/l, ES ⫽ 0.08, P ⫽
0.921) but moderately and markedly higher with ingestion of
30 and 60 g/h glucose (0.8, 0.0 to 1.6 and 1.8, 0.4 to 3.2 mU/l,
ES ⫽ 0.44 and 0.96, P ⫽ 0.434 and 0.099, respectively). As for
free fatty acid concentration, compared with the marked increase observed when the placebo was ingested (rest: 0.24 ⫾
0.25 mmol/l; average increase over the second hour of exercise: 0.16, 0.08 to 0.23 mmol/l, ES ⫽ 0.77, P ⬍ 0.001), the
increase was similar when glucose was ingested at a rate of 15
and 30 g/h (0.18, 0.08 to 0.29 and 0.12, 0.05 to 0.19 mmol/l,
ES ⫽ 0.71 and 0.96, P ⬍ 0.001 and P ⫽ 0.005 , respectively)
but was slightly blunted at the highest ingestion rate (0.05, 0.01
to 0.09 mmol/l, ES ⫽ 0.43, P ⫽ 0.268).
DISCUSSION
Results from the present experiment show that glucose
ingested at low doses over a 2-h exercise period at ⬃77%
V̇O2peak substantially improved performance during a subse-
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Endogenous CHO
15 g/h Glucose
30 g/h Glucose
15 g/h Glucose
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LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
quent 20-km simulated cycling time-trial completed in ⬃35
min. In terms of meaningful effect on performance for the
recreational cyclists studied, the chances of improvement increased with the dose ingested, with ingestion of 60 g/h
glucose being higher than with the lower doses. The progressive reduction in endogenous CHO oxidation with increasing
glucose ingestion rates was due to a reduction in the oxidation
of glucose released from the liver without any significant
change in muscle glycogen oxidation. Compared with the
placebo trial, the largest change in fuel selection, i.e., higher
CHO oxidation, was observed with the highest dose of glucose
ingested, which was associated with the highest chances of
improvement in performance.
It has been suggested that CHO ingestion during exercise
increases endurance performance by maintaining plasma
glucose level and CHO oxidation (6, 20, 21, 45). For this
reason, several studies have been conducted for the explicit
purpose of identifying the types and amounts of CHO to be
ingested to maximize exogenous CHO oxidation. Results
from these studies show that when large amounts of mixtures of multiple transportable CHO (glucose and fructose
as monomers or in the form of glucose polymers and
disaccharides) are ingested (up to 2.4 g/min or 144 g/h), the
oxidation rate of exogenous CHO could reach 1.75 g/min
[see Jeukendrup (21) for review]. Currell and Jeukendrup
(9) have reported a larger improvement in performance with
the ingestion of a mixture of glucose and fructose (1.2 and
0.6 g/min) than of glucose only (1.8 g/min) (8% quicker
time to complete ⬃925 kJ of work when glucose and
fructose are ingested compared with glucose only and a 19%
quicker time when glucose and fructose are ingested compared with water). This could suggest that the improvement
in performance increases with the amount of CHO ingested
and oxidized, although in this study the oxidation rate of
exogenous CHO was not measured. In fact, a relationship
between the dose of CHO ingested and improvement in
performance has not been clearly established (21). In some
studies that compared various doses of CHO (0.41 to 1.3
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Fig. 4. Plasma glucose, insulin, lactate, and free fatty acid (FFA) concentrations in response to exercise with ingestion of the placebo and 15, 30,
and 60 g/h glucose. Values are means ⫾ SD (see text for statistical
comparisons).
g/min), performance was improved with increasing ingestion rates (32, 41). However, this has not been a uniform
observation, since higher ingestion rates tested in some
studies did not result in peak performance (29, 31). In the
present experiment, compared with the placebo, the average
20-km time was lower with the lower ingestion rate (15 g/h).
Increasing the ingestion rate to 30 g/h further reduced the
20-km time, but compared with the 15-g/h ingestion rate, the
improvement was small and did not result in a substantial
increase in the chances of improving performance. In contrast, compared with the lower doses of glucose, the chances
of improving performance increased when 60 g/h glucose
were ingested.
Our data indicate that compared with the ingestion of a
placebo, a substantial improvement in endurance performance can be obtained with an ingestion rate of CHO as
small as 15 or 30 g/h, but chances of improving performance
are higher with an ingestion rate of 60 g/h. Although
improvements in performance have also been reported with
higher ingestion rates (32), direct comparative studies over
a large range of ingestion rates [up to 90 and 120 g/h such
as in the study by Currell and Jeukendrup (9)] are currently
lacking to conclude that the beneficial effects are larger at
ingestion rates greater than 60 g/h. It should be recognized
that post hoc power analyses using magnitude-based inferences showed that the number of subjects needed to firmly
conclude that the time trial performance did not improve
when the dose of glucose ingested increased from 15 to 30
g/h was much higher than the actual sample size (⬃200 vs.
12) and is very unlikely to be achieved in research on this
topic. In contrast, the number of subjects needed to firmly
conclude the comparisons between the lower and the higher
dose ingested (15 and 30 vs. 60 g/h) was much lower (n ⫽
22 and 15) and for the comparison between 30 and 60 g/h
glucose ingested was in fact close to the actual sample size
used in the present experiment. These observations add
support to the hypothesis of a relationship between the dose
of glucose ingested in the range from 15 to 60 g/h and
improvement in endurance performance. This hypothesis
could well be tested with sample sizes in the range computed in the present experiment (n ⫽ 15–22). In addition,
the sample size needed can be reduced by using tests with
lower coefficients of variation and including elite athletes
familiar with the tests chosen and able, in a given situation,
to consistently reproduce their performance with only small
difference from one trial to the other.
In the present experiment, due to the low ingestion rates
of exogenous glucose used, only modest changes in fuel
selection were observed. As expected, exogenous glucose
oxidation increased with the ingestion rates. The average
values computed over the second hour of exercise (0.17,
0.34, and 0.53 g/min) are in good accordance with data
compiled from the literature (20). As discussed by several
authors (e.g., Refs. 47, 49), with increasing ingestion rates
the percentage of exogenous glucose that escapes oxidation
increases (⬃30% for ingestion rates of 15 and 30 g/h, up to
⬃45% for 60 g/h), but the fate of the glucose ingested and
not oxidized remains to be determined. Jeukendrup et al.
(22) showed that over a wide ingestion rate (⬃36 to ⬃180
g/h), the rate of plasma glucose disappearance was not
significantly different from its rate of oxidation. This obser-
LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
J Appl Physiol • VOL
small in response to exercise, where the rate of plasma glucose
disappearance from [13C]glucose only underestimates by ⬃6 – 8%
the value computed using 6,6-[2H]glucose, which does not recycle. Moreover, this underestimation decreases with the amount of
glucose ingested, probably because of a reduction in the flux
through gluconeogenesis (22). In the present experiment, the
underestimation of plasma glucose oxidation was, thus, probably
larger when 15 rather than 60 g/h glucose were ingested, which
reinforces the conclusion that when glucose ingestion increases,
glucose release from the liver decreases without any changes in
muscle glycogen utilization.
Changes in fuel selection with ingestion of CHO were at
least partly associated with those in plasma glucose, insulin,
and free fatty acids, all of which play a role in plasma
glucose utilization during exercise (30). Compared with
placebo, no changes in these variables were observed with
ingestion of the lower dose of glucose. The contribution of
exogenous glucose oxidation to the energy yield was small
(⬃4%), and fat vs. CHO (total and endogenous) oxidation
was not modified. In contrast, ingestion of 60 g/h glucose
compared with ingestion of 15 g/h glucose resulted in higher
plasma insulin concentrations, which could have contributed
to the reduction in glucose release from the liver, in plasma
free fatty acid concentration, and in fat oxidation over the
second hour of exercise. In fact, the progressive reduction in
glucose release from the liver with increasing doses of
glucose ingested closely followed the increase in plasma
insulin concentration. In contrast, the rate of plasma glucose
oxidation was not related to the amount of glucose ingested
despite the marked difference in plasma insulin concentration. This is in line with the observation that the regulation
of plasma glucose uptake in working skeletal muscle
through the translocation of GLUT4 transporters is more
under the control of muscle contraction than the endocrine
effect of insulin (26).
In conclusion, glucose ingested at low rates (15 to 60 g/h)
during prolonged exercise has a beneficial effect on endurance performance, and this effect appears to increase with
the dose ingested, suggesting that a dose-performance relationship may exist, at least within the range of the doses
studied and for exercise lasting ⬃150 min. Exogenous
glucose oxidation, which, as expected, increased with the
ingestion rate, increased total CHO oxidation and reduced
fat and endogenous CHO oxidation in a dose-dependent
manner. The reduction in endogenous CHO oxidation with
increasing ingestion rate of exogenous glucose was entirely
due to a progressive inhibition of glucose released from the
liver (probably related to the higher plasma insulin concentration) without evidence for any muscle glycogen sparing.
Although the effect was small, these observations suggest
that the improvement in endurance performance due to CHO
ingestion during exercise may be associated with the increased oxidation rate of CHO but not with a reduction in
muscle glycogen utilization.
ACKNOWLEDGMENTS
We acknowledge the invaluable assistance of Melanie Wolfe, Nick Suffredin, and Mathieu Robitaille.
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vation strongly suggests that intestinal absorption could
be the limiting step for the oxidation of exogenous CHO
that may accumulate in the stomach and gut leading to
intestinal discomforts particularly for ingestion rates ⬎1
g/min (39). However, for lower ingestion rates such as those
used in the present experiment (15 and 30 g/h), a portion of
the glucose absorbed can also be removed by the liver on
first pass (27).
In the present experiment, the energy yield from exogenous glucose oxidation increased with the ingestion rate
from 3.9 ⫾ 1.6% for 15 g/h ingested to 12.4 ⫾ 4.3% for 60
g/h ingested. These values are in good agreement with those
computed from the data reported, for example, by Galloway
et al. (12) at similar %V̇O2peak (80%) values: ⬃5.5, ⬃11, and
⬃14.5% for 17, 53, and 105 g/h glucose ingested. These
contributions of exogenous glucose oxidation to the energy
yield resulted in only modest changes in overall fuel selection that were not closely related to the progressive improvement in performance with increasing ingestion rate.
The reduction in endogenous CHO oxidation, which was
modest (ES ⫽ 0.23 to 0.63), did not increase with the dose
administered. As for the increase in total CHO oxidation, it
was higher with the highest ingestion rate, at which the
chances for a meaningful improvement in performance were
also the highest. This could support the hypothesis that the
improvement in endurance performance with CHO ingestion
is due to the maintenance of a high rate of CHO oxidation (8).
However, an improvement in performance, albeit smaller, was
also observed when 15 and 30 g/h glucose were ingested, although total CHO oxidation was not different from that observed
with ingestion of the placebo.
Consistent data show that glucose release from the liver is
reduced when CHO is ingested during exercise (22, 23, 30,
49) and can even be totally suppressed with a very high
ingestion rate of glucose (164 g/h) (22, 23). In contrast,
except for some observations made during constant prolonged running (33) and variable load cycling (13), all the
studies using muscle biopsy to track muscle glycogen utilization (including all experiments during prolonged constant
load cycling) failed to observe muscle glycogen sparing
when CHO was ingested during exercise (31). The same
observation was made when muscle glycogen oxidation was
computed as the difference between total CHO oxidation
measured from gas exchange at the mouth and plasma
glucose oxidation or turnover (22, 48). Data from the
present experiment are well in line with these observations.
As shown in Fig. 1, when the ingestion rate increased, the
percentage of plasma glucose derived from the ingested
[13C]glucose (average value over the last hour: 22.2 ⫾ 6.1,
36.7 ⫾ 7.5, and 50.1 ⫾ 8.7% with ingestion of 15, 30, and
60 g/h glucose, respectively) increased almost in parallel
with the oxidation rate (average values over the last hour:
0.17 ⫾ 0.07, 0.33 ⫾ 0.11, and 0.52 ⫾ 0.17 g/min), whereas
the oxidation rate of glucose released from the liver decreased. As a consequence, the oxidation rate of plasma
glucose remained unaffected and no reduction in muscle
glycogen oxidation was observed (Fig. 1). It should be
recognized that since [13C]glucose is a recycling tracer, the oxidation rate of plasma glucose and, thus, of glucose released from
the liver could be underestimated. However, Jeukendrup et al.
(22) have shown that this phenomenon, which is large at rest, is
1527
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LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
DISCLAIMER
The findings, opinions, and/or views contained in this publication are those
of the authors and do not necessarily represent any official positions, opinions,
or views of PepsiCo, Inc. or its subsidiaries.
DISCLOSURES
23.
24.
J. W. Smith and J. J. Zachwieja are employed by the Gatorade Company.
This research was funded by the Gatorade Sports Science Institute.
25.
REFERENCES
J Appl Physiol • VOL
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
108 • JUNE 2010 •
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1. Brooks GA. Lactate production under fully aerobic conditions: the lactate
shuttle during rest and exercise. Fed Proc 45: 2924 –2929, 1986.
2. Burelle Y, Peronnet F, Charpentier S, Lavoie C, Hillaire-Marcel C,
Massicotte D. Oxidation of an oral [13C]glucose load at rest and prolonged exercise in trained and sedentary subjects. J Appl Physiol 86:
52–60, 1999.
3. Carter JM, Jeukendrup AE, Jones DA. The effect of carbohydrate
mouth rinse on 1-h cycle time trial performance. Med Sci Sports Exerc 36:
2107–2111, 2004.
4. Casa DJ, Armstrong LE, Hillman SK, Montain SJ, Reiff RV, Rich BS,
Roberts WO, Stone JA. National Athletic Trainers’ Association position
statement: fluid replacement for athletes. J Athl Train 35: 212–224, 2000.
5. Chambers ES, Bridge MW, Jones DA. Carbohydrate sensing in the
human mouth: effects on exercise performance and brain activity. J
Physiol 587: 1779 –1794, 2009.
6. Coggan AR, Coyle EF. Carbohydrate ingestion during prolonged exercise: effects on metabolism and performance. Exerc Sport Sci Rev 19:
1–40, 1991.
7. Coombes JS, Hamilton KL. The effectiveness of commercially available
sports drinks. Sports Med 29: 181–209, 2000.
8. Coyle EF, Coggan AR, Hemmert MK, Ivy JL. Muscle glycogen
utilization during prolonged strenuous exercise when fed carbohydrate. J
Appl Physiol 61: 165–172, 1986.
9. Currell K, Jeukendrup AE. Superior endurance performance with ingestion of multiple transportable carbohydrates. Med Sci Sports Exerc 40:
275–281, 2008.
10. Febbraio MA, Chiu A, Angus DJ, Arkinstall MJ, Hawley JA. Effects
of carbohydrate ingestion before and during exercise on glucose kinetics
and performance. J Appl Physiol 89: 2220 –2226, 2000.
11. Fritzsche RG, Switzer TW, Hodgkinson BJ, Lee SH, Martin JC, Coyle
EF. Water and carbohydrate ingestion during prolonged exercise increase
maximal neuromuscular power. J Appl Physiol 88: 730 –737, 2000.
12. Galloway SD, Wootton SA, Murphy JL, Maughan RJ. Exogenous
carbohydrate oxidation from drinks ingested during prolonged exercise in
a cold environment in humans. J Appl Physiol 91: 654 –660, 2001.
13. Hargreaves M, Costill DL, Coggan A, Fink WJ, Nishibata I. Effect of
carbohydrate feedings on muscle glycogen utilization and exercise performance. Med Sci Sports Exerc 16: 219 –222, 1984.
14. Harvey CR, Frew R, Massicotte D, Peronnet F, Rehrer NJ. Muscle
glycogen oxidation during prolonged exercise measured with oral
[13C]glucose: comparison with changes in muscle glycogen content. J
Appl Physiol 102: 1773–1779, 2007.
15. Hopkins WG. Estimating sample size for magnitude-based inferences.
Sportscience 10: 63–70, 2006.
16. Hopkins WG. A spreadsheet for deriving a confidence interval, mechanistic inference and clinical inference from a p value. Sportscience 11:
16 –20, 2007.
17. Hopkins WG, Hawley JA, Burke LM. Design and analysis of research
on sport performance enhancement. Med Sci Sports Exerc 31: 472–485,
1999.
18. Hopkins WG, Marshall SW, Batterham AM, Hanin J. Progressive
statistics for studies in sports medicine and exercise science. Med Sci
Sports Exerc 41: 3–13, 2009.
19. Jentjens RL, Moseley L, Waring RH, Harding LK, Jeukendrup AE.
Oxidation of combined ingestion of glucose and fructose during exercise.
J Appl Physiol 96: 1277–1284, 2004.
20. Jeukendrup AE. Carbohydrate intake during exercise and performance.
Nutrition 20: 669 –677, 2004.
21. Jeukendrup AE. Carbohydrate feeding during exercise. Eur J Sport Sci 8:
77–86, 2008.
22. Jeukendrup AE, Raben A, Gijsen A, Stegen JH, Brouns F, Saris WH,
Wagenmakers AJ. Glucose kinetics during prolonged exercise in highly
trained human subjects: effect of glucose ingestion. J Physiol 515: 579 –
589, 1999.
Jeukendrup AE, Wagenmakers AJ, Stegen JH, Gijsen AP, Brouns F,
Saris WH. Carbohydrate ingestion can completely suppress endogenous
glucose production during exercise. Am J Physiol Endocrinol Metab 276:
E672–E683, 1999.
Jeukendrup AE, Wallis GA. Measurement of substrate oxidation during
exercise by means of gas exchange measurements. Int J Sports Med 26,
Suppl 1: S28 –S37, 2005.
Karelis AD, Smith JW, Passe DH, Peronnet F. Carbohydrate administration and exercise performance: what are the potential mechanisms
involved? Sports Med. In press.
Lavoie C, Ducros F, Bourque J, Langelier H, Chiasson JL. Glucose
metabolism during exercise in man: the role of insulin in the regulation of
glucose utilization. Can J Physiol Pharmacol 75: 36 –43, 1997.
Livesey G, Wilson PD, Roe MA, Faulks RM, Oram LM, Brown JC,
Eagles J, Greenwood RH, Kennedy H. Splanchnic retention of intraduodenal and intrajejunal glucose in healthy adults. Am J Physiol Endocrinol
Metab 275: E709 –E716, 1998.
Maughan RJ, Bethell LR, Leiper JB. Effects of ingested fluids on
exercise capacity and on cardiovascular and metabolic responses to prolonged exercise in man. Exp Physiol 81: 847–859, 1996.
Maughan RJ, Fenn CE, Leiper JB. Effects of fluid, electrolyte and
substrate ingestion on endurance capacity. Eur J Appl Physiol Occup
Physiol 58: 481–486, 1989.
McConell G, Fabris S, Proietto J, Hargreaves M. Effect of carbohydrate ingestion on glucose kinetics during exercise. J Appl Physiol 77:
1537–1541, 1994.
Mitchell JB, Costill DL, Houmard JA, Fink WJ, Pascoe DD, Pearson
DR. Influence of carbohydrate dosage on exercise performance and
glycogen metabolism. J Appl Physiol 67: 1843–1849, 1989.
Murray R, Paul GL, Seifert JG, Eddy DE. Responses to varying rates
of carbohydrate ingestion during exercise. Med Sci Sports Exerc 23:
713–718, 1991.
Nicholas CW, Tsintzas K, Boobis L, Williams C. Carbohydrate-electrolyte ingestion during intermittent high-intensity running. Med Sci
Sports Exerc 31: 1280 –1286, 1999.
Osterberg KL, Zachwieja JJ, Smith JW. Carbohydrate and carbohydrate ⫹ protein for cycling time-trial performance. J Sports Sci 26:
227–233, 2008.
Pallikarakis N, Sphiris N, Lefebvre P. Influence of the bicarbonate pool
and on the occurrence of 13CO2 in exhaled air. Eur J Appl Physiol Occup
Physiol 63: 179 –183, 1991.
Palmer GS, Dennis SC, Noakes TD, Hawley JA. Assessment of the
reproducibility of performance testing on an air-braked cycle ergometer.
Int J Sports Med 17: 293–298, 1996.
Peronnet F, Rheaume N, Lavoie C, Hillaire-Marcel C, Massicotte D.
Oral [13C]glucose oxidation during prolonged exercise after high- and
low-carbohydrate diets. J Appl Physiol 85: 723–730, 1998.
Pottier A, Bouckaert J, Gilis W, Roels T, Derave W. Mouth rinse but
not ingestion of a carbohydrate solution improves 1-h cycle time trial
performance. Scand J Med Sci Sports 20: 105–111, 2008.
Rehrer NJ, Wagenmakers AJ, Beckers EJ, Halliday D, Leiper JB,
Brouns F, Maughan RJ, Westerterp K, Saris WH. Gastric emptying,
absorption, and carbohydrate oxidation during prolonged exercise. J Appl
Physiol 72: 468 –475, 1992.
Robergs RA, Pascoe DD, Costill DL, Fink WJ, Chwalbinska-Moneta
J, Davis JA, Hickner R. Effects of warm-up on muscle glycogenolysis
during intense exercise. Med Sci Sports Exerc 23: 37–43, 1991.
Rogers J, Summers RW, Lambert GP. Gastric emptying and intestinal
absorption of a low-carbohydrate sport drink during exercise. Int J Sport
Nutr Exerc Metab 15: 220 –235, 2005.
Ruzzin J, Peronnet F, Tremblay J, Massicotte D, Lavoie C. Breath
[13CO2] recovery from an oral glucose load during exercise: comparison
between [U-13C] and [1,2-13C]glucose. J Appl Physiol 95: 477–482, 2003.
Sawka MN, Burke LM, Eichner ER, Maughan RJ, Montain SJ,
Stachenfeld NS. American College of Sports Medicine position stand.
Exercise and fluid replacement. Med Sci Sports Exerc 39: 377–390, 2007.
Trimmer JK, Casazza GA, Horning MA, Brooks GA. Recovery of
13
CO2 during rest and exercise after [1-13C]acetate, [2-13C]acetate, and
NaH13CO3 infusions. Am J Physiol Endocrinol Metab 281: E683–E692,
2001.
Tsintzas K, Williams C. Human muscle glycogen metabolism during
exercise. Effect of carbohydrate supplementation. Sports Med 25: 7–23, 1998.
LOW-DOSE GLUCOSE INGESTION AND FUEL SELECTION
46. Van Montfoort MC, Van Dieren L, Hopkins WG, Shearman JP.
Effects of ingestion of bicarbonate, citrate, lactate, and chloride on sprint
running. Med Sci Sports Exerc 36: 1239 –1243, 2004.
47. Wagenmakers AJ, Brouns F, Saris WH, Halliday D. Oxidation rates of
orally ingested carbohydrates during prolonged exercise in men. J Appl
Physiol 75: 2774 –2780, 1993.
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48. Wallis GA, Dawson R, Achten J, Webber J, Jeukendrup AE. Metabolic response to carbohydrate ingestion during exercise in males and
females. Am J Physiol Endocrinol Metab 290: E708 –E715, 2006.
49. Wallis GA, Yeo SE, Blannin AK, Jeukendrup AE. Dose-response
effects of ingested carbohydrate on exercise metabolism in women. Med
Sci Sports Exerc 39: 131–138, 2007.
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