High rates of exogenous carbohydrate oxidation from a mixture of glucose
and fructose ingested during prolonged cycling exercise
Roy L. P. G. Jentjens and Asker E. Jeukendrup*
Human Performance Laboratory, School of Sport and Exercise Sciences, University of Birmingham, Edgbaston B15 2TT, UK
(Received 12 August 2004 – Revised 26 October 2004 – Accepted 4 November 2004)
A recent study from our laboratory has shown that a mixture of glucose and fructose ingested at a rate of 1·8 g/min leads to peak oxidation rates of approxi-
mately 1·3 g/min and results in approximately 55 % higher exogenous carbohydrate (CHO) oxidation rates compared with the ingestion of an isocaloric
amount of glucose. The aim of the present study was to investigate whether a mixture of glucose and fructose when ingested at a high rate (2·4 g/min)
would lead to even higher exogenous CHO oxidation rates (. 1·3 g/min). Eight trained male cyclists (VO
:68^ 1 ml/kg per min) cycled on three differ-
ent occasions for 150 min at 50 % of maximal power output (60^ 1% VO
) and consumed either water (WAT) or a CHO solution providing 1·2 g/min
glucose (GLU) or 1·2 g/min glucoseþ 1·2 g/min fructose (GLUþ FRUC). Peak exogenous CHO oxidation rates were higher (P, 0·01) in the GLUþ FRUC
trial compared with the GLU trial (1·75 (
SE 0·11) and 1·06 (SE 0·05) g/min, respectively). Furthermore, exogenous CHO oxidation rates during the last
90 min of exercise were approximately 50 % higher (P, 0·05) in GLUþFRUC compared with GLU (1·49 (
SE 0·08) and 0·99 (SE 0·06) g/min, respectively).
The results demonstrate that when a mixture of glucose and fructose is ingested at high rates (2·4 g/min) during 150 min of cycling exercise, exogenous CHO
oxidation rates reach peak values of approximately 1·75 g/min.
Substrate utilization: Stable isotopes: Intestinal carbohydrate transport
Numerous studies have shown that carbohydrate (CHO) sup-
plementation during prolonged exercise at moderate to high inten-
sities can increase exercise performance (Coyle et al. 1986;
Coggan & Coyle, 1987). This effect is thought to be due to the
prevention of hypoglycaemia and the maintenance of high rates
of CHO oxidation late in exercise when endogenous CHO
stores become depleted (Coyle et al. 1986; Bosch et al. 1994).
Therefore, high exogenous CHO oxidation rates have the poten-
tial to improve prolonged exercise performance.
In a recent review we suggested that the maximal oxidation rate
of (most) ingested carbohydrates is 1·0–1·1 g/min (Jeukendrup &
Jentjens, 2000). When large amounts of glucose or glucose poly-
mers are ingested (. 1·2 g/min; Jentjens et al. 2004b), intestinal
glucose transporters (SGLT1) may become saturated and there-
fore intestinal CHO absorption may be a limiting factor for
exogenous CHO oxidation (Hawley et al. 1992; Jeukendrup
et al. 1999; Jeukendrup & Jentjens, 2000; Jentjens et al.
2004b). Of note, free fructose and most probably fructose released
during sucrose hydrolysis use a different intestinal transporter
(GLUT-5) from glucose (SGLT1; Davidson & Leese, 1977;
Sandle et al. 1983; Burant et al. 1992; Ferraris & Diamond,
1997). Interestingly, Shi et al. (1995) demonstrated with an intes-
tinal perfusion study that a beverage containing glucose and fruc-
tose resulted in approximately 65 % higher CHO absorption rates
compared with an isoenergetic glucose solution. This effect was
attributed to the separate intestinal transport mechanisms for glu-
cose and fructose.
We have recently shown that a mixture of glucoseþ fructose
(Jentjens et al. 2004b), glucoseþsucrose (Jentjens et al. 2004c)
or glucoseþfructoseþ sucrose (Jentjens et al. 2004a) results in
approximately 20–55 % higher exogenous CHO oxidation rates
compared with the ingestion of an isocaloric amount of glucose
and can lead to peak oxidation rates of approximately 1·7 g/min
(Jentjens et al. 2004a). Although speculative, a faster intestinal
CHO absorption might have increased the availability of
exogenous CHO for oxidation and hence this could explain
the high exogenous CHO oxidation rates (. 1·1 g/min)
observed when a mixture of glucoseþfructose or glucoseþsucrose
(þsucrose) was ingested (Jentjens et al. 2004a,b,c). Interestingly,
ingestion of equal amounts of glucose and sucrose at a rate of
2·4 g/min resulted in relatively low oxidation rates (approximately
1·2 g/min; Jentjens et al. 2005). It has been suggested that when
SGLT1 transporters become saturated (either from free glucose
and/or glucose released from sucrose hydrolysis), hydrolysis of
sucrose is inhibited (Gray & Ingelﬁnger, 1966; Sandle et al. 1983)
and this might limit the amount of sucrose available for absorption
and subsequent oxidation. This could explain why exogenous CHO
oxidation rates were relatively low (1·2 g/min), despite a fairly high
CHO intake rate (2·4 g/min; Jentjens et al. 2005).
The results of the studies described above suggest that the
‘maximum’ rate of exogenous CHO oxidation may depend on
the amount of glucose and fructose available for absorption and
the ‘maximum’ intestinal transport capacity for glucose and
fructose. However, in our previous study (Jentjens et al. 2004b)
* Corresponding author: Dr Asker E. Jeukendrup, fax þ44 (0)121 414 4121, email A.E.Jeukendrup@bham.ac.uk
Abbreviations: CHO, carbohydrate; FRUC, fructose; GI, gastrointestinal; GLU, glucose; HR, heart rate; PDB, Pee Dee Bellemnitella (international standard); RPE, rate of
perceived exertion; WAT, water; W
, maximum power output.
British Journal of Nutrition (2005), 93, 485–492 DOI: 10.1079/BJN20041368
q The Authors 2005
the fructose ingestion rate (0·6 g/min) was relatively low and
hence it is possible that not all fructose transporters were satu-
rated. In an attempt to saturate the SGLT1 and GLUT-5 transpor-
ters, in the present study, fructose was ingested at a higher intake
rate (1·2 g/min) and glucose was ingested at a rate of 1·2 g/min.
Saturation of both CHO transport systems might further increase
the rate of intestinal CHO absorption and this could potentially
lead to even higher (and maximal) exogenous CHO oxidation
rates. Therefore, we hypothesized that a mixture of glucose and
fructose when ingested at a high rate (2·4 g/min) would further
increase the rate of exogenous CHO oxidation (. 1·3 g/min).
Eight trained male cyclists or triathletes took part in the present
study. Their characteristics are presented in Table 1. Prior to par-
ticipation, each of the subjects was fully informed of the purpose
and the risks associated with the procedures, and a written
informed consent was obtained. All subjects were healthy as
assessed by a general health questionnaire. The study was
approved by the Ethics Committee of the School of Sport and
Exercise Sciences of the University of Birmingham, UK.
At least 1 week before the start of the experimental trials an incre-
mental cycle exercise test to volitional exhaustion was performed
in order to determine the individual maximum power output
) and maximal oxygen consumption (VO
). This test
was performed on an electromagnetically braked cycle ergometer
(Lode Excalibur Sport, Groningen, The Netherlands), modiﬁed to
the conﬁguration of a racing bicycle with adjustable saddle height
and handlebar position. After reporting to the laboratory, body
mass and height were recorded. Subjects then started cycling at
95 W for 3 min, followed by incremental steps of 35 W every
3 min until exhaustion. Heart rate (HR) was recorded continuously
by a radiotelemetry heart rate monitor (Polar Vantage NV, Kem-
pele, Finland). W
was calculated from the last completed
work rate, plus the fraction of time spent in the ﬁnal non-com-
pleted work rate multiplied by the work rate increment (Kuipers
et al. 1985). The results were used to determine the work rate cor-
responding to 50 % W
, which was later employed in the exper-
imental exercise trials. Breath-by-breath measurements were
performed throughout exercise using an online automated gas
analysis system (Oxycon Pro, Jaeger, Hoechberg, Germany).
The volume sensor was calibrated using a 3 litre calibration syr-
inge and the gas analysers were calibrated using a CO
mixture (5·03 %:94·97 %). Oxygen uptake (VO
) was considered
to be maximal (VO
) when at least two of the three following
criteria were met: (1) a levelling off of VO
with increasing work-
load (increase of no more than 2 ml/kg per min); (2) HR within 10
beats/min of predicted maximum (HR 220 minus age); (3) RER
. 1·05. VO
was calculated as the average oxygen uptake
over the last 60 s of the test. The VO
during the incremental exercise test were 68 (
SE 1) ml/kg per
min and 376 (
SE 12) W, respectively (Table 1).
Each subject performed three exercise trials which consisted of
150 min of cycling at 50 % W
while ingesting a glucose
drink (GLU), a glucoseþfructose drink (GLUþ FRUC; ingested
glucose–fructose ratio of 1:1) or plain water (WAT). In order
to quantify exogenous glucose oxidation, corn-derived glucose
monohydrate (Cerestar, Manchester, UK) and crystalline fructose
(Krystar 300; A.E. Staley Manufacturing Company, Decatur, IL,
USA) were used which have a high natural abundance of
(2 10·70 and 2 10·69 d‰ v. Pee Dee Bellemnitella (PDB),
C-enrichment of the ingested glucose and
fructose was determined by elemental analyser-isotope ratio
mass spectrometry (IRMS; Europa Scientiﬁc GEO 20-20,
Crewe, UK). To all CHO drinks 20 mmol/l NaCl (Sigma-Aldrich,
Poole, UK) was added. The order of the experimental drinks was
randomly assigned in a crossover design. Experimental trials were
separated by at least 5 d. The composition of the experimental
drinks is shown in Table 2.
Diet and activity prior to testing
Subjects were asked to record their food intake and activity pat-
tern 2 d prior to the ﬁrst exercise trial and were then instructed
to follow the same diet and exercise activities before the other
three trials. In addition, 5–7 d prior to each experimental testing
day, they were asked to perform an intense training session
(‘Glycogen depleting’ exercise bout) in an attempt to empty
C-enriched glycogen stores. Subjects were further
instructed not to consume any food products with a high natural
C (CHO derived from C
plants: corn, sugar
cane) at least 1 week before and during the entire experimental
period in order to reduce the background shift (change in
) from endogenous substrate stores.
Subjects reported to the Human Performance Laboratory in the
morning (between 07.00 and 09.00 hours) after an overnight
fast (10–12 h) and having refrained from any strenuous activity
or drinking any alcohol in the previous 24 h. For a given subject,
all trials were conducted at the same time of the day to avoid any
Table 2. Composition of the three experimental
WAT GLU GLUþFRUC
Glucose (g/l) – 92·3 92·3
Fructose (g/l) – – 92·3
NaCl (mmol/l) – 20 20
GLU, ingestion of glucose; GLU þ FRUC, ingestion of glu-
cose and fructose; WAT, ingestion of water only.
Table 1. Subject characteristics
(Mean values with their standard errors of the mean for eight subjects)
Age (years) 26·3 2·6
Height (cm) 181·4 1·4
Body mass (kg) 74·3 1·8
(ml/kg per min) 68·1 0·6
(W) 376 12
(beats/min) 185 4
, maximal heart rate; W
, maximum power output.
R. L. P. G. Jentjens and A. E. Jeukendrup486
inﬂuence of circadian variance. On arrival in the laboratory, a
ﬂexible 21-gauge Teﬂon catheter (Quickcath, Baxter) was
inserted in an antecubital vein of an arm and attached to a
three-way stopcock (Sims Portex, Kingsmead, UK) to allow for
repeated blood sampling during exercise. The catheter was kept
patent by ﬂushing with 1·0–1·5 ml of isotonic saline (0·9 %;
Baxter) after each blood sample collection.
The subjects then mounted a cycle ergometer and a resting
breath sample was collected in 10 ml Exetainer tubes (Labco
Ltd, Brow Works, High Wycombe, UK), which were ﬁlled
directly from a mixing chamber in duplicate in order to determine
C ratio in the expired air.
Next, a resting blood sample (8 ml) was taken and stored on ice
and later centrifuged. Subjects then started a 150 min exercise bout
at a work rate equivalent to 50 % W
(60^ 1% VO
Additionally, blood samples were drawn at 15 min intervals
during exercise. Expiratory breath samples were collected every
15 min until the end of exercise. VO
and RER were measured every 15 min for periods of 4 min
using an online automated gas analysis system as previously
During the ﬁrst 3 min of exercise subjects drank an initial
bolus (600 ml) of one of the three experimental drinks: GLU,
GLUþFRUC or WAT. Thereafter, every 15 min a beverage
volume of 150 ml was provided. The total ﬂuid provided during
the 150 min exercise bout was 1·95 litres. The average rate of glu-
cose intake in the GLU and GLUþ FRUC trial was 1·2 g/min. Fur-
thermore, in the GLUþ FRUC trial subjects ingested on average
1·2 g/min fructose which brought the total CHO intake rate in
the GLUþFRUC to 2·4 g/min.
Subjects were asked to rate their perceived exertion (RPE) for
whole body and legs every 30 min on a scale from 6 to 20 using
the Borg category scale (Borg, 1982). In addition, subjects were
asked every 30 min to ﬁll in a questionnaire in order to rate
(possible) gastrointestinal problems (Jeukendrup et al. 2000). All
exercise tests were performed under normal and standard environ-
mental conditions (17–218C dry bulb temperature and 55 – 65 %
relative humidity). During the exercise trials subjects were
cooled with standing ﬂoor fans in order minimize thermal stress.
Subjects were asked to ﬁll out a questionnaire every 30 min during
the exercise trials. The questionnaire contained questions regard-
ing the presence of gastrointestinal (GI) problems at that moment
and addressed the following complaints; stomach problems, gas-
trointestinal cramping, bloated feeling, diarrhoea, nausea, dizzi-
ness, headache, belching, vomiting, and urge to urinate/defecate.
While subjects were on the bike and continued their exercise
each question was answered by simply ticking a box on the ques-
tionnaire that corresponded to the severity of the GI problem
addressed. The items were scored on a 10-point scale (1 ¼ not at
all, 10 ¼ very, very much). The severity of the GI symptoms
was divided into two categories: severe and non-severe symptoms,
as was previously described by Jeukendrup et al. (2000). Severe
complaints included nausea, stomach problems, bloated feeling,
diarrhoea, urge to vomit, stomach and intestinal cramps because
these are symptoms that commonly impair performance and may
bring with them health risks. The above symptoms were only regis-
tered as severe symptoms when a score of 5 or higher out of 10 was
reported. When a score below 5 was given, they were registered
as non-severe. All other symptoms were registered as non-severe
regardless of the score reported.
Blood samples were collected into pre-chilled EDTA-containing
tubes (Beckton Dickinson, Plymouth, UK) and centrifuged at
2300 g and 48C for 10 min. Aliquots of plasma were immediately
frozen in liquid nitrogen and stored at 2 258C until analyses for
glucose and lactate. Glucose (Glucose HK 125, ABX Diagnostics,
Shefford, UK) and lactate (Lactic Acid 10, ABX Diagnostics,
Shefford) were analysed on a COBAS MIRA semi-automatic ana-
lyser (ABX Diagnostics, Montpellier, France).
Breath samples were analysed for
C ratio by gas chroma-
tography continuous ﬂow isotope ratio mass spectrometry (GC-
IRMS; Europa Scientiﬁc). From indirect calorimetry (VO
) and stable isotope measurements (breath
ratio), oxidation rates of total fat, total CHO, endogenous CHO
and exogenous glucose were calculated.
(l/min), total CHO and fat oxidation rates
(g/min) were calculated using stoichiometric equations of Frayn
(1983) with the assumption that protein oxidation during exercise
CHO oxidation ¼ 4·55 VCO
2 3·21 VO
Fat oxidation ¼ 1·67 VO
2 1·67 VCO
The isotopic enrichment was expressed as d‰ difference between
C ratio of the sample and a known laboratory reference
standard according to the formula of Craig (1957):
per mil ð3Þ
C was then related to an international standard (PDB).
In the GLU and GLUþ FRUC trials, the rate of exogenous glu-
cose oxidation was calculated using the following formula
(Mosora et al. 1976):
Exogenous glucose oxidation
dExp 2 dExp
dIng 2 dExp
In which dExp is the
C enrichment of expired air during exer-
cise at different time points, dIng is the
C enrichment of the
ingested CHO solution, dExp
C enrichment of expired
air in the WAT trial (background) at different time points and k is
the amount of CO
(in litres) produced by the oxidation of 1 g of
glucose (k ¼ 0·7467 litres CO
per g glucose).
Endogenous CHO oxidation was calculated by subtracting
exogenous CHO oxidation from total CHO oxidation.
A methodological consideration when using
air to calculate exogenous substrate oxidation is the trapping of
in the bicarbonate pool, in which an amount of CO
from decarboxylation of energy substrates is temporarily trapped
(Robert et al. 1987). However, during exercise the CO
duction increases severalfold so that a physiological steady-state
condition will occur relatively rapidly, and
expired air will be equilibrated with the
Exogenous oxidation of glucose and fructose 487
respectively. Recovery of
from oxidation will approach
100 % after 60 min of exercise when dilution in the bicarbonate
pool becomes negligible (Robert et al. 1987; Pallikarakis et al.
1991). As a consequence of this, all calculations on substrate
oxidation were performed over the last 90 min of exercise
Two-way ANOVA for repeated measures was used to compare
differences in substrate utilization and in blood-related parameters
over time between the trials. A Tukey post hoc was applied in the
event of a signiﬁcant F ratio. Where appropriate, comparison of
variables between two conditions was conducted by using a Stu-
dent’s t test for paired samples. Data evaluation was performed
using SPSS for Windows version 10.0 software package (SPSS,
Chicago, IL, USA). All data are reported as means with their stan-
dard errors. Statistical signiﬁcance was set at P, 0·05.
Changes in isotopic composition of expired CO
to exercise with ingestion of water (WAT), glucose (GLU)
or a mixture of glucose and fructose (GLUþFRUC) are shown
in Fig. 1(A). In the GLU and GLUþFRUC trials,
enrichment of expired breath increased (P, 0·01) from 225·87
SE 0·16) and 2 25·89 (SE 0·20) d‰ v. PDB at rest to 2 20·88
SE 0·20) and 2 18·31 (SE 0·26) d‰ v. PDB by the end of the
150 min exercise, respectively. From the 45 min point onwards,
enrichment in the GLUþ FRUC trial was signiﬁ-
cantly (P, 0·01) higher compared with the GLU trial. During
the WAT trial, there was also a signiﬁcant increase in
enrichment of the expired air (P, 0·01). The rise in background
enrichment during the WAT trial was relatively small
(approximately 10– 14 %) compared with the rise in breath
enrichment observed during the two CHO trials. Although
the background shift was small in the present study, a background
correction was made for the calculation of exogenous CHO oxi-
dation in the two CHO trials by using the data from the WAT
Oxygen uptake, rate of perceived exertion, total carbohydrate and
Data for VO
, RER, total CHO and fat oxidation over the
60–150 min exercise period are shown in Table 3. There was
no signiﬁcant difference in VO
between the three experimental
trials. RER in the WAT trial was signiﬁcantly lower (P, 0·01)
compared with the GLU and GLUþFRUC trial. During the
90–120 min and the 120–150 min exercise periods, RER was sig-
niﬁcantly higher in GLUþFRUC compared with GLU. The aver-
age CHO oxidation rates during the last 90 min of exercise were
SE 0·13), 2·26 (SE 0·12) and 2·57 (SE 0·15) g/min for WAT,
GLU and GLUþ FRUC, respectively. The rate of CHO oxidation
was signiﬁcantly higher (P, 0·01) after CHO ingestion compared
with WAT ingestion (Table 3). Furthermore, CHO oxidation
between 60 and 150 min was signiﬁcantly higher (P, 0·05) in
GLUþFRUC compared with GLU. The ingestion of CHO
(GLU and GLUþ FRUC) resulted in signiﬁcantly lower
(P, 0·01) fat oxidation rates compared with the WAT trial. Fur-
thermore, fat oxidation rates were signiﬁcantly lower (P, 0·01)
in GLUþ FRUC compared with GLU. The average fat oxidation
rates over the 60–150 min exercise period were 0·97 (
SE 0·05) and 0·51 (SE 0·04) g/min for WAT, GLU and
GLUþFRUC, respectively. The relative contribution of substrates
to total energy expenditure during the 60–150 min period of exer-
cise is depicted in Fig. 2. Fat oxidation represented 61 (
SE 3), 43
SE 3) and 34 (SE 3) % of total energy expenditure in WAT, GLU
and GLUþ FRUC, respectively (WAT . GLU . GLUþ FRUC;
P, 0·05) (Fig. 2).
Exogenous and endogenous carbohydrate oxidation
In the GLU and GLUþ FRUC trials, the rate of exogenous CHO
oxidation increased signiﬁcantly (P, 0·01) during exercise.
However, in GLU, exogenous CHO oxidation rates levelled
off after approximately 105–120 min of exercise (Fig. 1(B)),
while the rate of exogenous CHO oxidation in GLUþ FRUC
increased until the end of exercise (no levelling off). Peak
exogenous CHO oxidation rates were reached at the end of exer-
cise (150 min) and were signiﬁcantly higher (P, 0·01) in
the GLUþ FRUC trial (1·75 (
SE 0·11) g/min) compared with the
GLU trial (1·06 (
SE 0·04) g/min) (Fig. 1(B)). During the
60–150 min exercise period, exogenous CHO oxidation rates
Fig. 1. Breath
enrichment (A) and exogenous carbohydrate oxidation
(B) during exercise without ingestion of carbohydrate (WAT, B), with inges-
tion of glucose (GLU, W) or with ingestion of glucoseþ fructose (GLUþFRUC,
X). Values are means with their standard errors represented by vertical bars
(n 8). a, Signiﬁcant difference between WAT and GLUþ FRUC (P, 0·05); b,
signiﬁcant difference between WAT and CHO trials (P, 0·01); c, signiﬁcant
difference between GLU and GLUþ FRUC (P, 0·01). PDB, Pee Dee Bellem-
nitella (international standard).
R. L. P. G. Jentjens and A. E. Jeukendrup488
were approximately 50 % higher (P, 0·01) in GLUþFRUC com-
pared with GLU (Table 2; Fig. 1(B) and Fig. 2).
The rate of endogenous CHO oxidation was signiﬁcantly lower
(P, 0·05) in the two CHO trials compared with the WAT trial
(Table 3; Fig. 2). No signiﬁcant difference was found in endogen-
ous CHO oxidation rates between the GLU and GLUþFRUC
trial. The average endogenous CHO oxidation rates over the
60–150 min exercise period were 1·56 (
SE 0·13), 1·26 (SE 0·12)
and 1·07 (
SE 0·15) g/min for WAT, GLU and GLUþFRUC,
respectively. During the last 90 min of exercise, endogenous
CHO oxidation represented 39 (
SE 3), 32 (SE 3) and 28 (SE 4)
% of total energy expenditure in WAT, GLU and GLUþ FRUC,
respectively (WAT . GLU and GLUþFRUC; P, 0·05) (Fig. 2).
Plasma glucose and lactate
No differences were observed in fasting plasma glucose concen-
trations between trials (Fig. 3(A)). In the WAT trial, plasma
glucose concentrations decreased gradually during exercise,
reaching a nadir of 3·7 (
SE 0·2) mmol/l at the end of exercise
(t 150 min). In contrast, a large increase in plasma glucose was
observed following ingestion of GLU and GLUþFRUC, with
peak values of 5·8 (
SE 0·3) and 6·0 (SE 0·6) mmol/l respectively,
reached 15 min into the exercise period. Thereafter, plasma glu-
cose concentrations decreased to fasting levels and remained at
values varying between 4·6 and 5·0 mmol/l for the duration of
exercise. Plasma glucose concentrations were higher (P, 0·05)
throughout exercise in the two CHO trials compared with the
WAT trial. There were no signiﬁcant differences in plasma glu-
cose concentrations between the GLU and GLUþFRUC trials.
Plasma lactate concentrations at rest in the WAT, GLU and
GLUþFRUC trials were 1·1 (
SE 0·2), 1·0 (SE 0·1) and 1·1 (SE
0·1) mmol/l, respectively (P. 0·05; Fig. 3(B)). At all time
points during exercise, plasma lactate concentrations were
higher (P, 0·01) in the GLUþ FRUC trial compared with the
WAT and GLU trials. No differences in plasma lactate concen-
trations were observed between the GLU and WAT trials.
Gastrointestinal discomfort and ratings of perceived exertion
The most frequently reported complaints were urge to urinate,
belching and bloated feeling. There were no differences (i.e.
number of complaints or number of subjects that reported com-
plaints) in GI discomfort between the three experimental trials,
apart from one subject who reported severe stomach problems
in the GLUþFRUC trial (stomach burn and bloated feeling).
No signiﬁcant differences in RPE overall or RPE legs were
observed between the three conditions. The mean values for RPE
overall and RPE legs during 150 min of exercise were 11·7 (
0·4) and 11·8 (SE 0·4) for WAT, 11·6 (SE 0·3) and 11·9 (SE 0·4)
for GLU, and 11·8 (
SE 0·4) and 11·8 (SE 0·4) for GLUþFRUC.
The main ﬁnding of the present study was that combined inges-
tion of glucose and fructose at a rate of 1·2 and 1·2 g/min, respect-
ively, resulted in peak exogenous CHO oxidation rates of 1·75 g/
In a recent study from our laboratory, we have shown that
ingestion of glucose at a rate of 1·2 g/min in combination with
fructose at a rate of 0·6 g/min leads to peak exogenous oxidation
Table 3. Mean oxygen uptake (VOd
), rate of perceived exertion (RER), total carbohydrate (CHO) oxidation (CHOtot), total fat oxidation (FATtot), endogenous
CHO oxidation and exogenous glucose oxidation during cycling exercise with ingestion of water, glucose and glucoseþ fructose.
(Mean values with their standard errors for eight subjects)
(l/min) RER CHOtot (g/min) FATtot (g/min)
Time (min) Mean
SE Mean SE Mean SE Mean SE Mean SE Mean SE
WAT 60–90 3·10 0·12 0·83 0·01
90– 120 3·14 0·12 0·81 0·01
120– 150 3·16 0·16 0·81 0·01
GLU 60– 90 3·03 0·09 0·87 0·01 2·28 0·13 0·65 0·05
1·36 0·13 0·91 0·07
90– 120 3·06 0·09 0·87 0·01
2·27 0·11 0·67 0·05
1·25 0·12 1·03 0·07
120– 150 3·10 0·09 0·86 0·07
1·18 0·10 1·06 0·06
GLUþ FRUC 60– 90 2·94 0·10 0·89 0·01 2·49 0·15 0·53 0·05 1·18 0·15 1·31 0·07
90– 120 2·96 0·10 0·90 0·01 2·57 0·15 0·51 0·04 1·04 0·15 1·53 0·08
120– 150 2·98 0·10 0·90 0·01 2·64 0·18 0·50 0·04 0·97 0·16 1·67 0·10
GLU, ingestion of glucose; GLUþFRUC, ingestion of glucose and fructose; WAT, ingestion of water only.
Signiﬁcant difference between
WAT and GLUþFRUC (P, 0·01);
WAT and CHO trials (P, 0·01);
GLU and GLUþFRUC (P, 0·01);
GLU and GLUþ FRUC (P, 0·05);
WAT and GLU
Fig. 2. Relative contributions of substrates to total energy expenditure calcu-
lated for the 60 –150 min period of exercise without ingestion of carbohydrate
(WAT), with ingestion of glucose (GLU) or with ingestion of glucoseþ fructose
(GLUþ FRUC). Values are means with their standard errors (n 8). b, Signiﬁ-
cant difference between WAT and CHO trials (P, 0·05); d, signiﬁcant differ-
ence between GLU and GLUþ FRUC (P, 0·05). p, Fat; B, exogenous
carbohydrate; A, endogenous carbohydrate.
Exogenous oxidation of glucose and fructose 489
rates of 1·26 (SE 0·07) g/min (Jentjens et al. 2004b). When a
mixture of glucose and sucrose was ingested at a rate of 1·2
and 0·6 g/min, respectively, almost similar rates of exogenous
CHO oxidation were found (1·25 (
SE 0·07) g/min; Jentjens et al.
2004c). More importantly, combined ingestion of glucoseþ
sucrose and glucoseþ fructose resulted in approximately 20 –
55 % higher exogenous CHO oxidation rates compared with the
ingestion of an isocaloric amount of glucose (Jentjens et al.
2004b,c). These ﬁndings support the data of Shi et al. (1995)
who demonstrated that a beverage containing two or three trans-
portable CHO (glucose, fructose and sucrose) resulted in higher
CHO and/or water absorption rates compared with an isoenergetic
glucose solution (Shi et al. 1995). Our previous ﬁndings and those
of Shi et al. (1995) might be explained by the fact that free fruc-
tose and most probably fructose released during sucrose hydroly-
sis uses a different intestinal transporter (GLUT-5) than glucose
(SGLT1; Davidson & Leese, 1977; Sandle et al. 1983; Burant
et al. 1992; Ferraris & Diamond, 1997) and hence intestinal
CHO absorption might be increased when a mixture of multiple
transportable CHO is consumed. Furthermore, studies in
humans and rats have indicated that fructose absorption is
enhanced by the presence of glucose (Holdsworth & Dawson,
1964; Fujisawa et al. 1991; Hoekstra & van den Aker, 1996;
Shi et al. 1997; Corpe et al. 1999). The facilitated fructose
absorption probably occurs as a result of glucose-induced water
streaming through the mucosal layer, also known as solvent
drag (Holdsworth & Dawson, 1964; Fine et al. 1994; Hoekstra
& van den Aker, 1996; Shi et al. 1997). This process requires
the opening of tight junctions by glucose absorption and the sub-
sequent movement of water through the paracellular pathway.
Small solutes, including fructose, will move passively with
water through the same pathway. In addition, glucose-induced
water absorption increases intraluminal fructose concentrations
and this might also lead to increased fructose transport (Holds-
worth & Dawson, 1964; Fine et al. 1994). Thus, in addition to
the different intestinal transport mechanisms for glucose and fruc-
tose, the stimulating effect of glucose on fructose absorption
might further contribute to an increased intestinal CHO absorp-
tion rate when mixtures of multiple transportable CHO are
ingested. It has been postulated that a faster intestinal CHO
absorption might increase the availability of exogenous CHO
for oxidation (Jentjens et al. 2004a,b,c, 2005) and this might
explain the high exogenous CHO oxidation rates (approximately
1·25–1·75 g/min) observed in the present study and in our pre-
vious studies in which mixtures of glucose, sucrose and/or fruc-
tose were ingested (Jentjens et al. 2004a,b,c, 2005).
Ingestion of fructose in combination with other carbohydrates
(present study; Jentjens et al. 2004a,b; L Moseley, GI Mainwar-
ing, S Samuels, S Perry, CH Mann and AE Jeukendrup, unpub-
lished results) or when ingested alone (Macdonald et al. 1978;
Koivisto et al. 1981) has been shown to result in elevated lactate
concentrations. The increased lactate concentrations following
fructose ingestion might be due to the high activity of fructoki-
nase, stimulation of pyruvate kinase and the fact that fructolysis
bypasses phosphofructokinase (the main rate-controlling step in
glycolysis). Fructose is therefore rapidly phosphorylated, resulting
in increased concentrations of glycolytic intermediates which will
lead to an increased glycolytic ﬂux, evidenced by elevated plasma
lactate concentrations. Furthermore, studies in animals and
humans have shown that during absorption a considerable
amount of absorbed glucose (Hanson & Parsons, 1976; Porteous,
1978; Nicholls et al. 1983; Bjorkman et al. 1990) or absorbed
fructose (Bjorkman et al. 1984; Holloway & Parsons, 1984) is
converted in the intestine into lactate, most of which is secreted
into the portal vein. Most of the lactate will be converted into glu-
cose by the liver. However, some lactate might escape from the
liver into the systemic circulation and this could lead to increased
plasma lactate concentrations. Although speculative, the higher
plasma lactate concentrations following ingestion of GLUþ
FRUC may indicate faster intestinal CHO absorption and this
may have caused the higher exogenous CHO oxidation rates.
It has been shown that when equal amounts of glucose and
sucrose are ingested at a rate of 2·4 g/min (Jentjens et al. 2005),
exogenous CHO oxidation rates are not much different from the
oxidation rates found when glucose and sucrose are ingested at
a rate of 1·2 and 0·6 g/min, respectively (Jentjens et al. 2004c).
These ﬁndings indicate that the rate of exogenous CHO oxidation
does not increase when the rate of sucrose intake is increased
from 0·6 to 1·2 g/min and glucose is ingested simultaneously at
a rate of 1·2 g/min (Jentjens et al. 2004c, 2005). On the contrary,
the combined results from the present and a previous study
(Jentjens et al. 2004b) suggest that an increase in the rate of fruc-
tose ingestion from 0·6 to 1·2 g/min when coingested with glucose
at a rate of 1·2 g/min leads to higher peak oxidation rates
Fig. 3. Plasma glucose (A) and lactate (B) during exercise without ingestion
of carbohydrate (WAT, B), with ingestion of glucose (GLU, W) or with inges-
tion of glucoseþ fructose (GLUþ FRUC, X). Values are means with their
standard errors represented by vertical bars (n 8). a, Signiﬁcant difference
between WAT and GLUþFRUC (P, 0·05); b, signiﬁcant difference between
WAT and CHO trials (P, 0·01); e, signiﬁcant difference between WAT and
GLU (P, 0·05); f, GLUþFRUC signiﬁcantly different from GLU and WAT
(P, 0·05); g, GLUþ FRUC signiﬁcantly different from GLU and WAT
R. L. P. G. Jentjens and A. E. Jeukendrup490
(1·75 (SE 0·11) v. 1·26 (SE 0·07) g/min, respectively). These data
support the results of an earlier study from our laboratory, in
which a mixture of glucose, fructose and sucrose when ingested
at a rate of 1·2, 0·6 and 0·6 g/min, respectively, resulted in peak
exogenous CHO oxidation rates of 1·70 (
SE 0·07) g/min (Jentjens
et al. 2004a). The present data and previous ﬁndings from our
laboratory (Jentjens et al. 2004a) indicate that in order to achieve
high exogenous CHO oxidation rates (approximately 1·7 g/min) a
mixture of glucoseþ fructose (þsucrose) should be consumed at
high intake rates (i.e. 1·2 g/min glucoseþ 1·2 g/min fructose).
One potential limitation of our study is that we did not include
an isoenergetic glucose (only) trial and hence it may be difﬁcult
to compare the results of the two CHO trials. However, it
should be noted that we and others have previously demonstrated
that the rate of exogenous CHO oxidation does not increase when
the rate of glucose or maltodextrin ingestion is increased from 1·2
to 1·8 g/min (Wagenmakers et al. 1993; Jentjens et al. 2004b).
Furthermore, we have recently shown that when glucose is
ingested at a rate of 2·4 g/min, average exogenous glucose oxi-
dation rates during the last 90 min of exercise are 1·01 (
g/min (Jentjens et al. 2004a). The rate of exogenous glucose oxi-
dation in the present study (GLU trial) is almost similar to the
oxidation rate observed in our previous study (Jentjens et al.
2004a), despite a 50 % lower glucose ingestion rate (1·2 v. 2·4 g/
min, respectively). The above ﬁndings indicate that maximal
glucose oxidation rates are reached when glucose is ingested at
a rate of approximately 1·2 g/min. In the present study, glucose
and fructose were both ingested at rates of 1·2 g/min and therefore
the higher exogenous CHO oxidation rates in the GLUþ FRUC
trial could be fully attributed to the oxidation of ingested fructose,
which supports our previous ﬁndings (Jentjens et al. 2004b). Of
note, previous studies have shown that when fructose is ingested
alone, average oxidation rates vary between 0·32 and 0·44 g/min
for exercise durations up to 180 min (Massicotte et al. 1986,
1989, 1990; Jandrain et al. 1993; Adopo et al. 1994). Unfortu-
nately most studies did not report ‘peak’ exogenous CHO
oxidation rates. In some studies it was found that the oxidation
rate of ingested fructose reached peak values of approximately
0·50–0·64 g/min at the end of 120–180 min of cycling exercise
(Massicotte et al. 1986, 1990; Jandrain et al. 1993). During the
120–150 min exercise period in the present study, the difference
in the rate of exogenous CHO oxidation between GLU and
GLUþFRUC was approximately 0·6 g/min. If it is assumed that
this oxidation rate represents the oxidation rate of ingested fruc-
tose then these results suggest that the ingested fructose and glu-
cose in the GLUþ FRUC trial were both oxidized at peak rates
(approximately 0·6 and approximately 1·1 g/min, respectively).
Therefore, the exogenous CHO oxidation rate observed in the
GLUþFRUC trial (approximately 1·75 g/min) could be the high-
est oxidation rate that is physiologically possible when multiple
transportable CHO (i.e. glucoseþfructose) are ingested orally.
It should be noted that in order to reach very high rates of
exogenous CHO oxidation, it may be important that both glucose
and fructose transporters (SGLT1 and GLUT-5, respectively) are
saturated. As mentioned earlier, intestinal glucose transporters
(SGLT1) may become saturated when glucose or glucose poly-
mers are ingested at a rate of . 1·2 g/min (Jentjens et al.
2004b). Therefore, in the present study and in our previous studies
(Jentjens et al. 2004a,b,c, 2005), glucose was ingested at a rate of
at least 1·2 g/min. The absorption rate of fructose is, however,
much lower than that of glucose or sucrose (Ravich et al. 1983;
Riby et al. 1993; Rumessen & Gudmand-Hoyer, 1986) and thus
ingestion of large amounts of fructose should be avoided as the
unabsorbed fructose might accumulate in the GI tract which
might increase the risk of GI discomfort (Murray et al. 1989;
Fujisawa et al. 1993). In our previous study, the maximum
amount of fructose theoretically available for absorption was
0·9 g/min (0·6 g/min fructose and 0·3 g/min fructose released
from sucrose hydrolysis) and glucose was ingested at a rate of
1·2 g/min (Jentjens et al. 2004a). In the present study, a higher
fructose intake rate (1·2 v. 0·9 g/min) did not lead to higher
exogenous CHO oxidation rates (1·75 (
SE 0·11) v. 1·70
SE 0·07)). Furthermore, previous studies have shown that oxi-
dation rates of ingested fructose (alone) are highest when fructose
is ingested at a rate of approximately 0·8 g/min (Massicotte et al.
1986, 1990). Although speculative, GLUT-5 transporters may
become ‘saturated’ at a fructose ingestion rate of 0·8–0·9 g/min
and therefore no increase in exogenous fructose oxidation is
observed when fructose is ingested at higher rates.
In conclusion, combined ingestion of large amounts of glucose
and fructose during 150 min of cycling exercise resulted in peak
exogenous CHO oxidation rates of approximately 1·75 g/min
and resulted in approximately 50 % higher exogenous CHO oxi-
dation rates compared with the ingestion of glucose alone. The
present ﬁndings are in agreement with our earlier ﬁndings and
suggest that intestinal CHO absorption could be a rate-limiting
factor for exogenous CHO oxidation.
The authors would like to thank Cerestar (Manchester, UK) for
donating glucose monohydrate and A.E. Staley Manufacturing
Company (USA) for donating fructose. This study was sup-
ported by a grant of GlaxoSmithKline Consumer Healthcare,
Adopo E, Peronnet F, Massicotte D, Brisson GR & Hillaire-Marcel C
(1994) Respective oxidation of exogenous glucose and fructose given
in the same drink during exercise. J Appl Physiol 76, 1014–1019.
Bjorkman O, Crump M & Phillips RW (1984) Intestinal metabolism of
orally administered glucose and fructose in Yucatan miniature swine.
J Nutr 114, 1413– 1420.
Bjorkman O, Eriksson LS, Nyberg B & Wahren J (1990) Gut exchange of
glucose and lactate in basal state and after oral glucose ingestion in
postoperative patients. Diabetes 39, 747–751.
Borg G (1982) Ratings of perceived exertion and heart rates during
short-term cycle exercise and their use in a new cycling strength test.
Int J Sports Med 3, 153–158.
Bosch AN, Dennis SC & Noakes TD (1994) Inﬂuence of carbohydrate
ingestion on fuel substrate turnover and oxidation during prolonged
exercise. J Appl Physiol 76, 2364– 2372.
Burant CF, Takeda J, Brot-Laroche E, Bell GL & Davidson NO (1992)
Fructose transporter in human spermatozoa and small intestine is
GLUT5. J Biol Chem 267, 14523–14526.
Coggan AR & Coyle EF (1987) Reversal of fatigue during prolonged
exercise by carbohydrate infusion or ingestion. J Appl Physiol 63,
Corpe CP, Burant CF & Hoekstra JH (1999) Intestinal fructose absorption:
clinical and molecular aspects. J Pediatr Gastroenterol Nutr 28,
Exogenous oxidation of glucose and fructose 491
Coyle EF, Coggan AR, Hemmert MK & Ivy JL (1986) Muscle glycogen
utilization during prolonged strenuous exercise when fed carbohydrate.
J Appl Physiol 61, 165 –172.
Craig H (1957) Isotopic standards for carbon and oxygen and correction
factors. Geochim Cosmochim Acta 12, 133– 149.
Davidson RE & Leese HJ (1977) Sucrose absorption by the rat small
intestine in vivo and in vitro. J Physiol 267, 237–248.
Ferraris RP & Diamond J (1997) Regulation of intestinal sugar transport.
Physiol Rev 77, 257– 302.
Fine KD, Santa Ana CA, Porter JL & Fordtran JS (1994) Mechanism by
which glucose stimulates the passive absorption of small solutes by the
human jejunum in vivo. Gastroenterology 107, 389 –395.
Frayn KN (1983) Calculation of substrate oxidation rates in vivo from
gaseous exchange. J Appl Physiol 55, 628 – 634.
Fujisawa T, Mulligan K, Wada L, Schumacher L, Riby J & Kretchmer N
(1993) The effect of exercise on fructose absorption. Am J Clin Nutr 58,
Fujisawa T, Riby J & Kretchmer N (1991) Intestinal absorption of fructose
in the rat. Gastroenterology 101, 360– 367.
Gray GM & Ingelﬁnger FJ (1966) Intestinal absorption of sucrose in man:
interrelation of hydrolysis and monosaccharide product absorption.
J Clin Invest 45, 388 –398.
Hanson PJ & Parsons DS (1976) The utilization of glucose and production
of lactate by in vitro preparations of rat small intestine: effects of vas-
cular perfusion. J Physiol 255, 775– 795.
Hawley JA, Dennis SC & Noakes TD (1992) Oxidation of carbohydrate
ingested during prolonged endurance exercise. Sports Med 14, 27– 42.
Hoekstra JH & van den Aker JH (1996) Facilitating effect of amino acids
on fructose and sorbitol absorption in children. J Pediatr Gastroenterol
Nutr 23, 118–124.
Holdsworth CD & Dawson AM (1964) The absorption of monosacchar-
ides in man. Clin Sci 27, 371– 379.
Holloway PA & Parsons DS (1984) Absorption and metabolism of fruc-
tose by rat jejunum. Biochem J 222, 57–64.
Jandrain BJ, Pallikaris N, Normand S, Pirnay F, Lacroix M, Mosora F,
Pachiaudi C, Gautier JF, Scheen AJ, Riou JP & Lefe
bvre PJ (1993)
Fructose utilization during exercise in men: rapid conversion of
ingested fructose to circulating glucose. J Appl Physiol 74, 2146 –2154.
Jentjens RL, Achten J & Jeukendrup AE (2004a) High oxidation rates
from combined carbohydrates ingested during exercise. Med Sci
Sports Exerc 36, 1551–1558.
Jentjens RL, Moseley L, Waring RH, Harding LK & Jeukendrup AE
(2004b) Oxidation of combined ingestion of glucose and fructose
during exercise. J Appl Physiol 96, 1277–1284.
Jentjens RL, Venables MC & Jeukendrup AE (2004c) Oxidation of
exogenous glucose, sucrose, and maltose during prolonged cycling
exercise. J Appl Physiol 96, 1285– 1291.
Jentjens RLPG, Shaw C, Birtles T, Waring RH, Harding LE & Jeukendrup
AE (in press) Oxidation of combined ingestion of glucose and sucrose
during exercise. Metabolism.
Jeukendrup AE & Jentjens R (2000) Oxidation of carbohydrate feedings
during prolonged exercise: current thoughts, guidelines and directions
for future research. Sports Med 29, 407–424.
Jeukendrup AE, Vet-Joop K, Sturk A, Stegen JH, Senden J, Saris WHM &
Wagenmakers AJM (2000) Relationship between gastro-intestinal com-
plaints and endotoxaemia, cytokine release and the acute-phase reaction
during and after a long-distance triathlon in highly trained men. Clin
Sci 98, 47–55.
Jeukendrup AE, Wagenmakers AJM, Stegen JHCH, Gijsen AP, Brouns F
& Saris WHM (1999) Carbohydrate ingestion can completely suppress
endogenous glucose production during exercise. Am J Physiol 276,
Koivisto VA, Karonen SL & Nikkila EA (1981) Carbohydrate ingestion
before exercise: comparison of glucose, fructose, and sweet placebo.
J Appl Physiol 51, 783 –787.
Kuipers H, Verstappen FTJ, Keizer HA, Geurten P & van Kranenburg G
(1985) Variability of aerobic performance in the laboratory and its
physiologic correlates. Int J Sports Med 6, 197 –201.
Macdonald I, Keyser A & Pacy D (1978) Some effects, in man, of varying
the load of glucose, sucrose, fructose, or sorbitol on various metabolites
in blood. Am J Clin Nutr 31, 1305 –1311.
Massicotte D, Peronnet F, Allah C, Hillaire-Marcel C, Ledoux M &
Brisson G (1986) Metabolic response to [
C]glucose and [
ingestion during exercise. J Appl Physiol 61, 1180–1184.
Massicotte D, Peronnet F, Brisson G, Bakkouch K & Hillaire-Marcel C
(1989) Oxidation of a glucose polymer during exercise: comparison
with glucose and fructose. J Appl Physiol 66, 179– 183.
Massicotte D, Peronnet F, Brisson G, Boivin L & Hillaire-Marcel C
(1990) Oxidation of exogenous carbohydrate during prolonged exercise
in fed and fasted conditions. Int J Sports Med 11, 253–258.
Mosora F, Lefebvre P, Pirnay F, Lacroix M, Luyckx A & Duchesne J
(1976) Quantitative evaluation of the oxidation of an exogenous
glucose load using naturally labeled
C-glucose. Metabolism 25,
Murray R, Paul GL, Seifert JG, Eddy DE & Halaby GA (1989) The effects
of glucose, fructose, and sucrose ingestion during exercise. Med Sci
Sports Exerc 21, 275– 282.
Nicholls TJ, Leese HJ & Bronk JR (1983) Transport and metabolism of
glucose by rat small intestine. Biochem J 212, 183– 187.
Pallikarakis N, Sphiris N & Lefebvre P (1991) Inﬂuence of the bicarbon-
ate pool and on the occurrence of
in exhaled air. Eur J Appl Phy-
siol 63, 179–183.
Porteous JW (1978) Glucose as a fuel for small intestine. Biochem Soc
Trans 6, 534–539.
Ravich WJ, Bayless TM & Thomas M (1983) Fructose: incomplete intes-
tinal absorption in humans. Gastroenterology 84, 26 –29.
Riby JE, Fujisawa T & Kretchmer N (1993) Fructose absorption. Am J
Clin Nutr 58, 748S– 753S.
Robert JJ, Koziet J, Chauvet D, Darmaun D, Desjeux JF & Young VR
(1987) Use of
C-labeled glucose for estimating glucose oxidation:
some design considerations. J Appl Physiol 63, 1725–1732.
Rumessen JJ & Gudmand-Hoyer E (1986) Absorption capacity of fructose
in healthy adults. Comparison with sucrose and its constituent mono-
saccharides. Gut 27, 1161–1168.
Sandle GI, Lobley RW, Warwick R & Holmes R (1983) Monosaccharide
absorption and water secretion during disaccharide perfusion of the
human jejunum. Digestion 26, 53–60.
Shi X, Schedl HP, Summers RM, Lambert GP, Chang RT, Xia T & Gisolﬁ
CV (1997) Fructose transport mechanisms in humans. Gastroentero-
logy 113, 1171– 1179.
Shi X, Summers RW, Schedl HP, Flanagan SW, Chang R & Gisolﬁ CV
(1995) Effects of carbohydrate type and concentration and solution
osmolality on water absorption. Med Sci Sports 27, 1607– 1615.
Wagenmakers AJM, Brouns F, Saris WHM & Halliday D (1993) Oxi-
dation rates of orally ingested carbohydrates during prolonged exercise
in man. J Appl Physiol 75, 2774–2780.
R. L. P. G. Jentjens and A. E. Jeukendrup492