human psychopharmacology

Hum. Psychopharmacol Clin Exp 2010; 25: 310–317.

Published online in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/hup.1115

Effects of caffeine and glucose, alone and combined,

on cognitive performance
Ana Adan1,2* and Josep Maria Serra-Grabulosa1,3
1
Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain
2
Institute for Brain, Cognition and Behaviour (IR3C), University of Barcelona, Barcelona, Spain
3
Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

Objective To study the effects of consuming caffeine and glucose, alone and combined, on cognitive performance.
Methods Seventy-two healthy subjects (36 women; age range 18–25) were tested early in the morning, having fasted overnight. Using a
double-blind, randomised design, subjects received one of the following beverages: water (150 ml); water plus 75 mg of caffeine; water plus
75 g of glucose; water plus and 75 mg of caffeine and 75 g of glucose. Attention, manual dexterity, visuo-spatial and frontal functions, memory
(immediate, consolidation and working) and subjective state were all assessed.
Results The combination of caffeine and glucose had beneficial effects on attention (sequential reaction time tasks) and on learning
and consolidation of verbal memory, effects not being observed when either substance was administered alone. Caffeine only showed
improvement in simple reaction time and glucose in simple and one sequential reaction time tasks and in the manual dexterity assembly task.
Conclusions The results indicate that the synergistic effects of caffeine and glucose can benefit sustained attention and verbal memory, even
with adequate levels of activation of the subjects. However, further studies are required, controlling for different levels of cognitive effort and
also considering measurements of neural activity. Copyright # 2010 John Wiley & Sons, Ltd.

key words — caffeine; glucose; performance; reaction time; attention; memory

INTRODUCTION of reaction time and sustained attention tasks (Haskell

Caffeine and glucose are part of our everyday lives, the
former being taken for its stimulant effects, the latter for
its restorative effects, and both for their pleasurable
effects. Caffeine is present in coffee as well as in a wide
variety of other drinks (i.e. tea, soft drinks). The quantity
of caffeine in one cup of coffee is highly variable, the
estimated range being 50–180 mg. Caffeine is rapidly
absorbed (30–40 min) and has a half-life of between 3
and 6 h (Rogers, 2007). Glucose is the major source of
energy for the brain and is essential for the normal
functioning of the central nervous system (Sieber and
Traystman, 1992). Numerous studies have observed
that consumption of caffeine and/or glucose can benefit
cognitive performance.
A great number of studies have been carried out
into the effects of caffeine on human behaviour and
cognition. Caffeine has beneficial effects on measures
* Correspondence to: A. Adan, Department of Psychiatry and Clinical
Psychobiology, University of Barcelona Pg. Vall Hebron 171, Barcelona
08035, Spain. Tel: 34-933125060. Fax: 34-934021584
E-mail: aadan@ub.edu
et al., 2005; Kelemen and Creeley, 2001; Oei and
Hartley, 2005; Smith, 2002, 2009; Smith et al., 2005).
It has also been found to increase subjective alertness
and mood and reduce fatigue (Adan et al., 2008;
Hewlett and Smith, 2007; Smith, 2009; Smith et al.,
2005). It improves motor-skill performance in tasks
such as a simulated driving task (Brice and Smith,
2001) and handwriting (Tucha et al., 2006).
At low doses (less than 100 mg), caffeine does not
always produce beneficial effects, these being more
apparent at moderate and high doses (Childs and de
Wit, 2006) and in situations with a deficit in activation,
such as in the case of fatigued subjects (Brice and
Smith, 2001; Hogervorst et al., 2008; Smith et al.,
2005), and working at night or during sleep deprivation
(Killgore et al., 2006; Wesensten et al., 2005).
Moreover, sensitivity to the mood and performance-
enhancing effects of caffeine is related to habitual
intake levels; high-caffeine consumers are more likely
to perceive broadly positive effects (Attwood et al.,
2007; Ghisolfi et al., 2006; Hewlett and Smith, 2006;
Rogers et al., 2003, 2005). Although the administration
of caffeine does not improve either speed or precision

Received 22 December 2009

Copyright # 2010 John Wiley & Sons, Ltd. Accepted 24 February 2010
 EFFECTS OF CAFFEINE AND GLUCOSE ON PERFORMANCE
in memory tasks (Boxtel et al., 2003; Childs and de
Wit, 2006; Haskell et al., 2005; Hogervorst et al., 1998,
2008; Kelemen and Creeley, 2001; Oei and Hartley,
2005), in the first study to use functional magnetic
resonance imaging (Koppelstaetter et al., 2008), it was
recently found that it modulates neuronal activity
during performance of a working memory task.
Evaluation of the cognitive effects of glucose has
mainly focused on its learning and memory-improving
action, with beneficial effects observed on a number of
different parameters. It has been shown that glucose
increases immediate and delayed recall in episodic
memory tasks both in young and older healthy adults
(Foster et al., 1998; Messier, 2004; Riby et al., 2004,
2006), although these facilitation effects were more
pronounced in older subjects and mediated by each
individual’s gluco-regulatory efficiency. Cognitive
facilitatory effects have also been found in other
studies which evaluated declarative learning (Sünram-
Lea et al., 2002a, b) and memory performance
(Messier, 2004; Meikle et al., 2004; Riby et al.,
2004, 2006; Stone et al., 2005), with effects lasting up
to 24 hours after administration. However, there is little
evidence that glucose can boost semantic memory
retrieval (Messier, 2004; Riby et al., 2006). Some
studies also obtained beneficial effects of glucose
intake on non-mnemonic cognitive measures, such as
rapid information processing and executive functions,
that would appear to be associated with a relatively
high cognitive load (Kennedy and Scholey, 2000;
Meikle et al., 2004; Scholey et al., 2001, 2006). In
general, lower doses of glucose (25 g) appear to be
more effective in young adults while higher doses (50–
75 g) are more often found to improve performance in
older adults (Messier, 2004).
Although there is much evidence that glucose and
caffeine improve various aspects of cognitive per-
formance, very few studies have investigated the
effects of the two substances in combination.
Beneficial effects of combined caffeine and glucose
have been found in sustained attention and working
memory (Smit et al., 2006), and in situations of
extended cognitive demand (Kennedy and Scholey,
2004). Moreover, better performance was observed in a
selective attention task coupled with direct effects
on visual cortical processing and decision-making
assessed by event-related brain potentials (Rao et al.,
2005). The studies evaluating the effects of energy
drinks containing caffeine, glucose and other purport-
edly active ingredients have noted improvements
in attention and declarative memory tasks without
significant changes in mood (Scholey and Kennedy,
2004; Smit and Rogers, 2002). This has led to the
Copyright # 2010 John Wiley & Sons, Ltd.
311
suggestion that there may be a synergistic effect
between caffeine and glucose on performance, as these
results could not be explained by the effects of glucose
or caffeine individually (Scholey and Kennedy, 2004).
This study aims to analyse the effect of consuming
caffeine (75 mg) and glucose (75 g), alone and
combined, on a battery of performance tasks and
subjective state. Participants were healthy undergradu-
ate students, non-consumers or low consumers of
caffeine (<100 mg caffeine/day), who were evaluated
first thing in the morning, having fasted overnight,
under optimum activation conditions after a period of
normal, restorative sleep.
METHODS
Participants
Seventy-two right-handed healthy undergraduate stu-
dents (36 women; age range 18–25; 21.07
1.70 year)
were recruited from the University of Barcelona.
Subjects with chronic disorders, nervous system
disorders or history of mental illness were excluded,
as well as habitual drinkers or smokers and those
on medication. All participants had intermediate
circadian typology, were good sleepers and reported
an undisturbed sleep period of at least 6 h during the
night prior to the experimental session. Daily caffeine
consumption was controlled, with only non-consumers
(N ¼ 46; 63.9%) or low consumers (<100 mg/day;
N ¼ 26; 36.1%) included. Low consumers caffeine
consumption included a maximum of one coffee per
day and none of them were daily consumers of tea or
cola beverages. The participants abstained from
caffeine for a minimum of 18 h and fasted for at least
8 h prior to the experiment. Women had regular
menstrual cycles and were studied in their follicular
phase, when gastric emptying of glucose intake is
slower and glycaemia lower (Brennan et al., 2009). The
study was approved by the ethics committee of
Hospital Clı́nic de Barcelona. Written consent was
obtained from all participants, who were financially
compensated for taking part in the study.
Caffeine and glucose measurements. Blood glucose
levels (mg/dl) were determined using a Blood Glucose
Sensor and disposable Blood Glucose Test Strips
(Glucocard Gmeter Kit Menarini). Saliva samples for
caffeine levels were obtained by asking participants to
expectorate into a tube. Levels of caffeine (ng/ml) were
determined by high performance liquid chromatog-
raphy (HPLC) in the Scientific and Technical Depart-
ment of the University of Barcelona, following the
Hum. Psychopharmacol Clin Exp 2010; 25: 310–317.
DOI: 10.1002/hup
312 a. adan and j. m. serra-grabulosa
procedure described in Childs and de Wit (2006).
Samples of blood and saliva were taken immediately
on arrival at the laboratory in order to confirm
compliance with 8 h fasting for food and 18 h of
caffeine abstinence. A further saliva sample was taken
30 min after intake of the beverage and blood glucose
levels were repeated at 30 and 60 min post-intake.
Performance tasks
The set of performance tasks used required 30–45 min
to be completed and was applied to all the participants
in the following order.
Rey Auditory Verbal Learning Memory Test
(RAVLT; Schmidt, 1996)—Verbal declarative mem-
ory task (immediate and delayed recall): This consists
of the presentation of a list of 15 words which subjects
are asked to recall in five immediate trials (learning
function). Another 15-word list is then read out which
acts as interference before going on to request recall
of the first list in two further trials. The first trial
evaluates the effect of the interference and the second
delayed recall (20 min after the final trial of learning).
Delayed recall is regarded as an indicator of memory
consolidation (Boxtel et al., 2003). The difference
between number of words remembered in the last
learning trial vs. the delayed recall was obtained as an
estimation of forgetting.
Purdue-Pegboard (Lafayette Instruments Company,
1999)—Premotor test which measures fine motor
coordination, dexterity and manipulation speed: It
consists of taking a peg from a cup and inserting it into
a hole as quickly as possible, firstly with the dominant
hand (30 s), secondly with the non-dominant-hand
(30 s) and thirdly, with both hands (30 s). Lastly, there
is a task of assembling pegs, collars and washers,
alternating the dominant hand with the non-dominant
(60 s).
Benton Judgement of Line Orientation Test (Lezak
et al., 2004)—Evaluates visuo-spatial function: The
subject has to match lines to a model they are presented
with. The computerised version was used.
Wisconsin Card Sorting Test (WCST, 2003): The
computerised version was administered with the
paradigm of 128 trials with the sequence colour,
shape and number. This test measures prefrontal
functions, assessing different dimensions: cognitive
processing speed, concept formation, inhibition
capacity and cognitive flexibility.
California Computerized Assessment Package (Cal-
CAP; Miller, 1990)—Computerised reaction time
program which measures sustained attention, reaction
time and visual scanning speed: The abbreviated
Copyright # 2010 John Wiley & Sons, Ltd.
version with four tasks was used; simple reaction time
(press a key as soon as anything appeared in the
screen), choice reaction time (press a key as soon as a
specific number appeared), sequential reaction time 1
(press a key when two of the same number appeared in
sequence) and sequential reaction time 2 (press a key
only when two numbers in increasing order appeared).
Digit Span of WAIS (Wechsler, 2001)— Test in
which participants are read a progressively longer
series of numbers ranging from two to nine digits and
then asked to repeat the series forward (general
attention) and backward (verbal working memory):
The total score proposed as criteria in the test
(forward þ backward series remembered) was con-
sidered.
Lastly, a set of eight unipolar Visual Analogue Scales
(VAS; Adan et al., 2008) was used as a subjective
measure of activation and mood. Each scale is 100 mm
long and asks the subjects to mark a cross at some point
between ‘very little’ (left) and ‘very much’ (right),
based on how they feel at the time of response (range of
scoring 0–100), choosing from among alert, sad, tense,
energetic, satisfied, tired, calm and sleepy. The VAS
has two subscales: (a) concentrated, energetic, tired
and sleepy for subjective activation level; (b) happy,
calm, sad and tense for subjective effect. To obtain
the score for the two subscales, the following formulas
are used: subjective activation ¼ [concentrated þ
energetic þ 200  (tired þ sleepy)]/4; mood ¼ [happy þ
calm þ 200  (sad þ tense)]/4.
Experimental design
A first individual session was held to verify that
subjects met inclusion criteria, explain what the
experiment consisted of and the requirements of their
participation and to obtain their written consent. The
experiment started between 9 AM and 9:30 AM and after
baseline measurements of glucose, saliva and sub-
jective state, subjects received the treatment beverage.
In a double-blind randomised design, participants
received one of the four beverages (18 subjects, nine
women per group). The individual beverages com-
prised: (1) placebo containing water (150 ml); (2)
water plus 75 mg of caffeine; (3) water plus 75 g of
glucose; (4) water plus 75 mg of caffeine and 75 g
of glucose. There was no difference between groups
in habitual caffeine consumption (x23 ¼ 3.792;
p ¼ 0.285). On the basis of the pharmacokinetics of
caffeine and glucose, the performance recordings
started 30 min after oral intake of the beverage.
Subjective state was recorded again at 30 and 60 min
post-intake and after completion of the battery of tasks.
Hum. Psychopharmacol Clin Exp 2010; 25: 310–317.
DOI: 10.1002/hup
 EFFECTS OF CAFFEINE AND GLUCOSE ON PERFORMANCE
Statistical analysis. Performance in each task was
analysed by multivariate analysis of variance (MAN-
OVA), when more than one measure was recorded, or
by analysis of variance (ANOVA) when only one
measure was recorded, with the beverage as between-
subjects factor (placebo, caffeine, glucose and caffei-
ne þ glucose). A repeated measures analysis was
carried out to study the development of the learning
in the RALVT task and the subjective evaluations, as
well as the change in the measurements of blood
glucose and caffeine levels. Post-hoc comparisons
were made with contrast options implemented in the
analysis of variance. The partial eta squared (h2p ) was
used to measure the effect sizes considering that a
partial eta squared of 0.01 was small, 0.04 medium and
0.1 large. All analyses were carried out with the SPSS
package (version 15.0) and statistical tests were two-
tailed with type I error set at 5%.
RESULTS
There was no difference between beverage groups in
terms of mean age or number of hours of sleep, either in
general or the night before the recordings (Table 1).
Nor were there significant differences in baseline levels
of blood glucose, caffeine and subjective state
(activation and mood). Table 1 shows the descriptive
statistics and results of the contrasts in different
variables. The two post-intake glucose measurements
were highly significant between groups, with values
similar to baseline in the placebo and caffeine
groups and significantly higher in the glucose and
caffeine þ glucose groups ( p ¼ 0.0001). The post-
intake measurement of caffeine was similar to baseline
313
in the placebo and glucose groups, while there was a
significant increase in the caffeine and caffei-
ne þ glucose groups ( p ¼ 0.0001), the increase being
greater in the caffeine group than in the caffei-
ne þ glucose group ( p ¼ 0.001).
Table 2 shows the descriptions for the performance
of the four CalCAP tasks for the beverage groups.
A main effect of beverage was obtained for the
simple reaction time task, considering mean
response time (F(3,68) ¼ 3.280; p ¼ 0.026; h2p ¼ 0.128)
z-score (F(3,68) ¼ 3.494; p ¼ 0.020; h2p ¼ 0.135) and
percentile (F(3,68) ¼ 2.759; p ¼ 0.049; h2p ¼ 0.110). In
all cases, the post-hoc comparisons showed poorer
performance in the water group with respect to the other
three (0.006 > p < 0.044), with no significant differ-
ences between the caffeine, glucose and caffei-
ne þ glucose groups (Table 2). No main effect of
beverage was obtained in the choice reaction time
task (F(3,68) < 0.804; p > 0.496), the sequential reac-
tion time 1 task (F(3,68) < 2.099; p > 0.110) or the
sequential reaction time 2 task (F(3,68) < 2.291;
p < 0.085). However, the post-hoc contrasts in the
sequential tasks revealed differences between the
beverage groups in execution. In the sequential
reaction time 1 task, the placebo group had a greater
mean response time than the glucose group ( p ¼ 0.042)
and the caffeine þ glucose group (0.028), in addition to
a lower z-score (placebo-glucose: p ¼ 0.052; placebo-
caffeine þ glucose: p ¼ 0.026) and lower percentile
(placebo-glucose: p ¼ 0.044; placebo-caffeine þ
glucose: p ¼ 0.048) (Table 2). In the sequential reaction
time 2 task, execution was poorer in the placebo group
than in the caffeine þ glucose group, with a greater
mean response time ( p ¼ 0.016), a lower z-score

Table 1. Descriptive statistics (mean and standard error) for age, habitual sleep and sleep pre-test (night before recordings) in hours and minutes for each
beverage group. Recordings of glucose (mg/dl), caffeine (ng/ml) and subjective activation and mood (visual analogue scales from 0–100) performed during the
experimental sessions (pre10 ¼ 10 min before beverage; post30 and post60 ¼ 30 and 60 min after beverage; final ¼ measure on completion of the performance
tasks)

Placebo Caffeine Glucose Caffeine þ glucose F(3,68); p

Age 21.00
0.44 20.72
0.45 21.55
0.40 21.00
0.28 0.775; 0.523
Habitual sleep 7:34
0:07 7:55
0:09 7:46
0:07 7:53
0:08 1.284; 0.287
Sleep pre-test 7:07
0:08 7:22
0:09 7:11
0:07 7:19
0:06 0.706; 0.552
Glucose pre10 76.50
2.12 75.39
1.28 80.67
3,24 79.56
1.18 1.373; 0.258
Glucose post30 75.93
2.30 74.69
2.39 157.67
12.36 141.20
8.01 32.958; 0.0001
Glucose post60 71.06
2.05 70.78
1.48 128.39
13.14 124.22
7.81 17.090; 0.0001
Caffeine pre10 4.41
0.84 5.76
1.36 5.37
1.01 6.58
1.08 0.680; 0.567
Caffeine post30 4.10
0.82 267.85
29.23 5.38
0.92 174.28
24.94 46.153; 0.0001
Activation pre10 57.59
3.72 53.78
3.83 56.12
2.49 59.20
2.98 0.487; 0.693
Activation post30 62.21
3.52 62.61
4.18 63.04
3.68 61.04
2.39 0.059; 0.981
Activation post60 58.46
3.85 64.57
4.55 63.02
1.99 66.18
3.14 0.896; 0.448
Activation final 66.89
3.56 64.45
4.53 70.64
2.73 67.17
3.01 0.520; 0.670
Mood pre10 76.81
2.11 76.14
3.05 74.82
1.73 76.93
2.91 0.149; 0.930
Mood post30 77.47
2.57 75.96
3.19 71.68
2.31 75.19
3.26 0.730; 0.536
Mood post60 74.21
2.60 74.32
3.04 75.07
1.82 75.12
2.75 0.035; 0.991
Mood final 77.68
2.32 78.31
3.16 75.87
1.88 77.79
2.64 0.174; 0.914

Copyright # 2010 John Wiley & Sons, Ltd. Hum. Psychopharmacol Clin Exp 2010; 25: 310–317.
DOI: 10.1002/hup
314 a. adan and j. m. serra-grabulosa
Table 2. Performance data (mean and standard error) for four tasks of abbreviated California Computerized Assessment Package (CalCAP). Reaction time in
milliseconds

Tasks Placebo Caffeine Glucose Caffeine þ glucose

Simple
Reaction time 389.35
18.50 320.16
17.98 318.16
17.04 336.44
14.02
z score 0.699
0.204 0.112
0.110 0.080
0.108 0.080
0.142
Percentile 36.70
4.95 54.56
3.88 53.33
3.45 47.78
4.81
Choice
Reaction time 401.28
10.58 391.67
10.77 381.39
9.95 390.11
8.74
z score 0.187
0.254 0.574
0.229 0.674
0.150 0.448
0.216
Percentile 59.77
6.51 67.17
6.96 71.33
4.51 63.11
6.51
Sequential 1
Reaction time 487.72
17.75 468.83
13.99 441.77
14.08 431.28
18.83
z score 0.636
0.189 0.850
0.144 1.132
0.154 1.245
0.195
Percentile 68.61
5.07 77.56
4.52 83.33
3.42 83.06
4.24
Sequential 2
Reaction time 581.41
26.52 525.61
22.42 549.83
24.47 498.22
20.71
z score 0.262
0.244 0.782
0.200 0.537
0.214 0.948
0.175
Percentile 58.00
6.50 74.06
5.74 65.78
6.11 77.67
4.54

( p ¼ 0.024) and a lower percentile ( p ¼ 0.019)
(Table 2).
Table 3 shows the descriptions for performance in
the Purdue Pegboard, Benton Judgement of Line
Orientation Test and RAVLT (total words remembered
in learning trials, interference and forgetting). Signifi-
cant differences between beverage groups were only
found in the Purdue Pegboard assembly task
(F(3,68) ¼ 2.938; p ¼ 0.039; h2p ¼ 0.116). Post-hoc com-
parisons between groups uncovered differences
between the glucose and the placebo ( p < 0.023)
and the caffeine ( p < 0.008), performance being better
in the glucose group. The MANOVA performed for the
Benton test measures (adjusted total score, errors and
reaction time) only revealed significant differences for
the beverage in reaction time (F(3,68) ¼ 2.912;
p ¼ 0.041; h2p ¼ 0.115). Post-hoc comparisons between
groups show a shorter execution time in the glucose
and caffeine þ glucose groups, the differences being
significant with respect to the caffeine group
( p ¼ 0.009 and p ¼ 0.017, respectively).
There were no significant differences between
beverage groups in the WAIS Digit Span subtest
(F(3,68) ¼ 0.772; p ¼ 0.514; h2p ¼ 0.033). The total score
in this working memory task was similar regardless of
the beverage administered (placebo: 18.50
0.81;
caffeine: 18.11
0.82; glucose: 17.22
0.61 and
caffeine þ glucose: 17.00
0.79). Nor was a signifi-
cant main effect of beverage found in any estimation of
execution in the WCST (F(3,68) < 0.736; p > 0.536),
either when considering the quality (number of trials,
correct trials, perseverative errors, learning) or the
speed, in this frontal-function task.
There were no significant differences between
beverage groups in the RAVLT learning when
considering the function of the five memory trials
(F(3,68) ¼ 1.181; p ¼ 0.324; h2p ¼ 0.050). In all cases,
the number of words remembered followed an

Table 3. Performance data (mean and standard error) for each beverage group in Purdue Pegboard, Benton Judgement of Line Orientation Test (total score
with correction for gender) and Rey Auditory Verbal Learning Memory Test (RAVLT)

Tasks Placebo Caffeine Glucose Caffeine þ glucose

Purdue Pegboard
Dominant hand 14.66
0.44 14.39
0.42 14.62
0.44 15.34
0.45
Non-dominant hand 13.48
0.39 14.12
0.36 14.12
0.39 14.51
0.39
Both hands 22.44
0.68 23.59
0.79 23.44
0.77 23.33
0.78
Assembly 35.75
1.51 34.86
1.44 40.74
1.32 37.85
1.50
Benton
Total score 26.50
0.79 27.19
0.73 26.78
0.77 26.65
0.85
Errors 4.51
0.90 3.72
0.73 4.19
0.85 5.30
0.90
Reaction time 5417.22
474.36 6344.16
481.55 4618.73
333.71 4769.95
424.71
RAVLT
Total words learning 56.50
1.35 58.78
1.32 56.89
1.28 60.56
1.14
Interference 1.28
0.32 1.22
0.42 1.61
0.39 1.17
0.34
Forgetting 1.55
0.35 0.84
0.33 1.66
0.42 1.16
0.30

Copyright # 2010 John Wiley & Sons, Ltd. Hum. Psychopharmacol Clin Exp 2010; 25: 310–317.
DOI: 10.1002/hup
 EFFECTS OF CAFFEINE AND GLUCOSE ON PERFORMANCE
ascending pattern from the first to the last trial.
Differences were found, however, when memory was
analysed for the groups in each of the five trials
individually, with differences found in the second to
last (RALVT 4: F(3,68) ¼ 4.218; p ¼ 0.009; h2p ¼ 0.157)
and the last (RALVT 5: F(3,68) ¼ 6.125; p ¼ 0.001;
h2p ¼ 0.213). In both cases, the mean number of words
remembered is higher in the caffeine þ glucose group
than in the other three (0.05 < p > 0.001), with no
difference being observed between the placebo,
caffeine and glucose groups (Figure 1). Lastly, there
were no differences between beverage groups in the
RAVLT when analysing the total words remembered in
learning trials (F(3,68) ¼ 2.155; p ¼ 0.101), the inter-
ference effect (F(3,68) ¼ 0.295; p ¼ 0.829) and forget-
ting (F(3,68) ¼ 1.14; p ¼ 0.338). However, the post-hoc
contrasts in the total words remembered revealed
differences between the beverage groups, the caffei-
ne þ glucose group had greater recall than the placebo
( p ¼ 0.028) and the glucose group (0.046) (Table 3).
Finally, differences were found in the memory
consolidation (F(3,68) ¼ 3.321; p ¼ 0.025; h2p ¼ 0.128)
that was also greater in the caffeine þ glucose group
than the placebo group ( p ¼ 0.023) or the glucose
group (0.004) (Figure 1).
Although a significant linear variation was obtained
for the four temporal recordings taken of subjective
activation (F(3,68) ¼ 31.93; p ¼ 0.0001; h2p ¼ 0.320),
there were no differences between beverage groups
(F(3,68) ¼ 1.834; p ¼ 0.149). Regardless of the bev-
erage, an increase in subjective activation was
observed from baseline to the final recording at the
end of the experiment. Moreover, none of the inter-
recording analyses found differences between any of
the groups ( p > 0.125). The evaluations of mood
showed significant quadratic evolution for the four
temporal recordings taken (F(3,68) ¼ 5.505; p ¼ 0.022;
h2p ¼ 0.075), although the changes were similar in all
15
Placebo
13
Caffeine
11
Glucose
9 Caffeine +
Glucose
7 Compared to placebo, the consumption of glucose
A1 A1 A3 A4 A5 20'
Figure 1. Number of words remembered in Rey Auditory Verbal Learning
Memory Test (RAVLT) for each trial of immediate recall (A1-A5) and for
delayed recall or memory consolidation recorded 20 min after (20’)
Copyright # 2010 John Wiley & Sons, Ltd.
315
the beverage groups (F(3,68) ¼ 1.272; p ¼ 0.291). Once
again, none of the inter-recording analyses found
differences between beverage groups ( p > 0.455). The
evaluations of mood fell between the first and third
recordings, only to go up again in the fourth and last
recording, regardless of the beverage consumed.
DISCUSSION
We found a differential pattern between the three
beverages with active substance them of beneficial
effects on cognitive performance, although the effects
were modest compared to placebo. Only very few
studies have specifically set out to evaluate the synergy
between caffeine and glucose, and none has considered
such an extensive battery of tasks as has been used in
our study. Moreover, the recordings were taken under
conditions with no arousal deficit, since different
variables which could have affected performance and
biased the results, such as sleep quality and duration
and the circadian typology of the participants, were
controlled. The doses selected in our study (low for
caffeine and high in the case of glucose) correspond
with the approximate contents of two soft drinks
containing caffeine and had not been used in previous
studies.
The administration of caffeine only provided a
beneficial effect in the execution of the simple reaction
time task compared to placebo. Moreover, in the
Benton visuo-spatial task, the speed of execution was
similar to placebo and lower than the groups which
consumed glucose and caffeine þ glucose. This is
consistent with the earlier literature; improvements in
performance are particularly observed in activation
deficit situations (Brice and Smith, 2001; Smith et al.,
2005; Wesensten et al., 2005; Killgore et al., 2006) and
in moderate or high caffeine consumers (Attwood
et al., 2007; Ghisolfi et al., 2006; Hewlett and Smith,
2006). Thus, we observed that 75 mg of caffeine had a
minimal impact upon behavioural performance in
habitual non-consumers or low consumers (Rogers
et al., 2003, 2005) recorded first thing in the morning
under adequate activation conditions. Future studies,
however, should investigate whether or not caffeine
increases neuronal activity during the performance of
several cognitive tasks in the absence of effects on
execution estimations, as was observed for the working
memory (Koppelstaetter et al., 2008).
had beneficial effects on execution in the simple
reaction time tasks and sequential reaction time 1 task
(press a key when two of the same number appeared in
sequence) and the Purdue Pegboard test assembly task.
Hum. Psychopharmacol Clin Exp 2010; 25: 310–317.
DOI: 10.1002/hup
316 a. adan and j. m. serra-grabulosa
Studies which have investigated the effects of glucose
consumption on execution have not tended to
incorporate manual dexterity tasks and attention tasks
of reaction time. Our results signal the need for future
studies which determine the dose-response ratio in
the execution of such tasks, since it is possible that the
beneficial effects only occur at high doses such as that
selected in this study. In contrast, consumption of
glucose was not found to have any beneficial effects on
the learning and memory tasks (Digit Span and
RAVLT) or on executive function (WCST). Many
previous studies have obtained beneficial effects from
the consumption of glucose on verbal memory tasks
such as RAVLT or more complex tasks (Meikle et al.,
2004; Messier, 2004; Riby et al., 2004, 2006; Stone
et al., 2005; Sünram-Lea et al., 2002a, b). This
discrepancy may be due to the dose of glucose we used,
since all the significant data with young subjects were
obtained at low doses (25 g).
The combined administration of glucose and
caffeine, compared to placebo, has been shown to
improve execution in all reaction time tasks except
choice, and learning (immediate memory) and memory
consolidation of RAVLT. In accordance with previous
studies, results indicate that the synergistic effects of
caffeine and glucose can benefit high-demand sus-
tained attention processes (Kennedy and Scholey,
2004; Rao et al., 2005; Smit et al., 2006) such as the
sequential 2 task, the most complex and last to be
executed of the CalCAP, and verbal memory (Scholey
and Kennedy, 2004; Smit and Rogers, 2002). This does
not occur with the consumption of caffeine or glucose
alone, suggesting that combined caffeine and glucose
may be a more effective cognition enhancer for this
type of task (Scholey and Kennedy, 2004), even under
circumstances of adequate levels of activation in
young subjects. Further research is needed to evaluate
the potential pharmacokinetic interactions of the co-
administration of caffeine and glucose and their
impact on behaviour. While it is known that the co-
administration increases intestinal glucose absorption
(Van Nienwenhoven et al., 2000), our data suggest that
caffeine absorption could also be different when taken
alone or combined with glucose, although there is not
any publication to this regard.
Subjective state (activation and mood) was indepen-
dent of the type of beverage administered, both when
considering the change over the course of the experiment
and for each recording taken. This result is consistent
with the only previous study to have evaluated the effects
of glucose in self-assessments of activation and stress
(Riby et al., 2004) and with two studies in which caffeine
and glucose were administered at lower doses (Kennedy
Copyright # 2010 John Wiley & Sons, Ltd.
and Scholey, 2004; Smit and Rogers, 2002). However, it
contrasts many studies which have observed beneficial
effects on activation with the administration of caffeine
at low doses (Adan et al., 2008; Brice and Smith, 2001;
Hewlett and Smith, 2007; Smith, 2002, 2009; Smith
et al., 2005). The wide dispersion within groups in self-
assessments and the non-naturalistic administration
may be the factors responsible for our data. It should
be emphasised that the administration of 75 mg of
caffeine and 75 g of glucose had no negative effects on
mood (tension, nervousness, anxiety, etc.), as might be
expected after consuming two soft-drinks containing
caffeine very quickly. Nevertheless, further study should
investigate the effects of caffeine, glucose and their
combination in extreme-time periods or during the post-
lunch, and also in subjects with high fatigue levels or
sleep deprivation and in different pathological con-
ditions. Under such conditions, greater benefits might be
expected, both in performance and subjective state, as is
already well established with the administration of
caffeine (Brice and Smith, 2001; Killgore et al., 2006;
Rogers, 2007; Smith et al., 2005; Wesensten et al., 2005)
and, to a lesser extent, glucose (Messier, 2004; Riby
et al., 2004, 2006; Stone and Seidman, 2008), although
to date, the possibility of such benefits with caffeine and
glucose combined has yet to be explored.
Finally, we should mention several limitations in our
study. Firstly, we used a single dose in each condition,
and it is therefore difficult to determine the real degree
of the synergistic effect between caffeine and glucose.
Secondly, the results of this study can only be
generalised to young healthy subjects fasted for food
and recorded early in the morning, and under non-
naturalistic conditions. In addition, we cannot rule out
the fact that other factors, such as those intrinsic to the
beverage (e.g. sensory attributes, smell and taste) or of
a psychological nature (e.g. expectancy), may play a
significant role in mediating the responses. Moreover,
further studies are required to investigate the effects of
caffeine and glucose, alone and in combination, with
repeated doses, controlling for different levels of
cognitive effort, and also considering measures of
neural activity such as event-related brain potentials
or functional neuroimaging.
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