Acute effects of brewed cocoa consumption on attention, motivation to perform cognitive work and feelings of anxiety, energy and fatigue: a randomized, placebo-controlled crossover experiment

Abstract

Acute effects of caffeinated and non-caffeinated cocoa on mood, motivation, and cognitive function are not well characterized. The current study examined the acute influence of brewed cocoa, alone and with supplemental caffeine, on attention, motivation to perform cognitive tasks and energy and fatigue mood states. A randomized, double-blinded, within-subjects crossover trial was conducted with four 473-milliliter brewed beverage treatments: cocoa, caffeinated cocoa (70 milligrams caffeine total), placebo (flavored and colored brewed water) and positive control (placebo plus 66 milligrams caffeine, “caffeine alone”). Participants (n = 24) were low consumers of polyphenols without elevated feelings of energy. Before and three times after beverage consumption, a 26-minute battery was used to assess motivation to perform cognitive tasks, mood and attention (serial subtractions of 3 and 7, the continuous performance task, and the Bakan dual task) with a 10-minute break between each post-consumption battery. The procedure was repeated with each beverage for each participant at least 48 h apart and ±30 min the same time of day. Data were evaluated using Treatment X Time analysis of covariance controlling for hours of prior night’s sleep. Compared to placebo, cocoa reduced overall false alarm errors progressively across time with 0.92, 1.44 and 2.35 fewer false alarms on average 22–48, 60–86 and 98–124 min post-consumption (η
2 = 0.08, p = 0.019). Caffeinated cocoa: (i) attenuated the anxiety-provoking effects of cognitive testing found after drinking caffeine alone (η
2 = 0.064, p = 0.038), and (ii) increased accuracy (η
2 = 0.085, p = 0.01) and reduced omission errors (η
2 = 0.077, p = 0.016) on the Bakan primary task compared to cocoa alone. Brewed cocoa can acutely reduce errors associated with attention in the absence of changes in either perceived motivation to perform cognitive tasks or feelings of energy and fatigue. Supplemental caffeine in brewed cocoa can enhance aspects of attention while brewed cocoa can attenuate the anxiety-provoking effects found from drinking caffeine alone. ClinicalTrials.gov Identifier: NCT01651793
. Registered July 25, 2012.

Full text

R E S E A R C H A R T I C L E Open Access
Acute effects of brewed cocoa
consumption on attention, motivation to
perform cognitive work and feelings of
anxiety, energy and fatigue: a randomized,
placebo-controlled crossover experiment
Ali Boolani
1
, Jacob B. Lindheimer
2,3
, Bryan D. Loy
4
, Stephen Crozier
5*
and Patrick J. O’Connor
6
Abstract
Background: Acute effects of caffeinated and non-caffeinated cocoa on mood, motivation, and cognitive function are
not well characterized. The current study examined the acute influence of brewed cocoa, alone and with supplemental
caffeine, on attention, motivation to perform cognitive tasks and energy and fatigue mood states.
Methods: A randomized, double-blinded, within-subjects crossover trial was conducted with four 473-milliliter brewed
beverage treatments: cocoa, caffeinated cocoa (70 milligrams caffeine total), placebo (flavored and colored brewed
water) and positive control (placebo plus 66 milligrams caffeine, “caffeine alone”). Participants (n= 24) were low
consumers of polyphenols without elevated feelings of energy. Before and three times after beverage consumption, a
26-minute battery was used to assess motivation to perform cognitive tasks, mood and attention (serial subtractions of
3 and 7, the continuous performance task, and the Bakan dual task) with a 10-minute break between each post-
consumption battery. The procedure was repeated with each beverage for each participant at least 48 h apart
and ±30 min the same time of day. Data were evaluated using Treatment X Time analysis of covariance controlling for
hours of prior night’ssleep.
Results: Compared to placebo, cocoa reduced overall false alarm errors progressively across time with 0.92, 1.44
and 2.35 fewer false alarms on average 22–48, 60–86 and 98–124 min post-consumption (η
2
= 0.08, p= 0.019).
Caffeinated cocoa: (i) attenuated the anxiety-provoking effects of cognitive testing found after drinking caffeine
alone (η
2
= 0.064, p= 0.038), and (ii) increased accuracy (η
2
=0.085,p= 0.01) and reduced omission errors (η
2
=0.077,
p= 0.016) on the Bakan primary task compared to cocoa alone.
Conclusions: Brewed cocoa can acutely reduce errors associated with attention in the absence of changes in either
perceived motivation to perform cognitive tasks or feelings of energy and fatigue. Supplemental caffeine in brewed
cocoa can enhance aspects of attention while brewed cocoa can attenuate the anxiety-provoking effects found from
drinking caffeine alone.
Trial registration: ClinicalTrials.gov Identifier: NCT01651793. Registered July 25, 2012.
Keywords: Anxiety, Attention, Caffeine, Cocoa, Energy, Fatigue, Flavanols, Mood, Theobromine, Vigilance
* Correspondence: scrozier@hersheys.com
5
The Hershey Company, Hershey, PA 17033, USA
Full list of author information is available at the end of the article
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Boolani et al. BMC Nutrition (2017) 3:8
DOI 10.1186/s40795-016-0117-z
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Background
Past researchers have examined the cardiovascular
health effects of acute and chronic cocoa consumption
[1, 2] and acute brain vascular changes after cocoa con-
sumption also have been documented [3, 4]. However, the
potential short-term effects of cocoa on mood, motivation
and cognitive function are less well characterized.
To date, cocoa has been examined in forms containing
other ingredients that can impact mental performance.
For example, drinks containing caloric energy that in-
crease blood glucose consistently improve performance
on memory and attention tasks [5, 6]. Caffeine also has
well documented attention, motivation and mood
enhancing effects [7–9] and these effects may occur as
quickly as 10 min (mins) post-consumption [10]. Cocoa
contains a small amount of caffeine (approximately 5-fold
and 20-fold less caffeine per ounce than cola and coffee,
respectively), but even small amounts of caffeine can in-
fluence attention and mood [11, 12]. Despite the existence
of commercially available cocoa products with added
caffeine, investigations examining the psychological
consequences of interactions between constituents in
chocolate or cocoa-containing beverages are rare. Related
studies, such as those examining glucose and caffeine or
cocoa and theobromine, suggest possible synergistic
effects on aspects of cognitive performance [13–15].
Conversely, there is inconsistent evidence from small
studies showing that the consumption of cocoa with milk
can reduce the bioavailability of flavanols [16]. If this is
true then the potential effects of cocoa flavanols on mood
and cognitive performance may be underestimated when
cocoa is co-consumed with dairy products. Only one other
study has examined cocoa in the absence of dairy or calo-
ries and it was found that the consumption of tablets
containing 250 mg cocoa transiently improved self-
reported mental fatigue and serial sevens performance
compared to placebo [17].
Chocolate and cocoa-containing beverages, which are
often made or consumed with milk, contain compounds,
such as choline and tryptophan, that cross the blood-
brain barrier and could influence mood, motivation or
cognitive performance [18]. The potential effects of
cocoa on mood and cognition also have been hypothe-
sized to result from cocoa flavanols or the dominant
methylxanthine contained in cocoa –theobromine [19].
There is a small but growing body of research on the
cognitive and mood consequences of chocolate and
cocoa consumption [17, 20–23]; however, there appear
to be only a few studies concerning the influence of the
consumption of cocoa flavanols per se on acute changes
in cognitive performance or mood. One experiment
found that, compared to white chocolate containing
trace amounts of flavanols, the consumption of dark
chocolate containing 773 milligrams (mg) of cocoa
flavanols improved spatial memory and reaction time
during the predictable phase of an attention task per-
formed 2 to 2.75 h (hrs) post-consumption [24]. Mood
and motivation were not measured in that study, but
motivation is a factor that could plausibly be influenced
by cocoa and is known to impact tasks of attention [25].
A second experiment examined effects of two identical
dairy-based drinks with doses of cocoa flavanols of either
520 or 994 mg on both mood and a cognitive performance
test battery. The drink containing 520 mg of cocoa flava-
nols had the largest and most consistent psychological
effects - increased performance accuracy during a test of
attention and reduced ratings of mental fatigue from 1.5
to 2.5 h post-consumption [26]. A third experiment
showed no effect of 100 mg, 200 mg or 300 mg theobro-
mine delivered in a cocoa-based beverage on mood state
or vigilance [27]. Hrs of sleep the night before testing was
not considered in any of these studies despite strong evi-
dence that variations in sleep can result in meaningful
changes in mood and cognitive performance [28–30].
The aim of the present experiment was to examine the
acute influence of brewed ground cocoa, both alone (no
dairy, no calories) and with supplemental caffeine (49 mg
added resulting in 70 mg total, an amount not exceeding
the US Food and Drug Administration limit for cola
drinks), on attention, motivation to perform cognitive
tasks, and energy and fatigue mood states.
A second purpose was to determine if the mood, mo-
tivation, or cognitive effects occur sooner than 1.5 h
after consumption. Prior studies used a 1.5 to 2.75 h
post-consumption time frame because increases in cere-
bral blood flow were found 2–4 h post-consumption [4].
This brain blood flow study [4], however, did not exam-
ine any time periods less than 2 h post-consumption.
The bioavailability of active ingredients in cocoa and the
subsequent mood, motivation, and cognitive effects
plausibly could occur more quickly when cocoa is con-
sumed in the absence of dairy products as has been shown
for antioxidant levels after consumption of chocolate with
and without milk consumption [16].
The study hypotheses were that during tests of attention
(i) brewed cocoa alone would quickly (i.e., in less than 2 h
and in as little as 22 to 48 min post-consumption) im-
prove performance on attention tasks, motivation to
complete the cognitive tasks, and feelings of energy and
fatigue, and (ii) that caffeinated brewed cocoa, compared
to either brewed cocoa alone or caffeine alone, would
result in improved attention, motivation, and feelings of
energy and fatigue.
Methods
Design
A placebo-controlled, double-blinded, within subjects,
randomized cross-over experiment examined the effects
Boolani et al. BMC Nutrition (2017) 3:8 Page 2 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

of two brewed treatments, a positive control, and a pla-
cebo (each 473 milliliters; ml). The treatments were
cocoa (21 mg caffeine, 179 mg theobromine, 499 mg
flavanols and one packet Truvia sweetener) and cocoa
+ caffeine (70 mg caffeine, 179 mg theobromine,
499 mg flavanols and 1 packet Truvia sweetener). In
order to better interpret potential null findings, a “caf-
feine-only”condition (473 ml brewed water containing
66 mg caffeine, caramel coloring and one packet Truvia
sweetener) matched to the cocoa + caffeine condition
was used to document whether the participants were
responsive to a stimulus known to alter motivation,
mood, and cognitive performance. The fourth condition
was a placebo containing neither cocoa nor caffeine
(473 ml of brewed water, caramel coloring and one
packet Truvia sweetener). A mental energy test battery
was administered before and three times after (22–48,
60–86 and 98–124 min) beverage consumption.
Screening
Potential participants were recruited from (i) large uni-
versity classes, (ii) announcements on buses, bulletin
boards, and electronic listservs, and (iii) through word
of mouth. Potential participants were invited to
complete screening questionnaires (medical history,
diet, mood) administered online using Zoomerang
>http://www.zoomerang.com/<.
Potential participants were excluded with body mass
index > 30 or who reported: (i) an allergy to cocoa,
chocolate, or caffeine, (ii) any smoking, or (iii) above
average feelings of energy (scores > 12) during the week
prior to the screening using the vigor scale of the 30-item
Profile of Mood States (POMS) questionnaire [31]. Poten-
tial participants were also excluded because of over-the-
counter and prescription medication use (except for con-
traceptives) or high consumption of flavanols during
the prior month (>39 total combined servings of cocoa,
caffeine, fruits or vegetables high in flavanols) using
medical history and diet questionnaires described previ-
ously [32, 33].
Participants
An a priori statistical power analysis showed that 24 par-
ticipants would provide statistical power of 0.81 to de-
tect a 2 Group x 4 Time interaction effect size of 0.65
given a p-value of 0.05 and assuming a correlation across
the repeated measures on Time of 0.70. [34]. One female
was excluded due to outlying data. Characteristics of the
final sample (n= 23) are reported in Table 1.
The number of hrs of reported sleep the night before
each of the four testing sessions did not significantly dif-
fer between conditions (p= 0.767) and all participants
reported refraining from cocoa or caffeine consumption
during the 24-hrs prior to each testing day.
Salivary caffeine, theobromine and paraxanthine levels
Saliva samples were obtained by passive drool using the
SalivaBio collection system (Salimetrics, State College,
PA, USA). Samples were collected at the start of each
testing day in order to confirm compliance with the
instructions to avoid cocoa- and caffeine-containing
foods and beverages. Post-test session saliva samples
were obtained to estimate the association between
changes in selected methylxanthines and changes in
mood and cognitive performance. The saliva samples
were frozen at −80 °C. After all samples were collected,
they were shipped overnight in coolers with dry ice to
the Department of Laboratory Medicine, Children’s
Hospital Boston. The samples were analyzed for theo-
bromine, caffeine and paraxanthine with liquid chroma-
tography–tandem mass spectrometry using previously
described methods [35].
Mental energy test battery
Consistent with prior related research, the mental energy
test battery was comprised of self-reported motivation
(0–10) [7], mood measures (i.e., mental and physical en-
ergy and fatigue state scales [7, 36] and the POMS [31])
and computerized cognitive tasks of attention (i.e., Serial
3 and 7 subtraction tasks [26], Bakan and Continuous
Performance Tasks [7]. The mood and motivation ques-
tionnaires were completed online using Zoomerang.
This approach required the mental and physical energy
and fatigue scales to be modified from usual (0 to 100)
to a 0 to 10 format. The timing of the mental energy test
battery is detailed in Table 2.
Table 1 Participant characteristics
Sex (males/females) 17/6
Age (years) 20.25 ± 2.23
Height (cm) 168.28 ± 1.19
Weight (kg) 67.05 ± 14.87
Body Mass Index (kg/m
2
) 23.26 ± 3.84
Race
White 15
Black 6
More than one race 2
Amount of sleep on a typical night in
the past month (hrs)
7.4 ± 1.1
Consumption of high-flavanol foods or
beverages during the past month
Caffeinated drinks (servings) 0.79 ± 2.25
Cocoa (servings) 2.88 ± 2.29
Fruits (servings) 4.13 ± 3.1
Vegetables (servings) 14.88 ± 6.53
Data are reported as means ± standard deviations where appropriate
Boolani et al. BMC Nutrition (2017) 3:8 Page 3 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

All cognitive testing was performed in a seated pos-
ition in a thermoneutral (23 ± 1 °C), sound-attenuated
[~60 dB(A) below ambient] chamber with lighting at
~80 lux. Visual stimuli were presented that required a
finger response. Participants used either the keyboard or
a key pad (RB-530 key pad, Cedrus, San Pedro, CA,
USA) to respond to information presented on a 20”
computer monitor. The Continuous Performance Task
and the Bakan test were scored using Cedrus Data
Viewer. Due to software scoring limitations, two
research assistants manually scored the subtraction tasks
independently and discrepancies were resolved.
Test beverages
The participants consumed one of four 473 ml beverages
on each testing day. The beverages were brewed in a cof-
fee maker (Mr. Coffee model#BVMGEHX23, Keurig®,
Cleveland, OH) to a temperature of ~167 °F, and then
allowed to cool uncovered for 7–8 min in a 1500 ml
Vanity Fair Insulair cup until the temperature reached
~140 °F prior to being consumed. Six cups of distilled
water were filtered through the coffee maker with ~1474
grams (cocoa or placebo) to produce 473 ml of beverage.
The drinks were prepared by a research assistant who
was not otherwise involved in testing that day. The drink
was brewed after the completion of questionnaires ask-
ing about sleep and the consumption of caffeine, cocoa,
or medications in the last 24 h. Dark coloring (DDW
The Colour House- product 034, Lot# 201205080070)
was added to the beverages to provide a uniform color
to aid in blinding. Participants also wore a nose clip
during beverage consumption and a lid covered the cup
while the beverage was being consumed. Participants
consumed the beverage within 10 min of being served
(before min 48 of the experiment as shown in Fig. 1).
Test products were manufactured and supplied by
the Hershey Company in individually wrapped bags,
coded with a two-digit number that identified the test
beverage. These products were stored in a cool (~24 °F),
dry environment in a light-impenetrable container prior
to preparation. A chemical analysis, performed by the
Hershey Company, is provided in Table 3.
Procedure
Approval for the study was granted by the University of
Georgia Institutional Review Board (Study # 00000311).
Prior to all testing days the participants were advised
to abstain from chocolate/cocoa, caffeine and alcohol
consumption, and the use of all medications except for
oral contraceptives for a minimum of 24 h prior to each
testing day. Participants were also advised to get a typical
amount of sleep.
Familiarization Days 1–2. On Day 1, a 30–45 min
single trial run of all daily assessments was conducted.
On Day 2, the entire 2.75 h protocol was completed.
Data from these familiarization days were not analyzed.
Testing Days 3–6: Four different treatment orders were
used to minimize potential order effects. Participants
were randomly allocated to complete one of four bever-
age orders (coded as 1-2-3-4, 2-3-4-1, 3-4-1-2 and 4-1-2-3)
in blocks of four, such that each of the four orders was
completed by six participants. With one exception there
was a minimum of 48 h between testing days. Each partici-
pant was tested at the same time of day (±30 min) to
minimize potential diurnal variation. Because sleep loss has
substantial effects on mood and cognitive performance
[37], participants who reported 2 h more or less than their
usual sleep duration (reported during the screening) were
not tested that day and rescheduled, as were those who
reported drug use or the consumption of cocoa or caffeine
containing beverages or foods within the prior 24 h. The
key testing events and their timing are presented in Fig. 1.
Data treatment and statistics
Preliminary analyses
Questionnaire data were downloaded into Excel from
Zoomerang. Cognitive data were summarized using
Cedrus Data Viewer (Cedrus Corp, 2007). All data were
exported into SPSS (Version 20) for analysis. All statis-
tical analyses were performed prior to breaking the
blind. One individual had cognitive task performance
scores that were deemed as error-dominated outliers
(>3 standard deviations from the mean, invariant
responding resulting in zero correct answers on multiple
days, ID 54321). Data from this individual were excluded
from the primary analysis. Scatterplots and descriptive sta-
tistics were evaluated. Variables that were not normally
distributed (i.e., assessed from Kolmogorov-Smirnov tests,
p< .05) were transformed using either a square root or log
transformation prior to the primary analyses. The post-
treatment minus pre-treatment changes in salivary con-
centrations of caffeine, theobromine and paraxanthine in
the placebo, caffeine, cocoa and caffeinated cocoa condi-
tions were examined using t-tests to examine whether the
treatments influenced salivary methylxanthine concentra-
tions in expected ways (e.g., caffeine increasing in caffeine
Table 2 Timing of the mental energy test battery
Task Approximate Times (minutes)
Motivation to perform cognitive tasks 0.5
Likert scales of energy and fatigue 1
POMS fatigue and vigor scales 2.5
Serial subtraction of the number three 2
Serial subtraction of the number seven 2
Continuous performance task 2
Bakan task 16
The total duration of the mental energy test battery was 26 min
Boolani et al. BMC Nutrition (2017) 3:8 Page 4 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

conditions; theobromine increasing in theobromine
conditions).
Two participants (ID: 27051 & 34122) had baseline
saliva samples on two of four testing days that contained
>0.5 μg/ml caffeine and paraxanthine suggesting that
they had failed to comply with the instructions to abstain
from caffeine. When data from these participants were in-
cluded, one-way ANOVAs revealed non-significant differ-
ences between the conditions in pre-testing salivary
caffeine (p= 0.50) or paraxanthine (p= 0.22). Since the
conclusions of the investigation were unchanged whether
these participants were included or excluded, their data
were included in the analysis. The conclusions of the
investigation also were unchanged when the participants
who used contraceptives were excluded.
Primary analyses
Hypotheses were tested using a series (i.e., all outcome
variables) of two Treatment x 4 Time point, repeated
measures ANCOVAs that controlled for the prior night’s
sleep time. The primary interests were the presence of
statistically significant (p< 0.05) interactions of time and
either cocoa versus placebo, cocoa + caffeine versus
cocoa, or cocoa + caffeine versus caffeine-only. Adjust-
ments for sphericity, when needed, were made using
Huynh-Feldt epsilon. Significant interactions were
decomposed using one-way ANOVAs and t-tests with
familywise error controlled using Least Significant Dif-
ference post-hoc tests. Effect size is presented as η
2
or
Cohen’sd(calculated based on the mean change over
time in a treatment condition minus the mean change
over the same time in the placebo condition, and this
difference score was divided by the baseline pooled
standard deviation). Cohen’sdvalues of .20, .50, and .80
are considered small, medium, and large effect sizes,
respectively [38]. Pearson correlations (r) were used to
explore linear associations between changes in salivary
methylxanthines and changes in motivation, cognition,
and mood.
Results
Expected changes in salivary methyxanthines were ob-
served. Caffeine levels were increased significantly in
the caffeine-only (mean change = 5.3 μmol
.
L
−1
;t= 8.676, df
= 44, p< 0.001) and cocoa + caffeine (mean = 5.0 μmol
.
L
−1
;
t= 9.311, df = 44, p< 0.001) conditions, and caffeine levels
did not differ between these two conditions (p> 0.50).
Theobromine levels were increased significantly in the
cocoa (mean = 26.2 μmol
.
L
−1
;t= 11.655, df = 44, p<0.001)
and cocoa + caffeine (mean = 28.9 μmol
.
L
−1
;t= 11.232,
df = 44, p< 0.001) conditions and theobromine levels
did not differ between these two conditions. Para-
xanthine levels were increased significantly in the caffeine-
only (mean = 1.4 μmol
.
L
−1
;t= 2.689, df = 44, p= 0.01) and
cocoa + caffeine (mean = 1.1 μmol
.
L
−1
;t= 2.199, df = 44,
p= 0.033) conditions and paraxanthine levels did not
differ between these two conditions. There were no sta-
tistically significant changes in all three methylxan-
thines in the placebo condition. Means and standard
deviations for motivation, mood, and cognitive per-
formance outcomes are available from the authors.
Effects of cocoa versus placebo
Compared to placebo, cocoa had significant interaction ef-
fects on both the reaction time response to the secondary
targets on the Bakan test (F= 2.679, df = 3, 129, η
2
=0.071,
p= 0.05) and the overall false alarms on the Bakan test
(F= 3.735, df = 2.498, 107.42, η
2
= 0.08, p= 0.019). Reac-
tion times were faster at all post-test time points after
consuming cocoa compared to pre-consumption baseline
(range = 11–17 ms) while the comparable data after
placebo were uniformly slower compared to baseline
(range = 4–11 ms); the post-hoc tests were not statistically
significant (p> 0.05). After taking cocoa the participants
averaged 1.6 fewer false alarms compared to baseline
while after placebo they averaged 2.4 more false alarms
compared to baseline. At post-test time 3, the interaction
Fig. 1 Schematic of order and timing of testing procedures
Table 3 Chemical analysis of the test beverages
Beverage
a
Total Flavanols
(mg)
Theobromine
(mg)
Caffeine
(mg)
Cocoa 499 179 21
Flavored
placebo
400
Flavored caffeine 4 0 66
Caffeinated
cocoa
455 179 70
a
Including monomers, oligomers, and polymers
Boolani et al. BMC Nutrition (2017) 3:8 Page 5 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

was significant (t= 2.28, df = 44, p=0.05) and large
(d= 0.76). No interactions were found for the other
cognitive, mood and motivation variables.
Effects of cocoa + caffeine versus caffeine-only
Compared to caffeine-only, cocoa + caffeine had signifi-
cant interaction effects on anxiety (F= 2.963, df = 2.8,
120.399, η
2
= 0.064, p= 0.038). These data are illustrated
in Fig. 2. At the final testing time anxiety levels increased
by an average of 0.57 raw score units after caffeine alone
but decreased by 0.17 raw score units after caffeinated
cocoa. At the final testing time the effect size for the
difference between conditions was large (d= 0.84) and
statistically significant (t= 2.27, df = 44, p=0.028). No
significant interactions were found for all other mood,
motivation and cognitive variables.
Effects of cocoa + caffeine versus cocoa
Compared to cocoa alone, cocoa + caffeine had significant
interaction effects on the number of correct responses
(i.e., accuracy) (F= 3.971, df = 4.561, 1.149, η
2
= 0.085,
p= 0.01) and the number of omission errors (F= 3.583,
df = 3, 129, η
2
= 0.077, p= 0.016) on the primary Bakan
task. These interactions are illustrated in Fig. 3. The
number of correct targets for the Bakan primary test
steadily increased from baseline for cocoa + caffeine,
whereas with cocoa alone the number correct was
below baseline at post-test times 2 and 3 after a slight
increase at post-test time 1. At the final testing time
the effect size for the difference between the conditions
in the number of correct responses was significant (t= 2.45,
df = 44, p=0.0183) and large (d=0.94). Cocoa + caffeine
also resulted in a steady decrease of the number of
omission errors whereas cocoa alone led to increases.
At the final testing time the size of the difference between
the conditions in the number of omission errors was
significant (t=2.14, df=44, p= 0.0379) and moderate
(d= 0.50). No interactions were found for all other cog-
nitive, motivation and mood variables.
Effects of caffeine-only versus placebo
No interactions were found for all cognitive, motivation
and mood variables except for anger (F= 4.419, df = 2.297,
98.770, η
2
=0.093, p= 0.011). At the final testing time
anger levels increased by an average of 0.66 raw score
units after placebo, but were unchanged after caffeine-
only. At the final testing time the size of the difference
between the conditions was large and significant (d=1.07;
t= 2.18, df = 44, p=0.035).
Relationships between changes in methylxanthines and
changes in motivation, cognition and mood
Changes in the methylxanthines were weakly and insig-
nificantly related to changes in motivation, mood, and
cognitive performance in all the treatment conditions
except caffeine-only. In the caffeine-only condition,
changes in salivary caffeine were significantly related to
changes in physical fatigue (r= 0.45; p= 0.031) while
changes in theobromine were positively correlated with
changes in accuracy (r= 0.51; p= 0.013) and negatively
correlated with changes in errors of omission (r=−0.51;
p= 0.013) in the Bakan primary task. These relationships
remained significant after partialling out correlated
changes in caffeine (r
partial
= 0.50 and r
partial
=−0.50;
both p= 0.018). Changes in paraxanthine were positively
correlated with changes in accuracy (r= 0.43; p= 0.041)
and negatively correlated with changes in errors of omis-
sion (r=−0.43; p= 0.041) in the Bakan secondary task.
These relationships strengthened after partialling out
correlated changes in caffeine (r
partial
= 0.58; p= 0.005
and r
partial
=−0.56; p= 0.007).
Discussion
Cocoa versus placebo
Cocoa enhanced two aspects of Bakan dual task per-
formance compared to placebo. Cocoa reduced overall
false alarm errors progressively across time with 0.92,
1.44 and 2.35 fewer false alarms on average at 22–48,
60–86 and 98–124 min post-consumption. Cocoa also
improved processing speed during the secondary task of
the Bakan dual task. The improvement in reaction time
(11 ms faster) was apparent at 22–48 min post-
consumption and there was a slight additional improve-
ment (a total of 17 ms faster) that was maintained
throughout the subsequent two testing times. Regression
to the mean could not be ruled as an explanation for the
significant effects of cocoa on the Bakan test because there
were significantly fewer false alarm errors (mean = 4.6) and
slower reaction time (mean = 25 ms) at baseline in the
placebo condition compared to the cocoa condition.
Mood states (i.e., POMS) were not improved after
Fig. 2 Post-beverage state-anxiety. Mean change from baseline scores
in self-reported anxiety across time in the treatment conditions
Boolani et al. BMC Nutrition (2017) 3:8 Page 6 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

taking cocoa alone compared to placebo which is con-
sistent with studies that found no effect of theobromine
on mood [14], but inconsistent with prior work suggesting
that higher feelings of energy can increase performance in
the high-event rate component of a dual task [39].
It is difficult to compare the Bakan secondary task re-
sults directly to other cocoa investigations because dual
tasks were not used in the prior related cocoa studies
[24, 26]. One prior study did not show fewer false alarms
after 520- or 994-mg cocoa [26]. The failure of cocoa to
significantly improve reaction time on the primary task
of the Bakan test, serial three accuracy, serial seven er-
rors, and feelings of mental fatigue were in contrast to
the results of the study by Scholey and colleagues that is
most similar in design to the present study [26]. A key
difference between the present study and the Scholey
study is the absence of dairy and calories in the present
study compared to the dairy-based cocoa drink with
~217 kcals used by Scholey and colleagues. The Bakan
test used in this study also may have different psycho-
metric properties from the conceptually similar rapid
visual information processing test used in the Scholey et
al. [26] study which may have contributed to different
results. For example, the reliability or the sensitivity for
measuring change might differ between the Bakan and
the rapid visual information processing test because of
procedural differences in the tests. The rapid visual infor-
mation processing test requires participants to react to
both odd and even sequences while the Bakan requires
responses to odd sequences as a primary task and a single
even number as a secondary task. Also, the Bakan task
duration was three times longer and the stimuli in the
rapid visual information processing test were presented at
a rate of 100 per minute while the Bakan test presented
Fig. 3 Post-beverage performance on the Bakan primary task. Mean change from baseline scores in accuracy (aat top) and omission errors (bat
bottom) across time for the primary task of the Bakan dual task in the cocoa + caffeine and cocoa conditions depicting the significant Condition
x Time interaction. There was a large standardized difference of 0.94 and a moderate difference of 0.50 at the 98–124 min post-treatment time
for accuracy and omission errors, respectively. Thus, caffeinated cocoa increased accuracy and reduced omission errors on the primary task of the
Bakan test compared to cocoa alone
Boolani et al. BMC Nutrition (2017) 3:8 Page 7 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

stimuli at a rate of 60 per minute. Another study using a
500-mg cocoa drink showed results that appear to be
generally consistent with the present findings, but two
of three testing times were confounded by the post-cocoa
consumption of a lunch [40], which reduces the ability to
make meaningful comparisons to the calorie-free cocoa
drink used here.
Cocoa + caffeine versus caffeine-only
Cocoa + caffeine compared to caffeine-only allowed for
an assessment of the potential role of cocoa flavanols
combined with theobromine, which were both absent in
the caffeine-only drink. Anxiety was the only significant
interaction observed. Cocoa + caffeine attenuated the in-
crease in anxiety that occurred at the final testing time
in the caffeine-only condition. Elevated anxiety is a com-
mon side effect of caffeine consumption in low caffeine
consumers [41] (such as those in this study) and many
participants in past studies using similar protocols have
anecdotally reported that repeatedly completing the
attention task is stressful [7, 42]. Thus, the anxiety eleva-
tion at the final testing time in the placebo condition,
while not hypothesized, is not unexpected. Theobromine
and flavanols, or their metabolites, could plausibly influ-
ence anxiety by binding to adenosine or benzodiazepine
receptors [42–44]. One study found that 500 mg cocoa
acutely increased calmness; however, increased calmness
did not occur after an acute cocoa administration at the
start of the investigation but only after an acute adminis-
tration was preceded by 30-days of daily cocoa supple-
mentation [40], as could plausibly occur because of
receptor up-regulation [45].
Cocoa + caffeine compared to cocoa
Cocoa + Caffeine compared to cocoa allowed for an
assessment of the impact of 49 mg of supplemental caf-
feine on the outcomes. Supplemental caffeine improved
accuracy and resulted in fewer omission errors on the
primary task of the Bakan test, but otherwise had no sta-
tistically significant motivation, mood or cognitive inter-
action effects. Improved accuracy and fewer omission
errors on the primary Bakan task occurred after the caf-
feine alone condition but the effect was smaller. Caffeine
can improve vigilance performance by improving accur-
acy, reducing errors and reducing reaction time [46, 47]
so it is unclear why the effects of supplemental caffeine
were limited to the primary task of the Bakan test. One
possibility is that the participants in the present study
were not especially responsive to the mood, motivation
and attention enhancing influence of caffeine. Genetic
factors are known to influence caffeine sensitivity and
relevant genotypes, such as for adenosine A
2A
receptors,
were not assessed in this study [42]. Another possibility
is that caffeine may only influence the most challenging
component of the more difficult dual task. It has been
suggested that while high event tasks take more cogni-
tive resources, low event tasks, such as the primary task
of the Bakan, require greater vigilance [48].
Caffeine-only versus placebo
Caffeine alone resulted in small changes that were gen-
erally in the direction expected based on prior research
[49] but were small in magnitude and statistically non-
significant. For instance, compared to pre-test, there were
small, non-significant increases in motivation, feelings
of energy and accuracy in the cognitive tests as well as
small decreases in fatigue, errors and reaction times.
Mean anger scores did not change in the caffeine con-
dition, as is consistent with prior studies [50]; however,
a significant interaction emerged because anger in-
creased in the placebo condition. We speculate that
anger scores increased in response to the stress of com-
pleting 104 total mins (4 x 26 mins sessions) of sus-
tained vigilance testing across 2.75 h testing sessions
and caffeine attenuated the effect.
Possible mechanisms
Caffeine crosses the blood-brain barrier and exerts central
nervous system (CNS) effects by antagonizing adenosine
receptors [51]. Dietary flavonoids are less well studied but
experiments in rodents and pigs show that polyphenols
can traverse the blood-brain-barrier and accumulate
throughout the brain [52] and act on neural or glial cell-
signaling pathways and increase cerebral blood flow [53].
One human study showed increased cerebral blood flow
2–4 h after consuming cocoa flavanols and a subsequent
study found a similar increase in elderly persons, except
that it was delayed until 8 h after ingestion [4, 54].
Thus, it is possible that the cognitive effects observed
inthepresentstudyweretheresultofchangesinbrain
blood flow, although no study has measured such
responses < 2 h after cocoa administration. Adequate
brain blood flow is known to be required for normal cog-
nitive performance [55] but nutrition-induced increases in
blood flow do not always produce improvements in
cognitive performance [56]. Adequate blood flow to
cognition-related neural circuitry is necessary but cognitive
performance also appears to depend on a host of exci-
tatory and inhibitory neurotransmitters (e.g., gamma-
aminobutyric acid and glutamate), neuromodulators
(e.g., dopamine and norepinephrine) and neuropeptides
(e.g., cholecystokinin, corticotropin releasing factor,
galanin) [57]. For example, caffeine can reduce overall
and regional brain blood flow [58, 59] yet cognitive per-
formance is often improved after caffeine is consumed.
Therefore, it is plausible that the effects observed in the
present study were not exclusively explained by blood
flow changes.
Boolani et al. BMC Nutrition (2017) 3:8 Page 8 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Brain neurons use glucose for energy and the treat-
ment effects observed here could stem from actions on
glucose or its regulation [6]. Both caffeine and dietary
flavonoids can impair glucose regulation [60, 61]; conse-
quently, improvements in blood flow may have been
opposed by alterations in glucose regulation. Also, the
methylxanine treatments may have stimulated the release
of neurotransmitters or neuromodulators. Increased
dopamine release in the frontal, prefrontal and medial
cortices is hypothesized to deactivate the default mode
network and is known to play a role in attentional pro-
cessing [62, 63]. It is thought that caffeine antagonizes
adenosine receptors in the basal ganglia which is
known to contribute to the modulation of the default
mode network [63, 64]. Increased dopamine in the nucleus
accumbens also plays a role in motivation and feelings of
energy [65]. One study comparing the mood and cognitive
effects of theobromine and caffeine concluded that
theobromine might exert anti-anxiety effects by lowering
blood pressure rather than directly influencing the CNS.
In short, the methylxanthines studied here potentially
work via multiple, complex, interacting central and
peripheral mechanisms. The present study was not
designed to obtain data directly related to any of these
potential mechanisms.
This study did obtain correlational data that could,
indirectly, have relevance for the mechanisms involved
in the behavioral effects observed here. In the caffeine
only condition, changes in theobromine and para-
xanthine were positively related to changes in accuracy
and negatively related to changes in omission errors, but
only in the more difficult Bakan dual task. These as-
sociations were attenuated when caffeine was com-
bined with cocoa or when cocoa was consumed
alone. The overall pattern of results suggests changes
in cognitive performance and changes in salivary
methylxanthine metabolites measured 2-hrs after 66-mg
caffeine consumption are only modestly related, task
dependent, and attenuated by the co-consumption of
cocoa.
The correlational finding related to mood suggests
that participants with higher salivary caffeine 2-hrs
post-consumption, and hence with a slower metabolism
of caffeine, also showed a greater increase in feelings of
physical fatigue 2 h after caffeine had been consumed. It is
uncertain why a correlation of a similar magnitude did
not emerge for mental fatigue also measured with a visual
analog scale (r= 0.12) or fatigue measured with the POMS
category scale (r= 0.26). It should be noted that physical
activity is not required to induce feelings of physical
fatigue. Indeed, recent studies show that sitting and
being sedentary for extended periods can contribute to
feelings of fatigue [66]. This effect may be exacerbated
by cognitive work involving attention.
Limitations
The study reported here had several features that may
limit the generalizability of the findings. First, recruit-
ment was limited to those reporting average or lower
than average consumption of fruits and vegetables and
other foods and beverages containing flavanols. Second,
not all participants were medication-free, a relatively
small number of participants were tested, and the timing
and composition of the meals preceding testing were not
controlled. Third, the potential role of sensory aspects of
cocoa were not examined; there is evidence that sensory
aspects of another drink made from cacao beans (e.g.,
mouth exposure to chocolate milk) can produce specific
brain responses (e.g., increased blood flow in the orbito-
frontal region) which may have contributed to changes
in attentional task performance that were more rapid
than any that stemmed from drink consumption [67, 68].
Fourth, we did not obtain saliva samples between comple-
tion of beverage consumption and the second mental
energy test battery, so it is unclear if caffeine and me-
tabolites were bioavailable prior to initiating the second
mental energy test battery; however, previous evidence
suggests the amount of time that orally consumed caffeine
takes to reach peak bioavailability was within the time-
range of the second mental energy test battery [69]. In
addition, the cocoa or caffeine dose was not administered
relative to bodyweight, but was absolute (i.e., 70 mg
caffeine), which limits direct comparison to studies that
did administer caffeine relative to body weight. Finally,
the study design was block randomized (not fully ran-
domized) and multiple statistical tests were conducted
which increases the risk that one of the statistically sig-
nificant results occurred by chance.
Conclusions
After statistically controlling for variation in the prior
night’s sleep duration, dairy- and calorie-free brewed
cocoa can acutely influence aspects of attention but has
little effect on motivation to perform cognitive tasks or
mood states such as feelings of energy and fatigue. The
caffeine in caffeinated cocoa can enhance attention while
the brewed cocoa can attenuate the anxiety provoking
effects of caffeine alone. The mechanisms by which these
effects were caused remain to be elucidated.
Abbreviations
ANCOVA: Analysis of covariance; ANOVA: Analysis of variance; C: Centigrade;
CNS: Central nervous system; dB (A): Decibels of sound pressure; hrs: Hours
mg, milligrams; mins: Minutes; ml: Milliliters; ms: Milliseconds; POMS: Profile
of mood states; SD: Standard deviation
Acknowledgements
This work was supported by the Hershey Company. BDL supported by NIH-
NCCIH T32 AT002688. The authors thank: 1) the volunteers for their participation,
2) Jessica Alves, Christina Hartigan and Dr. Roy Peake for technical expertise with
the saliva assays, 3) Lauren Clapper, Justin Drew, Alexandra Ely, Sally Hoang,
David Kupshik and Shaan Uppal for assistance with data collection and
Boolani et al. BMC Nutrition (2017) 3:8 Page 9 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

entry, 3) Amanda Caravalho and Kathryn Wilson for help administering the
beverages, and 4) Dr. Debra L. Mill er without whom this research would
not have been conducted. The contents of this document do not represent
the views of the U.S. Department of Veterans Affairs or the United States
Government.
Availability of data and materials
All non-identifying data for this manuscript are available upon request to the
senior author at poconnor@uga.edu.
Authors’contributions
PJO and SC conceptualized the study design. AB, JBL and BDL participated
in collection of data. PJO and AB analyzed and interpreted the data and
wrote the manuscript with comments from JBL, BDL and SC. PJO and JBL
formatted the manuscript for submission. All authors read and approved of
the final manuscript.
Competing interests
SC is a paid contractor for The Hershey Company.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Approval for the study was granted by the University of Georgia Institutional
Review Board (Study # 00000311). All participants read and signed the
approved consent form.
Author details
1
Department of Physical Therapy, Clarkson University, Potsdam, NY 13699,
USA.
2
Department of Veterans Affairs, New Jersey Healthcare System, War
Related Illness and Injury Study Center, East Orange, NJ 07018, USA.
3
Department of Kinesiology, University of Wisconsin, Madison, WI 53706,
USA.
4
Department of Neurology, Oregon Health & Science University,
Portland, OR 97239, USA.
5
The Hershey Company, Hershey, PA 17033, USA.
6
Department of Kinesiology, University of Georgia, Athens, GA 30602, USA.
Received: 11 July 2016 Accepted: 12 December 2016
References
1. Hooper L, Kay C, Abdelhamid A, Kroon PA, Cohn JS, Rimm EB, et al. Effects
of chocolate, cocoa, and flavanols on cardiovascular health: a systematic
review and meta-analysis of randomized trials. Am J Clin Nutr. 2012;95:740–51.
2. Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke:
a prospective cohort of men and meta-analysis. Neurology. 2012;79:1223–9.
3. Small DM, Zatorre RJ, Dagher A, Evans AC, Jones-Gotman M. Changes in
brain activity related to eating chocolate: from pleasure to aversion. Brain.
2001;124:1720–33.
4. Francis ST, Head K, Morris PG, Macdonald IA. The effect of flavanol-rich
cocoa on the fMRI response to a cognitive task in healthy young people.
J Cardiovasc Pharmacol. 2006;47:S215–20.
5. Messier C. Glucose improvement of memory: a review. Eur J Pharmacol.
2004;490:33–57.
6. Riby LM. The effects of age, glucose ingestion and gluco-regulatory control
on episodic memory. Age Ageing. 2004;33:483–7.
7. Maridakis V, Herring MP, O’Connor P. Sensitivity to change in cognitive
performance and mood measures of energy and fatigue in response to
differing doses of caffeine or breakfast. Int J Neurosci. 2009;119:975–94.
8. Nehlig A. Is caffeine a cognitive enhancer? J Alzheimers Dis. 2010;20:85–94.
9. Olson CA, Thornton JA, Adam GE, Lieberman HR. Effects of 2 adenosine
antagonists, quercetin and caffeine, on vigilance and mood. J Clin
Psychopharmacol. 2010;30:573–8.
10. Adan A, Serra-Grabulosa JM. Effects of caffeine and glucose, alone and
combined, on cognitive performance. Hum Psychopharmacol Clin Exp.
2010;25:310–7.
11. Haskell CF, Kennedy DO, Milne AL, Wesnes KA, Scholey AB. The effects of
l-theanine, caffeine and their combination on cognition and mood. Biol
Psychol. 2008;77:113–22.
12. Smit HJ, Rogers PJ. Effects of low doses of caffeine on cognitive
performance, mood and thirst in low and higher caffeine consumers.
Psychopharmacology (Berl). 2000;152:167–73.
13. Scholey AB, Kennedy DO. Cognitive and physiological effects of an “energy
drink”: an evaluation of the whole drink and of glucose, caffeine and herbal
flavouring fractions. Psychopharmacology (Berl). 2004;176:320–30.
14. Mitchell ES, Slettenaar M, Vd Meer N, Transler C, Jans L, Quadt F, et al.
Differential contributions of theobromine and caffeine on mood, psychomotor
performance and blood pressure. Physiol Behav. 2011;104:816–22.
15. Young HA, Benton D. Caffeine can decrease subjective energy depending
on the vehicle with which it is consumed and when it is measured.
Psychopharmacology (Berl). 2013;228:243–54.
16. Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A. Plasma
antioxidants from chocolate. Nature. 2003;424:1013.
17. Massee LA, Ried K, Pase M, Travica N, Yoganathan J, Scholey A, et al. The
acute and sub-chronic effects of cocoa flavanols on mood, cognitive and
cardiovascular health in young healthy adults: a randomized, controlled trial.
Front Pharmacol. 2015;6:1–14.
18. Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure
and function of the blood–brain barrier. Neurobiol Dis. 2010;37:13–25.
19. Smit HJ. Theobromine and the pharmacology of cocoa. Hanbook Exp
Pharmacol. 2011;200:201–34.
20. Meeusen R. Exercise, nutrition and the brain. Sports Med. 2014;44:47–56.
21. Scholey A, Owen L. Effects of chocolate on cognitive function and mood:
a systematic review. Nutr Rev. 2013;71:665–81.
22. Wang J, Varghese M, Ono K, Yamada M, Levine S, Tzavaras N, et al. Cocoa
extracts reduce oligomerization of amyloid-beta: Implications for cognitive
improvement in alzheimer’s disease. J Alzheimers Dis. 2014;41:643–50.
23. Camfield DA, Scholey A, Pipingas A, Silberstein R, Kras M, Nolidin K, et al.
Steady state visually evoked potential (SSVEP) topography changes associated
with cocoa flavanol consumption. Physiol Behav. 2012;105:948–57.
24. Field DT, Williams CM, Butler LT. Consumption of cocoa flavanols results in
an acute improvement in visual and cognitive functions. Physiol Behav.
2011;103:255–60.
25. Tomporowski PD, Tinsley VF. Effects of memory demand and motivation on
sustained attention in young and older adults. Am J Psychol. 1996;109:187.
26. Scholey AB, French SJ, Morris PJ, Kennedy DO, Milne AL, Haskell CF.
Consumption of cocoa flavanols results in acute improvements in mood
and cognitive performance during sustained mental effort. J
Psychopharmacol. 2010;24:1505–14.
27. Judelson DA, Preston AG, Miller DL, Muñoz CX, Kellogg MD, Lieberman HR.
Effects of theobromine and caffeine on mood and vigilance. J Clin
Psychopharmacol. 2013;33:499–506.
28. Deaconson TF, O’hair DP, Levy MF, Lee MB, Schueneman AL, Condon RE. Sleep
deprivation and resident performance. J Am Med Assoc. 1988;260:1721–7.
29. Jewett ME, Dijk D, Kronauer RE, Dinges DF. Dose-response relationship
between sleep duration and human psychomotor vigilance and subjective
alertness.pdf. Sleep. 1998;22:171–9.
30. Minkel JD, Banks S, Htaik O, Moreta MC, Jones CW, McGlinchey EL, et al.
Sleep deprivation and stressors: evidence for elevated negative affect in
response to mild stressors when sleep deprived. Emotion. 2012;12:1015–20.
31. McNair DM, Lorr M, Heuchert JWP, Droppelman LE. Profile of mood states:
brief form. North Tonawanda: Multi-Health Systems; 2003.
32. Motl RW, O’Connor PJ, Tubandt L, Puetz T, Ely MR. Effect of caffeine on leg
muscle pain during cycling exercise among females. Med Sci Sports Exerc.
2006;38:598–604.
33. O’Connor PJ, Caravalho AL, Freese EC, Cureton KJ. Grape consumption’s
effects on fitness, muscle injury, mood, and perceived health. Int J Sport
Nutr Exerc. 2013;23:57–64.
34. D’Amico EJ, Neilands TB, Zambarano R. Power analysis for multivariate and
repeated measures designs: a flexible approach using the SPSS MANOVA
procedure. Behav Res Methods Instrum Comput. 2001;33:479–84.
35. Ptolemy AS, Tzioumis E, Thomke A, Rifai S, Kellogg M. Quantification of
theobromine and caffei ne in saliva, plasma and urine via liquid
chromatography–tandem mass spectrometry: a single analytical
protocol applicable to cocoa intervention studies. J Chromatogr B.
2010;878:409–16.
36. Moore RD, Romine MW, O’Connor PJ, Tomporowski PD. The influence of
exercise-induced fatigue on cognitive function. J Sports Sci. 2012;30:841–50.
37 Pilcher JJ, Huffcutt AI. Effects of sleep deprivation on performance: a meta-
analysis. Sleep. 1996;19:318–26.
Boolani et al. BMC Nutrition (2017) 3:8 Page 10 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

38 Cohen J. A power primer. Psychol Bull. 1992;112:155–9.
39 Matthews G, Davies DR. Individual differences in energetic arousal and
sustained attention: a dual-task study. Personal Individ Differ. 2001;
31:575–89.
40 Pase MP, Scholey AB, Pipingas A, Kras M, Nolidin K, Gibbs A, et al. Cocoa
polyphenols enhance positive mood states but not cognitive performance:
a randomized, placebo-controlled trial. J Psychopharmacol (Oxf). 2013;27:451–8.
41 Alsene K, Deckert J, Sand P, de Wit H. Association between A2a receptor
gene polymorphisms and caffeine-induced anxiety.
Neuropsychopharmacology. 2003;28:1694–702.
42 Rogers PJ, Hohoff C, Heatherley SV, Mullings EL, Maxfield PJ, Evershed RP, et
al. Association of the anxiogenic and alerting effects of caffeine with
ADORA2A and ADORA1 polymorphisms and habitual level of caffeine
consumption. Neuropsychopharmacology. 2010;35:1973–83.
43 Alexander SPH. Flavonoids as antagonists at A1 adenosine receptors.
Phytother Res. 2006;20:1009–12.
44 Bouayed J. Polyphenols: A potential new strategy for the prevention and
treatment of anxiety and depression. Curr. Nutr. Food Sci. 2010;6:13–8.
45 Shi D, Daly JW. Chronic effects of xanthines on levels of central receptors in
mice. Cell Mol Neurobiol. 1999;19:719–32.
46 Foxe JJ, Morie KP, Laud PJ, Rowson MJ, de Bruin EA, Kelly SP. Assessing the
effects of caffeine and theanine on the maintenance of vigilance during a
sustained attention task. Neuropharmacology. 2012;62:2320–7.
47 Hewlett P, Smith A. Effects of repeated doses of caffeine on performance
and alertness: new data and secondary analyses. Hum Psychopharmacol
Clin Exp. 2007;22:339–50.
48 Parasuraman R, Mouloua M. Interaction of signal discriminability and task
type in vigilance decrement. Percept Psychophys. 1987;41:17–22.
49 Einöther SJL, Giesbrecht T. Caffeine as an attention enhancer: reviewing
existing assumptions. Psychopharmacology (Berl). 2013;225:251–74.
50 Lieberman HR, Wurtman RJ, Emde GG, Roberts C, Coviella ILG. The effects of
low doses of caffeine on human performance and mood.
Psychopharmacology (Berl). 1987;92:308–12.
51 Nehlig A, Daval J-L, Debry G. Caffeine and the central nervous system:
mechanisms of action, biochemical, metabolic and psychostimulant effects.
Brain Res Rev. 1992;17:139–70.
52 Schaffer S, Halliwell B. Do polyphenols enter the brain and does it matter?
Some theoretical and practical considerations. Genes Nutr. 2012;7:99–109.
53 Spencer JPE. Beyond antioxidants: the cellular and molecular interactions of
flavonoids and how these underpin their actions on the brain. Proc Nutr
Soc. 2010;69:244.
54 Sorond FA, Lipsitz LA, Hollenberg NK, Fisher ND. Cerebral blood flow
response to flavanol-rich cocoa in healthy elderly humans. Neuropsychiatr
Dis Treat. 2008;4:433.
55 Jacobson AM, Ryan CM, Cleary PA, Waberski BH, Weinger K, Musen G, et al.
Biomedical risk factors for decreased cognitive functioning in type 1
diabetes: an 18 year follow-up of the diabetes control and complications
trial (DCCT) cohort. Diabetologia. 2011;54:245–55.
56 Kennedy DO, Wightman EL, Reay JL, Lietz G, Okello EJ, Wilde A, et al. Effects
of resveratrol on cerebral blood flow variables and cognitive performance
in humans: a double-blind, placebo-controlled, crossover investigation.
Am J Clin Nutr. 2010;91:1590–7.
57 Carlson NR. Physiology of Behavior. 11th ed. New York: Pearson; 2012.
58 Field AS, Laurienti PJ, Yen Y-F, Burdette JH, Moody DM. Dietary caffeine
consumption and withdrawal: confounding variables in quantitative
cerebral perfusion studies? Radiology. 2003;227:129–35.
59 Kennedy DO, Haskell CF. Cerebral blood flow and behavioural effects of
caffeine in habitual and non-habitual consumers of caffeine: a near infrared
spectroscopy study. Biol Psychol. 2011;86:298–306.
60 Koch CE, Ganjam GK, Steger J, Legler K, Stöhr S, Schumacher D, et al. The
dietary flavonoids naringenin and quercetin acutely impair glucose
metabolism in rodents possibly via inhibition of hypothalamic insulin
signalling. Br J Nutr. 2013;109:1040–51.
61 Lane JD. Caffeine, glucose metabolism, and type 2 diabetes. J Caffeine Res.
2011;1:23–8.
62 Park C-A, Kang C-K, Son Y-D, Choi E-J, Kim S-H, Oh S-T, et al. The effects of
caffeine ingestion on cortical areas: functional imaging study. Magn Reson
Imaging. 2014;32:366–71.
63 Tomasi D, Volkow ND, Wang R, Telang F, Wang G-J, Chang L, et al.
Dopamine transporters in striatum correlate with deactivation in the default
mode network during visuospatial attention. PLoS One. 2009;4:e6102.
64 Kaasinen V, Aalto S, Nagren K, Rinne JO. Expectation of caffeine induces
dopaminergic responses in humans. Eur J Neurosci. 2004;19:2352–6.
65 Salamone JD, Correa M, Farrar A, Mingote SM. Effort-related functions of
nucleus accumbens dopamine and associated forebrain circuits.
Psychopharmacology (Berl). 2007;191:461–82.
66 Ellingson LD, Kuffel AE, Vack NJ, Cook DB. Active and sedentary behaviors
influence feelings of energy and fatigue in women. Med Sci Sports Exerc.
2014;46:192–200.
67 Nobre AC, Coull JT, Frith CD, Mesulam MM. Orbitofrontal cortex is activated
during breaches of expectation in tasks of visual attention. Nat Neurosci.
1999;2:11–2.
68 Kringelbach ML, O’Doherty J, Rolls ET, Andrews C. Activation of the human
orbitofrontal cortex to a liquid food stimulus is correlated with its subjective
pleasantness. Cereb Cortex. 2003;13:1064–71.
69 Blanchard J, Sawers SJA. The absolute bioavailability of caffeine in man.
Eur J Clin Pharmacol. 1983;24:93–8.
• We accept pre-submission inquiries
• Our selector tool helps you to find the most relevant journal
• We provide round the clock customer support
• Convenient online submission
• Thorough peer review
• Inclusion in PubMed and all major indexing services
• Maximum visibility for your research
Submit your manuscript at
www.biomedcentral.com/submit
Submit your next manuscript to BioMed Central
and we will help you at every step:
Boolani et al. BMC Nutrition (2017) 3:8 Page 11 of 11
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

1.
2.
3.
4.
5.
6.
Terms and Conditions
Springer Nature journal content, brought to you courtesy of Springer Nature Customer Service Center GmbH (“Springer Nature”).
Springer Nature supports a reasonable amount of sharing of research papers by authors, subscribers and authorised users (“Users”), for small-
scale personal, non-commercial use provided that all copyright, trade and service marks and other proprietary notices are maintained. By
accessing, sharing, receiving or otherwise using the Springer Nature journal content you agree to these terms of use (“Terms”). For these
purposes, Springer Nature considers academic use (by researchers and students) to be non-commercial.
These Terms are supplementary and will apply in addition to any applicable website terms and conditions, a relevant site licence or a personal
subscription. These Terms will prevail over any conflict or ambiguity with regards to the relevant terms, a site licence or a personal subscription
(to the extent of the conflict or ambiguity only). For Creative Commons-licensed articles, the terms of the Creative Commons license used will
apply.
We collect and use personal data to provide access to the Springer Nature journal content. We may also use these personal data internally within
ResearchGate and Springer Nature and as agreed share it, in an anonymised way, for purposes of tracking, analysis and reporting. We will not
otherwise disclose your personal data outside the ResearchGate or the Springer Nature group of companies unless we have your permission as
detailed in the Privacy Policy.
While Users may use the Springer Nature journal content for small scale, personal non-commercial use, it is important to note that Users may
not:
use such content for the purpose of providing other users with access on a regular or large scale basis or as a means to circumvent access
control;
use such content where to do so would be considered a criminal or statutory offence in any jurisdiction, or gives rise to civil liability, or is
otherwise unlawful;
falsely or misleadingly imply or suggest endorsement, approval , sponsorship, or association unless explicitly agreed to by Springer Nature in
writing;
use bots or other automated methods to access the content or redirect messages
override any security feature or exclusionary protocol; or
share the content in order to create substitute for Springer Nature products or services or a systematic database of Springer Nature journal
content.
In line with the restriction against commercial use, Springer Nature does not permit the creation of a product or service that creates revenue,
royalties, rent or income from our content or its inclusion as part of a paid for service or for other commercial gain. Springer Nature journal
content cannot be used for inter-library loans and librarians may not upload Springer Nature journal content on a large scale into their, or any
other, institutional repository.
These terms of use are reviewed regularly and may be amended at any time. Springer Nature is not obligated to publish any information or
content on this website and may remove it or features or functionality at our sole discretion, at any time with or without notice. Springer Nature
may revoke this licence to you at any time and remove access to any copies of the Springer Nature journal content which have been saved.
To the fullest extent permitted by law, Springer Nature makes no warranties, representations or guarantees to Users, either express or implied
with respect to the Springer nature journal content and all parties disclaim and waive any implied warranties or warranties imposed by law,
including merchantability or fitness for any particular purpose.
Please note that these rights do not automatically extend to content, data or other material published by Springer Nature that may be licensed
from third parties.
If you would like to use or distribute our Springer Nature journal content to a wider audience or on a regular basis or in any other manner not
expressly permitted by these Terms, please contact Springer Nature at
onlineservice@springernature.com