CURRENT TOPICS IN NUTRACEUTICAL RESEARCH Vol. 13, No. 2, pp. 61-70, 2015
ISSN 1540-7535 print, Copyright © 2015 by New Century Health Publishers, LLC
All rights of reproduction in any form reserved
THE EFFECT OF CHICKEN ESSENCE ON COGNITION
AND MOOD: A RANDOMIZED CONTROLLED TRIAL
D. Benton and H.A. Young
Department of Psychology, University of Swansea, Swansea SA2 8PP, Wales, United Kingdom
[Received August 6, 2014; Accepted December 29, 2014]
[Communicated by Prof. Chandan Prasad]
ABSTRACT: Young adults (n=147) were tested after
consuming either BRAND’S® Essence of Chicken (EOC) or
a placebo for ten days. EOC resulted in feeling energetic,
decision times (reaction time test) were quicker; reaction
times on the focused attention task were also quicker; working
memory improved; cortisol levels recovered more quickly after
a stressor. e possibility that EOC might act via mechanisms
associated with either serotonin or the metabolism of carnosine
was considered by looking at various polymorphisms of enzymes
associated with these neurochemicals. If those with genetic
variations, associated with diﬀerences in the eﬃciency of these
mechanisms, diﬀerentially responded to EOC then this would
indicate the mechanism of action. In the event the alleles of
16 polymorphisms did not inﬂuence the response to EOC. In
the case of rs1050565, a polymorphism associated the serotonin
transporter, a possible risk factor for dementia, EOC beneﬁtted
the decision times of those with the GG allele.
KEY WORDS: Chicken extract, Essence of chicken, Mood,
Reaction times, Serotonin
Corresponding Author: Professor David Benton, Department of
Psychology, University of Swansea, Swansea SA2 8PP, Wales,
United Kingdom; Phone ++44 1792 295607; Fax ++44 1792
295679; Email: firstname.lastname@example.org
Essence of chicken (EOC), a chicken meat extract, is a
popular supplement in Southeast Asia and is traditionally
consumed for a number of ailments, such as improving
cognition and reducing fatigue. EOC consists mainly of
proteins, amino acids and is high in the peptides carnosine
and anserine, that are also found in high concentrations in the
human brain (Kohen et al., 1988). Previous research has found
that drinking EOC reduced the fatigue that was associated
with a mental task (Nagai et al., 1996). After a stressor the
recovery of serum cortisol levels was also enhanced in those
who consumed EOC (Nagai et al., 1996). More recently it
has been reported that drinking EOC improved working and
episodic memory during times of stress (Azhar and Syed,
2003; Azhar et al., 2008). An aim of the present study was to
replicate and extend these ndings in a larger sample of young
adults. In particular, the study focuses on the ability of EOC to
improve cognition and reduce the subjective and physiological
stress associated with demanding mental eort. A second aim
was to consider the inuence of a range of polymorphisms
on the inuence of EOC and in this way consider the role of
possible mechanisms of action.
Inevitably there is a range of possible active ingredients
in EOC and hence various mechanisms by which it may
be inuential. Li et al. (2012) analysed EOC and found it
consisted of “proteins, dipeptides (such as carnosine and
anserine), polypeptides, minerals, trace elements, and multiple
amino acids”. Carnosine, homocarnosine, anserine and other
histidine derivatives, all have antioxidant activity that could
benet cognition. In addition, Tsuruoka et al. (2012) puried
a serotonin transporter inhibitor from EOC, that suppressed
serotonin uptake from rat brain synaptosomes, and identied it
as the diketopiperazine (DKP) cyclo (L-Phe-L-Phe). DKPs are
naturally-occurring cyclic dipeptides and this DKP increased
extracellular levels of the cerebral monoamines serotonin,
norepinephrine and dopamine in the medial prefrontal cortex,
and acetylcholine in the ventral hippocampus of freely moving
animals. Previously EOC had been reported to increase the
5-hydroxyindole acetic acid levels in the cerebrospinal uid of
the rat (breakdown product of serotonin), that was consistent
with increased brain serotonin activity (Xu and Sim, 1997).
It has been proposed that this peptide may act as an anti-
dementia agent and improves learning and memory (Tsuruoka
and Watanabe, 2012).
Two possibilities were therefore considered by looking at the
interactions between various single nucleotide polymorphisms
62 Chicken extract, mood and cognition
(SNP) and the eect of consuming EOC. In particular,
the possibilities that modifying serotonin activity may be a
mechanism, and that carnosine may play a role, were examined.
It was argued that if those with various polymorphisms of
enzymes associated with particular pathways dierentially
responded to EOC then this would be suggestive of the
mechanism of action.
MATERIALS AND METHODS
e sample consisted of 152 subjects of whom 147 (96.7%)
completed the study and were paid £60. Of the ve subjects
that did not return for their second visit two were allocated
to the placebo and three to the active condition. ose
nishing the study were well matched. ose taking EOC
were on average 21.6 (3.7) years and the placebo 21.2 (2.7)
years. Similarly the BMI of the two groups did not dier
(EOC 23.1(3.6) and placebo 23.5(3.2)). 45 females and 28
males drank EOC whereas 44 females and 30 males consumed
the placebo. When the baseline data for the test battery
were examined there were no signicant dierences between
those who subsequently consumed EOC and those who
subsequently drank the placebo.
After giving informed consent, participants were randomly
allocated, under a double blind procedure, to one of two
groups who consumed either BRAND’S® Essence of Chicken
(EOC) or a placebo (caramel and gelatine) each day. e
Swansea University Psychology Ethics Committee approved
the procedure. At baseline and after ten days of consumption,
participants completed a cognitive test battery (in the order
presented below) and completed a number of questionnaires
about their recent mood and general health. Subjects were
told they could either take the supplement straight or add it to
a vegetable based soup to increase palatability. A bottle of EOC
(70 ml) contained 83 mg protein and peptide, 3.1 mg free
amino acids, 0.8 mg hexose, and 0.4 mg fat (Li et al. 2012). It
also contained b-alanyl- L-histidine (carnosine) and b-alanyl-
l-methyl-L-histidine (anserine) as active dipeptides (Li et al.
2012). e dose of EOC used in the present study was based
on previous human studies (Azhar and Syed, 2003; Azhar et
al., 2008; Yamano et al., 2013). A bottle of placebo (70 ml)
contained 83 mg milk casein and 3 mg caramel to produce a
protein content, caloric content and colour similar to EOC.
Casein is chosen as an ingredient in the placebo because it does
not include peptides reported to have eects on fatigue but
has a similar amino-acid composition as EOC. e EOC and
placebo samples were provided by Cerebos Pacic Ltd.
Episodic memory - Word list recall
Using the MRC Psycholinguistic Database two lists of
thirty words were constructed and matched for the number
of syllables, image-ability and the frequency with which they
occur in English. Using a recorder words were presented at
a rate of one word every two seconds. Immediately after
presentation participants wrote down as many words as they
could remember (immediate recall). Approximately 25 min
later, after completion of the other tasks, subjects were again
asked to recall as many words as possible (delayed recall).
Working memory – Serial sevens
A computerized version of the serial sevens task was used in
which subjects were required, from a starting number between
800 and 999, to say whether a second number was exactly
seven less. e test was scored and the total number of correct
subtractions and the average of the time taken in milliseconds
to perform each subtraction were reported.
Working memory – Letter number sequencing
Letter number sequencing is a sub-test of the Wechsler
Adult Intelligence Scale that measures working memory. An
example of the type of question was: repeat the sequence Q-1-
B-3-J-2 in numerical and alphabetical order.
Sustained attention - Rapid Information Processing Task
A computer generated a series of digits at the rate of 100 per
minute. Subjects pressed the space bar when they detected
three consecutive odd or consecutive even digits. Eight
target sequences were presented every minute. Following the
presentation of the third consecutive digit, 1500 milliseconds
were allowed for a correct response to be made. Responses
made at any other time were recorded as errors. A minimum
of 5 and a maximum of 30 digits separated any two target
sequences. e task was performed for ve minutes and any
change in performance over time was examined. e number
of correctly identied sequences and the time taken to respond
to a correct sequence (in milliseconds) were analysed.
Selective attention - Arrow Flankers Test
A modied version of the Eriksen and Eriksen (1974)
anker task was used to measure selective attention. e
Arrow Flankers test measures the ability to direct attention and
ignore peripheral information. e anking pairs of symbols
could be squares (□□<□□), crosses (xx<xx), congruent arrows
(pointing in the same direction (>>>>>)) or incongruent
arrows (pointing in the opposite direction (>><>>)). A stimulus
remained on screen until the key press was registered and there
was a randomly varying inter-stimulus interval of between 1
and 3seconds. e task was to indicate whether the middle
arrow is pointing to the right or left: the reaction times (in
milliseconds) and accuracy (number incorrect) were recorded.
e reaction time procedure was based on that of Jensen
(1987). On a panel eight lamps were arranged in a semicircle
5.5 inches from a central button (the home key). e index
nger was placed on the home key. Within one to two seconds
an auditory warning signal sounded and after a random interval
of one to four seconds one of the lamps illuminated. e subject
Chicken extract, mood and cognition 63
then extinguished the light by depressing a button directly below
that lamp, using the nger initially on the home key.
All subjects completed a practice session of 20 trials utilising
all eight lamps. Simple reaction times were measured for
20 trials using one lamp. Choice reaction times were then
measured over three sets of 20 trials when one of 2, 4 or 8
lamps could be potentially illuminated. Decision times, the
time taken to lift the nger from the home key, were analysed.
Prole of Mood States
e Prole of Mood States Bi-Polar Form (POMS; Lorr
and McNair, 1984) is a 72-item self-report questionnaire that
measures six dimensions of mood: (1) Composed - Anxious;
(2) Energetic - Tired; (3) Elated - Depressed; (4) Clear-headed
- Confused; (5) Agreeable - Hostile; (6) Condent-Unsure.
Participants were presented with a list of words or phrases and
had to rate on a scale of 0-3 (0 ‘not at all’, 3 ‘a lot like this’)
how much they had felt like this in the past week including
today. ere were twelve words for each mood dimension – six
positive and six negative. In addition, an overall mood score
was calculated by adding all six dimensions.
General Health Questionnaire (GHQ)
e GHQ is a 30-item self-report questionnaire that was
developed to detect, in a community sample, those who would
benet from seeing a psychiatrist (Goldberg and Williams,
1988). e participant responds to various statements
concerning mental health by rating themselves on a four point
scale that ranges from ‘better / healthier than normal’; ‘same
as usual’; ‘worse / more than usual’ to ‘much worse / more
than usual’. ese were scored using a scale 0-1-2-3, as the
responses varied from positive to negative, such that a higher
score indicated a greater incidence of psychiatric problems.
Perceived Stress Scale
e Perceived Stress Scale (Cohen et al. 1983) is a 10-item
self-report questionnaire that assesses the degree to which
situations in one’s life are perceived as stressful. e participants
were required to answer questions about the extent to which
they have had stressful thoughts and feeling during the last
week, for example, “In the last week, how often have you been
upset because of something that happened unexpectedly?”
e participant responds on a 5-point scale (ranging from 0 =
Never - 4 = Very Often). One overall score was produced by
summing all items.
Before and after completing the test battery, and after a 45
minute recovery period, a sample of saliva was collected and
used to assay cortisol levels. Testing was carried out in the
afternoon to avoid the high levels of cortisol that are found in
the rst ve hours after waking. Analysis was carried out using
an immunoassay supplied by Salimetrics Europe, Newmarket,
e data were examined using appropriate analysis of co-
variance designs with performance on day 2 as the dependant
variable and performance on day 1 as the covariate. EOC/
placebo and gender were entered as between-subjects factors.
Where applicable additional repeated measures factors were
also included, for example with mood the measures before
after testing were entered. When interactions were signicant,
appropriate post hoc tests were conducted to determine the
nature of the interaction. Unless otherwise stated the main
eect of the covariant was signicant. ere were no occasions
where gender interacted with treatment. e data reported are
adjusted means (SE).
When the baseline data for the test battery were examined
on no occasion was there a signicant dierence between those
who subsequently consumed EOC and those who subsequently
drank the placebo. To assess compliance to the experimental
protocol, subjects were also asked how many drinks they
actually consumed; they were informed that this would not
aect their payment. 76.2% (n=112) reported consuming all
ten drinks as instructed; the number of subjects who reported
consuming all ten drinks was similar in both conditions (Chi2
(1, n = 147) = 1.50, n.s.). Of those that did not consume all
ten drinks, 13.6% (n=20) consumed nine drinks, 5.4% (n=8)
consumed eight drinks, 3.4% (n=5) had drunk seven, 1 person
(0.7%) reported consuming only six and 1 person (0.7%) only
four drinks; again there were no dierences depending on the
type of drink consumed (Chi2 (4, n = 147) = 4.36, n.s.). To
exclude the possibility of bias an intention treat analysis was
carried out that included all subjects.
When asked if they thought they were taking an active
ingredient, a placebo, or were unsure, there were no signicant
dierences in responses depending on which drink they had
been taking (Chi2 (2, n = 143) = 1.24, n.s.); thus the blind was
successful. When asked about any side eects, 83.7% (n=123)
reported no side eects, 2% (n=3) reported changes in their
thirst/appetite, 0.7% (n=1) reported feeling calmer, 3.4%
(n=5) reported having experienced more headaches, 5.4%
(n=8) said they had either felt sick or vomited after taking
a drink, 4.1 (n=6) reported that they slept less or needed to
sleep less and 0.7% (n=1) reported that they had found it
harder to concentrate during the supplementation period.
e symptoms reported were similar for both the placebo and
active treatments (Chi2 (6, n = 147) = 6.29, n.s.).
Cortisol was measured when participants arrived at the
laboratory (Time 1), immediately following the test battery
(Time 2), and after a 45 minute recovery period (Time 3).
64 Chicken extract, mood and cognition
e interaction EOC/placebo X Time (1, 2, 3) was non-
signicant (F (2,258) = 1.45, n.s.). However, as Nagai et al.
(1996) reported that it was the recovery from a stressor that
was inuenced by EOC, the changes in cortisol from Time 2 to
Time 3 were calculated, a reection of the rate of recovery after
the stressor. e recovery measure just missed signicance (F
(1,134) = 3.49, p < 0.06; -0.47 for EOC, -0.27 for Placebo;
Figure 1): that is there was a trend for the cortisol levels of
participants who had drunk EOC to recover more quickly.
Working memory- Letter number task
ere was a signicant eect of EOC (F (1,141) =4.05,
p<0.04; Figure 2); participants who had drunk EOC gave
more correct responses than those who consumed the placebo.
Working memory – serial sevens
Neither the accuracy of performance (F (1,144) = 2.09, n.s.),
nor reaction times (F (1,144) = 0.60, n.s.), were inuenced by
the consumption of EOC.
Focused attention – arrow ankers
Although consuming EOC did not inuence the accuracy
of the task (F (1,142) = 0.32, n.s.) the speed of responding
diered (F (1,143) = 4.39, p<0.03; Figure 3). Participants
who had drunk EOC had faster reaction times.
With the vigilance task neither the accuracy of performance
(EOC/placebo X Minute of test; F (4, 552) = 0.86, n.s.) nor
the speed of responding (EOC/placebo X Minute of test; F
(4, 540) = 0.86, n.s.) achieved statistical signicance.
e interaction EOC/placebo X number of lamps was
signicant (F (3, 435) = 5.55, p<0.001; Figure 4). Follow up
FIGURE 1. The effect of EOC on cortisol recovery. Data are mean (SE) for the
number of correct responses. Time 2 – cortisol levels immediately after the 30minute test
battery. Time 3 – cortisol levels 45minutes after the test battery. The cortisol levels of
participants who had drunk EOC recovered more quickly
FIGURE 1. e eect of EOC on cortisol recovery. Data
are mean (SE) for the number of correct responses. Time 2 –
cortisol levels immediately after the 30minute test battery. Time
3 – cortisol levels 45minutes after the test battery. e cortisol
levels of participants who had drunk EOC recovered more quickly
FIGURE 2. e eect of EOC on letter number task
performance. Data are mean (SE) for the number of correct
responses. Participants who had drunk EOC performed signicantly
better than those who had consumed the placebo (p<0.04).
FIGURE 2. The effect of EOC on letter number task performance. Data are mean (SE)
for the number of correct responses. Participants who had drunk EOC performed
significantly better than those who had consumed the placebo (p<0.04).
FIGURE 4. The effect of EOC on simple and choice decision times.
Data are mean (SE) for decision times (ms). Subjects who had consumed EOC responded
more quickly to the 8 lamp task (p<0.04).
FIGURE 4. e eect of EOC on simple and choice
decision times. Data are mean (SE) for decision times (ms).
Subjects who had consumed EOC responded more quickly to
the 8 lamp task (p<0.04).
FIGURE 3. The effect of treatment on focused attention reaction times. Data are mean
(SE) for focused attention reaction times (ms). Participants who had consumed EOC had
significantly faster reaction times (p<0.002).
FIGURE 3. e eect of treatment on focused attention
reaction times. Data are mean (SE) for focused attention
reaction times (ms). Participants who had consumed EOC
had signicantly faster reaction times (p<0.002).
Chicken extract, mood and cognition 65
tests revealed that those who consumed EOC responded more
quickly to the most dicult 8 lamp task (p<0.04). ere were
no signicant dierences between those who had drunk the
placebo and those who had drunk EOC with 1, 2 or 4 lamps.
e interaction EOC/placebo) X Immediate/delayed was
non-signicant (F (1, 144) =0.23, n.s.).
Perceived Stress Questionnaire.
e main eect of variant (EOC/Placebo) was non-
signicant (F (1,134)= 0.66, n.s.).
General Health Questionnaire
e main eect of the drink (EOC/placebo) was non-
signicant (F (1,144) = 0.26, n.s.).
Prole of Mood States
When the Energetic/tired dimension was considered the
eect of EOC approached signicance (F (1,141)=3.6.4,
p<0.06; Figure 5). Participants who consumed EOC
reported having more energy than those who had drunk the
placebo (Placebo -0.3(0.7): EOC 1.5(0.7)). ere were no
signicant eects with any of the other subscales: Agreeable/
Hostile, Clearheaded/Confused, Composed/Anxious, Elated/
Depressed or Condent/Unsure.
THE INFLUENCE OF POLYMORPHISMS ON THE
RESPONSE TO CHICKEN ESSENCE
Where in the previous section a measure was inuenced
by the consumption of EOC the data were further analysed
depending on the alleles of a range of Single Nucleotide
Polymorphisms (SNPs). us the eect on ratings of energy,
decision times with eight lamps and the number letter task
were considered. e data were analysed as in the previous
section except that in addition the alleles of SNPs listed below
were added to the analysis of variance. Where fewer than ten
individuals had a particular allele a variant was not considered.
Samples were taken using Isohelix Buccal Swabs (http://
www.isohelix.com) from which DNA was extracted and
analysed by LGC Genomics (http://www.lgcgenomics.com)
using a proprietary competitive allele specic PCR system
(KASPar) for SNP analysis.
e approach taken was to consider various polymorphisms
of enzymes associated with the metabolisms of serotonin
and carnosine. e argument was if these substances played
a key role in the inuence of EOC then the response to its
consumption would dier in those with dierent SNPs.
e relevant metabolic pathways are therefore outlined
and the polymorphisms considered indicated. Tryptophan
hydroxylase (TPH) catalyzes the conversion of tryptophan
to 5-hydroxytryptophan (5-HTP), and is the rate limiting
step in the synthesis of serotonin. Until ten years ago it was
thought that there only was a single TPH gene (TPH1; SNP
rs1800532) but a second form was found in the human brain
(TPH2; rs1843809). After its release into the synapse the
serotonin transporter protein (5-HTT: rs1050565) removes
the neurotransmitter from the synapse to the presynaptic
neuron. An increasing number of receptors and sub-receptors
have been found including HT1A (rs6295), 5HT1B (rs6296),
5HTR2A (rs6314) and 5HTR2A (rs6311) amongst others.
Carnosine synthetase (CARNS 1) is a member of the ATP-
grasp family of ATPases and catalyzes the formation of carnosine
and homocarnosine, mainly in skeletal muscle and the central
nervous system (rs1626067). Carnosinase1 (CNDP1)
drives the reverse reaction and is the rate-limiting enzyme
in the hydrolysis of carnosine into β-alanine and L-histidine
(rs11151964; rs234601). Tissue carnosinase (CNDP2), or
peptidase A, is a nonspecic dipeptidase rather than a selective
carnosinase, that hydrolyzes a variety of dipeptides including
L-carnosine (rs7577; rs808885). Histidine decarboxylase
(HDC) is the key enzyme for histamine production from
histidine (rs854163; rs854158; rs854150). Histamine
N-methyltransferase (HNMT) activity is key to the rate of
histamine degradation in the brain (rs11558538).
To save journal space, and for brevity, only results that
achieved statistical signicance will be detailed. e three
measures that had been found to be inuenced by EOC were
considered; the letter number task, decision times with eight
lamps and ratings of energy. In the case of the various SNPs
associated with the metabolism of carnosine on no occasion
did a particular polymorphism inuence the response to EOC
with either decision times or the energy rating. With the
letter number task there was one signicant interaction. One
HDC SNP (rs854150; F (2,122)= 3.14, p<0.05), although
FIGURE 5. The effect of EOC on subjective energy levels. Data are mean (SE) for ratings
of energy (POMS). Participants who had consumed EOC reported having more energy than
those who had drunk the placebo (p<0.06).
FIGURE 5. e eect of EOC on subjective energy
levels. Data are mean (SE) for ratings of energy (POMS).
Participants who had consumed EOC reported having more
energy than those who had drunk the placebo (p<0.06).
66 Chicken extract, mood and cognition
not another SNP of this enzyme (rs854158, F (1,118) =
0.10, n.s.), inuenced the response to EOC. However, an
examination of the data found that the signicant interaction
reected baseline dierences in those with the same alleles and
therefore the nding was dismissed as a chance nding.
In no instance did a serotonin associated SNPs inuence
the EOC-induced eect on the number-letter task. With
the ratings of energy again with only one SNP was there
a signicant interaction: with one (rs6311; F (2.210) =
3.45, p<0.03), but not another, SNP (rs6314; F (1,124)
= 1.00, n.s.) of 5HTR2A. Again an examination of the
signicant interaction found dierences at baseline prior
to the consumption of the drinks that suggested a chance
nding. Finally when the decision times with eight lamps
was examined there was one signicant interaction, with the
5HTT polymorphism (rs1050565; F (2,132) = 3.84, p<0.02),
that is illustrated in Figure 6. When the changes in response
time from before to after the consumption of either EOC or a
placebo were considered there was a signicant EOC/placebo
X Before/after interaction (F (2,132) = 3.84, p<0.02). In those
with the GG allele there was a signicant dierence in decision
time after the consumption of the drinks (p<0.006) but not at
baseline. Whether rs1050565 inuenced changes in cortisol
was also examined although EOC did not interact with SNP
to aect the stress response (F (4,258) = 0.56, n.s.). ere was,
however, throughout the study a dierence in cortisol values
depending on the allele (F (2,129) = 2.99, p<0.05; AA 0.19
(0.01), GG 0.24 (0.03), GA 0.17 (0.01)) albeit they did not
inuence the eect of EOC.
e rst aim was to examine the inuence of EOC on
cognition. e letter – number task, used as a test of working
memory and performance, was better in those who had drunk
EOC (Figure 2), a nding similar to Azhar et al. (2008). It had
also been reported that EOC improved digit span performance
(Azhar et al., 2003), although as the lists of numbers forward
and backwards were added together it is unclear whether
this was a measure of working memory as such. Although,
an improvement in mental arithmetic, that relies heavily on
working memory, also occurred (Azhar and Syed, 2003, Azhar
et al., 2008), these eects did not reect a dierence between
EOC and the placebo but rather a change over time in those
who had consumed EOC, an eect that was not observed with
the placebo. Nagai et al. (1996) also reported fewer errors in
a test of mental arithmetic after supplementation with EOC;
however, the eect just missed statistical signicance. e
present ndings similarly did not support the view that EOC
beneted mental arithmetic. It is unclear why EOC would
improve performance on the letter –number task but not
serial sevens task, given that both involve working memory.
However, it has been suggested that serial sevens performance
is heavily inuenced by basic arithmetic skill (Karzmark, 2000)
and hence individual dierences in arithmetic ability may have
been more important.
Only a few studies have examined the inuence of EOC on
short term memory and the ndings are inconsistent. Azhar
and Syed (2003) reported an improvement in a ‘ree minute
memory test’ and recall of a paragraph. Azhar et al. (2008)
also found improvements in short term memory (digit span
forward) after consuming EOC. However, the present study
also found no eects of EOC on the recall of word lists. Given
these discrepancies there is a need for further research.
Performance of the focused attention task (arrow ankers)
was faster when EOC had been drunk (Figure 3). Similarly,
Yamano et al. (2013) studied the eect of consuming EOC
and found that it quickened reaction times on a modied
Stroop task. e Stroop task is similar to the arrow anker
task, as it requires focused attention while ignoring irrelevant
information. Consuming EOC was also related to faster
decision times on the reaction time task (Figure 4). Although
to our knowledge there is no previous literature that addresses
FIGURE 6. Changes in decision times after consuming EOC depending on the
alleles of rs1050565. The data are mean decision times for those with the three alleles of
rs1050565: AA, n=77; AG, n=51; GG n=10. In those with GG the decision times of those
consuming EOC were significantly quicker than after the placebo (p <0.006).
FIGURE 6. Changes in decision times after consuming
EOC depending the alleles of rs1050565 e data are mean
decision times for those with the three alleles of rs1050565:
AA n=77; AG n=51; GG n=10. In those with GG the
decision times of those consuming EOC were signicantly
quicker than after the placebo (p <0.006).
Chicken extract, mood and cognition 67
the inuence of EOC on choice reaction times, overall there
is an impression that drinking EOC resulted in a faster speed
A second aim was to examine the eect on mood. ere
was no association between taking EOC and the subjective
response to testing. However, when asked to reect on how
they had been feeling during the ten day supplementation
period, participants who consumed EOC tended to report
having more energy (Figure 5). ese ndings are consistent
with recent studies by Yamano et al. (2013) and Young and
Benton (2015) who also reported that EOC improved mood.
EOC has also been associated with reduced fatigue when
facing a demanding mental task (Nagai et al., 1996; Yamano
et al., 2013).
In summary there is increasing evidence that consuming
EOC reduces fatigue and enhances energy. Young and Benton
(2015) found an increase in the Low / High Frequency ratio
(index of Heart Rate Variability that represents sympathetic/
parasympathetic balance). An increase in this ratio would
represent either an increase in sympathetic activity or vagal
withdrawal which may result in an increase in energy. e
mechanisms mediating the benecial eects of EOC on
energy levels are not, however, well understood. However, an
interesting hypothesis is that by virtue of histidine containing
peptides, it may inuence histaminergic system in the brain
(Li et al., 2012). Histidine is the precursor to histamine and
has a role in the maintenance of wakefulness (Panula and
Nuutinen, 2013), a possible mechanism for reducing fatigue.
It has been previously reported that after a mental workload
the speed of recovery of serum cortisol levels was enhanced in
those who consumed EOC (Nagai et al., 1996); the present
study tended to conrm these ndings (Figure 1; p<0.06).
Given that elevated cortisol levels are associated with poorer
cognition (Vedhara et al., 2000) and mood (Burke et al.,
2005), the enhanced cortisol recovery may partially explain
the benecial eects of EOC on cognition and mood.
Since EOC contains many dierent components it is dicult
to identify the active ingredient: it consists mainly of proteins,
peptides and free amino acids (Li et al., 2012). Among the
peptides carnosine and anserine are present at relatively high
concentrations in the human brain (Kohen et al., 1988) and
may contribute toward neuronal protection (Boldyrev et al.,
2004), possibly via their antioxidant (Kang et al. 2002; Kohen
et al. 1988) or antiglycation (Hipkiss 2005) actions. Although
it has been suggested that histidine containing peptides, such
as carnosine and anserine, may prevent cognitive decline
(Mong et al., 2011) and even Alzheimer’s disease (Corona et
al., 2011), to our knowledge only two studies have examined
the eects of carnosine in isolation on cognitive performance.
Baraniuk et al. (2013) studied the eects, in Gulf war
veterans, of consuming carnosine and found a signicant
dierence in digit symbol substitution test scores, a task
associated with activation of the fronto-parietal network
(Usui et al., 2009). However, taking carnosine produced no
dierences in fatigue, quality of life or accelerometer scores
although the fatigue experienced by Gulf war veterans is
greater than by a healthy population such that minor eects
might not be observed. Chez et al. (2002) studied the eects
of carnosine in children with autistic spectrum disorders who
showed signicant improvements on the Gilliam Autism
Rating Scale and the Receptive One-Word Picture Vocabulary
test. Although these nding cannot be generalised to healthy
populations they support the possibility that carnosine, and
perhaps anserine, may be the active components of EOC.
Future research should consider the cognitive/subjective
eects of carnosine or anserine in isolation to elucidate the
role, if any, played by these peptides.
Interestingly consuming chicken soup (also rich in
carnosine and anserine) not only improved mood but also
increased peripheral blood ow (Midoh and Noguchi, 2008).
Carnosine and anserine are powerful antioxidants and these
eects are consistent with antioxidant induced vasodilation
(Wray et al., 2012). e supply of blood to brain cells relies
upon neurovascular coupling, that is neuronal activity being
associated with increases in the diameter of blood vessels
resulting in greater blood ow (Kuschinsky, 1997). is
process is highly dependent on the ability of the endothelium
to vasodilate (Girovard and Ladecola, 2006). As dierences in
endothelial functioning have been related to brain activation
during a working memory task (Gonzales et al., 2010), you
can speculate that improvements in working memory after
consuming EOC may be mediated by increased cerebral blood
An examination of various polymorphisms oers a way of
examining potential mechanisms. For example carnosinase is
the rate limiting step involved in the metabolism of carnosine
and hence polymorphisms that inuence its activity might
be expected to inuence any benecial response to EOC,
should that is, carnosine be part of the underlying mechanism.
Although a case can be made for carnosine having a role in
the action of EOC, the results from the carnosine-related
SNPs presently examined gave no support for this suggestion.
An alternative is that EOC has an inuence on serotonergic
mechanisms. ere is also evidence that EOC modulates
cerebral levels of 5-HT as Xu and Sim (1997) found that
it increased the level of 5-hydroxyindoleacetic acid, the
metabolite of 5-HT, in cerebrospinal uid. A peptide has
also been identied in EOC that acts as a serotonin transport
inhibitor, indicating a possible mechanism (Tsuruoka et al.,
In this context the nding of an interaction between
rs1050565 and the response to EOC is of considerable interest.
Rs1050565 is often studied because of its association with
the transporter responsible for serotonin reuptake, although
its role is more complex. It occurs in the promoter region of
5HTT and is non-synonymous, that is it changes the protein
sequence. e 5HTT gene is of interest: it has been associated
with depression (Belzeaux et al., 2010) and may play in the
development of psychotic and aggressive tendencies in those
with Alzheimer’s disease (Pritchard et al., 2007).
68 Chicken extract, mood and cognition
Testicular cancer patients may be treated with the cytotoxic
drug bleomycin, that is broken down by the enzyme
Bleomycin hydrolase, a cysteine protease encoded by the
BLMH gene whose only known function is the inactivation
of bleomycin. e enzyme has been highly conserved by
evolution and is found throughout the body including the
hippocampus with its role in memory, and the amygdala
with its role in emotion. Rs1050565 is also a SNP in the
BLMH gene and those with testicular cancer, and the GG
rather than AA or GA genotype, are ve times more likely
to die when being treated with bleomycin (de Haas et al.,
2007). As it has been proposed that EOC may act as an anti-
dementia agent (Patent WO 2012160713 A8), it is relevant
that a possible association between BLMH and Alzheimer’s
disease has been discussed. e expression of this enzyme is
less in the brains of those with this disorder (Namba et al.,
1999; Malherbe et al., 2000). e polymorphism results
in the substitution of Adenine by Guanine at position 1450
resulting in the ineciency of the BLMH enyzyme (de Haas
et al., 2008; Altes et al., 2013). It has been reported that
those with the GG allele, who did not have the APOE 4
allele, were four times more likely to have Alzheimer’s disease
(Montoya et al., 1998; Farrer et al., 1998; Papassotiropoulos
et al., 2000; Ximenez et al., 2013), although not all studies
have reported this association (Prince et al., 2001; Smach et
al., 2010). It has also been suggested that the BLMH gene
inuences the production of the amyloid precursor protein
and hence the proteolytic fragment Amyloid-β that plays a
role in Alzheimer’s disease (Namba et al., 1999; Malherbe et
Although it is easy to see an association between an
interaction between the rs1050565, EOC (Figure 6) and the
above discuss of the association between BLMH and dementia,
the present ndings must be viewed with caution. ere was
no a priori hypothesis, and as the sample size was small there
is a need for replication. e eect of rs1050565 was not on
memory as might be predicted if there was a direct inuence
of EOC on the mechanisms associated with dementia. Rather
the eect was on reaction times, however, if the BLMH gene
was important then the eect in Figure 6 might be a marker for
the later production of the amyloid plaques that characterize
Alzheimer’s disease. Clearly these are speculative suggestions
and the nding should be viewed as hypothesis generating
rather than hypothesis testing. However, if the nding is
replicated then an insight may have been given into the action
of EOC, with implications for the disease state.
In conclusion consuming EOC improved working memory
decision times and increased ratings of energy. Future research
should focus on isolating the active ingredients of EOC and
the mechanisms mediating its eects, including possible eects
on peripheral and cerebral blood ow. In particular the role of
the serotonin transporter should be examined.
We are grateful to thank and acknowledge Cerebros, Pacic,
Ltd, Singapore, for the supply of products and the funding of
Altés, A., Paré, L., Esquirol, A., Xicoy, B., Rámila, E., Vicente,
L., López, R., Orriols, J., Vall-Llovera, F., Sánchez-González,
B., Del Río, E., Sureda, A., Páez, D. and Baiget, M. (2013).
Pharmacogenetic analysis in the treatment of Hodgkin
lymphoma. Leukemia and Lymphoma 54: 1706-1712.
Azhar, M.Z. and Syed, M.S.J. (2003). Eect of taking
chicken essence on stress and cognition of human volunteers.
Malaysian Journal of Nutrition 9: 19-29.
Azhar, M.Z., Zubaidah, J.O. and Norjan, K.O.N. (2008).
Eect of taking chicken essence on cognitive functioning
of normal stressed human volunteers. Malaysian Journal of
Medicine and Health 4: 57-68.
Belzeaux, R., Formisano-Treziny, C ., Loundou, A., Boyer,
L, Gabert, J., Samuelian, J.C., Feron, F., Naudin, J. and
Ibrahim, E. (2010). Clinical variations modulate patterns
of gene expression and dene blood biomarkers in major
depression. Journal of Psychiatric Research 44: 1205-121.
Boldyrev, A., Bulygina, E., Leinsoo, T., Petrushanko, I.,
Tsubone, S. and Abe, H. (2004). Protection of neuronal
cells against reactive oxygen species by carnosine and related
compounds. Comparative Biochemistry and Physiology Part B:
Biochemistry and Molecular Biology 137: 81-88.
Baraniuk, J. N., El-Amin, S., Corey, R., Rayhan, R. and
Timbol, C. (2013). Carnosine Treatment for Gulf War Illness:
A Randomized Controlled Trial. Global Journal of Health
Science 5: 69-81.
Burke, H.M., Davis, M.C., Otte, C. and Mohr, D. C. (2005).
Depression and cortisol responses to psychological stress: a
meta-analysis. Psychoneuroendocrinology 30: 846-856.
Chez, M. G., Buchanan, C. P., Aimonovitch, M. C., Becker, M.,
Schaefer, K., Black, C. and Komen, J. (2002). Double-blind,
placebo-controlled study of L-carnosine supplementation in
children with autistic spectrum disorders. Journal of Child
Neurology 17: 833-837.
Cohen, S., Kamarck, T. and Mermelstein, R. (1983). A global
measure of perceived stress. Journal of Health and Social
Behavior 24: 386-396.
Corona, C., Frazzini, V., Silvestri, E., Lattanzio, R., La
Sorda, R., Piantelli, M., Canzoniero., L.M., Ciavardelli,
D., Rizzarelli, E. and Sensi, S. L. (2011). Eects of dietary
supplementation of carnosine on mitochondrial dysfunction,
amyloid pathology, and cognitive decits in 3xTg-AD mice.
Chicken extract, mood and cognition 69
PloS One 6: e17971.
de Haas, E.C., Zwart, N., Meijer, C., Nuver, J., Boezen,
H.M., Suurmeijer, A.J.H., Hoekstra, H.J. , van der Steege,
G., Sleijfer, D.T. and Gietema, J.A. (2008). Variation in
bleomycin hydrolase gene is associated with reduced survival
after chemotherapy for testicular germ cell cancer. Journal of
Clinical Oncology 26: 1817-1823.
Eriksen, B. A. and Eriksen, C. W. (1974). Eects of noise
letters upon identication of a target letter in a non- search
task. Perception and Psychophysics 16: 143–149.
Farrer, L.A., Abraham, C.R., Haines, J.L., Rogaev, E.A., Song,
Y., McGraw, W.T., Brindle, N., Premkumar, S., Scott, W.K.,
Yamaoka, L.H., Saunders, A.M., Roses, A.D., Auerbach,
S.,A., Sorbi, S., Duara, R., Pericak-Vance, M.A. and St
George-Hyslop, P.H. (1998) Association between bleomycin
hydrolase and Alzheimer’s disease in Caucasians. Annals of
Neurology 44: 808-811.
Girouard, H. and Iadecola, C, 2006. Neurovascular coupling
in the normal brain and in hypertension, stroke, and Alzheimer
disease. Journal of Applied Physiology 100: 328-335.
Goldberg, D. and Williams, P. (1988) A user’s guide to the
general health questionnaire. (Windsor: NFER-Nelson).
Gonzales, M.M., Tarumi, T., Tanaka, H., Sugawara, J., Swann-
Sternberg, T., Goudarzi, K. and Haley, A. P. (2010). Functional
imaging of working memory and peripheral endothelial
function in middle-aged adults. Brain and Cognition 73: 146-
Hellhammer, D.H., Wüst, S. and Kudielka, B.M.
(2009). Salivary cortisol as a biomarker in stress research.
Psychoneuroendocrinology 34: 163-71.
Hipkiss, A. R. (2005). Glycation, ageing and carnosine:
Are carnivorous diets benecial? Mechanisms of ageing and
development 126: 1034-1039.
Jamieson, J. (1999). Dealing with baseline dierences:
two principles and two dilemmas. International Journal of
Psychophysiology 31: 155-161.
Jensen, A.R. (1987) Individual dierences in the Hick
paradigm. In: Vernon PA (ed) Speed of information-processing
and intelligence, (Ablex, New Jersey, pp 101-175).
Kang, J. H., Kim, K. S., Choi, S. Y., Kwon, H. Y., Won, M.
H. and Kang, T. C. (2002). Protective eects of carnosine,
homocarnosine and anserine against peroxyl radical-mediated
Cu, Zn-superoxide dismutase modication. Biochimica et
Biophysica Acta (BBA)-General Subjects 1570: 89-96.
Kohen, R., Yamamoto, Y., Cundy, K. C. and Ames, B. N.
(1988). Antioxidant activity of carnosine, homocarnosine,
and anserine present in muscle and brain. Proceedings of the
National Academy of Sciences 85: 3175-3179.
Kuschinsky, W. (1997). Optimal imaging of brain function
and metabolism 2: Physiological basis and comparison to other
functional neuroimaging methods. Advances in Experimental
Medicine and Biology 413: 167-176.
Li, Y.F., He, R.R., Tsoi, B. and Kurihara, H. (2012).
Bioactivities of chicken essence. Journal of Food Science 77:
Lorr M. and McNair D. M. (1984) Prole of Mood States,
Bipolar Form (Educational and Industrial Testing Service, San
Namba, Y., Ouchi, Y., Takeda, A., Ueki, A. and Ikeda K.
(1999). Bleomycin hydrolase immunoreactivity in senile
plaque in the brains of patients with Alzheimer’s disease. Brain
Research 830: 200-202.
Malherbe, P., Faull, R.L. and Richards, J.G. (2000). Regional
and cellular distribution of bleomycin hydrolase mRNA in
human brain: comparison between Alzheimer’s diseased and
control brains. Neuroscience Letters 3: 281, 37-40.
Midoh N. and Noguchi T. (2009). Eect of Chicken Soup
Intake on Mood States and Peripheral Blood Flow in Humans.
Journal of Health Science 55: 56-61.
Mong, M. C., Chao, C. Y. and Yin, M. C. (2011). Histidine
and carnosine alleviated hepatic steatosis in mice consumed
high saturated fat diet. European Journal of Pharmacology 653:
Montoya, S.E., Aston, C.E., DeKosky, S.T., Kamboh, M.I.,
Lazo, J.S. and Ferrell, R.E. (1998). Bleomycin hydrolase is
associated with risk of sporadic Alzheimers disease. Nature
Genetics 18: 211-212.
Nagai, H., Harada, M., Nakagawa, M., Tananka, T., Gunadi,
B., Setiabudi, M.L., Uktolseja, J.L. and Miyata Y. (1996).
Eect of chicken extract on the recovery from fatigue caused
by mental workload. Applied Human Science - Journal of
Physiological Anthropology 15: 281-286.
Panula, P. and Nuutinen, S. (2013). e histaminergic
network in the brain: basic organization and role in disease.
Nature Reviews Neuroscience 14: 472-487.
Papassotiropoulos, A., Bagli, M., Jessen, F., Frahnert, C.,
Rao, M.L., Maier, W. and Heun, R. (2000), Conrmation
of the association between bleomycin hydrolase genotype and
70 Chicken extract, mood and cognition
Alzheimer’s disease. Molecular Psychiatry 5: 213- 215.
Prince, J.A., Feuk, L., Sawyer, S.L., Gottfries, J., Ricksten, A.,
Nägga, K., Bogdanovic, N., Blennow, K. and Brookes, A.J.
(2001). Lack of replication of association ndings in complex
disease: An analysis of 15 polymorphims in prior candidate
genes for sporadic Alzheimer disease. European Journal of
Human Genetics 9: 437- 444.
Pritchard, A.L., Pritchard, C.W., Bentham, P. and Lendon,
C.L. (2007). Role of serotonin transporter Polymorphisms
in the behavioural and psychological symptoms in probable
Alzheimer disease patients. Dementia and Geriatric Cognitive
Disorders 24: 201-206.
Smach, M.A., Charfeddine, B., Lammouchi, T., Othman,
L.B., Letaief, A., Nafati, S., Dridi, H., Bennamou, S. and
Limem, K. (2010). Analysis of association between bleomycin
hydrolase and apolipoprotein E polymorphism in Alzheimer’s
disease. Neurological Sciences 31: 687-691.
Tsuruoka N., Beppu Y., Koda H., Doe N., Watanabe H. and
Abe, K. (2012) A DKP Cyclo (L-Phe-L-Phe) Found in Chicken
Essence Is a Dual Inhibitor of the Serotonin Transporter and
Acetylcholinesterase. PLoS ONE 7: e50824.
Tsuruoka, N and Watanabe H (2012). World patent WO
Usui, N., Haji, T., Maruyama, M., Katsuyama, N., Uchida, S.,
Hozawa, A. Omori, K., Tsuji, I., Kawashima, R. and Taira,
M. (2009). Cortical areas related to performance of WAIS
Digit Symbol Test: A functional imaging study. Neuroscience
Letters 463: 1-5.
Vedhara, K., Hyde, J., Gilchrist, I. D., Tytherleigh, M. and
Plummer, S. (2000). Acute stress, memory, attention and
cortisol. Psychoneuroendocrinology 25: 535-549.
Wray, D. W., Nishiyama, S. K., Harris, R. A., Zhao, J.,
McDaniel, J., Fjeldstad, A. S., and Richardson, R. S. (2012).
Acute reversal of endothelial dysfunction in the elderly after
antioxidant consumption. Hypertension 59: 818-824.
Yamano, E., Tanaka, M., Ishii, A., Tsuruoka, N., Abe, K. and
Watanabe, Y. (2013). Eects of chicken essence on recovery
from mental fatigue in healthy males. Medical Science Monitor
Young, H., Benton, D. and Carter, N. (2015) e eect of
chicken extract on mood, cognition and heart rate variability.
Nutrients 7: 887-904.
Ximenez, J.P.B., Rasmussen, L.T., Orcini, W.A., Labio, R.W.,
Arruda, G.V., Bertolucci, P.H.F., Smith, M.A. and Payão
S.L.M. (2013). BLMH and APOE genes in Alzheimer Disease:
A possible relation. Advances in Alzheimer’s Disease 2: 117-121.
Xu, C. L. and Sim, M. K. (1997). Eect of oral feeding of
essence of chicken on the level of 5-hydroxyindoie acetic acid
in the cerebrospinal uid of the rat. International Journal of
Food Sciences and Nutrition 48: 113-117.
Reproduced with permission of the copyright owner. Further reproduction prohibited without