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Tea has anecdotally been associated with stress relief, but this has seldom been tested scientifically. To investigate the effects of 6 weeks of black tea consumption, compared with matched placebo, on subjective, cardiovascular, cortisol and platelet responses to acute stress, in a parallel group double-blind randomised design. Seventy-five healthy nonsmoking men were withdrawn from tea, coffee and caffeinated beverages for a 4-week wash-out phase during which they drank four cups per day of a caffeinated placebo. A pretreatment laboratory test session was carried out, followed by either placebo (n = 38) or active tea treatment (n = 37) for 6 weeks, then, a final test session. Cardiovascular measures were obtained before, during and after two challenging behavioural tasks, while cortisol, platelet and subjective measures were assessed before and after tasks. The tasks induced substantial increases in blood pressure, heart rate and subjective stress ratings, but responses did not differ between tea and placebo treatments. Platelet activation (assessed using flow cytometry) was lower following tea than placebo treatment in both baseline and post-stress samples (P < 0.005). The active tea group also showed lower post-task cortisol levels compared with placebo (P = 0.032), and a relative increase in subjective relaxation during the post-task recovery period (P = 0.036). Compared with placebo, 6 weeks of tea consumption leads to lower post-stress cortisol and greater subjective relaxation, together with reduced platelet activation. Black tea may have health benefits in part by aiding stress recovery.
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ORIGINAL INVESTIGATION
The effects of tea on psychophysiological stress responsivity
and post-stress recovery: a randomised double-blind trial
Andrew Steptoe & E. Leigh Gibson & Raisa Vounonvirta &
Emily D. Williams & Mark Hamer & Jane A. Rycroft &
Jorge D. Erusalimsky & Jane Wardle
Received: 12 June 2006 / Accepted: 9 August 2006 / Published online: 30 September 2006
#
Springer-Verlag 2006
Abstract
Rationale Tea has anecdotally been associated with stress
relief, but this has seldom been tested scientifically.
Objectives To investigate the effects of 6 week s of black
tea consumption, compared with m atched placebo, on
subjective, cardiovascular, cortisol and platelet responses
to acute stress, in a parallel group double-blind randomised
design.
Materials and methods Seventy-five healthy nonsmoking
men were withdrawn from tea, coffee and caffeinated
beverages for a 4-week wash-out phase during which they
drank four cups per day of a caffeinated placebo. A
pretreatment laboratory test session was carried out,
followed by either placebo (n=38) or active tea treatment
(n=37) for 6 weeks, then, a final test session. Cardiovas-
cular measures were obtained before, during and after two
challenging behavioural tasks, while cortisol, platelet and
subjective measures were assessed before and after tasks.
Results The tasks induced substantial increases in blood
pressure, heart rate and subjective stress ratings, but
responses did not differ between tea and placebo treat-
ments. Platelet activation (assessed using flow cytometry)
was lower following tea than placebo treatment in both
baseline and post-stress samples (P<0.005). The active tea
group also showed lower post-task cortisol levels compared
with placebo (P=0.032), and a relative increase in
subjective relaxation during the post-task recovery period
(P=0.036).
Conclusions Compared with placeb o, 6 weeks of tea
consumption leads to lower post-stress cortisol and greater
subjective relaxation, together with reduced platelet activa-
tion. Black tea may have health benefits in part by aiding
stress recovery.
Keywords Tea
.
Stress
.
Cortisol
.
Heart rate
.
Blood pressure
.
Platelet activation
.
Caffeine
.
Mood
Introduction
Drinking tea has traditionally been associated with stress
relief, and many people say that drinking tea helps them
relax after facing the vicissitudes of everyday life. Howev-
er, scientific evidence for the relaxing properties of tea is
very limited. Black tea drinking has been found to enhance
positive moods acutely (Quin lan et al. 2000), and to
maintain alertness over the day (Hindmarch et al. 2000).
Steptoe and Wardle (1999) showed significant associations
between tea drinking and positive mood in a diary study,
particularly among respondents who reported high social
support.
If tea does have relaxing properties, these might derive
either from direct biological effects or from the social
Psychopharmacology (2007) 190:8189
DOI 10.1007/s00213-006-0573-2
Funding: This research was supported by a Link award from the
Biotechnology and Biological Sciences Research Council, UK, by
Unilever Research Colworth, and by the British Heart Foundation.
A. Steptoe (*)
:
E. L. Gibson
:
R. Vounonvirta
:
E. D. Williams
:
M. Hamer
:
J. Wardle
Department of Epidemiology and Public Health,
University College London,
1-19 Torrington Place,
London WC1E 6BT, UK
e-mail: a.steptoe@ucl.ac.uk
J. A. Rycroft
Unilever Research Colworth,
Bedford, UK
J. D. Erusalimsky
Wolfson Institute for Biomedical Research,
University College London,
London WC1E 6BT, UK
context in which it is consumed. Animal studies indicate
that tea flavonoids have antagonistic effects on sympathetic
nervous system activity (Perez-Vizcaino et al. 2002) and
reduce blood pressure in spontaneousl y hypertensive rats
(Duarte et al. 2001). Henry and Stephens-Larson (1984)
demonstrated in a mouse psychosocial stress model that 3
to 5 months of decaffeinated tea consumption reduced
blood pressure and a number of psychobiological markers
of stress compared with drinking water. Components of tea
also have central nervous system effects. For example, oral
administration of theanine (an amino acid found in tea)
stimulates increased α-wa ve activity in the occipital and
parietal regions in human volunteers within 40 min (Juneja
et al. 1999). The principal catechin in tea, epigallocatechin
gallate (EGCG), has sedative effects, and reduces cortico-
sterone responses to separation stress (Adachi et al. 2006).
These responses were attenuated by the γ-aminobutyric
acid (GABA)
A
receptor antagonist, picrotoxin, suggesting
partial mediation through GABAnergic pathways. At the
same time, tea is frequently consumed under conditions that
are conducive to relaxation that may, themselves, be
responsible for the apparent benefits. The most rigorous
way to rule out this possibility is to carry out a placebo-
controlled double blind trial, so that the direct impact of tea
can be evaluated.
A widely accepted method of assessing stress responsiv-
ity and post-stress recovery in humans is psychophysiolog-
ical stress testing, in which subjective and physiological
variables are recorded while people are administ ered
standardised behavioural challenges (Schneiderman and
McCabe 1989). Psychophysiological stress testing has been
used to evaluate cardiovascular disease risk (Steptoe 1997),
psychological characteristics such as depression (Kibler and
Ma 2004), habitual physical activity levels (Hamer et al.
2006a), and other factors, including the influence of
functional foods on biological responsivity (Hamer et al.
2005). The method has largely been used to analyse
cardiovascular and neuroendocrine responses. However, it
has been extended to evaluate immune and inflammatory
processes and biological responses relevant to cardiovascu-
lar disease such as platelet activation (Brydon et al. 2006).
The present study investigated the influence of 6 weeks
of black tea compared with matched placebo on subjective,
cardiovascular, cortisol and platelet responses. Caffeine
intake is positively associated with cortisol and cardiovas-
cular stress responses (James 2004; Lovallo et al. 2005), so
the tea and placebo conditions were matched for caffeine
levels. In view of the notion that tea has relaxing properties,
we assessed both acute biological responses and rate of
post-stress recovery. A dou ble-blind methodology was
adopted, so that the influence of tea could be evaluated
independently of the normal cues and circumstances
surrounding tea drinking.
Materials and methods
Study design
The study involved an initial laboratory assessment session
that is not described here, but has been analysed in relation
to coffee consumption (Hamer et al. 2006b). It was
followed by a 4-week washout phase, during which
participants were withdrawn from ordinary tea, coffee and
other caffeinated beverages, and drank fruit-flavoured
caffeinated placebo tea. Use of aspir in, ibuprofen, caffeine
and dietary supplements was prohibited. Various fruits and
vegetables rich in flavonoids were either excluded from
participants diets altogether, or restricted to no more than
one portion per day (citrus fruits and berries, apples and
chocolate products). Otherwise, participants conti nued with
their usual diets. The washout phase was designed both to
standardise tea and caffeine conditions before random-
isation and to screen out volunteers who did not co mply
with instructions. At the end of the washout phase, the
baseline psychophysiological assessment was carried out,
and participants wer e then randomised to 6 weeks tea or
placebo in a double-bli nd parallel group design.
The tea and placebo were presented in the form of fruit-
flavoured powders of a different flavour (apple or lemon)
from the one consumed during the washout phase. This
masked any sensory changes that the active tea group might
otherwise have detected. All powders were tea coloured.
The composition of the powders is detailed in Table 1. The
composition of the tea treatm ent was based on the
constituents of an average cup of black tea. Treatments
were equated for taste and caffeine content and differed
only in the presence of active tea constituents. Four sachets
dissolved in hot water were consumed each day. The tea
sachets contained 6.4% flavonols and treatment was
equivalent to drinking four cups of strong black tea per
day. All investigators who had contact wi th participants
were blind to group allocation. Compliance was asses sed
by repeated measurements of caffeine in saliva to ensure
that caffeine levels were maintained in the appropriate
range and participants were informed that saliva samples
would be analysed to assess absorption of caffeine and the
constituents of tea. A posttreatmen t psychophysiological
assessment session was conducted a fter 6 weeks of
treatment, and participa nts were paid an honorarium. The
study was approved by the UCL/UCLH Committee on the
Ethics of Human Research.
Participants
Community volunteers were recruited through printed and
email invitations to local employers and commercial
outlets. We recruited apparently healt hy, male, nonsmoking
82 Psychopharmacology (2007) 190:8189
tea drinkers aged 1855 years. People who were diabetic or
who reported significant medical or psychiatric histories
were excluded, as were those who were currently pre-
scribed medication or who followed vegetarian or restricted
diets. Volunteers were told that the aim of the study was to
understand how tea influences mental and physical func-
tion, particularly the blood vessels and substances circulat-
ing in the blood. One hundred five individuals were
recruited, of whom 13 were discharged during the washout
phase for lack of compliance. Seventeen other participants
for whom there were insufficient data were excluded from
all analyses. The remaining 75 were randomized to tea (37)
or placebo (38). Participants who completed the study were
given an honorarium of £250.
Psychophysiological stress testing
Testing was carried out in the morning, in a quiet, air-
conditioned room. Before arrival in the laboratory, partic-
ipants consumed one serving of their allocated beverage so
as to avoid any confound due to caffeine withdrawal durin g
testing (James and Rogers 2005). Weight and height were
measured for the calculation of body mass index (BMI),
and the first blood sample was drawn from the antecubital
fossa. Participants then rested for 10 min while blood
pressure and heart rate were measured continuously using a
Finapres (TNO Biomedical Instrumentation, Amsterdam,
The Netherlands) which derives measures from the finger
using the v ascula r unloading techniq ue. The Finapres
provides beat by beat data, so it detects the full profile of
cardiovascular responses that cannot be provided by
intermittent measures using sphygmomanometry. The last
5 min of data were averaged to constitute the baseline.
Participants then completed ratings of stress and relaxation
using 7-point scales where 1=low to 7=high. The baseline
was followed by two standardised behavioural challenges
that have been used extensively in previous research
(Steptoe et al. 2003; Strike et al. 2006). The first was a
socially evaluating speech task in which participants were
given one of three stressful situations assigned at random
(threat of unemployment, a shop lifting accusation and an
incident in a nursing home involving a close relative). They
were instructed to prepare a verbal response for 2 min and
then to speak for 3 min, and performance was recorded on a
video came ra. The seco nd task was mirror t racing,
involving the tracing of a star with a metal stylus, which
could only be seen in a mirror image (Lafayette Instru-
ments, Lafay ette, IN, USA), and this was also carried out
for 5 min. Cardiovascular monitoring continued throughout
each task, and ratings of perceived stress were obtained
immediately after each task. Participants also rated the
difficulty and controllability of tasks and task involvement
on 7-point scales. A second blood sample was drawn
10 min post-task, and recovery heart rate, blood pressure
were then monitored for a further 5 min, and recovery
ratings of stress and relaxation were obtained. Saliva
samples were obtained at baseline, immediately after tasks,
and then at 15, 30 and 50 min post-stress for the assessment
of salivary cortisol.
Biological assays
Platelet activation was measured with flow cytomet ric
assessment of circulating leukocyteplatelet aggregates as
described previ ously (Steptoe et al. 2003). Blood was
drawn using a butterfly needle with Luer adapter connect ed
to a sodium citrate Vacutainer, and the first 2 ml of each
sample were discarded. Whole blood samples (10 μl) were
diluted with 90 μl Hepes buffered saline and then incubated
at room temperature for 20 min with 10 μl each of
fluorescein isothiocyanate- con jugate d mouse antihuman
CD45 monoclonal antibody (clone H130, BD PharMingen,
Oxford) and R-Phycoerythrin (PE)-conjugated mouse anti-
human CD42a monoclonal anti body (clone ALMA.16, BD
PharMingen) which recognize leukocytes and platelets,
Table 1 Composition of the treatments in the study
Tea Placebo
Component Dose (mg) Component Dose (mg)
Tea extract 1,050
Maltodextrin 4,200 Maltodextrin 4,200
Lemon/apple
flavouring
150 Lemon/apple
flavouring
150
Caramel colour 157 Caramel colour 157
Citric acid 96 Citric acid 96
Malic acid 21 Malic acid 21
Caffeine (naturally
occurring)
72 Caffeine 72
Black tea formulation (Galenic form)
Component Percentage (%)
Gallic acid 1.078
Theobromine 0.346
Epicatechin 1.167
Catechin 0.230
Epigallocatechin 0.524
Epicatechin-3-gallate 1.445
Epigallocatechin-3-
gallate
2.548
Theaflavin 0.252
Theaflavin-3-
monogallate
0.205
Theaflavin-3-
monogallate
0.064
Caffeine 6.450
Theaflavin-3-digallate <0.05
Psychopharmacology (2007) 190:8189 83
respectively. An isotype matched PE-conjugated antibody
was used as a negative control. After fixation, total platelet
leukocyte aggrega tes and their subsets were quantified
using a Becton Dickinson FACScan Flow Cytometer and
Cellquest software. Results are presented as percentages of
monocytes, neutrophils and tot al leukocytes bound to
platelets. Saliva free cortisol was assessed at the University
of D resden using a time-resolved immunoassay with
fluorescence detection.
Statistical analysis
Blood pressure and heart rate data were averaged into four
5-min trials (baseline, speech, mirror tracing and recovery).
Pretreatment psychophysiological responses were analysed
using repeated measures analysis of variance with group
(tea, placebo) as the between-subject factor and trial as the
within-subject factor. The analysis of cortisol involved five
trials within sessions (baseline, immediately post-task, and
15, 30 and 50 min post-task). The GreenhouseGeisser
correction for degrees of freedom was applied when
appropriate, and post hoc tests were made using Tukeys
least significant difference (LSD) test. Additionally, total
cortisol output over each session was computed using area
under the curve methods (Pruessner et al. 2003). The effect
of tea was assessed with repeated measures analysis of
covariance of posttreatment data, using corresponding
pretreatment values for each trial as covariates. Complete
data from all 75 participants were available for BP and
platelet activat ion, but missing values resulted in one
person missing from heart rate analyses, two from
subjective rating analyses and four from cortisol analyses.
Results are presented as means±standard deviation.
Results
The characteristics of participants in the two groups are
summarised in Table 2. The mean age of men in this study
was 33.2 years, and the majority were white Europeans and
well educated. Mean BMI was 25.5±3.2, and 1 9%
exercised vigor ously at least three times per week. There
were no group differences in any of these characteristics.
Pretreatment stress responsivity
There were significant changes over trials in the repeated
measures analysis of variance of systolic and diastolic BP
(F(3,219 )=246.9 and 216.5, p<0.001), heart rate (F(3 ,216 )=
123.1, p<0.001), subjective stress responses (F(3,219)=96.2,
p<0.001), relaxation ratings (F(1,73)=9.18, p =0.003),
platelet activation indexed by plateletmonocyte aggregates,
plateletneutrophil aggregates and total plateletleukocyte
aggregates, (F(1,73)=10.620.6, all p<0.001) and cortisol (F
(4,276)=21.3, p<0.001). There were no significant differences
between tea and placebo groups in any of these responses
(Table 3). Blood pressure, heart rate and subjective stress
increased in response to speech and mirror tracing tasks,
returning towards baseline during the post-task recovery
period. The stress responses were greater for speech than
mirror tracing tasks in systolic BP and heart rate, but not in
diastolic BP or subjective ratings. Participants became more
relaxedduringrecoverycompared with the baseline period.
All measures of platelet activation showed significant
increases in response to stress tasks, with rises averaging 4
to 8%. Cortisol was not elevated following tasks, but rather,
decreased over the laboratory session, reflecting the usual
circadian morning decline. Participants rated tasks as moder-
ately difficult (mean 4.17±0.96), controllable (mean 4.60±
1.02) and highly involving (mean 5.71±0.76). There were no
differences between groups in these task appraisals. The
ratings of the difficulty and controllability of the speech and
mirror tracing tasks did not differ , but mirror tracing was rated
as more involving than speech (F(1,73)=121.9, p
<0.001).
Effects of tea and placebo treatments
There were no significant differences between groups and
no group by trial interactions in the analyses of posttreat-
ment systolic and diastolic BP, heart rate or subjective
ratings of stress, adjusting for pretreatment values. In each
case, there was a main effect of trial (F(3, 218)=4.2843.6,
all p<0.005). These results are illustrated in Fig. 1, where it
is evident that the increase in activation during tasks and
decrease in the recovery trial were very similar in the tea
and placebo conditions. The treatment effect approached
significance for diastolic BP (F(1,72) =3.69, p=0.059), and
Table 2 Characteristics of participants in the two experimental groups
Tea group
(n=37)
Placebo group
(n=38)
Age (years) 33.2±8.6 33.1±8.1
Ethnicity: White (%) 94.3% 78.4%
Marital status: married (%) 40% 39.5%
Education: GCSE/A-level (%) 31.4% 18.4%
Degree and above 68.6% 81.6%
Body mass index (kg m
2
) 25.6±3.2 25.4±3.1
Former smokers (%) 31.3% 41.4%
Vigorous physical activity (2 weeks)
None 25.6% 18.9%
13 times 37.2% 43.2%
4 times or more 37.2% 37.8%
Baseline tea consumption (cups/day) 2.19±1.8 2.20±1.9
Mean±standard deviation and percentages
84 Psychopharmacology (2007) 190:8189
heart rate (F(1,71)=3.61, p=0.061). Heart rate was slightly
lower in the tea than placebo condition throughout, while
diastolic BP was higher in the tea than placeb o conditions.
There were significant group differences in the analyses
of plateletmonocyte aggregates, plateletneutrophil aggre-
gates and total plateletleukocyte aggregates posttreatment
(F(1,72)=4.24, 4.25 and 4.99, respectively, all p<0.005).
Additionally, there were significant effects for trial (base-
line vs stress) in the analyses of plateletneutrophil and
plateletleukocyte aggregates (F(1,72)=13.9 and 9 .53,
respectively, p<0.005) but no group by trial interactions.
As can be seen in Fig. 2, platelet activation on all three
measures was lower following treatment with tea than
placebo. Platelet activation responses to stress were main-
tained in plateletneutrophil and plateletleukocyte but not
plateletmonocyte aggregates.
The analysis of cortisol over the session (with corre-
sponding pretreatment values as covariates) demonstrated a
significant group by trial interaction (F(4,275)=4.57, p<
0.001), illustrated in Fig. 3. Baseline cortisol was the same
in the two groups posttreatment , and the total area under the
curve for cortisol did not differ. But levels declined after
tasks to a greater extent in the tea than placebo conditions.
Thus, the groups differed significantly at 50 min post-tasks
(p=0.035), and the change between baseline and 50 min
was greater in the tea condition (p=0.032). This result
suggests that tea may promote more effective reductions in
neuroendocrine activity post-stress.
Treatment effects were also evident in subjective
relaxation ratings. Repeated measures analyses of covari-
ance of baseline and recovery ratings revealed a significant
group by trial interaction (F(1,70)=4.54, p=0.037). The
two groups did not differ in baseline relaxation ratings, but
the change in relaxation between baseline and recovery was
positive in the tea and negative in the placebo condition (p=
0.036). The rating of relaxation incre ased by 6.26% in the
tea condition but fell by 3.19% in the placebo group. This
corresponds to just under a 10% difference in change in
relaxation rating. There were no significant changes over
sessions or differences between groups in ratings of task
difficulty, controllability or involvement.
Discussion
This study used laboratory psychophysiological testing to
evaluate the influence of chronic tea intake on cardiovas-
cular, neuroen docrine, platelet and subjective stress
responses. It was carried out using placebo-controlled,
double-blind methodology. The main findings are that tea
had no effect on blood pressure or heart rate stress
reactivity or recovery. Participants in the tea condition had
lower platelet activation, an effect that was present both in
Table 3 Biological and subjective responses pretreatment
Baseline Speech task Mirror tracing Post-task
1 min
Post-task
10 min
Post-task
15 min
Post-task 20
25 min
Post-task
30 min
Post-task
50 min
Systolic BP (mmHg) 121.4±11.5
a
160.9±22.2
b
156.0±21.2
c
130.2±14.9
d
Diastolic BP (mmHg) 72.6±8.9
a
94.8±12.2
b
93.7±13.9
b
78.0±10.8
c
Heart rate (bpm) 68.5±12.1
a
83.4±16.8
b
75.6±14.6
c
65.8±11.0
d
Stress rating (17) 2.36±1.1
a
4.23±1.3
b
4.51±1.2
b
2.05±1.0
c
Relaxation rating (17) 5.36±1.1
a
5.72±0.89
b
Plateletmonocyte aggregates (%) 5.91±1.4
a
6.38±1.5
b
Plateletneutrophil aggregates (%) 4.60±0.95
a
4.88±1.0
c
Plateletleukocyte aggregates (%) 5.02±0.94
a
5.23±1.0
b
Cortisol (nmol/l) 11.7±6.3
a
11.0±5.8
a
10.9±6.3
a
9.63±5.7
b
7.21±4.1
c
Values in each row with different superscripts are significantly different from one another using Tukeys LSD.
Psychopharmacology (2007) 190:8189 85
baseline and stress samples. Tea also led to lower cortisol
towards the end of the post-task recover y period and to
greater subjective relaxation post-tasks. Tea, therefore,
appears to influence the effectiveness of post-stress recov-
ery, rather than the magnitude of stress responses them-
selves. These effects cannot be attributed to bias on the part
of participants or investigators.
Studying the psychophysiological effects of tea presents
particular difficulties. Unlike substances such as Ginkgo
biloba that can readily be presented in the form of placebo
capsules (Jezova et al. 2002), a placebo drink that tastes
like black tea cannot be manufactured. Many studies of
psychological and biological responses have, therefore,
compared tea with water (e.g., Duffy et al. 2001;
Hindmarch et al. 1998; Quinlan et al. 1997). Under these
conditions, both the participants and investigators are aware
of treatment condition, so, bias cannot be ruled out. In the
present study, we overcame this problem by administering
tea and placebo in fruit flavoured forms. These not only
masked any sensory changes when switching from placeb o
to active tea but also removed the beverage from the normal
set of sensory cues associated with tea drinking, so that the
effects of tea could be studied independently of potential
confounders.
3
4
5
6
7
3
4
5
6
7
Baseline Post-task
Baseline Post-task Baseline Post-task
3
4
5
6
7
% aggregates
% aggregates
% aggregates
Total PLA
PNA
PMA
Fig. 2 Mean percentage of total
plateletleukocyte aggregates
(PLA), plateletmonocyte
aggregates (PMA) and platelet
neutrophil aggregates (PNA)at
baseline and following tasks in
the posttreatment session. These
posttreatment values are adjust-
ed for pretreatment responses.
Tea conditionsolid bars; pla-
cebo conditionhatched bars.
Error bars are standard error of
the mean (SEM)
160
150
140
130
120
110
100
90
80
70
60
Base Speech MT Recovery
Base S
p
eech MT Recover
y
Base Speech MT Recovery
mmHg
mmHg
85
80
75
70
65
60
55
bpm
1
2
3
4
5
6
7
rating
Base S
p
eech MT Recover
y
Fig. 1 Mean levels of systolic
BP (upper left), diastolic BP
(upper right), heart rate ( lower
left) and subjective stress (lower
right) during baseline, speech
task, mirror tracing (MT) task
and recovery trials following
6 weeks treatment with tea
(solid line) or placebo (dashed
line). These posttreatment val-
ues are adjusted for pretreatment
responses
86 Psychopharmacology (2007) 190:8189
The pattern of subjective and physiological responses to
behavioural tasks was typical of results obtained with these
stimuli (Steptoe et al. 2002, 2003). Blood pressure, heart
rate and subjective ratings of stress all increased acutely,
returning toward baseline during the post-task recovery
period. Recovery of systolic and diastolic BP was incom-
plete 20 min post-stress, as noted in previous investigations.
The increase in cardiovascular activity was substantial, with
BP rises of more than 30% (Table 2). By contrast, although
platelet ac tivation increased reliably, the magnitude of
responses was relatively small (<10%). We were only able
to sample blood twice during experimental sessions, and
the timing of the post-stress blood draw (10 min after tasks)
may not have been optimal for all individuals. The small
magnitude of responses limited the scope for observing
reduced stress responsivity following tea treatment. The
absence of a stress-free condition prevented assessment of
any increase in cortisol in response to the tasks, though it
could be argued that the expected diurn al decline in cortisol
was arrested by the stress tasks, as evidenced by the lack of
cortisol decline between immediate and 15 min post-stress
samples (Fig. 3). Cortisol responses to acute challenges
vary greatly in relation to situational factors and the type of
demand imposed (Dickerson and Kemeny 2004), and we
have observed small responses in previous studies using
these stimuli (Kunz-Ebrecht et al. 2003). Furthermore, the
placebo and active tea drinks contained equal amounts of
caffeine, so that any differential effects were independent of
caffeine, unlike many previous studies of effects of tea.
The first hypothesis tested in this study was that chronic
tea administration would reduce stress-induced cardiovas-
cular and platelet activation. This hypothesis was not
confirmed, as we found no evidence that the magnitude of
stress responses was systematically reduced by tea admin-
istration. There was a tendency for heart rate to be lower
following tea than placeb o administration, but set against
this is the slightly higher level of diastolic BP in the tea
condition (Fig. 1). One explanation of the lack of differ-
ences may be that caffeine intake was equated across
experimental groups. Caffeine is a central nervous system
stimulant and promotes modest increases in blood pressure
and cortisol (James 2004; Lovallo et al. 2005). This effect
may have outweighed any influence of the more specific
constituents of tea.
There was a significant group difference posttreatment in
platelet activation, as shown in Fig. 2. This was evident
both in baseline and post-task samp les, so was not an effect
on stress reactivity but on tonic levels. We have discussed
the baseline difference elsewhere (Steptoe et al. 2006).
However, the fact that plateletleukocyte aggregate levels
were lower during both baseline and stress samples
following tea treatment may be significant for cardiovas-
cular health. Platelets play an important role in the
development of coronary atherosclerosis and in the acute
processes underlying acute coronary syndrome (Brydon
et al. 2006 ; Monaco et al. 2005). Earlier studies of stress
and platelet activation have used indirect measures such as
aggregation in response to physi ological agonists (collagen,
adenosine diphosphate (ADP)) and measuremen t of a
concentration of platelet products in plasma (von Kanel
et al. 2001). An important limitation to these techniques is
the sample manipulation required before analysis, and
plasma separation can lead to artefactual platelet activation.
Whole blood flow cytometry involves little sample manip-
ulation as cells are maintained in their native milieu.
Michelson et al. (2001) have argued that the measure-
ment of plateletleukocyte aggrega tes by flow cytometry
provides a more accurate assessment of platelet activation
than other measures. The polyphenols in black tea have
previously been shown to inhibit platelet activation in vitro
(Formica and Regelson 1995; Neiva et al. 1999), but two
studies comparing tea and water administration over
4 weeks did not show any effect on platelet aggregation
stimulated by collagen, ADP or thrombin receptor activat-
ing peptide (Du ffy et al. 2001; Hodgson et al. 2001). Our
results may have been due to the longer period of
administration (6 weeks) or the method of assessing platelet
activation. The fact that plateletleukocyte aggregate levels
during stress were diminished after tea treatment suggests
that this might be a mechanism through which tea drinking
contributes to reduced cardiovascular disease risk (Peters
et al. 2001).
The second hypothesis was that tea consumption would
enhance psychophysiological recovery following stress.
The recovery arm of physiological responses has attracted
increasing attention over recent years, as prolonged
activation may be an important disease-related process
(Brosschot et al. 2005). In the allostatic model developed
by McEwen (McEwen 1998), impaired post-stress recovery
is an indicator of chronic allostatic load. Slow recovery
following acute stress has been associated with increased
Baseline Post-task 15 min 30 min 50 min
4
6
8
10
12
nmol/l
Fig. 3 Mean salivary cortisol across the posttreatment session
(adjusted for pretreatment values) in the tea (solid line) and placebo
(dashed line) conditions. Error bars are SEM
Psychopharmacology (2007) 190:8189 87
cardiovascular disease risk and heightened mortality in
prospective investigations (Cole et al. 1999; Steptoe and
Marmot 2005).
Evidence that tea enhances post-stress recovery was
provided by two measures. First, ratings of relaxation
during the recovery period were more positive in the tea
than in the placebo conditions. As there were no differences
in subjective stress responses to the tasks or in cognitive
appraisal of tasks, this finding suggests that tea drinking
had a specific effect on subjective recovery from stress.
Second, cortisol showed a greater decline following stress
in the tea condition (Fig. 3). By the final sample 50 min
post-stress, cortisol had fallen to 53% of baseline in the
tea compared with 73% of baselin e in the placeb o
condition. It is notable that this response took an
extended period to evolve. Post-stress recovery of BP
and heart rate were measured 20 min after tasks, and this
may have been too early to detect beneficial effects of tea
consumption.
Both natural and synthetic flavonoids have affinities for
the benzodiazepine binding sites of GABA
A
receptors, and
this may be an important mechanism in the effects of tea
flavonoids on the central nervous system (Dekermendjian et
al. 1999; Paladini et al. 1999). As noted in the Introduction
section, another component of tea that could contribute to
enhanced recovery from stress is theanine, which may
inhibit action of excitatory amino acid neurotransmitters
and has been foun d to reduce anxiety under resting
conditions but not in response to experimental stress (Lu
et al. 2004). Preliminary evidence suggests that theanine
may potentiate some actions of caffeine on cognitive
function and arousal, and this might explain the dissocia-
tion between the effect of tea on post-task cortisol recovery
and relaxation and the lack of effect on cardiovascular
reactivity (Haskell et al. 2005).
The strengths of the study were the randomised double-
blind placebo-controlled design, so that neither the partic-
ipants nor the investigators were aware of group assign ment,
the use of standardised psychophysiological stress testing,
assessment of platelet acti vation of whole blood flow
cytometry, continuous beat to beat measures of blood
pressure and heart rate and treatment conditions that lasted
6 weeks. Most studies of the biological effects of chronic
tea consumption have involved a 4-week intervention
phase, and this may not be long enough for differential
response patterns to develop. The limitations of the study
include the fact that participants were young, apparently
healthy men, so we do not know whether other groups
would respond similarly. Platelet stress responses were
small, and there was no absolute increase in cortisol level.
Future studies would benefit from a non-stress control
condition. Additionally, we relied on participants to report
deviations from compliance with the dietary restrictions
imposed, and adherence to these restrictions was not
assessed object ively.
In summary, 6 weeks of drinking the equivalent of four
cups of black tea per day lead to lower post-stress cortisol
and greater subjective relaxation under laboratory condi-
tions, together with reduced platelet activation, compared
with placebo. These results suggest that black tea con-
sumption may have benefits to health, in part, by aiding
recovery from stress, mediated through psychoneuroendo-
crine and inflammatory pathways.
Acknowledgements We are grateful to Peirluigi Giac obazzi and
Kesson Magid for their assistance in data collection and bi ologica l
assays. Leigh Gibson is now at Roehampton University, London,
Raisa Vounonvirta at the Institute of Cancer Research, Sutton, UK,
and Jorge Erusalimsky is at the Unive rsity of Wales Institute,
Cardiff.
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Aims Low socioeconomic status is associated with increased cardiovascular disease risk. We hypothesized that psychobiological pathways, specifically slow recovery in blood pressure and heart rate variability following mental stress, partly mediate social inequalities in risk. Methods and Results Participants were 123 men and 105 women in good health aged 47–58 years drawn from the Whitehall II cohort of British civil servants. Grade of employment was the indicator of socioeconomic status. Cardiovascular measures were monitored during performance of two behavioural tasks, and for 45min following stress. Post-stress return of blood pressure and heart rate variability to resting levels was less complete after 45min in the medium and low than in the high grade of employment groups. The odds of failure to return to baseline by 45min in the low relative to the high grade of employment groups were 2·60 (95% CI 1·20–5·65) and 3·85 (1·48–10·0) for systolic and diastolic pressure, respectively, and 5·19 (1·88–18·6) for heart rate variability, adjusted for sex, age, baseline levels and reactions to tasks. Subjective ratings of task difficulty, involvement and stress did not differ by socioeconomic status. Conclusions Lower socioeconomic status is associated with delayed recovery in cardiovascular function after mental stress. Impaired recovery may reflect heightened allostatic load, and constitute a mechanism through which low socioeconomic status enhances cardiovascular disease risk.
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The flavonoid quercetin is metabolized into isorhamnetin, tamarixetin, and kaempferol, the vascular effects of which are unknown. In the present study, the effects of quercetin and its metabolites were analyzed on isometric tension in isolated rat thoracic and abdominal aorta, in isolated intact and β-escin-permeabilized iliac arteries, and on perfusion pressure in the isolated mesenteric resistance vascular bed. In noradrenaline-precontracted vessels, the four flavonoids produced a vasodilator effect, which was inversely correlated with the diameter of the vessel studied; i.e., quercetin, isorhamnetin, tamarixetin, and kaempferol were 5-, 25-, 4-, and 6-fold, respectively, more potent in the resistance mesenteric bed (−log IC50 = 5.35 ± 0.15, 5.89 ± 0.11, 5.34 ± 0.10, and 5.66 ± 0.06, respectively) than in the thoracic aorta (−log IC50 = 4.68 ± 0.08, 4.61 ± 0.08, 4.73 ± 0.11, and 4.81 ± 0.13, respectively; n = 4–6). The vasodilator responses of quercetin and isorhamnetin were not significantly modified after removal of the endothelium in the thoracic aorta or in the mesenteric bed. Furthermore, the guanylate cyclase inhibitor ODQ (1 H -[1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one; 10−6 M), the adenylate cyclase inhibitor SQ22536 [9-(tetrahydro-2-furanyl)-9 H -purin-6-amine; 10−6 M], KCl (40 mM), or ouabain (10−3 M) had no effect on isorhamnetin-induced vasodilation in the mesenteric bed. In permeabilized iliac arteries stimulated with Ca2+(pCa of 5.9), isorhamnetin was also significantly more potent (−log IC50 = 5.27 ± 0.15) than quercetin (−log IC50 = 4.56 ± 0.15). In conclusion, quercetin and its metabolites showed vasodilator effects with selectivity toward the resistance vessels. These effects are not due to or modulated by endothelial factors and are unrelated to changes in cytosolic Ca2+.