ARTICLE IN PRESS

Complementary Therapies in Clinical Practice (2007) 13, 137–145

www.elsevierhealth.com/journals/ctnm

Evaluation of anxiety, salivary cortisol and

melatonin secretion following reflexology
treatment: A pilot study in healthy individuals
A.J. Mc Vicara, C.R. Greenwoodb, F. Fewella, V. D’Arcyb,
S. Chandrasekharanb, L.C. Alldridgeb,

a
Institute of Health and Social Care, Anglia Ruskin University, Bishop Hall Lane, Chelmsford,
Essex CM1 1SQ, UK
b
Helen Rollason Cancer Care Laboratory, Anglia Ruskin University, Bishop Hall Lane, Chelmsford,
Essex CM1 1SQ, UK

KEYWORDS Summary This pilot study sought to identify an appropriate methodology to

Reflexology; investigate the impact of reflexology in healthcare settings. The study involved
Stress; healthy volunteers to prevent unnecessary intervention to individuals who may
Biometric already be experiencing health related trauma. Thirty participants underwent either
evaluation; reflexology or no treatment (control), in a cross-over experimental design. Self-
Psychometric reported anxiety (Spielberger STAI), cardiovascular parameters (BP and pulse rate)
evaluation and salivary cortisol and melatonin concentrations were assessed before and after
reflexology. Control data were obtained at the same time points in identical
settings.
Reflexology had a powerful anxiety-reduction effect (‘state’; Po0.001) but no
significant effect on underlying anxiety (‘trait’). Cardiovascular parameters
decreased (Po0.001). Baseline salivary cortisol and melatonin were not significantly
correlated with STAI scores and did not change significantly following reflexology.
Reflexology reduced ‘state’ anxiety and cardiovascular activity within healthy
individuals, consistent with stress-reduction. Considering the connection between
stress/anxiety and well being, the effects of reflexology may have beneficial
outcomes for patients. These findings will be transferred to a study involving breast
cancer patients where effects may be more pronounced particularly since cancer
patients display disregulation of cortisol and melatonin secretion.
& 2006 Elsevier Ltd. All rights reserved.

Corresponding author. Tel.: +44 1245 493131x3098; fax: +44 1245 683095.
E-mail address: l.c.alldridge@anglia.ac.uk (L.C. Alldridge).

1744-3881/$ - see front matter & 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ctcp.2006.11.001
 ARTICLE IN PRESS
138
Introduction
Complementary therapy treatments are increas-
ingly being integrated into hospice and hospital
settings to improve the client’s psychological and
physical well being.1 However, some Health Orga-
nisations do not partake, possibly due to concerns
about the lack of appropriate evidence-based
research to support therapeutic claims.2–4 Most
clients report a reduction in anxiety, improvement
in general well being3–5 and even reduced pain.6
However, it is difficult to determine whether these
beneficial effects are the result of a specific
complementary therapy or of the therapeutic
relationship and general relaxation.
The potential for reflexology to reduce anxiety is
of interest in healthcare due to profound connec-
tions between anxiety following a stress event and
various disease processes.7 In addition, Schag and
Heinrich8 reported that 44% of cancer patients
experience anxiety, which can influence pain
sensation, sleep disturbance and anticipatory nau-
sea,9 and our unpublished work with cancer
patients has anecdotally observed a reduction in
anxiety following reflexology treatments. Stress is
speculated to be part of the cancer aetiology,10
which may be due to innumerable interactions, but
the immune system is postulated to play a
significant role.11 Whilst anxiety is normally viewed
as a cognitive experience and may be evaluated
quantitatively using psychometric measures,12 im-
mune changes are thought to involve metabolic and
endocrine responses that are also apparent. Two of
the most important of these include variations in
secretion of cortisol13 and melatonin.14
Cortisol exerts its action in a negative feedback
loop on the hypothalamic pituitary adrenal axis,
which is one of the primary biological pathways
linking psychological factors and the immune
system.15 Cortisol suppresses the immune system
and directly inhibits natural killer (NK) cell activ-
ity.16 More recently cortisol has been shown to
down regulate the protein NKp30 which correlates
strongly with reduced NK cytolytic activity.17 A
high percentage of breast cancer patients
have been shown to display abnormal secretion
patterns of the hormone cortisol such as flattened
diurnal cortisol, consistently high levels or erratic
fluctuations18,19 which have been linked to poor
prognosis.20 The cause of this circadian deregula-
tion in cancer is unknown, but aberrations of
cortisol rhythms have been linked both with the
physical stress of cancer21 and with psychological
stress.22
Melatonin is secreted by the pineal gland and
binds to receptors in the suprachiasmatic nuclei of
A.J. Mc Vicar et al.
the hypothalamus to directly influence circadian
rhythms related to light/dark cycles, especially the
sleep–wake cycle.23 Melatonin also acts as an
immunoenhancer by increasing the mitogenic, and
reducing apoptotic, responses.24 Immunoregulatory
roles of melatonin have been widely demonstrated
in cancer, aging, physical stress, and treatment
with corticoids.14,25–27 Interestingly, melatonin has
been shown to be a hormonal regulator of
neoplastic cell growth28,29 and an association
between low levels of melatonin and human breast
cancer have been reported.30 It has also recently
been identified as a potential cancer-modulating
therapeutic.31
Better health outcomes for cancer patients who
receive psychological support have been reported
but the mechanisms behind such effects are
unknown. A bio-psychosocial model has been
formulated in which coping and psychological
adjustment is associated with alterations in cortisol
levels as well as immune function and long-term
outcomes for breast cancer patients.32 Recently, it
was shown that massage therapy improves the
medical and psychiatric condition of people,
decreasing their stress perception, decreasing
cortisol levels, and improving sleep patterns and
immune function.33 Complementary therapies such
as reflexology therefore could potentially have a
significant role in reducing patient stress.
Despite claims that reflexology reduces anxiety,
little is known of the magnitude of this effect, or of
its impact on biometric, and psychometric mea-
sures. The aims of this study are to investigate the
association between anxiety, salivary cortisol and
melatonin, blood pressure, pulse rate (PR) and
reflexology in healthy volunteers as a prelude to a
study involving cancer patients. This will establish
our methodology and so enable us to transfer it to a
larger study that will evaluate the effects of
reflexology on physiological, biochemical and psy-
chological measures of anxiety and stress in breast
cancer patients.
Methods
This study applied a cross-over design, with
participants acting as their own controls on one
occasion and receiving treatment on another, to
strengthen the potential for detecting treatment
effects in a small sample. Weaknesses are noted for
this design but were negated:
 Carry-over effects. Possible impacts of receiving
treatment on the second visit were reduced by
ensuring at least 3 days between attendance.
 ARTICLE IN PRESS
A pilot study in healthy individuals
 Treatment sequence. An influence of time-
related events independent of treatment was
avoided by some participants attending on non-
treatment (control) days followed by treatment
days, whilst for others the sequence was
reversed.
 Drop-out. The findings presented here are only
those for participants who attended both occa-
sions in the trial, and for whom full sets of data
were obtained on each occasion. In reality, drop-
out and/or non-completion of research tools was
very low.
Ethical considerations
All participants were informed of the details of the
study and gave their written consent. The study
was approved by the Ethical Committee of Anglia
Ruskin University.
Participants
Thirty healthy volunteers were recruited through
internal advertisements within the university. A
wide age range of 16–59 years was included as a
pragmatic approach in consideration of the likely
participants within the follow-up study in a cancer
centre proposed to follow this pilot. Participants
with stimulated/deficient steroid secretion were
excluded: Cushing’s disease, Adrenal tumours,
Addison’s disease, Adrenocorticotropic hormone
deficiency disease, pregnancy, and women on oral
contraceptive. Participants were requested not to
eat, drink or smoke 60 min before giving saliva
samples. Health behaviours that potentially affect
the endocrine system were also recorded to detect
and eliminate unrelated sample variability, these
included caffeinated drink and alcohol consump-
tion (servings weekly), smoking (per day), exercise
(weekly), average sleep per night, self-rated
quality of sleep (poor, adequate good) and self-
rated quality of diet (poor/adequate/good).
The recruited healthy volunteers were randomly
divided into two trials. Trial A investigated the
immediate effect of reflexology, whilst Trial B
repeated the main measures but expanded the
salivary cortisol and melatonin measurements. This
was necessary to more precisely assess any impact
on the diurnal patterns of secretion through
measurement of night-time and waking levels.
Immediate effects may not be seen due to time
required for production and secretion, whereas
longer term measurements may be more informa-
tive.
139
Reflexology treatment
Reflexology is the systematic application of special
touch or pressure to reflex points on the foot or hand.
The specific foot chart and technique employed here
is detailed by Fewell34 and uses gentle, precise
pressure. The most commonly adopted movement is
the ‘caterpillar’ technique and this is used by most
reflexologists as the precise, fluid movements allow
for pressure to be exerted without inducing pain. At
Anglia Ruskin University, we have developed a gentle
approach to reflexology as opposed to the deeper
treatment sometimes applied by reflexologists. This
is based on our experiences from over nearly 30 years
of working with patients presenting with complex
health conditions, pain and altered pain perception
for example during chemotherapy. Our unpublished
findings confirm that there are no negative effects
from using gentle pressure.
For both Trials, participants were divided into a
therapy group, who were treated with reflexology
for 60 min (12.00 noon–1.00 pm), and a non-
treatment (control) group. Whilst the treatment
group received reflexology, the non-treatment
group sat quietly together in the adjoining room.
The ambience (colour of the walls, temperature,
background music) was the same in both rooms, in
order to control for any changes in anxiety arising
from relaxation and social support. Three days
later the participants in the non-treatment group
underwent reflexology treatment while those in the
treatment group now formed the control group.
This cross-over design allowed each participant to
provide their own control data.
Psychometric assessment
Spielbergers state trait anxiety inventory for adults
(STAI) was used to assess changes in transitory
anxiety experienced by participants prior to and
following treatment.12 The STAI is a well-validated
tool and differentiates between the temporary condi-
tion of ‘‘state anxiety’’ and the more general and long-
standing quality of ‘‘trait anxiety.’’ Scores increase in
response to psychological stress, and decrease as a
result of relaxation training or therapies.
Biometric measurements
Blood pressure and pulse rate
Systolic and diastolic blood pressure (BP) was
measured by auscultation over the brachial artery
using a mercury sphygmomanometer, and radial PR
was measured manually, whilst sitting prior to and
following reflexology treatment, and at identical
 ARTICLE IN PRESS
140
times during control sessions. Measures were taken
by a nurse assistant experienced in the methods.
Collection and analysis of saliva samples
Cortisol is secreted diurnally with levels peaking in
the early morning and decreasing over the course of
the day.35 Secretion of melatonin is stimulated by
the dark and inhibited by the light and so also
exhibits a diurnal rhythm. These hormones are
excreted in saliva in their free form and salivary
concentrations have been shown to be an accurate
indicator of free or biologically active hormone in
human serum.36–38 Collecting saliva is a relatively
non-invasive procedure and evaluating hormone
concentrations in saliva has become a widely used
method to evaluate serum changes, and hence
changes in glandular secretion.
Participants collected saliva samples using cotton
swabs or ‘‘salivettes’’ (Sarstedt, Inc.) at time points
elucidated from a small preliminary trial where
saliva samples were collected from the research
team over 2 days. The need to adhere to collection
times in early morning and in the evening, that is
when participants were away from the university,
were strongly emphasised.
In Trial A, saliva samples were collected at midday,
1.15 pm (i.e. 15 min after reflexology treatment), and
at 8 pm (i.e. 7 h post-treatment). Multiple samples
were taken for greater precision. This allowed
comparison of short-term changes in hormonal levels.
As no changes were apparent, samples in Trial B were
taken at 1.15 pm, 11 pm and on waking the next day
to incorporate late evening and early morning values.
The data from both trials allowed comparison of
hormone concentrations at the times allocated but
also enabled evaluation of the early morning peaks for
cortisol and the dark induced peak for melatonin to
assess ‘responders/reactors’.39 The non-treatment
data provided the mean base-line readings.
Saliva samples were centrifuged for 4 min at
2500 rpm to remove the saliva from the swab, stored
at +4 1C and assayed within 5 days. Cortisol and
melatonin concentrations in saliva were assayed in
duplicate by enzyme-linked immunosorbant assay
(ELISA). (Cortisol: Salimetrics, State college PA;
Melatonin; Buhlmann laboratories AG, Switzerland.)
Standards (cortisol 1.8–0.007 mg/dl; melatonin
81–3 pg/ml) were assayed simultaneously. Samples
were quantified by colorimetric analysis at 450 nm.
Statistical analysis
All data were collated using Statistical Package for
the Social Sciences (SPSS; Version 13). Data are
expressed as means7standard error of the mean
A.J. Mc Vicar et al.
(sem). Time matched data for all measures were
compared using an independent (Student) t-test for
between-group differences. Pre- vs. post-treatment
changes within groups were also analysed using a
paired t-test. Pre-treatment and time-matched con-
trol data were also analysed for evidence of correla-
tion between the two psychometric scales of the
STAI, and between these measures and hormone
concentration, using bivariate analysis (Pearson’s).
Results
‘State’ and ‘trait’ anxiety scores following
reflexology
The two trials were performed on separate occa-
sions, with 12.00 noon as the starting point on each
occasion. No significant differences were noted
between the baseline ‘state/trait’ anxiety data on
non-treatment or treatment days for each trial, or
between trials. The ‘state’ and ‘trait’ anxiety
measures at this time point were significantly
correlated (all participants: r ¼ 0:583, Po0.001,
n ¼ 52) suggesting that perceptions of participants
on the day of attendance (viz ‘state’) were
associated with their underlying anxiety trait.
Trait anxiety is considered unlikely to alter in the
short-term, and the ‘trait’ scores did not change
significantly either on the non-treatment or treat-
ment day (Table 1). No significant change in ‘state’
score was observed with time on the non-treatment
day for individual Trials but pooling the data for
both Trials and subjecting it to paired analysis
indicated a small but significant reduction
(3.571.2, Po0.01) (Table 1).
There was a profound decrease in the ‘state’
score following treatment with reflexology; the
post-treatment value was significantly lower (all
participants, independent t-test Po0.001) than the
time-matched value observed on the non-treat-
ment day (Table 1) and within-group analysis also
identified a pre–post treatment change (10.47
1.7, Po0.001). Closer within-group analysis of the
20 items that comprised the ‘state’ component of
the STAI identified significantly reduced scoring in
11 items (Q1,2,3,4,5,7,15,16,17,19 and 20) consis-
tent with an increased feeling of ease and a
reduction in anxiety.
Systolic blood pressure, diastolic blood
pressure and resting PR following reflexology
treatment
No significant time-related changes in systolic
blood pressure, diastolic pressure or PR were
 ARTICLE IN PRESS
A pilot study in healthy individuals 141

Table 1 Comparison of time-matched data (mean7sem) for ‘state’ and ‘trait’ anxiety scores from the non-
treatment and treatment days, for both trials.

‘State’ anxiety ‘Trait’ anxiety

12.00 h 13.15 h 12.00 h 13.15 h

Trial A
Non-treatment day 36.171.8 33.171.3 41.171.8 39.471.7
n ¼ 19
Treatment day 36.172.0 26.271.2 39.671.6 38.072.0
n ¼ 19
Trial B
Non-treatment day 37.473.8 32.873.0 40.973.5 41.073.9
n¼8
Treatment day 40.373.8 28.773.2 43.873.2 42.875.0
n¼6
Both trials
Non-treatment day 36.571.6 33.071.2 41.071.6 39.971.6
n ¼ 27
Treatment day 37.171.5 26.871.1 40.671.5 39.271.9
n ¼ 25
Between group differencea Not significant Po0.001 Not significant Not significant
a
Difference between groups shown. Difference within groups between 12.00 and 13.15 h: Po0.05, Po0.01, Pp0.001.

observed within individuals on the non-treatment developed a methodology for measurement of

day (Table 2). Although no significant between-
group differences were observed on the treatment
day, a within-group comparison identified that
reflexology significantly reduced systolic blood
pressure (all participants, 6.371.6 mmHg,
Po0.001) and PR (all participants, 7.971.3
beats/min, Po0.001), but not diastolic blood
pressure (all participants, 2.471.3 mmHg, NS).
Salivary cortisol and melatonin following
reflexology treatment
No statistically significant differences in salivary
cortisol or melatonin concentrations or the rele-
vant peaks were evident between the treatment
and non-treatment days in either Trial A or Trial B
at any of the time points measured (Tables 3 and 4).
Discussion
There is a dearth of scientific-based evidence to
consolidate therapeutic claims of complementary
treatments in healthcare settings. Such evidence
will be crucial in aiding informed decision making
for patients and future health strategies involving
complementary therapies, including reflexology.
This pilot study involving healthy subjects has
psychometric, biometric and hormonal levels be-
fore and following reflexology treatment. These
data have provided the necessary information to
enable us to proceed to a study of efficacy of
reflexology in breast cancer patients who have
been shown to display different cortisol, melato-
nin, biometric and anxiety baseline data.40 The
methodology proved to be non-invasive, of minimal
disruption, accurate and suitable for transfer to a
larger study to acquire multidisciplinary scientific
data to help clarify the efficacy and impact of
reflexology.
In addition to methodological advances, we have
also shown a highly significant decrease in state
anxiety following reflexology in healthy subjects.
This reduction was considerably more pronounced
than that observed in the non-treatment group who
simply relaxed in a similar environment: relaxation
and support were controlled for as these have been
shown to affect salivary cortisol.41 Closer analysis
of the types of questions in which there were
significant changes in participants’ mean responses
suggest that feelings of tension and worry were
reduced following reflexology, whereas feelings of
well being (such as calmness, security, relaxation)
were increased.
Baseline state and trait anxiety scales taken at
noon were significantly correlated but there was no
evidence for an influence of ‘trait’ anxiety on the
 ARTICLE IN PRESS
142 A.J. Mc Vicar et al.

Table 2 Comparison of time-matched data (mean7sem) for cardiovascular parameters for both trials.

Non-treatment day Treatment day

12.00 h 13.15 h 12.00 h 13.15 h

Trial A
Systolic BP mmHg 126.975.5 122.774.4 130.473.4 124.573.7
n ¼ 13
Diastolic BP mmHg 69.972.8 68.572.3 74.572.1 71.972.5
n ¼ 13
Pulse beats/min 66.372.0 62.772.0 73.172.8 63.371.6
n ¼ 13
Trial B
Systolic BP mmHg 126.974.9 123.373.9 126.774.9 119.674.5
n ¼ 11
Diastolic BP mmHg 76.873.5 73.472.8 75.672.5 73.472.4
n ¼ 11
Pulse beats/min 68.472.4 65.472.2 68.471.7 62.671.6
n ¼ 11
Both trials
Systolic BP mmHg 128.173.6 123.072.9 128.772.9 122.572.9
n ¼ 24
Diastolic BP mmHg 73.172.3 70.771.8 75.071.6 72.671.7
n ¼ 24
Pulse beats/min 67.371.5 63.971.5 70.971.8 63.071.1
n ¼ 24

Time-matched, treatment vs. non-treatment differences between groups not significant. Within-group differences between
12.00 and 13.15 h: Po0.05, Po0.01, Pp0.001.

Table 3 Time-matched data for salivary cortisol (mg/ml; means7sem) on non-treatment and treatment days,
for each trial.

12.00 h 13.00 h 20.00 h 23.00 h Waking next day

Trial A
Non-treatment day 0.1570.03 0.1370.04 0.0670.01
n ¼ 10
Treatment day 0.1570.02 0.1570.03 0.0770.02
n ¼ 10
Trial B
Non-treatment day 0.2670.09 0.3370.11 0.3770.07
n¼8
Treatment day 0.2470.10 0.3070.11 0.3970.05
n¼8

No significant differences were seen at any time point either between or within groups.

‘state’ response to reflexology. The changes may be
a real effect of the therapy and so suggest that in
healthy participants the state-scale of the STAI is
sensitive to the effects of treatment. Whether the
effects resulted from the impact of reflexology or
massage per se cannot be ascertained as the
additional benefit of thigmotropism (i.e. respond-
ing to physical contact)42 was not specifically
controlled for in this study, though it can intrinsi-
cally produce supportive effects and even reduce
anxiety.43 It may be that touch alone has a state
anxiety reducing effect.
In addition, the control group were placed
together in the same room and although they were
staff and students and thus ‘familiar faces’ this
situation may have caused anxiety to some parti-
cipants. To maximise relaxation we created an
ambience, played relaxing music and asked the
 ARTICLE IN PRESS
A pilot study in healthy individuals
Table 4 Time-matched data for salivary melatonin (pg/dl, means7sem) on non-treatment and treatment days,
for each trial.
12.00 h 13.15 h
Trial A
Non-treatment day 2.6470.88 3.2071.64
n ¼ 10
Treatment day 0.7470.34 2.3170.93
n ¼ 10
Trial B
Non-treatment day 0.8170.19
n¼8
Treatment day 1.4970.65
n¼8
No significant differences were seen at any time point between or within groups.
participants to sit quietly. In this environment we
saw no evidence of collective increased anxiety in
fact there was a small reduction in state score on
the non-treatment day. The main study that will
follow this pilot will incorporate a design to avoid
strangers being placed in the same room as a
control group.
Trait anxiety, on the other hand was not
significantly affected by the reflexology (nor were
changes observed in the non-treatment data). This
is an expected result, since trait anxiety, unlike
state, is not a transitory state and any changes in
trait anxiety would not be expected in the
time-course of this study. From a methodological
viewpoint, the divergence of the state anxiety and
trait anxiety data following reflexology in this
particular setting supports a sensitivity of the STAI
tool and also reduces concerns over the reapplica-
tion of the tool so soon after the initial scores were
taken.
We have also shown that systolic BP and PR are
reduced following reflexology. These responses are
consistent with a reduction in sympathetic activity,
which would support a reduction in state anxiety.
However, reflexology appeared to have no immedi-
ate or delayed effect on the secretion of cortisol
and melatonin. Thus, in healthy individuals changes
in cognitive stress perceptions may not be simulta-
neously translated into endocrine responses. The
lack of correlation between hormone concentra-
tions and state or trait STAI scores could also
support dissociation with cognitive appraisal, but
‘spot’ hormone concentrations at specific time
points may not be an accurate evaluation of
stress-related secretion. However, the lack of an
observable impact on diurnal patterns of hormone
secretion also suggests the dissociation. It is also of
note that baseline measures and the application of
reflexology were at a time when secretion rates
143
20.00 h 23.00 h Waking next day
6.672.38
2.8170.02
7.9171.88 5.6572.66
5.0971.30 2.9071.41
were already low and hence any responses con-
sistent with a reduction in stress might not be
discernible. A major consideration for the follow-
up study involving cancer patients will be that
changes in secretion may be more pronounced as
chronic stress levels appear to alter the secretion
patterns of stress-related hormones. If reflexology
can help to maintain and/or restore the normal
cortisol and melatonin secretion patterns, and to
reduce stress and the physiological and biochemical
effects of stress, then patient outcomes may be
improved. Through evaluation of the responses in
healthy individuals this study has provided valuable
parameters and a suitable methodology for asses-
sing the responses of cancer patients in a subse-
quent study.
Potential limitations of this pilot are encom-
passed in the reliable measurement of salivary
hormones. The range of time points, information on
food intake and health behaviours helped to
minimise the propensity for variation in cortisol
and melatonin between individuals. In addition it
cannot be ascertained whether the effects resulted
from the impact of reflexology or massage per se.
However, the study does exclude the significance of
the therapeutic relationship that builds over time
with one practitioner, as each participant only
received one reflexology treatment.
Conclusions
This study has defined safe non-invasive, accurate
and multidisciplinary methodological standards to
begin evidenced-based research into the efficacy of
complementary therapies for cancer patients and
other healthcare settings.
By evaluating psychometric and biometric
changes following reflexology, this pilot study has
 ARTICLE IN PRESS
144
also showed that reflexology significantly reduced
‘state’ anxiety and related cardiovascular para-
meters, but had no significant effect on stress-
related secretion of cortisol or melatonin in healthy
individuals, at the time points chosen.
Acknowledgements
This work was supported by Anglia Ruskin University
and Helen Rollason Heal Cancer Care Charity.
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