Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality

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DOI: 10.1007/s00394-011-0263-7 · Source: PubMed
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Background: Tart Montmorency cherries have been reported to contain high levels of phytochemicals including melatonin, a molecule critical in regulating the sleep-wake cycle in humans. Purpose: The aim of our investigation was to ascertain whether ingestion of a tart cherry juice concentrate would increase the urinary melatonin levels in healthy adults and improve sleep quality. Methods: In a randomised, double-blind, placebo-controlled, crossover design, 20 volunteers consumed either a placebo or tart cherry juice concentrate for 7 days. Measures of sleep quality recorded by actigraphy and subjective sleep questionnaires were completed. Sequential urine samples over 48 h were collected and urinary 6-sulfatoxymelatonin (major metabolite of melatonin) determined; cosinor analysis was used to determine melatonin circadian rhythm (mesor, acrophase and amplitude). In addition, total urinary melatonin content was determined over the sampled period. Trial differences were determined using a repeated measures ANOVA. Results: Total melatonin content was significantly elevated (P < 0.05) in the cherry juice group, whilst no differences were shown between baseline and placebo trials. There were significant increases in time in bed, total sleep time and sleep efficiency total (P < 0.05) with cherry juice supplementation. Although there was no difference in timing of the melatonin circardian rhythm, there was a trend to a higher mesor and amplitude. Conclusions: These data suggest that consumption of a tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and quality in healthy men and women and might be of benefit in managing disturbed sleep.
Effect of tart cherry juice (Prunus cerasus) on melatonin levels
and enhanced sleep quality
Glyn Howatson
Phillip G. Bell
Jamie Tallent
Benita Middleton
Malachy P. McHugh
Jason Ellis
Received: 7 July 2011 / Accepted: 10 October 2011
Ó Springer-Verlag 2011
Background Tart Montmorency cherries have been
reported to contain high levels of phytochemicals including
melatonin, a molecule critical in regulating the sleep-wake
cycle in humans.
Purpose The aim of our investigation was to ascertain
whether ingestion of a tart cherry juice concentrate would
increase the urinary melatonin levels in healthy adults and
improve sleep quality.
Methods In a randomised, double-blind, placebo-con-
trolled, crossover design, 20 volunteers consumed either a
placebo or tart cherry juice concentrate for 7 days. Measures
of sleep quality recorded by actigraphy and subjective sleep
questionnaires were completed. Sequential urine samples
over 48 h were collected and urinary 6-sulfatoxymelatonin
(major metabolite of melatonin) determined; cosinor anal-
ysis was used to determine melatonin circadian rhythm
(mesor, acrophase and amplitude). In addition, total urinary
melatonin content was determined over the sampled period.
Trial differences were determined using a repeated measures
Results Total melatonin content was significantly ele-
vated (P \ 0.05) in the cherry juice group, whilst no dif-
ferences were shown between baseline and placebo trials.
There were significant increases in time in bed, total sleep
time and sleep efficiency total (P \ 0.05) with cherry juice
supplementation. Although there was no difference in
timing of the melatonin circardian rhythm, there was a
trend to a higher mesor and amplitude.
Conclusions These data suggest that consumption of a
tart cherry juice concentrate provides an increase in
exogenous melatonin that is beneficial in improving sleep
duration and quality in healthy men and women and might
be of benefit in managing disturbed sleep.
Keywords Tart cherries Melatonin Sleep Recovery
Tart Montmorency cherries (Prunus cerasus), rich in
numerous phytochemicals, provide a range of health benefits
that include reduction in symptoms associated with gout [1],
down-regulation of circulating inflammatory markers [2],
analgesic effects following long-distance running [3],
reduced oxidative stress [4], improved recovery following
damaging exercise [57] and recently, improved sleep
quality in late-life insomnia [8]. Mechanistically, it is
thought the phenolic compounds within tart cherries act as
‘free radical’ scavengers that reduce oxidative stress [2]. In
addition, the anti-inflammatory properties [9] of tart cherries
have been reported to be at a level comparable to a number of
non-steroidal anti-inflammatory drugs [10]. In particular, the
anthocyanin content of tart cherries, which compares
G. Howatson (&) P. G. Bell J. Tallent J. Ellis
School of Life Sciences, Northumbria University,
Northumberland Building, Newcastle upon Tyne NE1 8ST, UK
e-mail: glyn.howatson@northumbria.ac.uk
G. Howatson
Centre for Aquatic Research, Department of Zoology,
University of Johannesburg, Johannesburg, South Africa
B. Middleton
Centre for Chronobiology, Faculty of Health and Medical
Sciences, University of Surrey, Guildford, UK
M. P. McHugh
Nicholas Institute of Sports Medicine and Athletic Trauma,
Lenox Hill Hospital, New York, NY, USA
Eur J Nutr
DOI 10.1007/s00394-011-0263-7
favourably with other fruits such as sweet cherries [11],
seems to be of most interest, and these are likely to be
responsible for the anti-oxidative and anti-inflammatory
A number of recent studies have shown that consump-
tion of tart cherry juice can accelerate recovery following
strenuous exercise [57], where temporary perturbations in
inflammation and oxidative stress can occur. These
recovery effects have been attributed to the actions of the
antioxidant and anti-inflammatory phytochemicals con-
tained in tart cherries. Pigeon et al. [8] anecdotally reported
claims of improved sleep with cherry juice supplementa-
tion in participants from a previous trial [6]. Interestingly,
in addition to the aforementioned phenolic compounds, tart
cherries contain high concentrations of melatonin [12].
Melatonin has a strong influence on the sleep-wake cycle in
humans and is associated with sleep-promoting properties
[13]. Physiologically, endogenous melatonin secretion
adjusts according to the light/dark cycle and can directly
influence nocturnal core temperature and hence facilitate
the propensity for sleep [14]. Additionally, a strong posi-
tive relationship between increased melatonin and total
sleep time in healthy, young individuals has been previ-
ously demonstrated [15]. Interestingly, the balance of evi-
dence would suggest that exogenous melatonin in the
treatment of insomnia is equivocal at best; however, there
is a good body of support for melatonin use in managing
circadian rhythm disturbance, such as those seen from
travelling time zones [16].
In a recent study, the efficacy of tart cherry juice con-
sumption on sleep indices in a population with late-life
insomnia was examined [8]. They reported modest
improvements in subjective quality of sleep; however, no
objective measures of sleep, such as actigraphy, were
taken, and the potential mechanisms responsible for the
reported sleep improvements (e.g. melatonin) were
impossible to discern. The authors [8] speculated that
increased dietary melatonin associated with consumption
of tart cherry juice might be responsible for the changes.
However, there is an alternative hypothesis; the anti-
inflammatory properties of tart cherries may have some
influence on the pro-inflammatory cytokines involved in
sleep regulation [17]. Given the potential benefits of tart
cherry juice in delivering exogenous melatonin and
improving sleep quality, we hypothesised that the con-
sumption of a tart cherry juice concentrate in young,
healthy adults would increase urinary 6-sulfatoxymelatonin
and improve indices of sleep quality. Therefore, the aim
of this investigation was to examine the effects of
tart Montmorency cherry juice concentrate on urinary
6-sulfatoxymelatonin and sleep quality using a double-
blind, placebo-controlled, crossover design.
Following institutional ethical approval from the School of
Life Sciences Ethics Committee at Northumbria Univer-
sity, UK in accordance with the Helsinki Declaration, 20
healthy men (n = 10) and women (n = 10) volunteered to
participate. The mean (±SD) age, height, body mass and
BMI were 26.6 (±4.6) years, 1.71 (±0.10) m, 72.5 (±15.0)
kg and 24.7 (±3.5) kg m
, respectively. The age range
was restricted to 18–40 years to reduce the potential for
age-related sleep disturbances that have been reported in
older adults [13]. In addition, all volunteers were physi-
cally active and participated in moderate physical exercise
for at least 150 min/week. After being informed of the
experimental procedures, participants were asked to com-
plete a health screening questionnaire to ascertain contra-
indications to participation (prescription medicines, sleep
disturbance, special dietary habits, shift work or underlying
medical pathology), and volunteers then provided written
informed consent.
Experimental overview and study design
Participants were supplemented with a tart cherry juice
concentrate or placebo in a randomised, double-blind,
placebo-controlled, crossover study design, during normal
daily routine. Dependent variables were urinary 6-sul-
phatoxymelatonin (aMT6s), diet recall, objective activity
recorded through actigraphy (variables) and subjective
sleep quality. A schematic of the study design is presented
in Fig. 1. Initially, participants provided sequential urinary
voids across a 48 h period (days 1 and 2) in order to ana-
lyse baseline measures of aMT6s. Over the same 2-day
period, participants were issued with an activity monitor
and completed online daily diet recalls and a sleep diary
immediately following morning awakening. Participants
then continued to complete the questionnaires and diaries
and wear the activity monitors for the remainder of the trial
Following the 48-h baseline period, participants were
randomly assigned to either the tart cherry juice concen-
trate or placebo (starting on day 3) for a period of 7 days;
this was based on loading phases from previous studies
showing efficacy using cherry juice [58]. Participants
were instructed to consume two servings of either tart
cherry juice concentrate or fruit-flavoured cordial each day,
for 7 days. In the last 48 h of this supplementation period,
urine was again collected in an identical manner as pre-
viously described for the baseline period. Following a
14-day washout period, participants repeated the baseline
Eur J Nutr
and experimental period whilst consuming the other
Dietary control
All volunteers completed a dietary recall throughout the
baseline and supplementation periods. Participants were
asked to replicate their diet during the first supplementation
period as closely as possible during the second period in
order to standardise the dietary intake between trials.
Additionally, in order to isolate dietary melatonin as clo-
sely as possible, participants were issued with a list of
foods that are known to contain or influence melatonin and
were subsequently asked to abstain from consuming these
for the duration of the trial. Portions of foods thought to
contain antioxidants were totalled for each day then aver-
aged across the experimental period.
Prior to starting the experiment, participants were informed
that the trial was to ascertain the influence of two fruit con-
centrates on melatonin levels and sleep quality; however, the
nature of the trial regarding tart cherry juice concentrate was
only revealed when the study had been completed. A serving
of 30 mL of tart Montmorency cherry juice (Prunus cerasus)
concentrate (Cherry Active, Sunbury, UK) was consumed
within 30 min of wakening and 30 min before the evening
meal on each of the 7-day supplementation periods. Each
30 mL serving was estimated to contain the equivalent of
approximately 90–100 tart cherries and was diluted with
approximately 200 mL of water. An independent laboratory
(Atlas Bioscience Inc., Tuscan, AZ) conducted melatonin
analysis of the cherry juice concentrate adapting an estab-
lished HPLC method [18]. The concentration of melato-
nin was 1.42 lgmL
, which equates to a dose of
*42.6 lg/30 mL serving or *85.2 lg day
. Literature
suggests that daily melatonin doses of *0.5–5 mg confer a
positive effect in managing disturbed sleep rhythm [19].
In addition, other active compounds contained within the tart
cherry juice were verified by the aforementioned laboratory
and included anthocyanins such as malvidin, cyanidin, pe-
largonidin, peonidin, delphinidin, petunidin (total anthocy-
anin content = 9.117 mg mL
), vitamin A—as beta-
carotene (22.64 IU mL
) and vitamin C—ascorbic acid
(0.324 mg mL
The placebo was a commercially available, economy,
mixed fruit cordial (containing less than 5% fruit) that was
reported to contain no melatonin or anthocyanins and a
trace of vitamin C. Participants were instructed to take the
same dose (30 mL) diluted with *200 mL of water.
Dependent variables
Urine collection and analysis
Sequential urinary voids were collected 48-h periods to
ensure the entire circadian cycle was captured during
each part of the trial to allow for cosinor analysis that
provided measures of acrophase, mesor and amplitude.
Urine was collected in a sterilised measuring cylinder.
Void volume, time and date were recorded, before a
10 mL aliquot of urine was retained, refrigerated and
returned to the laboratory the following morning for
labelling and immediate storage at -80 °C for later anal-
ysis for urinary aMT6s.
Urinary 6-sulphatoxymelatonin, aMT6s
Urinary 6-sulphatoxymelatonin, aMT6s (the major metab-
olite of melatonin) was analysed in duplicate using a
radioimmunoassay [20]. Samples belonging to the same
participant were measured in the same assay run; the intra-
assay coefficient of variation was \8%; the limit of
detection was 0.25 ng mL
. Evaluation of aMT6s profiles
was performed using cosinor analysis, based upon the least
square approximation of the time series using a cosine
function with a period of 24 h [21]. Parameters obtained
Fig. 1 A schematic outlining
the implemented protocol.
Supplementation periods
consisted of two 30-mL
servings per day of either a tart
cherry juice concentrate of
Eur J Nutr
from this analysis included the following: acrophase time:
the time of peak aMT6s concentration or the maximum of
the fitted cosinor function; mesor: the mean aMT6s values
for all samples included in the cosinor anlaysis; and
amplitude: the difference between mesor and peak aMT6
concentrations. Acrophase time was classed as normal if it
occurred between midnight and 06:00 h [22]. ‘Goodness of
fit’ measures were used to determine the validity of the
cosinor-derived indices: (1) the % rhythm or variability
accounted for by the cosine curve: 100% rhythm = all data
points fall on the cosine curve and 0% rhythm = none of
the data points fall on the cosine curve and (2) the likeli-
hood of data points fitting a straight line as opposed to a
cosine curve, expressed as a P value. Data were considered
acceptable if the cosinor fit was significant (P B 0.05) and
the % rhythm C50% [21]. Finally, the total aMT6s
excreted per 24 h was calculated and a mean for each 48-h
collection period determined.
Polysomnography (PSG) offers the most accurate assess-
ment of sleep and sleep quality; however, given the nature
of the study, we utilised actigraphy that has been shown to
be reliable and has good agreement with PSG [23]. Par-
ticipants were issued with actigraphy that was worn on the
wrist of the non-dominant arm (Actiwatch 7, CamnTech,
Cambridge, UK). These were worn for the duration of the
study and removed only for bathing, showering or other
aquatic activities. Participants were asked to activate the
marker function on the watch when getting into bed and
when rising the following morning. Analysis was made on
sleep efficiency (SE), sleep onset latency (SOL), time in
bed (TIB), fragmentation index (FRAGI), total sleep time
(TST) and sleep efficiency total (SET); these variables
were calculated using Actiwatch software (Actiwatch,
CamnTech, Cambridge, UK). The mean values for each
sample period were used for data analysis.
Subjective measures
Online subjective sleep diaries were reported immediately
following awakening each day during both baseline and
trial periods. This commonly used self-reporting method
tool has been to be a reliable (90%) measure [24] and
allowed calculation of the following: SE, SOL, wake after
sleep onset (WASO), napping (NAP), TST and SET [25].
Statistical analyses
Values are reported as mean (±SD), unless otherwise sta-
ted. The cosinor data, total aMT6s and all quantitative
(actigraphy)- and qualitative (questionnaire)-dependent
sleep variables were analysed with a repeated measures
ANOVA (condition, placebo vs. cherry juice 2; time, pre
vs. post). In addition, 95% confidence intervals were also
determined to illustrate the magnitude of change. Finally,
baseline measures were examined for differences using a
paired samples t test. Significance was set at an alpha level
of 0.05.
Baseline measures taken before the placebo and cherry
juice trials were not different for any of the dependent
variables (P [ 0.05). All variables returned an observed
power value ranging from 0.156 to 0.999. Although we
did not quantify all the food consumption using dietary
analysis, participants reported a similar diet across the
trials. In an attempt to quantify this more fully, we
recorded the number of food portions thought to contain
antioxidants (including melatonin) across the supplemen-
tation periods, 22.8 versus 22.4 for the cherry juice and
placebo groups, respectively. A paired samples t test
showed no significant differences between groups
(t = 1.162, P = 0.259).
Urinary 6-sulphatoxymelatonin (aMT6s)
The baseline measures preceding the placebo and cherry
juice supplements were not different (t
= 0.921,
P = 0.369). The repeated measures ANOVA showed a
significant trial effect (F = 23.0, P \ 0.001). A significant
interaction (F = 23.0, P \ 0.001) was also found and
post hoc analysis revealed that the cherry juice trial was
significantly greater than baseline and placebo trials
(P \0.001; 95% CI = 2,828–5,393 ng and 2,519–5,450 ng,
respectively); there was no difference between baseline or
placebo groups (Fig. 2).
Despite the significant increase in total urinary aMT6 s,
the cosinor analysis examining circadian rhythm of aMT6s
showed no differences between trials for any variable
(Table 1). Cosinor analysis relies on a significant ‘fit’ of
the melatonin response; of the 80 sets of data collected,
22.5% (n = 18) were excluded because they did not sig-
nificantly fit according to the cosinor algorithm. Of the
remaining data, there were small non-significant rises in the
amplitude and mesor in the cherry juice trial, whilst the
acrophase remained largely unchanged throughout. A
representative example where urinary voids were collected
for a single participant at similar times of the day between
the placebo and cherry juice trials is presented in Fig. 3;
these data span the circadian changes in aMT6s over
sequential 48-h periods.
Eur J Nutr
Sleep indices: subjective questionnaire and actigraphy
There was a 100% completion rate for the sleep ques-
tionnaires. There was no differences across the different
trials for SET, SOL, TST and WASO; however, napping
time did show a significant trial and interaction effect
(F = 5.591, P = 0.029), with significantly less napping
time in the cherry juice trial compared to baseline and
the placebo trials (P B 0.031; 95% CI = 0.7–13.6 and
0.7–11.1 min, respectively), and there were no differences
between baseline measures and the placebo trial (Table 2).
Whilst all participants wore the activity monitor for the
duration of the trials, 17 out of 80 trials (21.3%) were
excluded from analysis due to missing data. There were no
differences in SOL and FRAGI; however, there was a sig-
nificant trial and interaction effect for TIB (F = 7.056,
P = 0.016) where cherry juice significantly increased time
in bed compared to both baseline and placebo trails
(P B 0.017; 95% CI = 4.5–45.2 and 4.7–40.2 min,
respectively). Furthermore, TST showed a trial and inter-
action effect (F = 11.189, P = 0.003), where the cherry
juice trial was significantly greater TST than baseline and
placebo trials (P B 0.003; 95% CI = 15.2–39.7, 14.7–63.6,
respectively). In addition, SET showed significant trial and
interaction effects (F = 5.410, P = 0.031), where the
cherry juice trial was greater than the baseline and placebo
trials (P B 0.017; 95% CI = 2.1–7.5 and 0.5–9.4, respec-
tively). A summary of these data is presented in Table 3.
The aim of this investigation was to ascertain whether the
supplementation of tart Montmorency cherry juice con-
centrate would (1) increase the urinary aMT6s content
and (2) improve the objective and subjective sleep indices
of young, healthy individuals. We hypothesised that
urinary aMT6s would rise and that sleep parameters
would improve as a consequence. This is the first inves-
tigation to demonstrate that dietary tart cherry juice
concentrate increases urinary melatonin levels and pro-
vides improved sleep time and quality in a healthy adult
The sleep diary information showed that napping time
decreased with the administration of cherry juice, whereas
the actigraphy showed an increase in TIB, TST and SET, a
global measure of sleep quality. Notwithstanding the rel-
atively low baseline SET observed from the actigraphy in
these apparently good sleepers, the cherry juice nonetheless
showed a 5–6% increase in SET, which likely to be
influenced by the significant increase in TST. In addition,
given that napping decreased and total time in bed also
increased during the cherry juice trial, this is perhaps
unsurprising. What is also interesting to note is that there
Fig. 2 Mean (±SEE) urinary melatonin (aMT6) secretion for the
group following baseline placebo (control), placebo, baseline cherry
juice (control) and cherry juice trials.Asterisk denotes that cherry
juice supplementation resulted in significantly greater aMT6s than
baseline and placebo trials (P B 0.05)
Table 1 Mean (±SD) cosinor analysis based on melatonin circadian rhythm for all experimental conditions
Baseline placebo Placebo Baseline cherry juice Cherry juice
Mesor (ng 9 h
) 17.98 (6.04) 19.17 (7.37) 18.64 (9.76) 21.59 (6.85)
Amplitude (lg 9 h
) 27.39 (15.78) 27.54 (8.37) 27.05 (10.72) 28.57 (15.01)
Acrophase (time) 4.03 (1.03) 3.55 (1.22) 4.05 (1.40) 4.01 (1.01)
Of the possible 80 data sets, 18 did not significantly fit the cosinor curve and were excluded from the analysis
Fig. 3 A representative example of a single subject’s circadian
rhythm for urinary melatonin (aMT6s) during the placebo and cherry
juice trials over sequential 48-h periods
Eur J Nutr
were non-significant trends towards decreased SOL, which
is also likely to have influenced the SET.
Only one study has investigated tart Montmorency
cherry juice and sleep parameters (a fresh pressed cherry
juice blended with apple juice, as opposed to a pure cherry
juice concentrate) [8]. They found that elderly individuals,
with moderate/severe insomnia, reported improved sleep
quality, and it was hypothesised that this was due to the
increased exogenous melatonin content afforded by the
cherry juice. Unfortunately, they did not measure melato-
nin; however, data from our investigation lend additional
evidence that improved sleep quality is mediated by the
increase in dietary melatonin contained within the cher-
ries. Interestingly, a recent addition to the literature [26]
examined the increase in melatonin content from dietary
intake of Jert Valley cherries (seven varieties, none of
which were Montmorency tart cherries). They showed that
in a very small population of middle-aged and elderly
volunteers, there was an increase in urinary melatonin and
some modest improvements in sleep parameters. This
investigation [26] based its observations on the first
morning void only, whereas all urinary voids were captured
for a 48-h period during each part of the current trial. This
approach, whilst still having limitations, allows for cosinor
analysis and tracking of the circadian rhythm and provides
a more comprehensive picture of the dietary effects of
cherries on melatonin metabolism across the course of the
day. This is especially important when one considers that
the half-life of melatonin is relatively short and it is pos-
sible to miss fluctuations in melatonin throughout the day.
Further, there is no indication in the aforementioned
studies [8, 25] of an experimental control or record of
dietary intake, which makes interpretation of the data
problematic. Although we were not able to quantify the
exact nutritional content for each subject, food intake was
estimated. Participants replicated diet as closely as possible
from trial to trial. This was based on number of portions
thought to contain antioxidants—there were no differences
between trials. Support for the efficacy of this approach can
be seen by the fact that aMT6s and sleep parameters were
unchanged in baseline and placebo trials, whereas aMT6s
was significantly elevated in the cherry juice trial. Given the
dietary control used in the current investigation, coupled
with the significant changes melatonin, we can add support
to research showing cherries [26], and specifically in this
case, Montmorency cherries improve sleep parameters in
healthy individuals, which is likely due to the increase in
dietary melatonin. These data support previous work
showing improved sleep in healthy younger adults with
exogenous melatonin supplementation [14]; but addition-
ally, it provides a potential alternative to traditional mela-
tonin supplementation in the form of a functional food.
Table 2 Subjective sleep questionnaire variables for all conditions; values are mean (±SD)
Baseline placebo Placebo Baseline cherry juice Cherry juice
SE (%) 89.3 (7.3) 91.7 (4.0) 90.0 (6.2) 91.1 (4.9)
SOL (mins) 40.3 (31.6) 39.5 (23.2) 39.8 (25.6) 34.2 (20.5)
WASO (mins) 36.0 (33.0) 19.2 (31.2) 28.8 (30.6) 27.6 (28.2)
Naps (mins) 9.0 (15.1) 7.8 (10.7) 8.6 (13.2) 1.9 (3.5)*
TST (mins) 447 (60) 476 (31) 452 (49) 475 (30)
SET (%) 88.1 (6.8) 90.4 (4.4) 89.4 (5.8) 90.7 (4.9)
SE sleep efficiency, SOL sleep onset latency, WASO wake after sleep onset, total SET sleep efficiency total, TST total sleep time
* Denotes significantly different from all other conditions (P B 0.05)
Table 3 Actigraphy variables for all conditions; values are mean (± SD)
Baseline placebo Placebo Baseline cherry juice Cherry juice
SE (%) 82.8 (15.7) 84.1 (5.8) 83.9 (7.8) 86.8 (3.6)
SOL (mins) 28.9 (21.3) 30.5 (34.8) 29.1 (26.8) 21.4 (11.1)
Time in bed (mins) 491.8 (36.7) 492.2 (40.6) 490.0 (32.9) 514.7 (17.0)*
FRAGI (AU) 36.8 (8.2) 35.2 (9.3) 35.8 (8.9) 34.2 (7.6)
TST (mins) 392 (28) 380 (49) 385 (30) 419 (22)*
SET (%) 77.5 (5.9) 77.4 (8.5) 76.8 (6.9) 82.3 (3.6)*
Of the possible 80 data sets, 17 were excluded due to technical issues
SE sleep efficiency, SOL sleep onset latency, FRAGI fragmentation index, total SET sleep efficiency total, TST total sleep time
* Denotes significantly different from all other conditions (P B 0.05)
Eur J Nutr
The secretion of melatonin is influenced by light/dark
cycles and ultimately is instrumental in the sleep/wake
cycle [13]. From a physiological perspective, given that
endogenous melatonin influences core temperature and
facilitates sleep [14], it makes the expectation tenable that
increased exogenous melatonin will further facilitate
changes in core temperature and hence be responsible for
the improvements in sleep quality. Further work examining
the potential physiological outcomes (such as core tem-
perature and EEG in polysomnographic paradigms) from
exogenous melatonin, specifically from functional foods,
would be useful additions to the literature. In an attempt to
elucidate the relationship between the change in SET and
the change in melatonin, we conducted a Pearson’s corre-
lation coefficient analysis and found that there was a
modest relationship (r = 0.416, P [ 0.05), indicating that
other factors may influence the variables associated with
sleep quality. Importantly, a limitation with our data is that
*21% of the actigraphy data were missing, which may
have influenced this correlation and also the non-significant
trends in other actigraphy-dependent variables. Further-
more, 50% of our sample was women, and it is conceivable
that they were in different stages of the menstrual cycle,
which may also influence core temperature and hence the
propensity for sleep disturbance [27]. Future research
might wish to consider this issue in future experiments.
Melatonin is not the only candidate mechanism, given
that sleep regulation is also influenced by pro-inflammatory
cytokines [17]. Tart cherries have been shown to contain
numerous phenolic compounds that have anti-inflammatory
and antioxidant properties that can increase antioxidant
capacity [5, 26]. Furthermore, cherry juice has been shown
to decrease oxidative stress and inflammation following
strenuous exercise [5] making it possible that these anti-
oxidant and/or anti-inflammatory properties modulated
indices of sleep in this study, although this remains to be
demonstrated in an experimental model.
It has been previously speculated that the positive
effects on sleep seen from tart cherries might be due to
improvements in circadian regulation [8]. We observed no
changes in mesor, amplitude or acrophase, although there
was a trend towards a higher mesor (essentially equating to
the mean value across the circadian cycle). This is perhaps
not surprising given that the total urinary melatonin did
increase with cherry juice supplementation. An obvious
difference with the previous work lies within the subject
populations; Pigeon et al. [8] used older adults suffering
from moderate/severe insomnia and did not measure cir-
cadian rhythm or melatonin, whereas the current investi-
gation used asymptomatic younger adults (B37 years) and
did measure circadian rhythm and melatonin. Conceivably,
cherries might help regulate circadian rhythm in those with
disturbed sleep [8]; however, our evidence shows (from
cosinor analysis) that despite increased total sleep time and
improved sleep quality, this is not the case in asymptom-
atic, healthy younger adults. Notwithstanding this, aMT6s
levels are increased with tart cherry juice consumption, but
an investigation that examines elderly individuals, perhaps
with disturbed sleep, that incorporates measures of circa-
dian rhythms and sleep quality would be a valuable addi-
tion to the literature.
In conclusion, this is the first study to show direct evi-
dence that dietary supplementation with a tart Montmorency
cherry juice concentrate increases circulating melatonin and
can provide modest improvements in sleep time and quality
in healthy adults with no reported disturbed sleep. Although
the interaction of other phytochemicals cannot be com-
pletely ruled out, these data provide a mechanism of action
for the previously conjectural reports of improved sleep
quality with cherry juice supplementation. Subsequently,
Montmorency tart cherry juice concentrate might therefore
present a suitable adjunct intervention for disturbed sleep
across a number of scenarios in healthy and symptomatic
Acknowledgments Gratitude is extended to Kelly Mitcheson for
her help in data collection and to CherryActive (Sunbury, UK) for
donating the cherry juice concentrate.
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  • ... Improvements across several sleep indices (i.e., increased actual sleep time and immobility, fewer awakenings and decreases in sleep onset latency) were observed, with greater improvements identified in the middle-aged and elderly groups [20]. Likewise, another separate study investigating the consumption of Montmorency tart cherry juice reported that participants spent less time napping and more time sleeping, and had higher total sleep efficiency scores compared with baseline and placebo [46]. ...
    Full-text available
    Many processes are involved in sleep regulation, including the ingestion of nutrients, suggesting a link between diet and sleep. Aside from studies investigating the effects of tryptophan, previous research on sleep and diet has primarily focused on the effects of sleep deprivation or sleep restriction on diet. Furthermore, previous reviews have included subjects with clinically diagnosed sleep-related disorders. The current narrative review aimed to clarify findings on sleep-promoting foods and outline the effects of diet on sleep in otherwise healthy adults. A search was undertaken in August 2019 from the Cochrane, MEDLINE (PubMed), and CINAHL databases using the population, intervention, control, outcome (PICO) method. Eligible studies were classified based on emerging themes and reviewed using narrative synthesis. Four themes emerged: tryptophan consumption and tryptophan depletion, dietary supplements, food items, and macronutrients. High carbohydrate diets, and foods containing tryptophan, melatonin, and phytonutrients (e.g., cherries), were linked to improved sleep outcomes. The authors posit that these effects may be due in part to dietary influences on serotonin and melatonin activity.
  • ... The concentration of aMT6s excreted in urine after lentil extract and melatonin intake confirmed the highly efficient metabolism of melatonin in rats [62]. The consumption of several fruits and vegetables previously evidenced the bioavailability of melatonin observed as an increase in the concentration of urinary aMT6s [52,63,64]. Nonetheless, the differences observed between Lentil Sprouts and MEL groups should be emphasized. ...
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    Melatonin is a multifunctional antioxidant neurohormone found in plant foods such as lentil sprouts. We aim to evaluate the effect of lentil sprout intake on the plasmatic levels of melatonin and metabolically related compounds (plasmatic serotonin and urinary 6-sulfatoxymelatonin), total phenolic compounds, and plasmatic antioxidant status, and compare it with synthetic melatonin. The germination of lentils increases the content of melatonin. However, the phenolic content diminished due to the loss of phenolic acids and flavan-3-ols. The flavonol content remained unaltered, being the main phenolic family in lentil sprouts, primarily composed of kaempferol glycosides. Sprague Dawley rats were used to investigate the pharmacokinetic profile of melatonin after oral administration of a lentil sprout extract and to evaluate plasma and urine melatonin and related biomarkers and antioxidant capacity. Melatonin showed maximum concentration (45.4 pg/mL) 90 min after lentil sprout administration. The plasmatic melatonin levels increased after lentil sprout intake (70%, p < 0.05) with respect to the control, 1.2-fold more than after synthetic melatonin ingestion. These increments correlated with urinary 6-sulfatoxymelatonin content (p < 0.05), a key biomarker of plasmatic melatonin. Nonetheless, the phenolic compound content did not exhibit any significant variation. Plasmatic antioxidant status increased in the antioxidant capacity upon both lentil sprout and synthetic melatonin administration. For the first time, we investigated the bioavailability of melatonin from lentil sprouts and its role in plasmatic antioxidant status. We concluded that their intake could increase melatonin plasmatic concentration and attenuate plasmatic oxidative stress.
  • ... With respect to clinical trials, Howatson et al. (2012) found that 1 week of supplementing morning and evening meals with 30 mL of tart Montmorency cherry juice significantly improved sleep quality and was accompanied by higher urinary levels of melatonin when compared to placebo. Similarly, Pigeon et al. (2010) and Losso et al. (2018) demonstrated sleep improvements with consumption of concentrated cherry juice intake (dosages of 235 mL and 240 mL taken twice daily, respectively). ...
    Cherries are fruits rich in phytochemical compounds, particularly anthocyanins. Thus, consumption of cherries has gained attention in both clinical and sport-related fields for their antioxidant and anti-inflammatory properties. Mechanistically, anthocyanins from the intake of cherries may help to attenuate pain and decrease blood concentrations of biomarkers linked to skeletal muscle degradation, which in turn may provide ergogenic effects. In addition, the ability of anthocyanins to balance the redox state represents a conceivable target for rheumatic disorders (e.g. gout and arthritis). Moreover, cherry anthocyanins are emerging as a potential non-pharmacological remedy for cardiometabolic diseases (hypertension and dyslipidemia). Herein, we summarize the effects of cherry intake in sport and diseases, and discuss their purported mechanisms of action to provide insights into practical application.
  • ... In humans, the consumption of controlled amounts of sweet cherries, plums, or grape juice by young, middle-aged, and elderly subjects led also to an increase in urinary aMT6s [105][106][107][108]. Additionally, the intake of sweet cherries positively influences some sleep-quality parameters, such as sleep efficiency, sleep time, and nocturnal activity in volunteers [109]. The same effects have been observed in tart cherry juice [110]. In a cross-over trial, serum melatonin levels increased up to five times after the consumption of banana, orange, or pineapple, even though these tropical fruits contain very low levels of phytomelatonin [111,112]. ...
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    Melatonin is a pleiotropic molecule with multiple and various functions. In recent years, there has been a considerable increase in the consumption of melatonin supplements for reasons other than those related with sleep (as an antioxidant, for anti-aging, and as a hunger regulator). Although the chemical synthesis of melatonin has recently been improved, several unwanted by-products of the chemical reactions involved occur as contaminants. Phytomelatonin, melatonin of plant origin, was discovered in several plants in 1995, and the possibility of using raw plant material as a source to obtain dietary supplements rich in phytomelatonin instead of synthetic melatonin, with its corresponding chemical by-products was raised. This work characterizes the phytomelatonin-rich extract obtained from selected plant material and determines the contents in phytomelatonin, phenols, flavonoids, and carotenoids. Additionally, the antioxidant activity was measured. Finally, a melatonin-specific bioassay in fish was carried out to demonstrate the excellent biological properties of the natural phytomelatonin-rich extract obtained.
  • ... Ягоды плодовых вишен сбалансированы по биохимическому составу. Наряду с витаминами, минералами и микроэлементами плоды вишни содержат такие вещества как эллаговая кислота, которая имеет кардиопротекторную, противоопухолевую, антимутагенную, антиканцерогенную активность [15], и гормон мелатонин, являющийся важным регулятором циркадного цикла [16,17]. Так же плоды вишни обладают мощным антикоагулятивным свойством за счет входящих в состав кумарина и оксикумарина. ...
  • ... Results of two randomized-crossover trials showed that supplementation of tart or Jerte Valley cherry juice led to increases in objectively measured sleep parameters. 39,40 For example, total sleep time increased by 34 min over 7 d of consuming tart cherry juice while consumption of a fruit-flavored cordial (control) was associated with a 12 min decline in total sleep time. 39 Intake of Jerte Valley cherry juice also led to increases in sleep duration from baseline, with no effects observed with the control beverage. ...
  • ... Melatonin (N-acetyl-5-methoxytryptamine) is a hormone synthesized from the amino acid tryptophan via the 5-hydroxytryptophan and serotonin pathway found in the pineal gland of animals and plant tissues (Hattori et al., 1995;Lerner et al., 1958). Melatonin treats sleep disorders by alleviating insomnia for shift workers and ameliorating jet lag by controlling the human biological clock (circadian rhythms) (Arnao and Hern andez-Ruiz, 2006;Howatson et al., 2012;Tan et al., 2002). Melatonin also displays antioxidant properties; it scavenges broad reactive oxygen species and it also increases the activity of antioxidative enzymes such as glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (Aguilera et al., 2015;Rodriguez et al., 2004). ...
    Melatonin is a neurohormone that regulates circadian rhythms in the human body. It can also be taken to alleviate insomnia and sleep disorders. Pasteurized milk is a good source of nutrients and some bioactive compounds. Recently, the growing trend of healthy foods has resulted in higher competition with regard to milk products. Functional milk has been developed with higher bioactive compounds to respond to consumer demand. High melatonin pasteurized milk was developed using selected edible grains and mulberry leaves to fortify melatonin in pasteurized milk. Melatonin and free tryptophan of fourteen edible grains and mulberry leaves were determined using HPLC-FD. Highest melatonin concentrations were observed in white sesame, sunflower and soybean (75.24, 67.45 and 56.49 ng/g dry weight (dw), with highest concentrations of free tryptophan in soybean, red bean and mung bean (2617.83, 1527.23 and 845.27 ng/g dw, respectively), while melatonin and free tryptophan contents in fresh mulberry leaves were 51.57 ng/g and 210.53 ng/g dw, respectively. Soymilk powder and mulberry leaf tea were supplemented to prepare high melatonin pasteurized milk. Results showed that chemical compositions, melatonin and free tryptophan contents significantly increased (P < 0.05) with increasing amounts of soymilk powder and mulberry leaf tea. Sensory evaluation gave highest overall liking score for the treatment consisting of mulberry leaf tea (4.00%), soymilk powder (4.00%) and milk (89.80%). Findings indicated that mulberry leaves and soybean are both good sources of melatonin and free tryptophan and can be applied to prepare high melatonin pasteurized milk.
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    Integrative and Functional Medicine Nutrition Therapy provides an evidence-based approach to oncology designed to enhance health-related quality of life and improve clinical outcomes through diet and nutrition, lifestyle interventions, detoxification, mind-body medicine, and alternative therapies. With conventional cancer treatment focused solely on the cancer, a strategy is needed to optimize outcomes that focus on the whole person. Toxicity, nutrient insufficiency and deficiency, poor diet, environmental exposures, emotional health, genetics-epigenetic potential, and low-grade inflammation are all factors affecting metabolism that contribute to both a cancer diagnosis and the outcome.
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    The high mortality of deadly virus infectious diseases including SARS, MERS, COVID-19, and avian flu is often caused by the uncontrolled innate immune response and destructive inflammation. The majority of viral diseases are self-limiting under the help of the activated adaptive immune system. This activity is cell proliferation dependent and thus, it requires several weeks to develop. Patients are vulnerable and mortality usually occurs during this window period. To control the innate immune response and reduce the inflammation during this period will increase the tolerance of patients and lowers the mortality in the deadly virus infection. Melatonin is a molecule that displays respective properties, since it downregulates the overreaction of the innate immune response and overshooting inflammation, but also promotes the adaptive immune activity. Many studies have reported the beneficial effects of melatonin on deadly virus infections in different animal models and its therapeutic efficacy in septic shock patients. Furthermore, melatonin has a great safety margin without serious adverse effects. We suggest the use of melatonin as an adjunctive or even regular therapy for deadly viral diseases, especially if no efficient direct anti-viral treatment is available.
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    Background: Recent research has demonstrated an association between dietary intake and sleep health that can influence chronic disease risk factors. A scoping review of research studies investigating dietary intake and sleep was undertaken to determine the extent and scope of research in laboratory-based, free-living and mixed settings. Additionally, this review determines how well subpopulations and geographical locations are represented and the methodologies used to assess outcome measures. Methods: Five online databases were used to identify papers published between 1970 and 2017. Included studies were those conducted in adults and reported both outcomes of interest: (i) sleep health, including sleep restriction and sleep hygiene and (ii) dietary outcomes, including altered nutrients, dietary patterns and supplements. Results: In total, 129 publications were included with the majority being dietary interventions investigating sleep outcomes (n = 109) with fewer being sleep interventions investigating and reporting dietary outcomes (n = 20). Dietary interventions were most often carried out in free-living environments, in contrast to sleep interventions that were most often carried out in laboratory-based environments. The majority of dietary interventions investigated use of a supplement (n = 66 studies), which was predominantly caffeine (n = 49). Sleep interventions investigated sleep duration only, with the majority (n = 17) investigating the effect of partial sleep restriction under 5.5 h per night on dietary intake, while three studies investigating total sleep deprivation. Conclusions: Investigating broader aspects of dietary such as overall diet quality and dietary patterns and other components of sleep health such as quality, timing and sleep hygiene are important aspects for future research.
  • Article
    The anthocyanin contents of Balaton and Montmorency cherries were compared. The results indicate that both cherries contain identical anthocyanins. However, Balaton contains approximately six times more anthocyanins than does Montmorency. Also, hydrolysis of the total anthocyanins and subsequent gas chromatographic (GC) and nuclear magnetic resonance (NMR) experiments with the resulting products indicated that both varieties contain only one aglycon cyanidin. This observation contrasts with existing reports of the presence of peonidin glycosides in Montmorency cherry. Results of the present study suggest that the anthocyanins in Balaton and Montmorency cherries are anthocyanin 1 [3-cyanidin 2‘‘-O-β-d-glucopyranosyl-6‘‘-O-α-l-rhamnopyranosyl-β-d-glucopyranoside], anthocyanin 2 [3-cyanidin 6‘‘-O-α-l-rhamnopyranosyl-β-d-glucopyranoside], and anthocyanin 3 [3-cyanidin O-β-d-glucopyranoside]. Keywords: Prunus cerasus; fruit; Balaton; Montmorency; anthocyanin; cyanidin; cyanidin glucoside; quantification and characterization
  • Article
    Sleep is often assessed in circadian rhythm studies and long-term monitoring is required to detect any changes in sleep over time. The present study aims to investigate the ability of the two most commonly employed methods, actigraphy and sleep logs, to identify circadian sleep/wake disorders and measure changes in sleep patterns over time. In addition, the study assesses whether sleep measured by both methods shows the same relationship with an established circadian phase marker, urinary 6-sulphatoxymelatonin. A total of 49 registered blind subjects with different types of circadian rhythms were studied daily for at least four weeks. Grouped analysis of all study days for all subjects was performed for all sleep parameters (1062–1150 days data per sleep parameter). Good correlations were observed when comparing the measurement of sleep timing and duration (sleep onset, sleep offset, night sleep duration, day-time nap duration). However, the methods were poorly correlated in their assessment of transitions between sleep and wake states (sleep latency, number and duration of night awakenings, number of day-time naps). There were also large and inconsistent differences in the measurement of the absolute sleep parameters. Overall, actigraphs recorded a shorter sleep latency, advanced onset time, increased number and duration of night awakenings, delayed offset, increased night sleep duration and increased number and duration of naps compared with the subjective sleep logs. Despite this, there was good agreement between the methods for measuring changes in sleep patterns over time. In particular, the methods agreed when assessing changes in sleep in relation to a circadian phase marker (the 6-sulphatoxymelatonin (aMT6s) rhythm) in both entrained (n= 30) and free-running (n= 4) subjects.
  • Article
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    Tryptophan, serotonin, and melatonin, present in Jerte Valley cherries, participate in sleep regulation and exhibit antioxidant properties. The effect of the intake of seven different Jerte Valley cherry cultivars on the sleep-wake cycle, 6-sulfatoxymelatonin levels, and urinary total antioxidant capacity in middle-aged and elderly participants was evaluated. Volunteers were subjected to actigraphic monitoring to record and display the temporal patterns of their nocturnal activity and rest. 6-sulfatoxymelatonin and total antioxidant capacity were quantified by enzyme-linked immunosorbent assay and colorimetric assay kits, respectively. The intake of each of the cherry cultivars produced beneficial effects on actual sleep time, total nocturnal activity, assumed sleep, and immobility. Also, there were significant increases in 6-sulfatoxymelatonin levels and total antioxidant capacity in urine after the intake of each cultivar. These findings suggested that the intake of Jerte Valley cherries exerted positive effect on sleep and may be seen as a potential nutraceutical tool to counteract oxidation.
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    Full-text available
    Long distance running causes acute muscle damage resulting in inflammation and decreased force production. Endurance athletes use NSAIDs during competition to prevent or reduce pain, which carries the risk of adverse effects. Tart cherries, rich in antioxidant and anti-inflammatory properties, may have a protective effect to reduce muscle damage and pain during strenuous exercise. This study aimed to assess the effects of tart cherry juice as compared to a placebo cherry drink on pain among runners in a long distance relay race. The design was a randomized, double blind, placebo controlled trial. Fifty-four healthy runners (36 male, 18 female; 35.8 +/- 9.6 yrs) ran an average of 26.3 +/- 2.5 km over a 24 hour period. Participants ingested 355 mL bottles of tart cherry juice or placebo cherry drink twice daily for 7 days prior to the event and on the day of the race. Participants assessed level of pain on a standard 100 mm Visual Analog Scale (VAS) at baseline, before the race, and after the race. While both groups reported increased pain after the race, the cherry juice group reported a significantly smaller increase in pain (12 +/- 18 mm) compared to the placebo group (37 +/- 20 mm) (p < .001). Participants in the cherry juice group were more willing to use the drink in the future (p < 0.001) and reported higher satisfaction with the pain reduction they attributed to the drink (p < 0.001). Ingesting tart cherry juice for 7 days prior to and during a strenuous running event can minimize post-run muscle pain.
  • Article
    Full-text available
    This study ascertained whether a proprietary tart cherry juice blend (CherryPharm, Inc., Geneva, NY, USA) associated with anecdotal reports of sleep enhancement improves subjective reports of insomnia compared to a placebo beverage. The pilot study used a randomized, double-blind, crossover design where each participant received both treatment and placebo for 2 weeks with an intervening 2-week washout period. Sleep continuity (sleep onset, wake after sleep onset, total sleep time, and sleep efficiency) was assessed by 2-week mean values from daily sleep diaries and disease severity by the Insomnia Severity Index in a cohort of 15 older adults with chronic insomnia who were otherwise healthy. The tart cherry juice beverage was associated with statistically significant pre- to post-treatment improvements on all sleep variables. When compared to placebo, the study beverage produced significant reductions in insomnia severity (minutes awake after sleep onset); no such improvements were observed for sleep latency, total sleep time, or sleep efficiency compared to placebo. Effect sizes were moderate and in some cases negligible. The results of this pilot study suggest that CherryPharm, a tart cherry juice blend, has modest beneficial effects on sleep in older adults with insomnia with effect sizes equal to or exceeding those observed in studies of valerian and in some, but not all, studies of melatonin, the two most studied natural products for insomnia. These effects, however, were considerably less than those for evidence-based treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.
  • Article
    The ability of melatonin to shift biological rhythms is well known. As a result, melatonin has been used in the treatment of various circadian rhythm sleep disorders, such as advanced and delayed sleep phase disorders, jet lag and shiftwork disorder. The current evidence for melatonin being efficacious in the treatment of primary insomnia is less compelling. The development of agents that are selective for melatonin receptors provides opportunity to further elucidate the actions of melatonin and its receptors and to develop novel treatments for specific types of sleep disorders. The agonists reviewed here - ramelteon, tasimelteon and agomelatine - all appear to be efficacious in the treatment of circadian rhythm sleep disorders and some types of insomnia. However, further studies are required to understand the mechanisms of action, particularly for insomnia. Clinical application of the agonists requires a good understanding of their phase-dependent properties. Long-term effects of melatonin should be evaluated in large-scale, independent randomized controlled trials.
  • Article
    Full-text available
    This investigation determined the efficacy of a tart cherry juice in aiding recovery and reducing muscle damage, inflammation and oxidative stress. Twenty recreational Marathon runners assigned to either consumed cherry juice or placebo for 5 days before, the day of and for 48 h following a Marathon run. Markers of muscle damage (creatine kinase, lactate dehydrogenase, muscle soreness and isometric strength), inflammation [interleukin-6 (IL-6), C-reactive protein (CRP) and uric acid], total antioxidant status (TAS) and oxidative stress [thiobarbituric acid reactive species (TBARS) and protein carbonyls] were examined before and following the race. Isometric strength recovered significantly faster (P=0.024) in the cherry juice group. No other damage indices were significantly different. Inflammation was reduced in the cherry juice group (IL-6, P<0.001; CRP, P<0.01; uric acid, P<0.05). TAS was ~10% greater in the cherry juice than the placebo group for all post-supplementation measures (P<0.05). Protein carbonyls was not different; however, TBARS was lower in the cherry juice than the placebo at 48 h (P<0.05). The cherry juice appears to provide a viable means to aid recovery following strenuous exercise by increasing total antioxidative capacity, reducing inflammation, lipid peroxidation and so aiding in the recovery of muscle function.