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R E S E A R C H A R T I C L E Open Access
Effects of lemon verbena extract
(Recoverben®) supplementation on muscle
strength and recovery after exhaustive
exercise: a randomized, placebo-controlled
trial
Sybille Buchwald-Werner
1*
, Ioanna Naka
1
, Manfred Wilhelm
2
, Elivra Schütz
3
, Christiane Schoen
3
and
Claudia Reule
3
Abstract
Background: Exhaustive exercise causes muscle damage accompanied by oxidative stress and inflammation
leading to muscle fatigue and muscle soreness. Lemon verbena leaves, commonly used as tea and refreshing
beverage, demonstrated antioxidant and anti-inflammatory properties. The aim of this study was to investigate the
effects of a proprietary lemon verbena extract (Recoverben®) on muscle strength and recovery after exhaustive
exercise in comparison to a placebo product.
Methods: The study was performed as a randomized, placebo-controlled, double-blind study with parallel design.
Forty-four healthy males and females, which were 22–50 years old and active in sports, were randomized to
400 mg lemon verbena extract once daily or placebo. The 15 days intervention was divided into 10 days
supplementation prior to the exhaustive exercise day (intensive jump-protocol), one day during the test and four
days after. Muscle strength (MVC), muscle damage (CK), oxidative stress (GPx), inflammation (IL6) and volunteer-
reported muscle soreness intensity were assessed pre and post exercise.
Results: Participants in the lemon verbena group benefited from less muscle damage as well as faster and full
recovery. Compared to placebo, lemon verbena extract receiving participants had significantly less exercise-
related loss of muscle strength (p= 0.0311) over all timepoints, improved glutathione peroxidase activity by
trend (p= 0.0681) and less movement induced pain (p= 0.0788) by trend. Creatine kinase and IL-6 didn’t show
significant discrimmination between groups.
Conclusion: Lemon verbena extract (Recoverben®) has been shown to be a safe and well-tolerated natural
sports ingredient, by reducing muscle damage after exhaustive exercise.
Trial registration: The trial was registered in the clinical trials registry (clinical trial.gov NCT02923102).
Registered 28 September 2016
Keywords: Sports nutrition, Lemon verbena, Aloysia citriodora, Recoverben®, Muscle strength, Recovery,
Exhaustive exercise, eiMD, Muscle soreness, Glutathione peroxidases
* Correspondence: sybille.buchwald-werner@vitalsolutions.biz
1
Vital Solutions GmbH, Hausingerstrasse 6, 40764 Langenfeld, Germany
Full list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition
(2018) 15:5
DOI 10.1186/s12970-018-0208-0
Background
All kinds of training, moderate, exhaustive or unaccus-
tomed, cause so-called exercise-induced muscle damage
(eiMD) accompanied by oxidative stress and inflamma-
tion [1]. Delayed onset muscle soreness (DOMS) is the
most common symptom of eiMD, whereas histological
evidence of disruption of the myofibrillar structure and
myofibre necrosis, as well as inflammation, are the ul-
timate signs of eiMD [1]. DOMS is associated with
muscle fatigue and muscle soreness, symptoms, which
last for a number of days and have a negative impact on
the exercise performance of athletes and amateur sports
people, especially when they carry out long-term training
programs [1]. Incomplete regeneration of myofibrillar
structures and metabolic processes before the next train-
ing increases the risk for secondary injuries. Therefore,
it is important for the adherence to training plans and
for the training success that regeneration is as effective
and as short as possible.
A product that could accelerate recovery from DOMS
or muscular fatigue would be beneficial not only for high
performance athletes, but also for amateur athletes, en-
abling them to train more frequently or reduce the risk
of injury. As inflammation and ROS (reactive oxygen
species) are presumably the main cause of DOMS [1], it
is hypothesized that natural ingredients with anti-
inflammatory and antioxidative properties may help in
accelerating or supporting the regeneration after muscle
damage inducing exercise [2–4]. The use of supplements
with antioxidative or anti-inflammatory effects in the
sports nutrition is already widespread. Many of these
ingredients and products have been investigated in re-
cent years; for example, curcumin [5], omega-3 fatty
acids [6, 7] and polyphenols [2, 8–10].
Lemon verbena (Aloysia citriodora (L.)) is an annual
eatable herbaceous plant native to South America com-
monly used as tea, refreshing beverage, food, or spice.
Traditional medicinal applications are related to diges-
tion and nervous discomfort [11]. A literature search fo-
cusing on peer-reviewed publications showed that only
limited data are available for lemon verbena in connec-
tion with muscular recovery after exercise. PubMed
listed over 80 publications in June 2017, that investigated
lemon verbena as stand-alone product or in combination
with other ingredients in any context (keywords for
search were Aloysia citriodora,Lippia citriodora,Lippia
triphylla,Aloysia triphylla, and lemon verbena).
Analytical references demonstrate that water-based ex-
tracts out of lemon verbena leaves are high in polyphenols
[12, 13]. Several in vitro and in vivo studies have shown
antioxidative and anti-inflammatory effects [11, 14–18].
Out of six human studies [19–24], only one human pilot
study was published investigating lemon verbena extract
on the muscular damage biomarker, creatine kinase and
liver biomarker related to oxidative stress [19]. This study
showed some effects on cytokines and oxidative stress
markers in neutrophils, but no functional parameters like
muscle strength or muscle soreness were essessed. Fur-
thermore, this study used a high dosage of 1800 mg/day
which is not suitable for application in food supplements
as it would require the intake of approximatley nine cap-
sules per day. Therefore, further research to observe ef-
fects of lemon verbena on muscle damage, muscle
soreness, and recovery needs to be performed.
A proprietary lemon verbena extract (Recoverben®),
high in polyphenols, was developed and recently identi-
fied as an anti-inflammatory agent [25]. One mode of ac-
tion responsible for the anti-inflammatory properties is
the inhibition of cyclooxygenase (COX) [26]. COX in-
hibition properties have also been shown for curcumin
[27], which is also an natural ingredient shown to be
beneficial in recovery [5, 28]. Based on these data and
on data from literature, we hypothesized that a lemon
verbena extract (Recoverben®) could have beneficial ef-
fects on exercise induced muscle damage, muscle sore-
ness, and recovery. The aim of this study was to
investigate effects on functional, metabolic, and subject-
ive parameters of recovery. Furthermore, parameters in-
dicating antioxidative and anti-inflammatory properties
were included to document mode of action.
Methods
Study design
This study was a double blind, randomized controlled trial
with a parallel-group design that investigated the effects of
a proprietary lemon verbena extract (Recoverben®) supple-
mentation on muscle strength and recovery after exhau-
sive exercise. It was conducted in orientation to the ICH-
GCP guidelines, in compliance with the declaration of
Helsinki, and was reviewed by the Institutional Review
Board (IRB) “Landesärztekammer Baden Württemberg”
without concerns (F-2016-080 September 13th, 2016). All
subjects signed the IRB-approved informed consent prior
to any procedures. The study was performed from
October 2016 to March 2017 at BioTeSys GmbH,
Esslingen, Germany, an independent study site which is
focused on nutritional research.
Subjects
Subjects were recruited from internal database of the
study site, advertisements in local newspapers, and no-
tice boards in public buildings. Seventy subjects
responded to the advertising campaign and received de-
tailed information about the study. Out of these, 45 sub-
jects were invited for screening visits. Forty-four healthy,
non-smoking, moderately active (exercise 1–3 times per
week) men and women with an age between 22 and
50 years and a BMI between 19 and 30 kg/m
2
were
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition (2018) 15:5 Page 2 of 10
deemed eligible for the current study. Subjects had a
usual intake of five or less portions of fruits plus vegeta-
bles per day. Detailed inclusion- and exclusion criteria
are presented in Table 1. Eligibility was evaluated by
medical history, concomitant medication, physical exam-
ination, electrocardiogram, blood pressure, and anam-
nesis. Physical activity was assessed using the
International Physical Activity Questionnaire (IPAQ)
[29]. Nutrition pattern of subjects was determined dur-
ing the screening visit using a subjective, retrospective,
semi-quantitative nutrition frequency questionnaire. The
score ranges from 0 to 100, whereby 0 means a very
good nutrition pattern and 100 a very poor nutrition
pattern [30]. The questionnaire was developed for the
German-speaking area and tested in a neutral and geriat-
ric collective. Adequate determination of supply of
micronutrient was validated by comparing with a de-
tailed quantitative food frequency questionnaire [30]. A
score around 50 can be interpreted as balanced nutri-
tion. Amount of fruits and vegetables portions taken per
day was asked during screening, whereby one portion
was specified to be around 150 g. Subjects were re-
quested to refrain from intake of anti-inflammatory or
antioxidative drugs or supplements during the study, po-
tentially interfering with this trial. They were asked not
to change their dietary habits and physical activity dur-
ing the study. The evening before the study days, sub-
jects ate a standardized dinner low in polyphenols
(noodles with cheese sauce). During the study days, they
received a standardized breakfast (cereal bars) and a
standardized snack (white wheat roll with butter and
cheese). Amount and time were also standardized. Alco-
hol intake and exhaustive activities were prohibited 48 h
before the study days until 96 h after the exhaustive ex-
ercise. Subjects were asked for changes in nutrition
habits and sportive activity at the end of the study.
Subjects were randomly assigned to the study groups
and stratified by gender after assessing eligibility during
screening. To ensure double-blind performance, the
randomization scheme was created by the sponsor using
the software Randlist. All subjects, the investigator, and
study staff involved in study performance, and data ana-
lysis were blinded until database lock. Disposition of
subjects is summarized in Fig. 1.
Study product and supplementation
The investigated commercial product Recoverben® (batch
number 16P0007) is a proprietary lemon verbena extract
obtained by water extraction out of organic dried lemon
verbena leaves. Lemon verbena (Aloysia citriodora (L.))is
Table 1 In- and exclusion criteria
Inclusion criteria Exclusion criteria
Subject is able and willing to sign the Informed Consent Form prior
to screening evaluations
Relevant history, presence of any medical disorder or chronic intake of
medication/dietary supplements (e.g. polyphenols, anti-inflammatory or
antioxidative drugs or supplements, antihypertensive drugs) potentially
interfering with this study at screening
Healthy subjects: Subject is in good physical and mental health as
established by medical history, physical examination, electrocardiogram,
vital signs, results of biochemistry and haematology
For this study clinically relevant abnormal laboratory, vital signs or
physical findings at screening
Men and women Diabetes or serious cardiovascular diseases
Age ≥22 and ≤50 years Change of dietary habits within the 2 weeks prior to screening
(for instance start of a diet high in vegetables and fruits (≥5 portions
per day)
BMI: 19–30 kg/m
2
Diet high in vegetables and fruits ≥5 portions per day
Physically active 1–3 times per week Participants anticipating a change in their lifestyle or physical activity
levels during the study
Nonsmoker Subjects not willing to abstain from intake of analgesic medication
(e.g. Aspirin) 24 h prior to visit 2 until visit 5
Able and willing to follow the study protocol procedures Subjects with history of drug, alcohol or other substances abuse,
or other factors limiting their ability to co-operate during the study
Known hypersensitivity to the study preparation or to single ingredients
Pregnant subject or subject planning to become pregnant during the
study; breast-feeding subject
Known HIV-infection
Known acute or chronic hepatitis B and C infection
Blood donation within 4 weeks prior to visit 1 or during the study
Subject involved in any clinical or food study within the preceding
month
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition (2018) 15:5 Page 3 of 10
a member of the family Verbenaceae. The product is
a native extract without any additives, standardized to
more than 18% polyphenols. The extract is hydro-
philic and can easily be dissolved in water, and has a
high ORAC level of 170.000 μmol TE/100 g. Lemon
verbena extract (Recoverben®) as well as the placebo
were formulated in capsules, matching in size and
color, and were supplied by Vital Solutions GmbH,
Germany. Each capsule contained 200 mg lemon ver-
bena extract or placebo (maltodextrin). All subjects
were instructed to take two capsules daily in the
morning. Products were consumed 10 days before an
exhaustive exercise test, during the test day and four
days after the test. The ingredient is safe for human
consumption and its quality complies with EU legisla-
tion concerning hygiene, contaminants, and maximum
residuelevelsofpesticidesoffoodstuff[31,32].Add-
itionally, the extract has been tested for and shown to
be free of banned substances by a specialist anti-
doping laboratory (LGC Limited, UK), therefore dem-
onstrating suitability as a sports nutrition product.
Exhaustive exercise protocol
In the current study, maximal eccentric loading of the
lower extremity was induced by an intensive jump-
protocol 10 days after the start of supplementation,
which was modified based on a jump protocol used
previously [33]. The protocol comprised 200 counter-
movement jumps with an additional load of 10% of the
participant’s body weight. The 200 countermovement
jumps were performed in 10 sets of 20 jumps every four
seconds with 90 s rest between sets. Knee joint angle be-
tween the jumps had to be 90°, which was controlled by
the observer. At the end of the test, rating of perceived
exertion (RPE) was obtained using the Borg RPE scale
[34]. Borg RPE scale and jump repetitions were used to
ensure subjective exhaustion after exercise and to con-
trol comparability of jump protocol between groups.
Massive deviation from jump protocol was defined as
exclusion criteria from VCAS analysis for exclusion of
confounding factors.
Muscle function testing - maximal voluntary
contraction (MVC)
Changes in muscle function appear to be the best
marker for the degree of exercise induced muscle dam-
age [1]. Therefore, in the current study, MVC was inves-
tigated by assessing isometric strength of the M.
quadriceps femoris, with 90° knee angle, using a dyna-
mometer KM40 (2kN) from ME-Messsysteme GmbH
and a strength chair from fasttwitch, TTI GmbH. Sub-
jects were fixed in a seated position with a hip belt, had
their arms crossed in front of the chest, and had the free
leg hanging without contact to any surface to reduce
support by other body parts during the test. Before each
measurement, subjects performed a 3 min warm-up
(level 7, 70 rpm) on a cycle ergometer (Crane Power
Studio Ergometer). The strength measurement was per-
formed for the dominant leg. This was identified at
screening by a shove-test, where the subject was pushed
unexpected by the observer and the leg which was used
by subject to balance was defined as dominant leg. All
examinations were performed in triplicates, immediately
before and 3, 24, and 48 h after the exhaustive exercise
protocol. The highest value was used for analysis. Sub-
jects were familiarized to the measurement at screening.
For each subject, the settings of the strength chair
(position of back rest, leg rest and position of measure-
ment arm) were documented. All further measurements
were performed with the individual settings. First meas-
urement was performed during screening visit to avoid
training effects during study visits. Variability was checked
between screening and pre-exercise measurement.
Perceived muscle soreness
Muscle soreness was measured using two different
methods.
Movement induced pain (VAS)
Subjects were asked to sit down into and get up from a
chair and to rate the pain they experienced in doing so
Volunteer information given
(n=70)
Enrollment
Assessed for eligibility
(n=45)
Excluded (n=1)
• Not meeting inclusion
criteria (n=1)
Randomized (n=44)
men n=19 / women n=25
Allocated to Treatment
(n=22)
Received allocated
intervention (n=22)
Did not receive allocated
intervention (n=0)
Allocation
Discontinued intervention
(n=2)
due to AE (common cold)
Study completion
Analys is
Allocated to Placebo
(n=22)
Received allocated
intervention (n=22)
Did not receive allocated
intervention (n=0)
Discontinued intervention
(n=2) due to AE (common
cold) and personal
reasons (timing deviations)
Safety population (n=22)
ITT/ FAS-population
(n=20)
PP/ VCAS-Population
(n=17)
Safety population (n=22)
ITT/FAS-population
(n=20)
PP/VCAS-Population
(n=20)
Fig. 1 Dispostion of subjects following Concort
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition (2018) 15:5 Page 4 of 10
using a 100 mm visual analogue scale (VAS), which con-
sisted of a from zero mm (no pain) to 100 mm (worst
imaginable pain). This assessment was conducted imme-
diately before and 3, 24, 48, 72, and 96 h after the ex-
haustive exercise protocol. Using VAS is frequently
described in literature for assessing acute exercise in-
duced pain [2, 33, 35].
Retrospective pain (Likert scale)
A seven point retrospective pain questionnaire (7 point
Likert-scale for muscle soreness) by Vickers et al. was
used to evaluate retrospective perceived pain during
daily life activities with zero “a complete absence of
pain”and six “a severe pain that limits my ability to
move”[36]. The subjects were asked to answer the ques-
tionnaire immediately before the exhaustive exercise and
24, 48, 72, and 96 h after the jump test.
Biochemical analysis
Different biomarkers were analyzed to evaluate muscle
damage and antioxidative capacity to describe exercise-
induced oxidative stress.
Creatine kinase (CK)
CK is a biomarker for muscle damage typically increased
after intense exervcise. In our study, CK was determined
from blood samples obtained before and 3, 24, and 48 h
after the exhausting exercise protocol. Analyses were
carried out at Synlab Medizinisches Versorgungszentrum
Leinfelden using an enzymatic-kinetic test method [37].
Glutathione peroxidase (GPx)
Exercise training is accompanied with oxidative stress
via production of reactive oxygen species (ROS), and
modulating the endogenous antioxidant defense system,
including GPx. In a healthy organism, exercise induces
GPx levels, inactivating ROS and maintain them in
physiological levels [38, 39]. The determination in
plasma (GPxP) was carried out at the study lab via GPx-
Assay-Kit (Cayman Chemical Company, Ann Arbor, MI,
USA) pre-exercise and 3, 24, and 48 h post exercise.
Interleukin-6 (IL-6)
IL-6 is a multifunctional cytokine involved in pro- as
well as anti-inflammatory processes. Exercise-induced
IL6 response is dependent on intensity and duration of
the exercise [40]. The determination in serum was
carried out at the study lab via Quantikine® HS Human
IL-6 Immunoassay Kit (R&D Systems, Inc., MN, USA)
pre-exercise and 3, 24, and 48 h post exercise.
Safety and tolerability
At each visit, changes in physical conditions since the
last visit were reviewed with subjects. Based on entries
in subject diaries, complete blood count, and adverse
events were assessed. Tolerability of the study product
was assessed 96 h after exercise, and at the end of study.
The subjects rated overall tolerability by selecting out of
three categories: “well tolerated”,“slightly unpleasant”,
and “very unpleasant”.
Statistics
The study was planned as an exploratory trial. Sample
size was calculated based on different studies observing
the effects of lemon verbena and using a similar design
[19, 35]. Therefore, a sample size calculation was per-
formed with effect size f = 0.2, significance level 0.05,
power 80%, two number of groups and four measure-
ment time points (pre, 2 h, 24 h, 48 h), correlation
among repeated measures 0.5 and with nonsphericity
correction 1. With these suggestions, a total sample size
of 36 subjects was calculated. Considering a drop-out
rate of 10%, 40 subjects were planned to be included in
the study.
Objectives were the difference of muscle strength,
muscle soreness, retrospective pain, CK, IL-6, and gluta-
thione peroxidase after exhaustive exercise under lemon
verbena in comparison to placebo.
Data were analyzed using SAS Version 9.3 and Graph-
Pad Prism Version 5.04. All statistical tests were per-
formed two-sided. Significance level was set to 0.05. For
evaluation of treatment effects, a linear mixed model
with repeated measures was used. For retrospective pain,
a generalized linear mixed model with Poisson-
distribution for count data was used. Due to explorative
data analysis, no correction for multiple comparison was
performed. Gender, its interaction with treatment and
the respective pre value was included as covariates for
the biomarkers and MVC. For movement induced pain
and retrospective pain only gender and its interaction
with treatment were defined as covariates. Changes
within groups were assessed using one way ANOVA or
Friedmann test, as appropriate. All efficacy parameters
were checked for baseline differences. Results presented
below refer on valid case analysis set (VCAS). VCAS cri-
teria were pre-defined in the protocol: missing data, ad-
verse events or concomitant medication interfering with
study results, extreme outliers, and major protocol viola-
tion (compliance <85%, > 115%, drop outs / withdrawals,
major deviation of study performance).
Results
Group characteristics
Out of 44 subjects allocated to intervention, 40 subjects
(19 men and 21 women) completed the study according
to the protocol (full analysis set; FAS). Four subjects
dropped out after start of supplementation and before
efficacy testing. Three of these suffered from a common
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition (2018) 15:5 Page 5 of 10
cold, which did not allow them to perform the exhaust-
ive exercise test, and one dropped out due to personal
decision.
Thirty-seven subjects were analyzed for valid case ana-
lysis set (VCAS). One subject had a strong common cold
during the exhaustive exercise test, which may have in-
fluenced biomarker results. Another subject did not
meet compliance criteria for study product intake and
the third subject had major deviation of the exhaustive
exercise protocol. As these three subjects did meet ex-
clusion criteria for VCAS analysis, they were not consid-
ered in final analysis (VCAS).
Gender, age, BMI, blood routine markers, and blood
pressure did not differ significantly between the groups
prior to the study. Subject characteristics are summa-
rized in Table 2. The nutrition frequency questionnaire
scores were 45.35 ± 10.51 points in the lemon verbena
group and 42.65 ± 11.33 points in the placebo group
(p= 0.4597). Most subjects consumed between two and
four portions fruits plus vegetables per day (lemon ver-
bena: 82%, placebo: 70%). Intake of fruit and vegetables,
as supplier for polyphenols, were comparable between
groups. The protocol compliance of study product intake
was very good. For VCAS, all subjects met the compli-
ance criterion ≥85% and ≤115% of study preparation
consumed (lemon verbena group: 102 ± 5%, placebo:
101 ± 2%). For FAS, one subject had a compliance
>115% since much less products remained, bringing up
uncertainty about correct intake, which was the reason
for exclusion from VCAS. Borg scale data after exhaust-
ive exercise and jump repetitions were not significantly
different between groups (p= 0.8997, p= 0.1561). There-
fore, burden of subjects by the exhaustive exercise and
jump protocol was comparable between groups, so a
comparable stress could be expected.
Muscle function testing - maximal voluntary contraction
MVC was significantly less reduced after exercise in
the lemon verbena group than in the placebo group
(p= 0.0311), with significant time effect (p= 0.0051),
(Fig. 2, Table 3). In the lemon verbena group, muscle
strength was completely back to baseline after 48 h,
whereas strength was still reduced at that time point
in the placebo group.
Table 2 Subject characteristics at screening for FAS (N= 40, 19
men, 21 women)
Parameter
[unit]
Lemon verbena
(N= 20 59% men,
41% women)
Placebo
(N= 20 40% men,
60% women)
Inclusion criteria/
Reference range
Age
[years]
Mean 31.7 30.6 22–50
Sd 8.8 9.3
BMI
[kg/m
2
]
Mean 22.67 23.0 19–30
Sd 2.3 2.5
Activity
[MET min/week]
Mean 3209 2470.0 –
Sd 3957.0 2521
CHOL
[mg/dL]
Mean 172.5 180.0 100–200
Sd 23.0 31.85
TG
[mg/dL]
Mean 89.68 82.14 <160
Sd 43.53 24.71
HDL
[mg/dL]
Mean 58.91 58.95 >40
Sd 6.487 14.24
LDL
[mg/dL]
Mean 93.86 109.5 <150
Sd 16.32 28.7
Glucose
[mg/dL]
Mean 87.55 86.14 60–100
Sd 8.405 4.96
SBP
[mmhg]
Mean 121.6 121.6 120–129
Sd 12.8 12.8
DBP
[mmhg]
Mean 75.8 70.6 80–84
Sd 8.8 10.5
BMI body mass index, MET metabolic equivalent of task, CHOL cholesterol,
TG triglycerides, HDL high-density lipoprotein, LDL low-density lipoprotein,
SBP systolic blood pressure, DBP diastolic blood pressure
Fig. 2 Maximal voluntary contraction. Delta MVC [N] (Mean ± 95%
CI; product effect: p= 0.0311) * indicating significance against
baseline; & indicating significant group differeneces
Table 3 Statistical results within (one way-ANOVA) and
between groups (Linear mixed models with repeated measures
or in case of Ret. pain generalized linear mixed model with
poisson distribution for count data) for maximal voluntary
contraction (MVC), movement induced pain (VAS), retrospective
pain (Ret. pain), creatin kinase (CK), gluthation peroxidase (GPxP)
and interleukine-6 (IL-6)
Within group Between group
Lemon verbena Placebo Product effect Time effect
MVC 0.005 <0.0001 0.0311 0.0051
VAS <0.0001 <0.0001 0.0788 <0.0001
Ret. pain <0.0001 <0.0001 0.782 <0.0001
CK <0.0001 <0.0001 0.9412 <0.0001
GPxP 0.204 0.5895 0.0681 0.0624
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition (2018) 15:5 Page 6 of 10
Perceived muscle soreness
Movement induced pain (VAS) in the lemon verbena
group was less pronounced by trend (p= 0.0788) with a
significant time effect (p< 0.0001) in comparison to the
placebo group (Fig. 3, Table 3). Retrospective pain was
comparable between groups without significant differ-
ence (Fig. 4). Both groups showed significant increase in
soreness 24, 48, and 72 h after exercise in relation to
pre-exercise.
Biochemical analyses
Creatine kinase
Exercise-induced CK was not significantly different
between groups (p= 0.9412 with significant time ef-
fect (p < 0.0001) (Fig. 5, Table 3).
In the lemon verbena group, CK was significantly in-
creased above baseline at 24 h but not 3- or 48-h post-
exercise. In contrast, the placebo group showed signifi-
cant elevations of CK at all three time points relative to
baseline.
Glutathione peroxidase
The GPxP activity within lemon verbena group was in-
creased by trend compared to placebo group (p= 0.0681),
with time effect also by trend (p= 0.0624), (Fig. 6,
Table 3).
Interleukin 6
Only distinct increase of IL-6 could be observed after
exercise, without significant differences but high inter-
individual variability. Differences between groups were
not significant (p= 0.5824).
Safety and tolerability
Blood chemistry, vital signs, adverse events, and con-
comitant medication did not indicate any safety con-
cerns over 15 days. There was no statistical difference
between the two groups for adverse events (p= 0.231).
The most frequent adverse events were headache (lemon
verbena: 5%, placebo: 18%) and common cold (lemon
verbena 23%, placebo: 23%). None of the adverse events
were serious or related to the study products. The inter-
vention was well tolerated.
Discussion
The aim of this study was to investigate the effects of
supplementing with 400 mg of lemon verbena extract
(Recoverben®) on muscle strength and recovery in
healthy, moderately active adults. We found that con-
sumption of lemon verbena significantly attenuated loss
of muscle strength compared to placebo. Muscle
Fig. 3 Movement induced pain. Movement induced pain (VAS) [cm]
(Mean ± 95% CI; product effect: p= 0.0788) * indicating significance
against baseline
Fig. 4 Retrospective pain. Retrospective pain [score] (Mean ± 95% CI;
product effect: p= 0.7820) * indicating significance against baseline
Fig. 5 Creatine kinase. Delta Creatine kinase [U/L] (Mean ± 95% CI;
product effect: p= 0.9412) * indicating significance against baseline
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition (2018) 15:5 Page 7 of 10
strength loss is considered a reliable and valid functional
marker for assessing muscle damage [1]. Therefore, our
preliminary findings suggest that lemon verbena may re-
duce exercise-induced muscle damage.
Muscle strength was reduced by 21% in placebo group,
which is within the expected range of 20–50% and recov-
ery was not completed until two days post exercise. It is
generally accepted that two to seven days are necessary
for full recovery following exercise induced muscle dam-
age [1]. Compared to placebo, lemon verbena extract sig-
nificantly (p=0.0311) buffered strength loss after exercise.
MVC in the lemon verbena group was reduced by 11%,
which is defined as mild muscle damage [1]. Furthermore,
complete recovery was reached after 48 h. Based on these
findings, lemon verbena appears to not only speed recov-
ery, but also reduce fatigue directly after exercise.
These results were reflected by findings for per-
ceived muscle soreness. Movement induced pain, which
estimated actual perceived pain showed discrimination be-
tween study groups with slight superiority of lemon ver-
bena extract by trend. The less pronounced muscle
damage, seen by significantly less reduction of MVC,
seems to be reflected by less perceived pain under lemon
verbena extract if compared to placebo. Maximum of
muscle soreness was reported 48 h after exercise, fitting to
the general knowledge that muscle soreness peaks
24 h or 48 h after damaging exercise [1]. The extent
of muscle soreness was medium for both groups, sup-
porting that the exercise protocol caused mild to mod-
erate muscle damage. After 96 h, subjects were, on
average, not completely painless, even if muscle
strength at that time was already recovered in this
group. However, the same phenomenon has already
been observed by others [9, 33].
Increasing concentration of CK in the blood is an indi-
cation of muscle damage, being frequently used in sports
nutrition studies [9, 35]. The time course of CK increase
peaked at 24 h after exercise, which is comparable to
findings reported in literature [9, 35]. Exercise-induced
increases in CK are known to exhibit high interindivid-
ual variability, with some people showing large increases
(responders) and others showing only moderate in-
creases (non-responders) [1]. In our study, high levels of
interindividual variation in CK concentrations were
present, which could explain why we failed to observe a
significant between-group difference despite other
markers of muscle damage, such as MVC, favoring the
lemon verbena group.
Many research studies have shown that supplementa-
tion with dietary polyphenols has the potential to posi-
tively influence symptoms of exercise-induced muscle
damage [2, 5, 8–10, 41, 19]. However, underlying pro-
cesses are still unclear and it is not sure if antioxidative
effects are the primarily mechanisms [41]. Furthermore,
the benefit of reducing oxidative stress has been dis-
cussed diversely [41, 42]. Increased of oxidative stress
can lead to progressive cell damage and decline in
physical function [42, 43]. However, ROS act as bio-
logical stimuli in cellular processes of adaption to train-
ing [41, 42] and cells can adapt to repetitive increases of
ROS by improving antioxidant capacity [44, 45]. During
the current study, glutathione peroxidase in plasma was
selected as a parameter to supply information about an-
tioxidative capacity. Our results indicate an activation of
the antioxidative defense under lemon verbena extract
by up-regulating GPxP shortly after exercise. In contrast
to this, baseline GPxP was not increased by supplemen-
tation with lemon verbena extract. Therefore, it appears,
that supplementation with lemon verbena extract
strengthens the antioxidative defense system and enables
effective counteraction of oxidative stress, but only if
needed. Both groups experienced significant exercise-
induced increases in IL-6 without significant difference
between one another. Some evidence suggests that
changes in IL-6 depend in part on exercise intensity and
duration [1, 46, 40]. It is possible that the exhaustive ex-
ercise protocol used in our study was not intense and/or
long enough to elicit meaningful changes in IL-6 that
could have been effected by lemon verbena supplemen-
tation. Similar results were found in other human stud-
ies investigating natural ingredients for effects of muscle
strength and muscle damage, such as ashwagandha ex-
tract [47], curcumin [48], pomegranate extract [10], and
blueberry [2]. These natural ingredients are high in poly-
phenols, a trait shared by lemon verbena. It has been
proposed, that polyphenols could be useful to prevent
muscle damage or improve recovery [4]. The major bio-
logical functions of polyphenols are as antioxidants and
Fig. 6 Glutathione peroxidase. Delta Glutathione peroxidase [U/L]
(Mean ± 95% CI; product effect: p= 0.0681) * indicating
significance against baseline
Buchwald-Werner et al. Journal of the International Society of Sports Nutrition (2018) 15:5 Page 8 of 10
anti-inflammatory agents. Enhanced production of vaso-
dilation factors and the inhibition of synthesis of vaso-
constrictors have also been shown [49]. These could be
additionally beneficial by improving tissue oxygen supply
and removal of metabolic waste products. The propri-
etary lemon verbena extract (Recoverben®) investigated
in the current study has shown anti-inflammatory effects
[26] and is characterized by a high polyphenol content
and high ORAC level. Therefore, the observed reduction
in muscle strength loss and indicated accelerated recov-
ery in the present study might be explained by lemon
verbenas’constituents and their ability to prevent or re-
duce inflammatory processes or reduce oxidative stress.
Conclusion
In summary, our study showed that ingestion of a
400 mg/day proprietary lemon verbena extract
(Recoverben®) resulted in significantly less muscle
strength loss in healthy, moderately active adults. In-
fluences by trend on muscle soreness and antioxida-
tive capacity emphasizes the potential of the product
accelerating recovery after exhaustive exercise. Larger
studies could provide statistical evidence also for the
parameter, which only showed improvements by trend
in the study.
Abbreviations
CK: Creatine kinase; DOMS: Delayed onset of muscle soreness; eiMD: Exercise-
induced muscle damage; GPx: Glutathione peroxidase; GPxP: Glutathione
peroxidase in Plasma; IL-6: Interleukin 6; MVC: Maximal voluntary contraction;
ROS: Reactive oxygen species; RPE: Rating of perceived exertion; VAS: Visual
analogue scale
Acknowledgements
The authors would like to thank all subjects taking part in the trial.
Funding
Despite sponsoring by Vital Solutions GmbH, no further funding was
received.
Availability of data and materials
Please contact corresponding author for additional data.
Authors’contributions
The study was designed by CAR, ES and CS (BioTeSys GmbH) after
approach from SBW, IN (Vital Solutions GmbH). CAR, ES and CS undertook
management of the study, including study execution, overseeing data
collection, management, quality assurance and analyses. MW (Ulm
University of Applied Sciences) performed the statistical analysis. All
authors contributed to the study design and data interpretation. SBW and
CAR wrote the first draft of this paper and all authors were responsible
for subsequent critical revision of the manuscript. SBW is the corresponding
author for this paper. All authors read and approved the final manuscript.
Authors’information
SBW, Pharmacist, PhD in Pharmaceutical Chemistry, over 20 years experience
in the natural product industry for health and nutrition. Managing Director
and head of R&D at Vital Solutions GmbH, Hausingerstrasse 6, Langenfeld,
40,764, Germany.
IN, Dipl. Chemical engineer, Master in Natural product chemistry, Scientific
Manager at Vital Solutions GmbH, Hausingerstrasse 6, Langenfeld, 40,764,
Germany.
CS (Dipl. Nutrition science) and CAR (PhD Sports science and examin. Biol.),
both clinical research scientists at BioTeSys GmbH, a company with over
15 years experience in the field of nutrition research and clinical nutrition
studies. ES, student of molecular nutritional science at University of
Hohenheim and trainee at BioTeSys GmbH, Schelztorstrasse 54–56, Esslingen,
D-73728, Germany. MW, professor for mathematics and statistics at the. Ulm
University of Applied Sciences, Albert-Einstein-Allee 55, 89,081 Ulm, Germany.
Ethics approval and consent to participate
Ethical approval was obtained from the ethical committee of the
“Landesärztekammer Baden-Württemberg”without concerns (F-2016-080
September 13th, 2016) prior to study start and all subjects signed the IRB-
approved informed consent prior to any procedures.
Consent for publication
Not applicable.
Competing interests
The study was sponsored by Vital Solutions GmbH. The sponsors contributed
to discussion about study design and selection of outcome measures prior
to study start. During study realization and data analysis all data were
completely blinded and study realization, data analysis and report
generating were undertaken independently by BioTeSys GmbH and Ulm
University of Applied Sciences. Vital Solutions own the proprietary ingredient
used in the study. The authors from BioTeSys GmbH and Ulm University of
Applied Sciences declare that there is no conflict or interest regarding the
publication of this paper.
Publisher’sNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
Vital Solutions GmbH, Hausingerstrasse 6, 40764 Langenfeld, Germany.
2
Ulm
University of Applied Sciences, Albert-Einstein-Allee 55, 89081 Ulm, Germany.
3
BioTeSys GmbH, Schelztorstrasse 54-56, D-73728 Esslingen, Germany.
Received: 1 September 2017 Accepted: 5 January 2018
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