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S T U D Y P R O T O C O L Open Access
Effect of barberry (Berberis vulgaris)
consumption on blood pressure, plasma
lipids, and inflammation in patients with
hypertension and other cardiovascular risk
factors: study protocol for a randomized
clinical trial
Hadi Emamat
1
, Ali Zahedmehr
2
, Sanaz Asadian
3
, Hadith Tangestani
4
and Javad Nasrollahzadeh
1*
Abstract
Background: Cardiovascular diseases (CVDs) remain the leading causes of morbidity and mortality in the world.
Hypertension is an important and prevalent cardiovascular risk factor. The present study will be conducted to
investigate the effect of barberry as a cardio-protective fruit on the blood pressure in patients with hypertension and
other CVD risk factors. Furthermore, plasma concentrations of lipids and inflammatory biomarkers will be evaluated.
Methods/design: This is an 8-week, prospective, single-blinded, parallel assigned, randomized controlled clinical trial
(RCT) in which eligible men and women with hypertension and other cardiovascular risk factors will be randomized to
either placebo powder (PP; containing 9 g maltodextrin, 1 g citric acid, 1 g milled sucrose and edible red color (n=37))
or barberry powder (BP; containing 10 g milled dried barberry and 1 g of milled sucrose (n= 37)) groups. At baseline
and after 8 weeks of intervention, plasma lipids and inflammatory markers, 24-h urinary nitrite/nitrate and sodium
excretion, and 24-h ambulatory blood pressure monitoring (ABPM) will be measured. Anthropometric measures and
dietary assessment will be performed as well. Data analysis will be done using SPSS version-21 software.
Discussion: Theinterestinnaturalandfunctionalfoodproductshasincreasedglobally.ThisRCTwilladdtothegrowing
literature for the potential antihypertensive, lipid-lowering, and anti-inflammatory effects of barberry in humans.
Trial registration: ClinicalTrials.gov (NCT number) NCT04084847. Registered on 10 December 2019.
Keywords: Barberry, Berberis vulgaris, Blood pressure, Lipids, Inflammation, CVD
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
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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 in a credit line to the data.
* Correspondence: jnasrollahzadeh@gmail.com
1
Department of Clinical Nutrition & Dietetics, National Nutrition and Food
Technology Research Institute, Faculty of Nutrition Sciences and Food
Technology, Shahid Beheshti University of Medical Sciences, Tehran P.O.
19395-4741, Iran
Full list of author information is available at the end of the article
Emamat et al. Trials (2020) 21:986
https://doi.org/10.1186/s13063-020-04918-7
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Introduction
Cardiovascular diseases (CVDs) remain the leading
causes of morbidity and mortality in the world, as
they account for about 30% of mortality worldwide
[1]. These diseases are also one of the major priorities
of the Iranian healthcare system [2], and it is esti-
mated that the burden of the disease will increase
more than twice as the elderly population increases
until the 2025 years [3]. Hypertension is an important
and prevalent cardiovascular risk factor that imposes
a great burden on the healthcare system [4]. Accord-
ing to the World Health Organization (WHO) re-
ports, hypertension affects half of the adults
worldwide and its prevalence is dramatically increas-
ing in all age groups [5]. The production of nitric
oxide (NO) from arginine in vascular endothelial cells
is important in vasodilation, maintaining vascular tone
maintenance, and regulation of blood pressure (BP).
Most of the NO produced is metabolized to nitrite
and nitrate (NOx) and excreted in the urine [6].
A significant number of patients with hypertension
have several cardiovascular risk factors. Diabetes and
dyslipidemia are among the most important risk factors
known for CVDs [7] which may coexist with hyperten-
sion. Besides, inflammatory mediators are involved in
many cardio-metabolic disorders. Several inflammatory
biomarkers have been investigated to improve cardiovas-
cular risk prediction and to monitor the disease process.
Among the pro-inflammatory biomarkers, C-reactive
protein (CRP) and interleukin-6 (IL-6) are associated
with an increased risk of cardiovascular events and pro-
gression [8].
Epidemiologic studies have shown that a high intake
of fruits and vegetables reduces the risk of developing
cardiovascular disease [9]. This may be due to bio-
active compounds found in fruits and vegetables such
as polyphenols. Findings from experimental and epi-
demiological studies suggest that dietary intake of
polyphenol-rich foods could be effective in reducing
cardiovascular events. Higher intakes of fruit-based
flavonoids have been associated with a lower risk of
nonfatal myocardial infarction and ischemic stroke
[10,11]. The Berry family is rich in polyphenols such
as procyanidins, quercetin, phenolic acids, and especially
anthocyanins [12]. The anthocyanins are effective antioxi-
dants in preventing CVD due to inhibiting inflammatory
processes, reducing endothelial dysfunction and causing
vasodilation [13]. Studies have shown that consumption of
berry fruits such as Elderberry, Cranberry, Bilberry, Blue-
berry, Whortleberry, and Black Raspberry can have benefi-
cial effects on CVDs [14]. Regarding hypertension,
beneficial effects of berry fruits on blood pressure in
healthy as well as hypertensive individuals have also been
reported [15–18].
Berberis vulgaris commonly known as barberry is cul-
tivated in Europe and West Asia, among other countries,
and its fruit is used in several different forms for culinary
purposes, jams, and soft drinks. Owing to its berberine
and anthocyanins content, the effects of this plant have
been investigated concerning cardiovascular risk factors in
experimental studies [19,20]. There has been, however,
limited clinical trial related to the effect of barberry on
cardio-metabolic parameters. Lazavi et al. showed that
200 ml of barberry juice significantly improved systolic
and diastolic blood pressure, fasting blood sugar, and
blood lipids in people with type 2 diabetes [21]. Shidfar
et al. showed that a daily intake of 3 g of barberry extract
for 3 months had beneficial effects on blood lipids and li-
poproteins, glucose, and total antioxidant capacity in dia-
betic patients [22]. Recently, a meta-analysis showed that
barberry consumption is a safe approach for the manage-
ment of lipid parameters [23]. Nevertheless, the previous
studies regarding the effects of barberry on cardiovascular
risk factors, especially hypertension, had various limita-
tions. These include the lack of precise monitoring of
blood pressure by an accurate none-invasive method such
as 24-h ambulatory blood pressure monitoring (ABPM)
and also not measuring 24-h urine sodium excretion as an
estimate of sodium intake for its confounding influence in
evaluating the intervention’s effects on blood pressure.
Furthermore, the mechanism by which barberry may
modulate blood pressure has not been well studied, in-
cluding its potential effect on nitric oxide production,
which can be assessed by measuring the 24-h urine NOx
level. Considering the high prevalence of CVD and hyper-
tension as well as the limited number of clinical trials on
the effect of barberry on hypertension and other cardio-
vascular risk factor, further clinical trials are required in
this area. Therefore, the present randomized clinical trial
will be conducted to investigate the effect of supplementa-
tion with barberry fruit on the blood pressure by 24-h
ABPM and on 24-h urinary NOx and sodium excretion in
patients with hypertension and other CVD risk factors.
Furthermore, plasma concentrations of lipids, lipoproteins
and inflammatory biomarkers will be evaluated as the sec-
ondary outcomes.
Main aim
This study aims to investigate the effect of barberry con-
sumption on systolic blood pressure (SBP), diastolic blood
pressure (DBP), mean arterial blood pressure (MAP),
plasma lipids, and inflammation status in patients with
hypertension and other cardiovascular risk factors.
Primary objective
To evaluate the effect of 8-week barberry consumption
on variations in SBP measures in patients with hyperten-
sion and other cardiovascular risk factors.
Emamat et al. Trials (2020) 21:986 Page 2 of 9
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Secondary objectives
To compare within- and between-group variations in
DBP, MAP, plasma lipid profile including total choles-
terol (TC), low-density lipoprotein cholesterol (LDL-C),
high-density lipoprotein cholesterol (HDL-C), triglycer-
ide (TG), inflammatory biomarkers including plasma
CRP and interleukin-6, and 24-h urinary NOx in pa-
tients with hypertension and other cardiovascular risk
factors.
Hypotheses
Daily consumption of barberry will improve SBP, DBP,
and MAP in patients with hypertension and other car-
diovascular risk factors.
Plasma levels of lipids, CRP, and IL-6 will be reduced
by daily consumption of barberry in patients with hyper-
tension and other cardiovascular risk factors.
Urinary NOx will be increased by daily consumption
of barberry in patients with hypertension and other car-
diovascular risk factors.
Methods/design
Design
This is an 8-week, prospective, single-blinded, parallel
assigned, randomized controlled clinical trial (RCT) in
which men and women with hypertension and other car-
diovascular risk factors will be randomized to an inter-
ventional (barberry) or placebo group (Fig. 1).
Ethics, consent, and permissions
National Nutrition and Food Technology Research Insti-
tute (NNFTRI), Shahid Beheshti University of Medical
Sciences, will provide financial support for the current
project. The trial will be conducted in compliance with
the Declaration of Helsinki. The trial has received ethical
approval from the Ethics Committee of NNFTRI (2018-
10-20: Ethical code: IR.SBMU.nnftri.Rec.1397.248).
Participant recruitment
In this clinical trial, we will recruit a total of 80 partici-
pants both men and women (each group 40) with hyper-
tension and other cardiovascular risk factors (diabetes
and/or hyperlipidemia and/or smoking) in Tehran, the
capital of Iran. Volunteers among patients with a previ-
ous history of hypertension who have a medical record
in the academic hospital (Rajaei Cardiovascular, Medical
& Research Center, Tehran, Iran) and are regularly vis-
ited in the hospital clinics every 4–6 months if they meet
the eligibility criteria will be recruited. Besides, by pla-
cing an advertisement in the hospital, other volunteer
people who are referred to the hospital if they meet the
eligibility criteria are also included in the study. To guar-
antee achieving adequate participant enrolment, the
clinic staff at the hospital will be informed about the
study, and informational conversation with patients will
be held.
The trial is due to last 9 months. This assumes
5 months for participant recruitment and intervention,
2 months for laboratory testing, 1 month for data prep-
aration and analysis by SPSS software, and 1 month to
write the study report. The study protocol has been re-
ported in accordance with the Standard Protocol Items:
Recommendations for Clinical Interventional Trials
(SPIRIT) guidelines [24] (Additional file 1, SPIRIT
Checklist). The trial schedule is shown in Table 1. In-
formed consent will be obtained from all subjects before
collecting any information. After reviewing the consent
forms and answering any probable questions by study
staff, those who are interested will be asked to sign the
forms. A copy of the consent form will be given to par-
ticipants and all original signed consent forms will be
kept by the study staff (Additional file 2, consent form).
Eligibility
The inclusion criteria for subjects include (1) willingness
to participate in the study, (2) age between 20 and 65
years, (3) known hypertensive patients on medical treat-
ment, and (4) at least one other classical CVD risk fac-
tors, including hyperlipidemia, diabetes mellitus, or
smoking. Exclusion criteria include (1) unwillingness to
continue participation, (2) having BMI > 30, (3) patients
on nitrate drugs, (4) taking high doses of statins (Atorva-
statin> 40 mg/day or Rosuvastatin> 20 mg/day), (5) con-
sumption of vitamins or minerals supplements during
the past month, and (6) having chronic kidney disease
stage 4 or 5. The drop out criteria include any side ef-
fects, refusing to continue the study, missing telephone
responses, and any restrictive illness. Participants are
allowed to withdraw from the study at any time.
Setting
For those who are interested in participating in the trial,
cardiologist and study staff will confirm if they have eli-
gibility criteria, and the appointment will be set for their
first visit. In the first visit, the potential participants will
have the proposals of the research project fully explained
to them, and all participants will be asked to fill in the
consent form. A general information questionnaire, in-
cluding demographic information, disease history, the
type and dosage of their medications, occupation, educa-
tion and the smoking status, physical activity question-
naire, and three food recall questionnaire will be
completed from each participant. The next visit will be
after 2 weeks run-in period of weight maintenance, when
baseline data including body weight and fasting blood
sample will be obtained and the patient will be
instructed to collect urine within the next 24 h and an
ABPM device will be installed. After 24 h, the collected
Emamat et al. Trials (2020) 21:986 Page 3 of 9
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
urine sample will be delivered and the results of the
ABPM device will be stored. The patient will be given
barberry or placebo packages and instruction on how to
record their consumption. The next meeting will be at
the end of the study to collect end-of-study data.
Sample size
Sample size calculations were carried out using G*Power
V.3.1.9.2 software [25]. The sample size was calculated
based on data from Tjelle et al. [15], a relatively similar
polyphenol-rich berry juice intervention study that ob-
served a reduction in SBP of 6.2 mmHg compared to
placebo. Assuming equal standard deviation in both
group and by considering pooled value of the standard
deviation = 8.8, a significance level of α≤0.05 and statis-
tical power of 80%, the minimum sample size will be 66
patients will be required to detect a change of this size
in the SBP level. To account for a drop-out rate of ap-
proximately 20%, we plan to recruit 80 participants (40
randomized to each group).
Run-in
Hypertensive patients who have other cardiovascular risk
factors will be entered into the 2-week maintenance
weight program after the above steps have been taken.
Participants will be asked not to change their lifestyle
Fig. 1 CONSORT flow diagram
Emamat et al. Trials (2020) 21:986 Page 4 of 9
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
and keep researchers informed of any changes including
diet, physical activity, and medication use. At the end of
the first visit, a paper sheet will be given to the individ-
uals, containing the description of the study, a date for
the next visit, and the contact number. The presence of
this run-in period is essential for maintaining their
weight, as well as to test the participants’motivation to
continue the intervention.
Randomization/blinding
Participants will be randomized to receive either the bar-
berry or the placebo product. The randomization will be
performed with the aid of a sequence generated by using
a random number table. For this purpose, each row of
the table was considered as a block, and from the left, in
the order in the table, odd numbers were considered as
group A and even numbers were considered as group B.
If the first two allocations were for one of the A or B,
the next two allocations were considered for the second
group. The sequence of each block was placed in a
sealed opaque envelope. Diabetes and hyperlipidemia are
two other major CVD risk factors that may coexist with
hypertension. To achieve a balanced distribution of these
risk factors in each of the study groups, stratified block
randomization will be performed, with four strata: with
a history of diabetes, without a history of diabetes, re-
ceiving statins, and not receiving statins. A block size of
4 within each stratum will be used, with a 1:1
randomization between the two groups.
This trial has a single-blinded manner. Patients are
blinded to the type of product they are consuming, but
the main investigator who assigns patients to interven-
tion or placebo groups is not blinded. Placebo and bar-
berry powdered products are given to patients in
undetectable non-transparent packaging.
Study intervention and implementation
The package of powdered products will be either a pla-
cebo powder. The barberry or placebo powders will be
packaged in undetectable non-transparent wrappers. Pla-
cebo powder contains 9 g maltodextrin, 1 g citric acid, 1
g milled sucrose, and edible red color, and the barberry
powder contains 10 g milled dried barberry and 1 g of
milled sucrose. All dried barberry is purchased from the
local market. Each patient receives 60 packages, each
containing barberry or placebo powder for daily use.
The daily amount of 10 g of barberry powder was se-
lected based on a previous study by Shidfar et al. in
which the amount of extract obtained from 10 g of bar-
berry powder was investigated [22]. The time of con-
sumption of powders can be during any time of the day
and participants will not be imposed to take the supple-
ments at a specific time of the day. Since a change in
dietary habits or physical activity can affect the outcome
Table 1 Time table of protocol
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of the study, participants will be asked not to change
their daily diet and to continue their daily physical activ-
ity. Furthermore, patients will be instructed to maintain
their current type/dose of oral medication during this
trial period.
Compliance
All participants will be called biweekly to assess their
compliance. Participants will be asked to mark a re-
minder note for the daily consumption of the packages.
They will be given a sheet of paper that includes the
code, the next visit date, two columns entitled “one
package daily”and another column entitled “Date”to
record their regular consumption of package. Patients
are asked to bring empty packages to the hospital at the
end of the study period.
Outcome measurements
Dietary assessment
Before and after the 8-week intervention, a 3-day 24-h
dietary recall questionnaire will be obtained to evaluate
the usual dietary intake. It includes two workdays and
one weekend. Then, the obtained data from the ques-
tionnaire will be assessed using N4 software (NUTRI-
TIONIST 4, First Data Bank, San Bruno, CA, USA).
Anthropometry measures
The height will be measured without shoes by a stadi-
ometer (Seca, Germany) with a sensitivity of 0.1 cm and
weight with a digital scale (808 Seca, Germany) while
wearing light clothes (with no coat or raincoat) with a
sensitivity of 0.1 kg before and after of 8-week interven-
tion. Body mass index (BMI) will be calculated by divid-
ing the weight (in kilograms) by height squared (in
meters).
Blood pressure
Before and after of 8-week intervention, 24-h ABPM
with an automatic monitor in oscillatory mode will be
performed in the electrophysiology department of the
hospital. The change in blood pressure during the 24-h
period is recorded by this device. The blood pressure
cuff is placed and fixed around the upper left arm. The
digital blood pressure monitoring machine itself is at-
tached to a belt around the waist or hangs on the neck.
Technician checks that battery life is sufficient for 24 h
and checks if the machine operates well. The cuff in-
flates every 30 min in the day and every 1 h in night time
as per the settings and then slowly deflates to record the
blood pressure in its memory. Patients will be asked to
have their usual lifestyle and activities at this 24-h ambu-
latory blood pressure monitoring.
Laboratory investigations
Blood sampling A 10-mL venous blood sample will be
taken in a 12-h fasting state between 8:30 and 10:00 a.m.
by the hospital lab technician and stored in a heparin-
ized tube. Plasma separation will then be performed by
centrifugation at a speed of 1000gfor 15 min. Then, the
plasma will be collected into separate micro-tubes and
will be stored in a freezer at −80 °C until laboratory
analysis.
Blood chemistry TG, TC, HDL-C, and LDL-C concen-
trations will be measured by auto-analyzer Selectra
ProXL (Vital Scientific, Spankeren, The Netherlands)
using commercially available kits through enzymatic col-
orimetric methods as per the manufacturer’s instruc-
tions. Plasma CRP will be measured using a
turbidometric immunoassay kit by an auto-analyzer.
Plasma IL-6 will be measured using a commercially
available ELISA kit (BioLegend, USA).
Urinary test Twenty-four-hour urine will be collected
to measure its volume, creatinine, sodium, and nitrite/
nitrate-concentrations. Urinary sodium will be measured
by flame photometry to estimate sodium intake. Urine
nitrite/nitrate concentrations will be determined using a
colorimetric assay (Cayman Inc., USA). At baseline and
the end of the study, patients are given a 24-h urine con-
tainer to be filled by collected urine of the patient. The
24-h urine collection will be performed concurrently
with 24-h blood pressure monitoring and the patient will
return the container to the hospital the next day. The
volume of collected urine will be recorded and a sample
will be aliquoted into the micro-tubes to be stored in the
freezer at −80 °C until further measurements.
Atherosclerotic cardiovascular disease risk score
Ten-year risk of atherosclerotic cardiovascular disease
[26] will be determined at baseline and after the
intervention.
Safety procedures
We will record and report all adverse events. Partici-
pants with abnormal research samples will be referred to
a specialist.
Data collection
Data from questionnaires will be collected by HE and
one other trained questioners. The collected data will be
reviewed by HE at the end of the day, and in the case of
any discrepancies in data collection, the questioner is
asked to be more precise in the process of completing
the questionnaires to reduce bias.
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Data management and monitoring
Participants will be given a code number between 1
and 80. The master randomization list will be safely
stored. Interim analyses will not be performed. When
the intervention period is finished, the collected data
will be entered in the SPSS software (SPSS Inc., Chi-
cago, IL, USA).
The trial will be monitored by internal monitoring.
The study leader provides monitoring of overall trial
progress. During the study, regular meetings of the prin-
cipal investigator and study leader will be held to discuss
concerns and review the progress. Any information that
is available on serious adverse events believed to be due
to treatment will be supplied to the study cardiologist. If
there will be suspicion of harm, discontinuation of the
trial will be reviewed.
Protocol amendments
During the study, any changes and amendments will be
reviewed by the principal investigator and should be
agreed to by the other study investigators. If approved,
the amendments will be recorded with a justification
and will eventually be reported.
Statistical analyses
Data analysis will be done using SPSS version-21 soft-
ware. A per-protocol analysis will be carried out, in
which only participants who complete the full study
protocol will be included. All results will be assessed for
normality, and skewed distributions will be log-
transformed before analysis. To describe the quantitative
data, the mean and standard deviations will be used, and
to describe the qualitative data, frequency and percent
will be used. Between-group differences will be tested by
independent sample ttest and Mann-Whitney Utest as
the parametric and nonparametric tests respectively.
Paired-sample ttest and nonparametric Wilcoxon signed
ranks test will be used for evaluating within-group dif-
ferences in normally and non-normally distributed data,
respectively. Chi-square or Fisher exact tests will be used
for qualitative variables. Parametric or nonparametric
analysis of covariance (ANCOVA) will be used for
adjusting baseline levels for comparing between groups
results. In this study, Pvalue less than 0.05 will be con-
sidered statistically significant.
Auditing
The study will be conducted in accordance with the
current approved protocol and National Nutrition and
Food Technology Research Institute relevant regulations.
An auditor from the research committee members of
the National Nutrition and Food Technology Research
Institute will conduct audits during and after the study.
Ancillary and post-trial care
In these patients, if no specific side effects are observed,
if desired, the barberry powder for regular use will be
recommended to patients.
Discussion
Barberry may be useful as a functional food product for
the management of hypertension, hyperlipidemia, and
chronic inflammation in humans, to help prevent CVD.
According to a recent review, barberry has been claimed
to have potential cardioprotective effects [27].. Basic ani-
mal studies have been focused on the extract forms of
barberry. Hemmati et al. conducted a study on the anti-
atherogenic effect of hydro-alcoholic and aqueous ex-
tract of barberry, saffron, and jujube extracts on diabetic
rats. The intervention of 25 and 100 mg/kg body weight
for 21 days significantly reduced serum levels of fasting
glucose, triglycerides, VLDL, lipoprotein (a) with an in-
crease in total antioxidant capacity (TAC) ,and serum
adiponectin levels [28]. In the study of Fatehi et al. on
hypertensive rats, the MAP was significantly decreased
after 5 weeks of aqueous extract of barberry [29]. In an-
other study, Changizi et al. showed that alcoholic extract
of barberry can also improve lipid profile in a model of a
high-fat diet in the rat [30].
Human studies to date have used barberry in the form
of juice [21,31] or extract [22,32]. Daily consumption
of 200 ml barberry juice for 8 weeks significantly reduced
SBP and DBP, fasting blood sugar, TC, and TG in dia-
betic subjects [21]. In another study, 6-week supplemen-
tation with capsules containing barberry was able to
reduce oxidative status in patients with metabolic syn-
drome [31]. In patients with diabetes, daily supplementa-
tion with barberry extract (extracted from 10 g barberry)
for 3 months reduced blood lipids, glucose, and insulin
and increased TAC [22]. In another clinical trial supple-
mentation with barberry extract for 3 months reduced
serum liver enzymes in patients with non-alcoholic fatty
liver [32].
Strengths
This trial will be the first to examine the effects of sup-
plementation with dried powdered barberry on blood
pressure using the 24-h ambulatory blood pressure mon-
itoring methods. It will also be the first to investigate the
effects of barberry on 24-h urinary NOx and sodium.
There are also several features of this study designed to
add to the existing literature regarding the effect of bar-
berry on fasting blood lipids and inflammatory markers.
Limitations
The study participants are comprised of hypertensive pa-
tients with other cardiovascular risk factors on medica-
tion. Therefore, a potential limitation of the study will
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Content courtesy of Springer Nature, terms of use apply. Rights reserved.
be related to the generalizability of the results to the
whole population. However, a large percentage of adults
at risk for CVD are using at least one prescription medi-
cation to control hypertension or other cardiovascular
risk factors. As such, although a placebo control will be
applied in our study, we can assess only the complemen-
tary effect of barberry, because medications are a stand-
ard of care treatment for patients with cardiovascular
risk factors. Another limitation of the study is the lack of
measurement of urinary phenolic compound. Measure-
ment of urinary flavonoid or polyphenol will undoubt-
edly provide invaluable information regarding the intake
and absorption of polyphenols [33].
The interest in natural and functional food products
has increased globally. Reliable evidence is needed to
confirm the health claims related to functional foods
that are obtainable through replicated, randomized,
placebo-controlled, intervention trials in human sub-
jects. In this regard, it will be interesting to conduct re-
search aimed at evaluating the effectiveness of dried
barberry which is a rich source of polyphenol for use in
health promotion and disease prevention and manage-
ment. This RCT will add to the growing literature for
the potential antihypertensive, lipid-lowering, and anti-
inflammatory effects of barberry in humans.
Trial status
The current protocol is version 1, dated 26 March 2020,
and any changes to the protocol will be communicated
to all relevant parties, including participants. The re-
cruitment process has been started since 2020-01-20
and is anticipated to last for 5 months.
Supplementary information
Supplementary information accompanies this paper at https://doi.org/10.
1186/s13063-020-04918-7.
Additional file 1. SPIRIT 2013 Checklist: Recommended items to address
in a clinical trial protocol and related documents.
Additional file 2. Informed consent.
Abbreviations
ABPM: Ambulatory blood pressure monitoring; ANCOVA: Analysis of
covariance; BP: Barberry powder; BMI: Body mass index; CVD: Cardiovascular
disease; CRP: C-reactive protein; DBP: Diastolic blood pressure; HDL-C: High-
density lipoprotein cholesterol; IL-6: Interleukin-6; LDL-C: Low-density
lipoprotein cholesterol; MAP: Mean arterial blood pressure; NO: Nitric oxide;
NOx: Nitrite and nitrate; PP: Placebo powder; RCT: Randomized controlled
clinical trial; SBP: Systolic blood pressure; TG: Triglyceride; TC: Total
cholesterol; WHO: World Health Organization
Acknowledgements
The study is supported by National Nutrition and Food Technology Research
Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. We
thank the personnel of Shahid Rajaei Hospital. We are also grateful to the
volunteers who participate in the study.
Authors’contributions
J.N and H.E designed the initial idea of this work, which was further
developed by A.Z and S.A. J.N, H.E, and H.T contributed to drafting of the
manuscript. The manuscript has been read and approved by all authors.
Funding
The study is supported by National Nutrition and Food Technology Research
Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. There
is no active involvement of funding party, either in terms of the study
design, nor data collection, analysis, interpretation, or in writing of the
manuscript.
Availability of data and materials
The datasets generated and/or analyzed during the current study will be
available from the corresponding author on reasonable request.
Ethics approval and consent to participate
The trial has received ethical approval from the Ethics Committee of NNFTRI
(2018-10-20: Ethical code: IR.SBMU.nnftri.Rec.1397.248). Informed consent will
be obtained from all participants by HE.
Consent for publication
All authors gave their consent for publication. Consent from the patients has
been obtained for publications of non-identifiable information about them.
Competing interests
The authors declared that there is no conflict of interest.
Author details
1
Department of Clinical Nutrition & Dietetics, National Nutrition and Food
Technology Research Institute, Faculty of Nutrition Sciences and Food
Technology, Shahid Beheshti University of Medical Sciences, Tehran P.O.
19395-4741, Iran.
2
Cardiovascular Intervention Research Center, Shahid Rajaei
Cardiovascular, Medical & Research Center, Iran University of Medical
Sciences, Tehran, Iran.
3
Department of Radiology, Shahid Rajaie
Cardiovascular, Medical, and Research Center, Tehran, Iran.
4
Department of
Nutrition, Persian Gulf Tropical Medicine Research Center, Bushehr University
of Medical Sciences, Bushehr, Iran.
Received: 24 May 2020 Accepted: 18 November 2020
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