Complementary Therapies in Clinical Practice xxx (2015) 1e7

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Complementary Therapies in Clinical Practice

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Efficacy of the Malva sylvestris L. flowers aqueous extract for functional

constipation: A placebo-controlled trial
Mahin Elsagh a, Mohammad Reza Fartookzadeh b, Mohammad Kamalinejad c,
Majid Anushiravani d, Awat Feizi e, Farshad Amini Behbahani a, Rahmatollah Rafiei f,
Akbar Arjmandpour f, Peyman Adibi g, *
a
Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences, Tehran, Iran
b
Department of Ophthalmology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
c
Department of Pharmacognosy, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
d
Department of Traditional Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
e
Department of Biostatistics and Epidemiology, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
f
Department of Gastroenterology, Faculty of Medicine, Islamic Azad University, Najafabad Branch, Najafabad, Iran
g
Gastroenterology Section, Integrative Functional Gastroenterology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

a b s t r a c t
Keywords: Objective: To evaluate the efficacy of Malva sylvestris L. flowers extract for treatment of FC.
Constipation Method: Adults with FC were allocated to receive the M. sylvestris L. flowers aqueous extract syrup (MSL,
Herbal medicine
1 g extract/day) or placebo for four weeks. Frequency of constipation symptoms and stool forms were
Traditional medicine
Malva
assessed every week. Self-reported improvement was assessed after treatment.
Malvaceae Results: Compared with placebo, more increase was observed in defecation frequency (F ¼ 18.8,
P < 0.001) and more decrease was observed in frequency of all constipation symptoms by MSL (F ¼ 16.5
to 25.3, all P values <0.001). Also, the MSL group experienced more reduction in frequency of hard stool
forms (45.4% vs. 9.1%, P < 0.001) and reported more improvement in all symptoms (all P values <0.01)
than placebo.
Conclusion: The M. sylvestris L. flowers aqueous extract is efficacious and safe for the treatment of FC in
adult patients. Investigating the mechanisms of action is warranted. IRCT2014031617032N1.
© 2015 Elsevier Ltd. All rights reserved.

1. Introduction
Chronic constipation is a common gastrointestinal complaint
affecting up to 20% of the adults and 30% of the children in Western
countries [1,2]. In Iran, the reported prevalence of constipation
ranges from 1.4% to 37% [3]. Usually, there is no clear underlying
structural or biochemical abnormalities leaving the diagnosis of
functional constipation (FC) or chronic idiopathic constipation [4].
The prevalence of FC ranges from 12% to 17% in Western countries
* Corresponding author. Gastroenterology Section, Integrative Functional
Gastroenterology Research Center, Isfahan University of Medical Sciences, Hakim
Nezami Avenue, Isfahan, Iran. Tel.: þ98 912 313 9303; fax: þ98 313 668 7818.
E-mail addresses: elsaghm@yahoo.com (M. Elsagh), m_fartookzade@yahoo.com
(M.R. Fartookzadeh), mkamalinejad@yahoo.com (M. Kamalinejad), anushiravanim@
mums.ac.ir (M. Anushiravani), awat_feizi@hotmail.com (A. Feizi), farshadamini2@
yahoo.com (F.A. Behbahani), rahmatollahrafiei@yahoo.com (R. Rafiei),
arjmandakbar@yahoo.com (A. Arjmandpour), adibi@med.mui.ac.ir (P. Adibi).
[5], and from 2.4% to 11.2% in Iran [3]. It is associated with high
healthcare costs [6,7] and significant impairment in quality of life
[8].
Current medical treatments for FC include various laxatives (e.g.
bulking and osmotic) and prokinetic agents (e.g. 5- hydroxytryp-
tamine 3,4ereceptor (ant)agonists) [9]. A number of these treat-
ments are shown effective in the treatment of FC. However, not all
patients have satisfactory response to these medications and con-
cerns exist regarding the adverse effects as well [9]. Accordingly, a
large number of patients with FC try complementary and alterna-
tive medicine (CAM) for treatment with herbal therapies among
the most used CAM methods [10,11]. Several herbal medicines are
proposed for the treatment of constipation, but there is lack of
scientific evidence supporting their efficacy and safety [10,12e14].
The genus Malva L. (in the family Malvaceae) is represented by
about 40 taxa worldwide. The Malva sylvestris L. is an annual herb
with shallowly lobed leaves and purple flowers blooming at late
spring. This herb is native to Europe, North Africa, and South-west

http://dx.doi.org/10.1016/j.ctcp.2015.02.003
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Please cite this article in press as: Elsagh M, et al., Efficacy of the Malva sylvestris L. flowers aqueous extract for functional constipation: A
placebo-controlled trial, Complementary Therapies in Clinical Practice (2015), http://dx.doi.org/10.1016/j.ctcp.2015.02.003
2 M. Elsagh et al. / Complementary Therapies in Clinical Practice xxx (2015) 1e7
Asia especially Iran [15,16]. There is a long history of using
M. sylvestris L. in Iran where it is named as ‘Panirak’ (or ‘Khobazi’)
and commonly used as a vegetable as well as a medicinal plant [16].
The M. sylvestris L. is proposed for the treatment of burn and dermal
infected wounds, bronchitis, inflammations, and digestive prob-
lems including constipation [15,16]. Leaves, flowers, and aerial
parts are used as laxative in human and animals [15]. Mucilages are
one of the major components responsible for the therapeutic ef-
fects of Malva, and the Malvaceae family possesses the most
abundant deposits of mucilages. These mucilages, which can be
found mainly in leaves, flowers, and roots, are probably responsible
for the laxative effects of the M. sylvestris L [15].
Although several non-pharmacological therapies are claimed to
be beneficial for patients with FC, most of them lack supportive
qualified evidence. The M. sylvestris L. is suggested for the treatment
of constipation in traditional medicine documents [15]. However, to
our knowledge, there is no report from a placebo-controlled trial on
its application in the treatment of constipation. Accordingly, we
aimed to investigate the efficacy of M. sylvestris L., the flowers
extract, for the treatment of FC in adult patients. We hypothesized
that this herbal drug would result in improvement of stool frequency
and consistency, as well as improvement of constipation symptoms.
2. Methods
2.1. Participant and study setting
This study was conducted in the gastroenterology clinic of the
Shariati University Hospital in Isfahan city (Iran) between
December 2013 and October 2014. Inclusion criteria were age be-
tween 18 and 65 years and diagnosis of FC by a gastroenterologist
based on the Rome III criteria [4]. Appropriate work-ups were done
by the gastroenterologist according to the current standards [4].
Patients with active anal fissure, history of gastrointestinal surgery
(except appendectomy and cholecystectomy), and pregnant/
lactating women were not included into the study. Exclusion
criteria were no proper consumption or preservation of the drug,
using laxatives during the study, occurrence of any severe side ef-
fects, and willingness to discontinue the study for any reason. The
study was approved by the Ethics Committee of the Tehran Uni-
versity of Medical Sciences and informed consent was obtained
from patients. The study protocol was registered at the Iranian
Registry of Clinical Trials [http://www.irct.ir, registration code:
IRCT2014031617032N1].
2.2. Study design
2.2.1. Herbal drug preparation
The herbal medicine used in this trial was an aqueous extract of
the M. sylvestris L. (Malvaceae; Panirak or Khobazi). Preparation of
the M. sylvestris L. and placebo syrups was done in the Herbal
Medicine Laboratory of the Shahid Beheshti School of Pharmacy
(Tehran, Iran). The extract was produced from the dry flowers of the
herb which has been harvested in Kerman (Iran) [17] and pur-
chased from the local herbal medicine market (Tehran city, Iran).
The herbs were approved by the Herbarium of the Shahid Beheshti
School of Pharmacy.
One liter of boiled water (100c degree) was added to 100 mg of
dry flowers and kept in closed container in the laboratory for four
hours. The solvent was then removed under vacuum at 40c degree
using a rotatory vacuum evaporator. Sugar solution 50% was added
to the extract obtaining 50 mg of the extract in each 1 cc of the
syrup. Herb-to-extract ratio was then 6:1. Placebo was prepared
based on pharmacopoeia simple syrup formula including approved
color additives and looked the same as the M. sylvestris L. syrup.
Please cite this article in press as: Elsagh M, et al., Efficacy of the Malva sylvestris L. flowers aqueous extract for functional constipation: A
placebo-controlled trial, Complementary Therapies in Clinical Practice (2015), http://dx.doi.org/10.1016/j.ctcp.2015.02.003
2.2.2. Allocation, medication, blinding, and compliance
The study was a placebo-controlled clinical trial with two par-
allel groups. Patients were alternately and equally allocated into
two groups of M. sylvestris L. extract (MSL) and placebo and
consumed 10 cc of the syrup twice daily (2e3 h after breakfast and
lunch) for four weeks. Therefore, patients in the MSL group
received 1 g of the extract equal to 6 g of the herb/day. This dosage
of the product and duration of therapy was determined by referring
to the PDR for Herbal Medicines [18]. The MSL and placebo were
packed and alphabetically labeled in the same opaque and sealed
bottles. Attending physician, patients, outcome assessor, and data
analyzer were blinded to the study arms. A co-investigator who was
not involved in patients' recruitment or allocation or in outcome
assessment was aware of the drug codes and cleared it after data
analysis. The gastroenterologist enrolled the patients and assigned
them to their groups alternately. The outcome assessor checked
patients’ compliance every week by live interview or telephone call.
2.3. Measurements
Symptoms of constipation were assessed using an investigator
generated questionnaire based on the Rome III criteria 4. Items
evaluated the frequency of defecation as per week and frequency of
hard stool, straining during defecation, sensation of incomplete
evacuation, and manual maneuvers to facilitate evacuation as rated
from 0 (never) to 3 (always). The Bristol stool scale was used to
specify the stool form with types 1 and 2 considered as hard, 3 and
4 as normal, and 5 to 7 as loose stool forms [19,20]. Patients
completed this questionnaire at baseline, week 2, and week 4 at the
time of visit, and at week 1 and 3 by telephone interview. Overall
improvement in each symptom was assessed (self-rated) at the end
of therapy and rated from much improved to much worse. The
response categories were then merged to improved, same, and
worse. Side effects were assessed at weeks 2 and 4 by interview and
using a checklist.
2.4. Data analyses
2.4.1. Primary and secondary outcomes
The primary outcome of the study was the changes in defecation
and constipation symptoms’ frequency after treatment. Changes in
stool consistency, overall self-reported improvement in symptoms
after treatment, and side effects were considered as the secondary
outcomes.
2.4.2. Sample size calculation
Sample size was determined using the formula for repeated
measures design [21] where a and b as the type I and II error rates
were considered to be 5% and 20%, respectively. Minimum detect-
able standardized effect size (i.e. D) was considered to be of 0.26.
Sample size was then calculated as 55 patients in each study group
after about 20% drop-out rate was considered.
2.4.3. Statistical analyses
Data were analyzed using the SPSS software version 16.0 (SPSS
Inc., Chicago IL., USA.). Normal distribution of quantitative data was
checked with the KolmogoroveSmirnov Test. Data are reported as
mean ± standard deviation (SD) or number (%) for continuous and
categorical data, respectively. Comparisons between the two
groups were done with the Independent Sample t-Test, Man-
neWhitney U Test, and Chi-Square (or Fisher's Exact) Test.
Repeated measure analysis using linear mixed effect models was
done to test the trend of changes in scores of each outcome variable
over the study period while controlling for the baseline values (as
covariates). All analyses were performed based on the intention-to-
 M. Elsagh et al. / Complementary Therapies in Clinical Practice xxx (2015) 1e7 3

treat (ITT) principles. The linear mixed effects model and the last Table 1
observation carried forward method were applied. A two-tailed P Comparison of the baseline characteristics between the study groups.

value of <0.05 was considered as statistically significant in all M. sylvestris n ¼ 55 Placebo n ¼ 55 P value
analyses. Age, year 42.1 ± 12.0 41.5 ± 11.8 0.806a
Female/Male 36 (65.5)/19 (34.5) 42 (76.4)/13 (23.6) 0.294b
Disease duration, year 8.7 ± 9.9 4.8 ± 5.3 0.027c
3. Results
Data are presented as mean ± standard deviation or number (%).
a
3.1. Participant characteristics Independent sample t-test.
b
Chi-square test.
c
ManneWhitney U test.
A total of 203 patients referring with constipation were evalu-
ated during the study period from which 128 patients were eligible
and willing to participate in the study. Finally, 110 patients partic- between time and treatment (P < 0.01) as well as a significant effect
ipated and started the medication. During the 4-week study for treatment (P < 0.001) in this regard, Table 2 and Fig. 2.
duration 67 patients dropped-out of the study (Fig. 1). Compared Frequency of all symptoms was decreased over time in the MSL
with patients who remained in the study, those who discontinued group (all P values < 0.001). In the placebo group, changes in the
the study were younger (difference 5.2 ± 2.2 years, P ¼ 0.024), but frequency of hard stool and straining for defecation were not sig-
not significantly different regarding symptoms (P > 0.05). Consid- nificant (P ¼ 0.278 and 0.065, respectively). There was a significant
ering these drop-outs during the study period, all analyses were interaction between time and treatment (all P values < 0.001) for all
performed based on the ITT principles. Demographic characteristics symptoms as well as a significant effect of treatment (all P
are summarized in Table 1. The two groups were not similar values < 0.01) for all symptoms except manual maneuvers to
regarding some of the baseline symptoms’ characteristics as pre- facilitate evacuation; more improvements were observed for the
sented in Table 2. Accordingly, the baseline values of the outcome symptoms in MSL compared with placebo group, Table 2 and
variables were considered as covariates and controlled in the Figs. 3e6.
analyses.
3.3. Effects of intervention on stool form
3.2. Effects of intervention on symptoms’ frequency
Patients in the MSL group had more frequent hard stool forms at
Defecation frequency was increased in both the MSL (P < 0.001) baseline compared with the placebo group (P ¼ 0.017). After week
and placebo (P ¼ 0.003) groups. There was a significant interaction 2, patients in the MSL group had less frequent hard stool forms and

Fig. 1. Patients' flow diagram.

Please cite this article in press as: Elsagh M, et al., Efficacy of the Malva sylvestris L. flowers aqueous extract for functional constipation: A
placebo-controlled trial, Complementary Therapies in Clinical Practice (2015), http://dx.doi.org/10.1016/j.ctcp.2015.02.003
4 M. Elsagh et al. / Complementary Therapies in Clinical Practice xxx (2015) 1e7

Table 2
Tests of within- and between-subjects effects regarding changes in symptoms’ frequency over the study period in the study groups.

Variables Group Baseline Week 1 Week 2 Week 3 Week 4 Timeb Treatmentb Time  treatmentb

Defecation, per week M. sylvestris 4.61 ± 3.14 6.48 ± 3.43 7.25 ± 4.10 7.40 ± 3.97 7.00 ± 3.95 F ¼ 15.6, F ¼ 18.8 F ¼ 8.6
P < 0.001
Placebo 4.43 ± 2.72 5.09 ± 2.70 4.80 ± 2.65 5.12 ± 2.76 5.14 ± 2.74 F ¼ 4.0, P < 0.001 P < 0.001
P ¼ 0.003
a
P 0.931 0.018 0.001 0.002 0.012
Constipation symptomsc
Hard stool M. sylvestris 2.11 ± 0.83 1.38 ± 0.87 1.22 ± 0.90 1.12 ± 0.89 1.16 ± 0.94 F ¼ 29.6, F ¼ 25.3 F ¼ 11.1
P < 0.001
Placebo 1.65 ± 0.84 1.54 ± 0.74 1.52 ± 0.83 1.54 ± 0.78 1.54 ± 0.83 F ¼ 1.2, P < 0.001 P < 0.001
P ¼ 0.278
Pa 0.008 0.367 0.058 0.012 0.023
Straining during defecation M. sylvestris 2.23 ± 0.71 1.38 ± 0.78 1.30 ± 0.81 1.27 ± 0.80 1.27 ± 0.82 F ¼ 36.5, F ¼ 19.1 F ¼ 8.7
P < 0.001
Placebo 1.78 ± 0.73 1.61 ± 0.68 1.60 ± 0.80 1.58 ± 0.80 1.61 ± 0.80 F ¼ 2.7, P < 0.001 P < 0.001
P ¼ 0.065
Pa 0.002 0.171 0.075 0.069 0.032
Sense of incomplete M. sylvestris 1.94 ± 0.77 1.40 ± 0.80 1.21 ± 0.78 1.12 ± 0.74 1.14 ± 0.84 F ¼ 28.9, F ¼ 16.5 F ¼ 7.2
evacuation P < 0.001
Placebo 1.67 ± 0.81 1.52 ± 0.76 1.45 ± 0.76 1.45 ± 0.76 1.49 ± 0.81 F ¼ 3.4, P < 0.001 P < 0.001
P ¼ 0.022
a
P 0.081 0.504 0.119 0.028 0.030
Manual maneuvers to M. sylvestris 0.89 ± 0.99 0.61 ± 0.73 0.47 ± 0.66 0.41 ± 0.59 0.41 ± 0.59 F ¼ 14.7, F ¼ 0.1 F ¼ 10.2
facilitate evacuation P < 0.001
Placebo 0.56 ± 0.81 0.41 ± 0.68 0.52 ± 0.76 0.50 ± 0.71 0.52 ± 0.74 F ¼ 2.8, P ¼ 0.177 P < 0.001
P ¼ 0.041
a
P 0.077 0.105 0.912 0.608 0.561

Data are presented as mean ± standard deviation.

a
ManneWhitney U Test.
b
ANOVA repeated measures test for assessing time effect, treatment effect, and interaction between time and treatment.
c
Symptoms' frequency are rated from 0 (never) to 3 (always).

Fig. 2. Trends of change in stool frequency (per week) in the M. sylvestris and placebo Fig. 3. Trends of change in hard stool frequency (from 0 ¼ never to 3 ¼ always) in the
groups over the study period. M. sylvestris and placebo groups over the study period.

more frequent normal stool forms than the placebo groups (all P 3.5. Side effects
values < 0.05). Hard stool forms’ frequency was decreased from
81.8% to 36.4% with MSL (P < 0.001) and from 61.8% to 52.7% with Side effects were infrequent and mild with no significant dif-
placebo (P ¼ 0.125), Table 3. ference between the MSL and placebo groups, Table 5.

3.4. Effects of intervention on self-rated improvement of symptoms 4. Discussion

Patients in the MSL group reported more improvement in all We investigated the efficacy of M. sylvestris L. flowers aqueous
symptoms than the placebo group after treatment (all P extract for FC in adult patients. According to the findings, this
values < 0.01), Table 4. herbal product increased stool frequency and improved symptoms

Please cite this article in press as: Elsagh M, et al., Efficacy of the Malva sylvestris L. flowers aqueous extract for functional constipation: A
placebo-controlled trial, Complementary Therapies in Clinical Practice (2015), http://dx.doi.org/10.1016/j.ctcp.2015.02.003
 M. Elsagh et al. / Complementary Therapies in Clinical Practice xxx (2015) 1e7
Fig. 4. Trends of change in frequency of straining during defecation (from 0 ¼ never to
3 ¼ always) in the M. sylvestris and placebo groups over the study period.
Fig. 5. Trends of change in frequency of sense of incomplete evacuation (from
0 ¼ never to 3 ¼ always) in the M. sylvestris and placebo groups over the study period.
of constipation and stool consistency. The patients-reported overall
improvement for the symptoms was consistent with these results.
Considering very few and mild side effects associated with the
product, this study shows that the M. sylvestris L. syrup containing
flowers aqueous extract is efficacious as well as safe in the treat-
ment of FC in adult patients.
The underlying mechanisms of the observed effects of
M. sylvestris L. flowers extract on constipation symptoms are not
clear. This herb contains various ingredients including amino acids/
protein derivatives, flavonoids, mucilages, terpenoids, phenol de-
rivatives, enzymes, coumarins, vitamins, and fatty acids/sterols.
Among the main ingredients presumed to be responsible for much
of the medicinal effects of the herb are mucilages. Especially the
leaves, flowers, and roots which have laxative effects contain this
ingredient [15]. Mucilage consists mainly of glucuronic acid, gal-
acturonic acid, rhamnose, galactose, fructose, glucose, sucrose and
Please cite this article in press as: Elsagh M, et al., Efficacy of the Malva sylvestris L. flowers aqueous extract for functional constipation: A
placebo-controlled trial, Complementary Therapies in Clinical Practice (2015), http://dx.doi.org/10.1016/j.ctcp.2015.02.003
5
Fig. 6. Trends of change in frequency of manual maneuvers to facilitate evacuation
(from 0 ¼ never to 3 ¼ always) in the M. sylvestris and placebo groups over the study
period.
trehalose. Therefore, after hydrolysis, it may act like hydrophilic
laxatives, softening-wetting agents, as well as osmotic laxatives
[22]. Accordingly, the prompt observed laxative effects of the
M. sylvestris L. in our study can be attributed to its mucilages,
though other mechanisms are also plausible.
Altered gut microflora is proposed as one of the underlying
etiologies of various functional gastrointestinal disorders including
FC [23]. Some studies have shown the efficacy of altering gut
microflora, e.g. by prebiotics/probiotics, in the treatment of con-
stipation [24,25]. The M. sylvestris L. has anti-microbial and anti-
inflammatory effects, attributable to its flavonoids contents
[15,26]. Moreover, the monosaccharide sugar products of the
mucilage hydrolysis can be converted to acids (e.g. lactic acid) by
the gut bacteria [27], lowering the gut pH and helping in balancing
the intestinal microflora and normalizing the intestinal transit [28].
The extract from M. sylvestris L. has also acetylcholinesterase (AChE)
inhibitory effects. In one study, 28% of AChE inhibition was shown
with 0.1 mg/ml of the essential oil and 25% of inhibition with 5 mg/
ml of the herb decoction [29]. Acetylcholine is one of the main
neurotransmitters controlling the gut motility [30], and evidence
exists that drugs with AChE inhibition effects (e.g. pyridostigmine)
can improve symptoms of constipation [31,32]. Therefore, the ef-
fects of M. sylvestris L. on the gut microflora and its gut-stimulatory
properties by inhibiting AChE are other possible mechanisms of
action which may complement the laxative effects of this herb.
Because evidence suggesting these effects of the herb is scarce,
further studies are required in these regards.
Various herbal medicines are suggested by traditional medicine
documents for the treatment of constipation, but few of them are
investigated in controlled clinical trials. Psyllium (Ispaghula), a
derivative of the Plantago ovata plant, is shown to have bulking and
hydrophilic laxative effects and can improve stool frequency and
consistency [33]. Dried plums (prunes), called 'Alu-bukhara' in Iran,
are other popular natural products traditionally being used for the
treatment of constipation [34]. A recent randomized trial in chronic
constipation patients showed that prunes are more effective than
psyllium in improving stool frequency and consistency [35]. The
laxative properties of prunes has been attributed to its osmotic
(sorbitol), hydrophilic (water soluble fiber), and stimulant
6 M. Elsagh et al. / Complementary Therapies in Clinical Practice xxx (2015) 1e7

Table 3 of constipation, the studies have had generally low methodological

Comparison of changes in stool form over the study period between the study quality and a clear conclusion cannot be obtained on these medi-
groups.
cines [13].
Time Stool formb M. sylvestris n ¼ 55 Placebo n ¼ 55 P valuea There are some limitations to our study. 1) The study arms were
Baseline Hard stool 45 (81.8) 34 (61.8) 0.017 not similar in baseline characteristics. We conducted the analyses
Normal 10 (18.2) 21 (38.2) while controlling for the baseline values of the outcome variables to
Loose stool 0 0 solve this problem. 2) Drop-out rate was high in our study which
Week 1 Hard stool 22 (40.0) 27 (49.1) 0.130
might limit the generalizability of the results. Accordingly, we
Normal 27 (49.1) 27 (49.1)
Loose stool 6 (10.9) 1 (1.8) conducted the analyses based on the ITT principles. Although the
Week 2 Hard stool 18 (37.2) 31 (56.4) 0.002 ITT analyses may underestimate the effects of the interventions, our
Normal 28 (50.9) 24 (43.6) study found significant beneficial effects for the M. sylvestris L.
Loose stool 9 (16.4) 0
extract. 3) All outcomes in our study were subjective with possi-
Week 3 Hard stool 16 (29.1) 30 (54.5) 0.002
Normal 31 (56.4) 25 (45.5)
bility of recall-bias. Applying more objective outcomes such as
Loose stool 8 (14.5) 0 colonic transit time and stool water content can provide better data
Week 4 Hard stool 20 (36.4) 29 (52.7) 0.005 on mechanisms of action of the M. sylvestris L. extract. 4) We did not
Normal 26 (47.3) 26 (47.3) follow the patients after drug discontinuation. Hence, we could not
Loose stool 9 (16.4) 0
provide data on the possible long-term effects of the M. sylvestris L.
Data are presented as number (%). extract on constipation symptoms. 5) Producing a credible placebo
a
Chi-Square Test (or Fisher's Exact Test).
b
for herbs with same characteristics such as color, taste, smell, and
Hard stool: types 1e2, Normal stool: types 3e4, and Loose stool: types 5e7,
based on the Bristol stool scale.
texture is difficult. It is possible that our patients could guess about
the content of the allocated drug. Because we did not get feedback
from the patients in this regard, we cannot claim that the blinding
Table 4 process in our study was successful.
Comparison of self-report improvement for each symptom at week 4 between the In conclusion, the aqueous extract from M. sylvestris L. flowers in
study groups.
form of syrup is effective in treatment of FC in adult patients. The
Symptoms M. sylvestris n ¼ 55 Placebo n ¼ 55 P valuea beneficial effects of this herbal medicine in FC patients are
Hard stool increasing stool frequency and improving stool consistency and
Improved 45 (81.8) 22 (40.0) <0.001 constipation symptoms. The side effects of the M. sylvestris L.
No change 10 (18.1) 30 (54.5) flowers extract were infrequent and often mild. Accordingly, this
Worse 0 2 (3.6)
herbal product is efficacious as well as safe in the treatment of FC in
Straining
Improved 42 (76.3) 21 (38.1) <0.001 adult patients. The possible mechanisms of action of this herbal
No change 13 (23.6) 34 (61.8) medicine on constipation need to be discovered. Further trials are
Worse 0 0 warranted to investigate the efficacy of M. sylvestris L. extract for
Incomplete evacuation constipation in elderly as well as children patients. Dose determi-
Improved 37 (67.2) 13 (23.6) <0.001
No change 17 (30.9) 41 (74.5)
nation studies are also required in this regard.
Worse 0 1 (1.8)
Manual maneuvers Source of funding
Improved 24 (43.6) 11 (20.0) 0.007
No change 31 (56.3) 44 (80.0)
Tehran University of Medical Sciences.
Worse 0 0

Data are presented as number (%). Conflict of interest statement

a
Chi-Square Test (or Fisher's Exact Test).
None.

Table 5 Authors contributions

Comparison of side effects between the study groups.

Side effects M. sylvestris n ¼ 55 Placebo n ¼ 55 P valuea

ME: grant writing, data gathering, drafting of the manuscript;
PA: study design, data analyses and interpretation; MRF, MK, MA,
Diarrhea 4 (7.2) 0 0.118
and FAB: study idea and design, grant writing; AF: statistical
Acid regurgitation 4 (7.2) 0 0.118
Nausea 2 (3.6) 0 0.495 consultant, designing the study, data analyses and interpretation;
Worse constipation 1 (1.8) 3 (5.4) 0.618 RR and AA: subject recruitment, data gathering. All authors studied
Epigastric pain 1 (1.8) 0 >0.999 the manuscript and revised and approved its final version including
Heartburn 1 (1.8) 0 >0.999
the authorship list.
Urticaria 1 (1.8) 0 >0.999
Dry mouth 0 1 (1.8) >0.999
Increase appetite 0 1 (1.8) >0.999 Acknowledgments
Others 0 1 (1.8) >0.999

Data are presented as number (%).
a
Fisher's Exact Test.
(dihydroxyphenyl isatin) contents [35]. Senna, a stimulant laxative,
is another herbal drug used by patients with constipation. How-
ever, few studies have evaluated its efficacy, and side effects asso-
ciated with this drug are disturbing [33]. Several studies are also
conducted on Chinese herbal medicine for constipation. Although
some herbal medicines have shown to be effective in the treatment
This study was supported by the Tehran University of Medical
Sciences (grant # 1106). The sponsor had no role in the study
design, the collection, analysis and interpretation of data, writing of
the manuscript, or in the decision to submit the manuscript for
publication. We are thankful to patients who participated in the
study and personnel of the Gastroenterology Clinic of the Shariati
Hospital, Shahid Abbaspour Internal Medicine Polyclinic, and the
Integrative Functional Gastroenterology Research Center as well as
Dr. Mojgan Mehri who helped us in conducting the study. Also, we
are thankful to Dr. Ali Gholamrezaei who edited the manuscript.

Please cite this article in press as: Elsagh M, et al., Efficacy of the Malva sylvestris L. flowers aqueous extract for functional constipation: A
placebo-controlled trial, Complementary Therapies in Clinical Practice (2015), http://dx.doi.org/10.1016/j.ctcp.2015.02.003
 M. Elsagh et al. / Complementary Therapies in Clinical Practice xxx (2015) 1e7 7

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Please cite this article in press as: Elsagh M, et al., Efficacy of the Malva sylvestris L. flowers aqueous extract for functional constipation: A
placebo-controlled trial, Complementary Therapies in Clinical Practice (2015), http://dx.doi.org/10.1016/j.ctcp.2015.02.003