The Efficacy of an Herbal Medicine, Carmint, on the Relief of Abdominal Pain and Bloating in Patients with Irritable Bowel Syndrome: A Pilot Study

Abstract

Carmint contains total extracts of Melissa officinalis, Mentha spicata, and Coriandrum sativum, which have antispasmodic, carminative, and sedative effects. As abdominal pain/discomfort and bloating are commonly observed in patients with irritable bowel syndrome, we decided to evaluate the effectiveness of Carmint in relieving these symptoms in irritable bowel syndrome patients. We randomly assigned 32 irritable bowel syndrome patients to receive either Carmint or placebo, plus Loperamide or psyllium (based on their predominant bowel function), for 8 weeks. T-test analysis of the results showed that the severity and frequency of abdominal pain/discomfort were significantly lower in the Carmint group than the placebo group at the end of the treatment (P=0.016 and P=0.001, respectively), as were the severity and frequency of bloating (P=0.02 and P=0.002, respectively). This pilot study suggests that Carmint plus loperamide or Carmint plus psyllium (depending on the irritable bowel syndrome subtype) might be effective in these patients.

Full text

Dig Dis Sci (2006) 51:1501–1507
DOI 10.1007/s10620-006-9079-3
ORIGINAL PAPER
The Efficacy of an Herbal Medicine, Carmint, on the Relief
of Abdominal Pain and Bloating in Patients with Irritable
Bowel Syndrome: A Pilot Study
Reyhaneh Vejdani ·
Hamid Reza Mohaghegh Shalmani ·
Mina Mir-Fattahi · Faranak Sajed-Nia ·
Morteza Abdollahi · Mohammad Reza Zali ·
Amir Houshang Mohammad Alizadeh · Ali Bahari ·
Gholamreza Amin
Received: 13 July 2005 / Accepted: 4 October 2005 / Published online: 26 July 2006
C

Springer Science+Business Media, Inc. 2006
Abstract Carmint contains total extracts of Melissa offici-
nalis, Mentha spicata, and Coriandrum sativum, which have
antispasmodic, carminative, and sedative effects. As abdom-
inal pain/discomfort and bloating are commonly observed in
patients with irritable bowel syndrome, we decided to eval-
uate the effectiveness of Carmint in relieving these symp-
toms in irritable bowel syndrome patients. We randomly as-
signed 32 irritable bowel syndrome patients to receive either
Carmint or placebo, plus Loperamide or psyllium (based on
their predominant bowel function), for 8 weeks. T-test anal-
ysis of the results showed that the severity and frequency of
abdominal pain/discomfort were significantly lower in the
Carmint group than the placebo group at the end of the treat-
ment (P =0.016 and P =0.001, respectively), as were the
severity and frequency of bloating (P =0.02 and P =0.002,
respectively). This pilot study suggests that Carmint plus
R. Vejdani · H. R. M. Shalmani · M. Mir-Fattahi · F. Sajed-Nia ·
M. Zali · A. H. M. Alizadeh · A. Bahari
The Research Center for Gastroenterology and Liver Diseases
(RCGLD), Shaheed Beheshti University of Medical Sciences,
Tehran, Iran
M. Abdollahi
National Nutrition and Food Technology Research Institute
(NNFTRI), Shaheed Beheshti University of Medical Sciences,
Tehran, Iran
G. Amin
Department of Pharmacognosy, School of Pharmacy, Tehran
University of Medical Sciences,
Tehran, Iran
R. Vejdani (

)
Number 41, 5th Floor, Entrance Number 4, A3 Block, Phase 1,
Ekbatan, Tehran, Iran, 14437-36143,
e-mail:vejdani
r@yahoo.com
loperamide or Carmint plus psyllium (depending on the ir-
ritable bowel syndrome subtype) might be effective in these
patients.
Keywords Irritable bowel syndrome
.
Carmint
.
Herbal
medicine
.
Randomized placebo-controlled trial
Introduction
Irritable bowel syndrome (IBS) is a condition where patients
experience a variable combination of abdominal pain or dis-
comfort, bloating, and altered bowel function [1]. Its cause
and pathogenesis, however, remain poorly understood [2].
Depending on the bowel habit alteration, patients with IBS
may be grouped according to the predominant symptom: ei-
ther constipation or diarrhea. However, clinical experience
of many clinicians indicates that, often, the predominant
bowel pattern alternates between constipation and diarrhea
over a long period of time [3–5]. Although IBS is not a life-
threatening condition, it may lead to considerable impair-
ment of health-related quality of life and high health-care
costs [6].
Given the diversity of definitions and diagnostic criteria,
its prevalence has not been firmly established, but it has been
estimated that IBS affects 14–24% of women and 5–15%
of men in Western countries [7–9]. There are no exact data
on the prevalence of IBS in Iran, but in a study on two
populations its prevalence is reported to be around 4% [10].
Treatment of IBS is largely based on the use of antispas-
modics, antidepressants, and medications that modify bowel
habit, depending on whether constipation or diarrhea is the
predominant problem [11]. Increased dietary fiber or psyl-
lium products are frequently recommended for patients with
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1502 Dig Dis Sci (2006) 51:1501–1507
constipation-predominant IBS [12]. There is evidence that
fiber decreases whole-gut transit time, which may alleviate
constipation; fiber also may decrease intracolonic pressures,
which could reduce pain, because it is recognized that wall
tension is one of the factors that contributes to visceral pain
[13–15]. Practically, there is a significant improvement in
constipation if sufficient quantities of fiber (20–30 g/day)
are consumed [16, 17].
Diarrhea-predominant IBS is associated with acceleration
of small bowel and proximal colonic transit [16, 18]. Lop-
eramide (2–4 mg up to four times daily), a synthetic opioid,
decreases intestinal transit, enhances intestinal water and ion
absorption, and increases anal sphincter tone at rest. These
physiologic actions seem to explain the improvement in diar-
rhea, urgency,andfecal soiling observed in patients with IBS,
but there is no evidence that it results in pain relief [19, 20].
Carmint is a herbal drop which contains total extracts of
three medicinal plants: Melissa officinalis, Mentha spicata,
and Coriandrum sativum. Melissa officinalis is known to
have mild sedative and carminative, spasmolytic, antibacte-
rial, antiviral, antioxidative, and antihormonal effects. In folk
medicine, Melissa officinalis is used also for lower abdomi-
nal disorders and nervous gastric complaints. Mentha spicata
is used for digestivedisorders, as a remedy for flatulence. The
oil produced from this plant has antispasmodic, carminative,
and stimulant effects. In folk medicine, Coriandrum sativum
is used for digestive and gastric complaints. The essential oil
stimulates the secretion of gastric juices and is carminative
and spasmolitic [21–23]. No health hazards or side effects are
known in conjunction with the proper administration of des-
ignated therapeutic dosages of these three medicinal plants,
although Coriandrum sativum possesses a weak potential for
sensitization, as does the volatile oil of Mentha spicata due
to its menthol and L. Carvone content [21].
The aim of this study was to evaluate the effective-
ness of adding the herbal medicine, Carmint, or its placebo
to either loperamide or psyllium in the relief of abdomi-
nal pain/discomfort and bloating in patients with IBS us-
ing a randomized, double-blind, placebo-controlled study
design.
Materials and methods
Patients
Thirty-two patients, aged 18–65 years, with IBS (all bowel-
habit subtypes) diagnosed using the Rome II criteria [24],
were recruited from a gastroenterology clinic at a university
hospital in Tehran, Iran, and through two private offices of
two gastroenterologists.
Organic disease was ruled out by a sigmoidoscopic or
colonoscopic examination performed after the appearance
of symptoms and within the previous 5 years. Although
Table 1 Inclusion and exclusion criteria
Inclusion criteria
• Age 18–65 years
• Colonic evaluation (colonoscopy) within the previous 5 years
• Irritable bowel syndrome according to Rome II criteria
• Normal liver function test, thyroid tests, complete blood cell
count, chemistry panel, ESR, UA, and stool examination
Exclusion criteria
• Pregnancy or breast-feeding
• Liver diseases
• Nocturnal diarrhea
• Respiratory diseases
• Diabetes mellitus
• Lactose intolerance
• Major psychiatric disorder
• Other gastrointestinal disorders except dyspepsia
• Cancers
• Heart failure or MI
• Hypertension
• Peripheral neuropathy
• Medications: antibiotics, laxatives, anticholinergics, narcotics,
smooth muscle relaxants, antidepressants, iron supplements,
nonsteroidal anti-inflammatory drugs or other analgesics,
treatments for Parkinson’s disease, antipsychotics,
anticonvulsants, any herbal medicine for alleviating abdominal
pain/discomfort or bloating, colchicine, and enema preparations
• No consent; uncooperative or unreliable patients
no objective criteria exist for subgroups of IBS, physicians
assessed patients according to predominant bowel-function
pattern on the basis of the patient’s disease history. If diar-
rhea or constipation was present for at least 75% of the time
during which a patient’s IBS was active, the disease was clas-
sified as diarrhea-predominant or constipation-predominant,
respectively; otherwise, the patient was classified as having
alternating IBS. The study was carried out in accordance with
the Helsinki declaration and all patients signed the informed
consent prior to entry into the study. Patients could withdraw
from the study at anytime they wished. The inclusion and
exclusion criteria are listed in Table 1.
Medications affecting gastrointestinal motility and/or vis-
ceral perception, opioids, and analgesics were not permitted
during the study. Antispasmodic agents were not permitted
during the study; however, patients could receive Hyoscine
(40 mg/day) for no more than 3 days if they had bothersome
abdominal pain during the study.
Study design
This was an 8-week, double-blind, randomized, placebo-
controlled, multicenter clinical trial in outpatients with active
symptoms of IBS (or symptomatic IBS).
Patients were randomized to receive 30 drops of either
Carmint (n =14) or placebo (n =18) three times a day, taken
after each meal. Randomization was done using a random
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Dig Dis Sci (2006) 51:1501–1507 1503
number table, with odd numbers for Carmint and even num-
bers for placebo.
Patients also received loperamide (2 mg twice a day) if
they had diarrhea-predominant IBS (n =10) or 1 spoonful
of psyllium powder once a day if they had constipation-
predominant or alternating IBS (n =22).
Carmint and its placebo were provided by POUR SINA
pharmaceutical company (Tehran, Iran) as drops and were
comparable in color, odor, and taste. Prior to entry into the
study, a questionnaire about the patients’ demographic infor-
mation and details of their bowel habits was completed for
them and medications in the preceding weeks were recorded.
The patients were provided with weekly treatment follow-
up forms to fill out. The forms included questions regarding
severity and frequency of abdominal pain/discomfort, sever-
ity and frequency of bloating, stool frequency, stool consis-
tency, straining, general improvement, and any new adverse
events.
The symptoms were then rated as follows:
• Severity of abdominal pain/discomfort using a 4-point
scale (0 =none, 1 =mild, 2 =moderate, 3 =severe)
• Severity of bloating using a 4-point scale (0 =none,
1 =mild, 2 =moderate, 3 =severe)
• Frequency of abdominal pain/discomfort
• Frequency of bloating
• Frequency of hard or loose/watery stool
• Number of days without defecation
• Number of days with more than three bowel movements
per day
In the weekly questionnaires, patients also were asked if
they had taken their prescribed drugs properly, if they had
taken any other drugs in addition to their prescription in
this study, and if any major physical or emotional stress had
occurred for them each week. Patients had monthly visits
with the enrolling physicians to assess drug compliance and
occurrence of adverse events (AEs). All personnel involved
in the study remained blinded until the study was completed.
The primary efficacy end points in this study were ab-
dominal pain/discomfort and bloating. The secondary effi-
cacy end point was overall relief of IBS symptoms for at
least 1 week per month. The overall relief of IBS symp-
toms question was, In the last 7 days, how much have your
IBS symptoms improved? (The available answers were “no
improvement,” “slightly improved,” “much improved,” and
“absolutely improved.”) In the analysis, because of the small
sample size, the items “no improvement“ and “slightly im-
proved” were classified as one group and the items “much
improved“ and “absolutely improved” as another group.
Statistical analysis
Data were entered into a computer using ACCESS and
were analyzed using SPSS 11.5. Efficacy analysis was
by intention to treat and included all patients random-
ized. Patients’ demographic and baseline characteristics
and clinical information were summarized. T-test and
Mann-Whitney test were used to analyze the sever-
ity and frequency of abdominal pain/discomfort and
bloating.
Table 2 Patient demographics, baseline characteristics, and clinical
information (n =32)
Demographic
variable
Category/summery
statistics
Carmint
(N =14)
Placebo
(N =18)
Sex Male 9 (64.3%) 9 (50%)
Age (yr) Mean (SD) 31 (10.8) 46 (12.0)
Median 34 49
Weight (kg) Mean 64 71
Smoker Yes 3 2
Bowel move-
ments/wk
Mean 10 12
IBS subtype Diarrhea
predominant
55
Constipation
predominant
48
Alternating 5 5
IBS symptoms Pain severity score 1.8 1.8
Urgent defecation 6 5
Bloating severity
score
2.1 2.1
Straining for
evacuation
911
IBS symptoms
aggravated
by meal
Yes 5 8
IBS symptoms
aggravated
by stress
Yes 10 13
Abdominal
pain
Mild 5 8
Moderate 7 6
Severe 2 4
Abdominal
pain relieved
by defecation
Yes 10 12
No 2 4
Unknown 2 2
Bloating None 4 2
Mild 2 2
Moderate 5 11
Severe 3 3
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1504 Dig Dis Sci (2006) 51:1501–1507
Table 3 Percentage of patients
with overall improvement of
IBS symptoms per week in the
Carmint and placebo groups
Treatment
group
Week
Category 12345678
Carmint Improvement 7.7 30.8 38.5 40 50 40 50 60
Placebo Improvement 14.3 38.5 23 33.3 22.2 11.1 22.2 22.2
Results
Baseline characteristics
Of 32 patients randomized, 28 completed the treatment
follow-up questionnaires: 4 of the patients (1 in the Carmint
group and 3 in the placebo group) withdrew at the begin-
ning of the study because they did not start taking the study
medication or were lost to follow-up.
As summarized in Table 2, the distribution of male and
female patients was similar between the two treatment groups
(P =0.419). The mean age was lower in the Carmint group
than the placebo group (31 and 46 years, respectively). The
average number of bowel movements per week was similar
between the two treatment groups (12 and 10, respectively)
(P =0.76).
Relief of abdominal pain/discomfort
and bloating
A T-test analysis showed that the average abdominal
pain/discomfort severity scores were not significantly dif-
ferent between the Carmint group and the placebo group
at the midpoint of treatment (0.83 and 1.38, respectively;
P =0.13). This difference between the two treatment groups
became statistically significant at the end of the treatment
(0.28 and 1.50, respectively; P =0.016) (Fig. 1). The two
treatment groups had similar pain severity scores at base-
line.
A T-test analysis showed that the average number of days
with abdominal pain/discomfort was lower in the Carmint
group than the placebo group both at the midpoint of treat-
ment (0.66 and 1.92 days, respectively; P =0.02) and in
the last week of treatment (0.42 and 2.25 days, respec-
tively; P =0.001) (Fig. 2). The items which were signif-
icantly different between the two groups by T-test analy-
sis were also significantly different using Mann-Whitney
test.
A T-test analysis showed that the average bloating severity
scores were significantly lower in the Carmint group than
the placebo group both at the midpoint of treatment (2.08
and 2.46, respectively; P =0.005) and in the last week of
treatment (1.71 and 2.5, respectively; P =0.02) (Fig. 3). The
two treatment groups were similar at baseline for bloating
severity scores.
Reductions in the average number of days with bloating
were greater in the Carmint group compared with the placebo
group, both at the midpoint of treatment (1.08 and 1.84 days,
respectively; P< 0.001) and in the last week of treatment
(0.85 and 2.5 days, respectively; P =0.002) (Fig. 4). Mann-
Whitney test showed that Carmint significantly decreased
the average bloating severity score and the average number
of days with bloating at the end of the treatment (P =0.03
and P =006; respectively).
Fig. 1 Change in abdominal pain severity scores by week
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Dig Dis Sci (2006) 51:1501–1507 1505
Fig. 2 Average number of days with abdominal pain per week
Fig. 3 Change in bloating severity scores by week
Fig. 4 Average number of days with bloating per week
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1506 Dig Dis Sci (2006) 51:1501–1507
Fig. 5 Percentage of patients
with overall relief of IBS
symptoms per week
Overall relief from IBS symptoms
Percentages of patients with overall relief from IBS
symptoms are listed in Table 3. There was not a significant
difference between the two groups in overall relief of
IBS symptoms during the weeks of treatment. However,
during the treatment period, the percentage of patients
with overall relief increased notably in the Carmint group,
while no such improvement was observed in the placebo
group (Fig. 5).
Adverse events
Overall, 21.42% of the patients reported experiencing
AEs. 4 (30.77%) of 13 patients in the Carmint group and
2 (13.33%) of 15 patients in the placebo group reported
at least one AE during the course of the study (Table 4).
There were two discontinuations (7.14%) related to AEs.
Both of these patients were from the placebo group.
The AEs which led to discontinuation were bloating and
palpitation.
Discussion
IBS is a common health problem, often presenting at pri-
mary care as well as at internal medicine and gastroenterol-
Table 4 Number (%) of patients with adverse events
(whether or not drug related)
Adverse event Carmint group Placebo group
Anal pain before
defecation
1 (7.69) —
Disurea — 1 (6.66)
Malaise 2 (15.38) —
Anxiety/chest
pain/sweating
1 (7.69) —
Palpitation/headache — 1(6.66)
Bloating — 1(6.66)
ogy outpatient clinics. Therapeutic options are dominated
by drug therapies but there is uncertainty about their effec-
tiveness [25]. One of the major problems in developing a
treatment plan for patients with IBS is that IBS comprises a
group of functional intestinal disorders in which there are no
unique target receptors for pharmacotherapy [26]. Addition-
ally, there is a wide range of symptomatology.
Evidence on the effectiveness of herbal treatment in IBS
is limited, although some previous studies on the efficacy of
herbal medicines with antispasmodic and carminative prop-
erties in patients with IBS have shown good results [27, 28].
Carmint consists of the extracts of three medicinal plants
which are knownto have antispasmodic, carminative, and an-
tibacterial effects [20]. In this multicenter study, for the first
time we evaluated the effectiveness of this herbal medicine in
relieving abdominal pain/discomfort and bloating in patients
with IBS.
The results of our study show that the severity of pain
and severity of bloating started to differ from the beginning
of the second week of treatment, and the difference con-
tinued until the end of treatment. In addition, as the weeks
passed, the average number of days with pain and also the
average number of days with bloating obviously varied be-
tween the two groups; they decreased in the Carmint group.
Overall, in this study, Carmint plus loperamide and Carmint
plus psyllium were safe and well tolerated in patients
with IBS.
The limitation of our study was the small sample size. If
there had been more patients with each IBS subtype in the
trial, we could discuss the efficacy of Carmint with more
confidence. Our pilot study suggests that Carmint and lop-
eramide or Carmint and psyllium (depending on the IBS sub-
type) might be effective for patients with IBS. Larger clinical
trials are needed to prove the efficacy of this prescription in
patients with IBS.
Acknowledgments The authors would likex to thank POUR SINA
pharmaceutical company for providing Carmint and its placebo. This
study originated at The Research Center for Gastroenterology and Liver
Diseases, Shaheed Beheshti University of Medical Sciences, Tehran,
Iran.
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Dig Dis Sci (2006) 51:1501–1507 1507
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