Multiple herbs mixture for IBS symptoms

See discussions, stats, and author proﬁles for this publication at: https://www.researchgate.
net/publication/322256189
Vital factors to be considered when studying multiple herbs mixture

preparation to control Irritable Bowel Syndrome (IBS) symptoms in adult
patients (A review).
Article · January 2018
CITATIONS READS
0 15,069
1 author:
Jamil Al-Qudsi
University of Westminster
4 PUBLICATIONS 8 CITATIONS
SEE PROFILE
Some of the authors of this publication are also working on these related projects:
Irritable bowel syndrome, Herbal medicine, synergism of using multiple herbs, complementary medicine View project
All content following this page was uploaded by Jamil Al-Qudsi on 04 January 2018.
The user has requested enhancement of the downloaded ﬁle.

Alqudsi 2015, Vital factors in studying multiple herbs to control IBS symptoms
University of Westminster
Vital factors to be considered when studying multiple herbs mixture

preparation to control Irritable Bowel Syndrome (IBS) symptoms in adult
patients (A review).
Jamil Alqudsi, MD., Msc CAM.
Department of Complementary Medicine, University of Westminster
*Correspondence should be addressed to JA (Jamil.alqudsi@my.westminster.ac.uk)
Abstract
Multiple herb mixtures have been used as traditional and folk medicine in numerous cultures around the world
for hundreds of years, including for the control of symptoms relating to Irritable Bowel Syndrome (IBS). With a
UK prevalence rate of 10.5%, IBS is the most common diagnosis within gastroenterology clinics and the health,
social, financial and psychological burden on the individual and society is a significant burden. Anecdotal
evidence leads many patients to use multiple herb mixtures for the relief of symptoms, particularly as the evidence
suggests that current pharmaceutical interventions have limited success. It was apparent that a systematic review
of the research evidence of using multiple herb mixtures to control the symptoms of IBS might better inform both
medical professionals and patients in their use. To this end a systematic search was undertaken to identify relevant
published research. Ten eligible studies were subsequently systematically analyzed using an adapted CASP
framework and a narrative description of the pertinent results provided. All the reviewed studies provided a
highlight, of varying significance, that the use of multiple herb mixtures can be safe and effective in controlling a
variety of the symptoms of IBS, including abdominal pain, bloating, flatulence, abnormal bowel habits, colic and
general GIT symptoms. However none of the studies made reference to non-GIT symptoms such as anxiety,
depression, insomnia and sexual dysfunction and it is therefore apparent that further long-term studies are needed
to encourage the evidence-based use of multiple herb mixtures for the control of all IBS symptoms. Analyzing
these studies in the light of literature review, revealed multiple important factors that should be considered into
account when performing studies on multiple herb mixture use on IBS symptoms. These factors may play an
important role in pathogenicity, severity of symptoms, prognosis and outcome of IBS trials. Some of these factors
can be considered as influencing variables affect the methodology designs, data collection, data analysis and the
expected outcomes. It is significant to put these factors into consideration when performing replicable similar
clinical trials using multiple herbs to control IBS symptoms.
Abbreviations:
CAM: Complementary and Alternative Medicine.
CASP: Critical Appraisal Skills Program.
GIT: Gastrointestinal tract.
1
IBS: Irritable Bowel Syndrome.
OTC: Over The Counter.
RCT: Randomized Controlled Trials.
Introduction
Irritable bowel syndrome (IBS) is a common chronic disease with a nature of recurrent symptoms (Douglas, 2006;
Roasch, et al., 2006). It is the most common diagnosis in gastroenterology clinics (Thompson, et al., 2001). It has
the highest global prevalence ranging from 12–30% (Hungin, et al., 2003). Prevalence of IBS in UK is about
10.5% (Harkness, et al., 2013). According to (Taylor, et al., 2014). Surveys show that females are affected by
65% percent where men are affected by 35%. The cost of IBS is mainly related to its comorbidity, According to
Johansson, et al., (2010) the cost of IBS and its morbidity is around 120- 1855 Euro/Year, with
association of a workplace absenteeism up to 16.3 days / year and substantial economic loss.
IBS is a syndrome characterized by wide range of symptoms inside and outside gastrointestinal tract (GIT).
Altered stool frequency, form and passage (constipation, diarrhea or mixed), bloating, distension and passage of
mucus per rectum are among the inside GIT symptoms. However, depression, anxiety, migraine, sexual
dysfunction, urinary symptoms, dyspareunia, lower back pain and fatigue are among the outside GIT symptoms
(Farthing, M. J. G., 2004)
The pathophysiology of IBS is not completely understood, it is most likely multifactorial, including interaction
between brain–gut axis, low-grade inflammation, immunological changes, abnormal levels of gastrointestinal (GI)
neuropeptides and hormones, involvement of genetic factors, visceral hypersensitivity, altered GI motility and
psychological abnormalities (Ohman and Simren, 2007).
These wide range of symptoms and multifactorial pathophysiologies, necessitates using multiple categories of
medications, including; selective serotonin reuptake inhibitors, 5-hydroxytryptamine-3 receptor antagonists‫و‬
probiotics, melatonin, tricyclic antidepressant, anti-inflammatory, antispasmodics, fibre supplements,
antidiarrheal, osmotic, cathartics, bulking agents, tranquilizers, and sedatives. Unfortunately, none of the currently
available medications is globally effective in treating all IBS symptoms (Chang, F.Y. and Ching, L. L., 2009). In
clinical trials on pharmaceutical medication, effective therapies have only offered a therapeutic gain of 7-15%
over placebos (Chey, et al., 2011). Nonetheless, there is wide range of adverse reactions of conventional
medications used to control IBS, with dangerous proposed side effects, which limits their use by IBS patients
(Shah, et al., 2012).
According to Yoon, et al., (2011) more than 50% of IBS patients try complementary and alternative medicines
(CAM) as an alternative to conventional medicine. The most common CAM type used, is herbal medicine (Chey,
et al., 2011), Herbal medicine is considered the most common folk medicine used all over the world, including;
Chinese, Ayurvedic, Tibetan, Western Herbal medicine and many others (Snelling, 2006).
According to (Camilleri and Andresen, 2009), the diverse symptomatology and numerous mechanisms of action
in IBS, make it unlikely that a single medication, herb or single treatment can reliably treat all aspects of the
syndrome. In a comprehensive review Rahimi, and Abdollahi (2012) showed that solitary herb might help in one
or two symptoms or one or two mechanisms of action only.
It is evident that synergism princple is applicable among multiple herbs mixtures. According to Kiyohara, et
2
al., (2004), combination of multiple herbs in one mixture will provide a new effect based on physicochemical
interactions among the ingredients of the component herbs.
According to Wagner and Ulrich-Merzenich, (2009), the new generation of herbal preparations synergism could
lend phytotherapy a new legitimacy and enable their use to treat diseases better than using synthetic drugs alone.
In addition it is evident that using multiple herbs, in general, achieve the synergism principle, in which more
efficacy against the disease and less side effects of the herbal combination are achieved (Wagner, 2006). He
proposed that multiple herbs mixture would provide multi-target action of compounds on a molecular level or
partly by an improved resorption rate and a change of pharmacokinetic.
In more specific scope, using multiple herbs in controlling symptoms of IBS achieved better outcome at the level
of improving abdominal pain score, and total Irritable bowel syndrome symptoms score than using solitary herb
(Madisch, et al., 2004). However, literature is scanty regarding using multiple herbs in other symptoms of IBS
especially those related to outside GIT symptoms.
On the other hand, Berrin, et al., (2006) reported Multi-organ toxicity following ingestion of mixed herbal
preparations, as a case report, where the patient developed acute renal failure due to rhabdomyolysis, acute
hepatitis-like hepatotoxicity, and cardiotoxicity accompanied by angioedema after using multiple herbal mixture.
Despite the fact that the patient used this mixture for dyspeptic complaint not for IBS per se, it is important to put
into consideration that the used herbs in the mixture; Pimpinella anisum, Rosmarinus officinalis, Aloe ferox miller,
Matricaria chamomilla are usually used in IBS as well (Liu, et al., 2011).
In the light of the previous information, it is legitimate to ask: In adults suffering from irritable bowel syndrome,
what are the important factors to be considered when using multiple herbs mixture preparations to control their
symptoms?
Despite presence of multiple reviews evaluating the efficiency and safety of using herbs for IBS, and considering
important factors, such as (Melzer, et al., 2004; Liu, et al., 2011; Rahimi, and Abdollahi, 2012), none of these
explored reviews, evaluated in specific, the multiple herbs mixture effect on IBS; some of them evaluated the role
of solitary herbs, (Rahimi, and Abdollahi, 2012), others evaluated the effect of herbs in general without specific
focus on multiple herbs, (Liu, et al., 2011), and the last evaluated multiple herbs in a specific generic product like
STW 5 (Iberogast) (Melzer, et al., 2004). However, this is the first review directs its scope, to focus on multiple
herbs efficiency on IBS symptoms, addressing all types of herbal mixtures and preparations, whether those
mixtures prepared at home, with generic names, carrying cultural folk (Chinese, Japanese, Arabic), licensed by
health authorities, sold in herbal stores, prescribed by specialists or even used over the counter (OTC).
This review aims to highlight the scientific evidence documented in the literature for patients, practitioners,
medical doctors, health licensing authorities and interested individuals, through exploring the efficiency and safety
of using multiple herbs mixture preparations to control IBS symptoms. In addition, by reviewing available
controlled randomized Trials (RCT) related to multiple herbs use in IBS, enables the important factors affecting
validity of the trials of using these mixtures, such as those related to age, gender, diagnostic criteria, duration of
the study, follow up of participants, composition of multiple herbs mixture, number of herbs used in each mixture,
the form of mixture, route of administration, concentration of herbs used mixture, symptoms evaluated, symptoms
neglected
Methods
3
Rational for using Critical Appraisal Skills Programme (CASP) and Narrative approach (Appendix 1).
Presence of multiple aspects such as: complexity of IBS as multifactorial pathophysiologies syndrome, with
multiple unknown mechanisms of action, (Ohman and Simren, 2007), failure of conventional medicine to achieve
any significant improvement in IBS-QOL, (Chang, F.Y. and Ching, L. L., 2009), the increase demand among IBS
patients to use over the counter multiple herbs mixtures (Chey, et al., 2011). In addition, applying the guidelines
of (Jackson and Waters, 2005), in which reviewers should allocate sufficient time (up to 5 days) to develop, test
and re-test the review search strategy to ensure that it captures all of the relevant studies. It was discovered that
the literature related to using multiple herbs mixture to control IBS symptoms, is limited, and primary evaluation
showed poor quality of studies, and variant outcomes (discussed later in details). All these prime aspects
necessitate to design the review according to a simplified tool, to overcome the complexity of IBS and poor limited
researches of multiple herbs mixtures and to provide the interested professionals and researchers, with principals
factors to consider during implementation of their trials to improve the quality, validity and reliability of these
future trials. For this purpose Critical Appraisal Skills Programme (CASP) for systematic review and checklist
(Appendix 1) were used as simplified tools to establish systematic baseline, This appraisal tool helps to explore
the rigor of the approach, key research of methods in the study, credibility of the findings and relevance of the
reviewed trials in the light of the practical practice and the proper research design,
In the light of presence of complexity of IBS as multifactorial pathophysiologies, ambiguous mechanisms, wide
range of symptoms inside and out side GIT that affect all ages in both genders (Farthing, M. J. G., 2004), using
CASP helped to compose a comprehensive review question, addressing the population of the study, the modality
of intervention and targeted outcome.
With failure of conventional medicine to achieve any significant improvement in IBS-QOL, the increase demand
among IBS patients to use over the counter multiple herbs mixtures and limited researches regarding the use of
multiple herbs mixture to control IBS symptoms, CASP tools were used to scope systematically the choosing of
randomized controlled trial that can answer the review question. In addition, CASP helped in specifying the search
tools that included the web databases and article references.
With the poor quality of some of the reviewed studies, CASP supplied the steps to test the quality and rigor of
included studies for the review. In the light of presence of variant and sometimes contradictory outcomes, CASP
provided the guidelines for displaying and combining results in similar and different studies with critical
comparison between them when needed. CASP provided as well, the milestones for evaluating the results and
their confidence.
Since the reviewed trials were performed all over the world, CASP helped in defining the unique factors from the
reviewed studies and the guidelines for their generalization in future studies done in different countries and variant
cultures. Also CASP helped us to draw the important factors to be considered when performing future trials
regarding safety and cost of multiple herbs.
Role of narrative approach
Given the heterogeneity of studies in multiple aspects, such as type of herbs mixtures, number herbs in each
mixtures, using different herbs combinations from different folks, difference of methods of implantation and
variant outcomes, a narrative approach was deemed the most appropriate method as it uses text to summarize and
explain the findings of the synthesis. Since the strong evidence related to use of multiple herbs to improve IBS-
QOL is lacking, and since the availability of literature is limited. The narrative approach was used as a method of
4
bringing together evidence from research conducted, using a range of methods and scattered data. According to
Rodgers, et al., (2009), narrative synthesis can add meaning and value to the findings of meta-analysis, However,
there may be risks with over interpretation of study data, which can be limited by using framework, tools such as
CASP to increase the transparency and reproducibility of narrative synthesis.
How CASP was used?
Using CASP, a systematic search of the literature was performed, the critical appraisal of the included trials was
applied and a narrative approach was completed
Systematic search: Data sources and search strategy
Published papers in English were the defining initial search strategy. All data base websites (CENTRAL),
MEDLINE, EMBASE, AMED, and LILACS, from 1990 till end of 2014 were revised, using MeSH terms
Irritable bowel syndrome, IBS, multiple herb, multiple herbs mixture, multiple herbs preparations, we also
searched references of key articles. Only studies in English were included, however summarized studies in
English from original different languages were included, as well.
Critical appraisal
While extracting data, the study quality was evaluated using CASP (Critical Appraisal Skills Programme)
checklists for quantitative research; the checklist was slightly modified to fulfill our purposes (Appendix 6).
Inclusion/ Exclusion criteria for the review (see table 1).
Excluded from the review: (see appendix 2).
1. Animal studies.
2. In vitro and In vivo studies.
3. Studies reported in abstracts presented in scientific conferences.
4. Studies published in languages other than English, however, summarized studies in English from original
different languages were included.
5. Single herbs studies
6. Multiple herbs evaluated with other CAM practices studies were not included in the review.
7. Conventional or complementary intervention studies without using herbs.
8. Studies evaluating diagnostic methods not herbal interventions for IBS.
9. Studied related to multiple herbs use but not irritable bowel syndrome.
Details of excluded studies (see appendix 2).
Despite 47 studies are considered a good number to start the review, however after application inclusion and
exclusion criteria on these trials, only 10 were eligible for study, where 37 studies were excluded (appendix 1
shows the excluded studies and the reasons behind exclusion.
12 studies were excluded since they used herbs (single or multiple) together with one or more complementary
medicine methods in the same active group (Ko, et al., 2005; Astegiano, et al., 2006; Bittner, 2009). Using
5
complementary medicine method as different group from the multiple herbs mixture group was accepted and
considered eligible for the review. Examples of the excluded studies include using probiotics as an active group
either with using herbs mixture or without using them.
(Magge, 2011; Yoon, et al., 2011; Xing, et al., 2013; Magge and Wolf, 2013; Grundmann and Yoon, 2014) used
different complementary medicine methods either alone or with multiple herbs in the same group, and all were
excluded. (Reme, et al., 2010; Kennedy, et al., 2006) used cognitive therapy either with multiple herbs or without,
were excluded as well. Using multiple herbs mixture with other complementary medicine or conventional
methods, in the same study group, to evaluate effect on IBS symptoms, may obscure or overlap the evaluation of
individual explicit effect of multiple herbs on IBS symptoms. (See appendix 1).
6 studies were excluded as well because they were in Chinese language, not in English. Details: 3 studies (Gao,
2010; Gao, et al., 2010; Zhang, et al., 2012) fulfilled multiple herbs (Chinese traditional combination recipes)
effect on IBS symptoms; the only reason for excluding is the Chinese language. One study (Sun, et al., 2004) was
excluded because of Chinese language in addition to evaluating different outcome than IBS symptoms; namely
colon flora gut types and number in IBS patients. The last two trials (Gao, et al., 2011; Yu, et al., 2005) were
excluded due to use of Chinese language and using single individual herb effect on IBS symptoms, not multiple
herbs (Appendix1).
4 other studies in English were excluded because of their evaluation of single herb effect on IBS symptoms, not
multiple herbs (Bortolotti, 2011; van Tilburg, et al., 2014; Saito, et al., 2010; Davis, et al., 2006) (Appendix1).
Nonetheless, summarized studies in English from original different language were included.
4 studies (Cremonini and Talley 2004; Ohlsson, et al., 2009; Williams, et al., 2005; Stoicescu, et al., 2012) were
excluded because they were evaluating diagnostic tools, not the effect of IBS symptoms outcome (Appendix1).
Search using the words ‘multiple herbs’ AND’ irritable bowel syndrome’ produced 5 studies related to herbs
(Rösch, et al., 2006; Pieroni and Torry 2007; No authors listed, 2008; Seethapathy, 2012; Roozbeh, et al., 2013),
however they were not related to IBS but to different diseases or issues such as hemodialysis, DNA sequence of
raw herbs, functional dyspepsia, taste of herbs, all these studies were excluded (Appendix1).
6 of the search results were not randomized trials. There were reviews; systematic and nonsystematic, evaluating
single herbs effect on IBS studies, medications effect on IBS studies and only 3 of them were evaluating single
and multiple herbs effect on IBS symptoms, however they were excluded because the are reviews not controlled
trials (Appendix1). Despite exclusion, these reviews were used as source of more controlled studies that were
used for our review.
Table1: Inclusion/ Exclusion criteria

Inclusion/ Exclusion Criteria.
Exclusion Criteria.
Excluded from the review: • Animal studies.
• In vitro and In vivo studies.
• Studies presented in scientific conferences.
• Studies published in languages other than English (Summarized
studies in English from original different language were
included).
• Single herbs studies.
• Multiple herbs evaluated with other CAM practices studies.
• Conventional or complementary intervention studies without
6
using herbs.
• Studies evaluating diagnostic methods not herbal interventions
for IBS.
• Studied related to multiple herbs use but not irritable bowel
syndrome.
Inclusion criteria.
Type of included studies. Randomized controlled trials (RCTs) Referring to
• Clinical utility for IBS symptoms.

• Safety of multiple herbs preparations.
IBS Types and Symptoms. Types: constipation type, diarrheal or mixed type.
Symptoms:
• Inside GIT; Colic, diarrhea, constipation, gases, bloating,

distension and passage of mucus per rectum.
• Out side GIT: depression, sexual impairment, headache, sleep
disturbances, tension and anxiety.
Intervention (multiple herbs Number of herbs in each mixture;
mixture preparation).
Dual herbs or multiple.
Origin of mixture
• Folk medicine.
• Evidence-based studies.
Relation to folk
• Chinese.
• Western.
• Japanese.
• Arabic.
• Any cultural origin.
Forms of herbal mixtures
• Prepared at home.
• Manufactured herbal mixture preparation.
• Dry herbs.
• Herbal extracts.
• Herbal tablets or capsules.
Prescription of Herbal mixture
• By medical staff.
• By Herbal stores.
• Over the Counter (OTC).
• Licensed products.
Accepted outcomes. All outcomes were included:
• Outcomes supporting the active effect of the herbs on IBS

symptoms.
• Outcomes contradicting the positive effect of the herbs on IBS
symptoms.
• Outcomes supporting herbal safety.
• Outcomes denying herbal safety.
Studies evaluating
• Quality of life.
• Symptoms of IBS inside (GIT.)
7
Symptoms of IBS outside (GIT.)

•
Severity of symptoms of IBS.
•
CAM: Complementary and Alternative Medicine, GIT: Gastrointestinal tract, IBS: Irritable Bowel Syndrome,
OTC: Over The Counter, RCT: Randomized Controlled Trials.
Inclusion criteria: (See table 1).
Type of included studies:
Randomized controlled trials (RCTs) referring to the clinical utility or safety of the administration of multiple
herbs preparations for controlling symptoms of IBS were considered eligible for inclusion.
Inclusion and exclusion criteria for type of participants in selected studies: (see appendix 3).
The review included all studies assessing participants, diagnosed to have IBS, The review comprehends
participants from both sexes, all ethnicities, form all countries with age ranges from 18-100 years.
Inclusion and exclusion criteria for the problem (IBS): (see appendix 4).
The review-included studies comprehend all types of irritable bowel syndrome, constipation type, diarrheal or
mixed type. The review included all studies comprehend the symptoms of Irritable bowel syndrome whether these
symptoms were inside the gastrointestinal tract (GIT) such as, Colic, diarrhea, constipation, gases, bloating,
distension and passage of mucus per rectum, or outside GIT, such as, depression, sexual impairment, headache,
sleep disturbances, tension and anxiety.
Inclusion and exclusion criteria for the intervention-multiple herbs. (See appendix 5).
The review included all studies with multiple herbal mixture preparations, dual herbs or multiple, whether those
are considered as folk medicine or used according to evidence-based studies. The review included all forms of
herbal mixtures, prepared at home, manufactured herbal mixture preparation, dry herbs, herbal extracts, herbal
tablets or capsules, whether those herbs were prescribed by medical staff, taken as Over the Counter (OTC), as
licensed products or from herbal stores. The review included studies comprehended all types of herbs, whether
these herbs were, Chinese, western, Japanese, Arabic or from any other cultural origin.
What outcome measures are acceptable?
Since the review aim to evaluated the effectiveness and safety of multiple herbs mixtures preparations on IBS
objectively and to avoid exaggerated results, all outcomes were included; those supporting the active effect of the
herbs on IBS symptoms, and their safety and the contrary ones. (Liu, et al, 2011). Studies evaluating quality of
life, symptoms of IBS inside (GIT.) or outside (GIT.) and severity of these symptoms were included as well.
Data sources.
Electronic search was performed in The PubMed, EMBASE and MEDLINE databases, from January 1998 till
first of June 2014, to identify clinical trials eligible for inclusion in this review. The literature search strategy used
was ‘Irritable bowel syndrome' AND (Herbal mixture OR Herbal combination OR herbal safety) showed (6, 20,
21) results respectively.
Used critical tools (See Appendix 1& 6).
For appraising the reviewed studies critically, Modified Critical Appraisal Skills Program (CASP) was used
8
(Public Health Resource Unit, 2006). This appraisal tool explore the rigor of the approach, key research of
methods in the study, credibility of the findings and relevance of the study in the light of the practical practice.
Appendix 6 shows the prepared table, summarizing point to evaluate each study through the Critical Appraisal
Skills Program (CASP).
Data collection and analysis (see appendix 7).
Methodology was assessed depending on 4 quality components such as Generation of the allocation sequence,
allocation concealment, double blinding and follow-up (Jadad, 1996).
1. Generation of allocation sequence was considered adequate if it was generated through using computer
(generated randomized number). However it was considered inadequate of it was not described or used
other methodology of number generation.
2. Allocation concealment was considered adequate if it applied concealment conditions such as using the
sealed envelops, or any similar method, and considered inadequate if it was not mentioned in the study
or if it did not fulfill the concealment conditions such as using open table of random numbers.
3. Double blinding was considered adequate if it achieves identical placebo and the active group and
considered inadequate if it was not done or used different interventions such as multiple herbs group
versus conventional medication or if the participant or the investigator knew the used intervention
material.
4. Follow up was considered fulfilled if it mentioned the details related to withdrawn participants such as
reasons of withdrawal, and was considered inadequate of it did not mentioned these details.
For more details regarding applicability of these methods on reviewed studies (see appendix 7).
Data extraction (see appendix 8)
Data extraction process was a systematic organized process. Data were extracted according to logical division of
each study into 4 parts: the study and the used methods, participants, multiple herbs mixture preparation
(intervention) and Irritable bowel syndrome (the outcome). Each one of these divisions was subsequently
subdivided into more subcategories (see appendix 8).
• Data extraction related to the study and the used methods, were looked after for subcategories, such as
authors, year of publishing, used languages, randomization process, blinding process (if present), number
of center/s where participants were collected, how participants were randomized into groups, withdrawn
participants and the reason for dropout, duration of the study and the type of IBS symptoms evaluated
during the study (see appendix 8).
• Data extraction related to participants, were subdivided and extracted as the following subcategories:
Age, average age, gender, number of participant from each gender, ethnicity, number of participants in
each group and participants’ inclusion and exclusion criteria in each study (see appendix 8).
• Data extraction for the intervention (using multiple herbs mixture preparations) were subdivided and
extracted as the following subcategories: form of herb mixture used (tablet, capsule, oily, watery or
alcoholic extracts), composition of herbal mixture (types of herbs), number of herbs in each mixture,
route of delivery, dose and frequency of delivery, and details of intervention in the comparison group or
the placebo. (See appendix 8).
9
• Data extraction for the trials outcome (symptoms of IBS) were subdivided and extracted as the following
subcategories: type of diagnostic criteria for IBS, credibility of diagnostic tool, type of IBS explored in
each trial (constipation- diarrheal or mixed), presence of the inside GIT symptoms such as colic, diarrhea,
constipation, gases, bloating, distension and passage of mucus per rectum, the presence of the out side
GIT symptoms such as depression, sexual impairment, headache, sleep disturbances, tension and anxiety,
significance of each symptom change in comparison to control groups (results), side effects and adverse
reaction in active and control groups, possible documented interaction (if any) and measuring the
outcome end (time of intervention end and follow up of the participant) (see appendix 8).
Data synthesis
Outcomes were compared in the different groups of the study when possible:
Multiple herbs mixture groups were compared with placebo groups.
Multiple herbs mixture groups were compared with other conventional medicine group.
Multiple herbs mixture groups were compared other different herbal mixture groups.
Multiple herbs mixture forms groups were compared with other form of multiple herbs mixture in other groups.
Multiple herbs mixture groups dose were compared other multiple herbal mixture dose groups
Trials with similar outcomes were analyzed together.
Despite number of the reviewed randomized trials were limited, subgroup analysis were performed including the
gender of participants, diagnostic criteria used, age of participants, shape of multiple herb mixture used (capsule,
tablets, liquid, extract), intervention duration though out the study, however, the limited number of randomized
trials prevented to perform, sensitivity analysis to measure the influence of the quality on possible bias and
effective estimates.
RESULTS
Trials description
Participants: (see appendix 9).
The included studies were compared according to their participants’ number, male to female ratio and their age
range.
The total number of participants in the ten eligible studies was 849 participants, with an average of 83 participants
in each study, ranging from 6 participants (Micklefield, et al., 2000) in the smallest sample number study to 208
participants (Madisch, et al., 2004) in the largest sample number study.
Four of the studies (Madisch, et al, 2000; Reissenweber, 2008; Hawrelak and Myers, 2010; Sahib, 2013) did not
mention the gender of the examined patients. All the remaining studies mentioned the ratio of males to females
even inside each group (active, control or placebo) groups. Exclusion of the 4 studies total number participants
(which did not mention the gender) from the total number of the 10 studies will lead to: 849-196=653. 653 are the
number of participants in the remaining groups that mentioned the gender of participants. The total males number
in the 6 studies provided the male / female ratio is 303 where the total female in the same studies were 350 (see
10
appendix 9).
Male to female ratio in the 6 studies 303/350, which showed higher ratio of total females participants than males.
Only one of the 10 review studies did not mention the age of the participants (Madisch, et al., 2000). However all
the 9 remaining studies mentioned the age of the participant with mean age of all 9 studies of 42.7 years, starting
from 18 years old in 3 studies (Bensoussan, 1998; Vejdani,et al., 2006; Hawrelak and Myers, 2010). Reaching to
60 in other 3 studies (Brinkhaus, et al., 2008; Hawrelak and Myers, 2010; Sahib, 2013). One study only
(Bensoussan, 1998), included participants aged 75 years as highest upper age limit of all studies (see appendix
9)
Diagnosis tools description (see appendix 10).
4 of 10 of the review studies (Micklefield, et al., 2000; Zhang, et al., 2007: Brinkhaus, et al., 2008; Reissenweber,
2008) did not mention how participants were diagnosed to have IBS and who made the diagnosis. However
another 4 studies (Bensoussan, 1998; Madisch, et al., 2000; Madisch, et al., 2004; Vejdani,et al., 2006) mentioned
the participants were chosen and diagnosed to have IBS before applying the diagnosis criteria of the study through
multicenters. Nonetheless, none of these studies assured whether these different centers accredited similar
diagnostic criteria or not in IBS diagnosis. (Hawrelak and Myers, 2010; Sahib, 2013) mentioned that participants
were chosen and diagnosed to have IBS before applying the diagnosis criteria of the study through a solitary clinic
(see appendix 10).
Out of 10 studies (Madisch, et al., 2000; Micklefield, et al., 2000; Brinkhaus, et al., 2008) did not mention any
diagnostic criteria scale used during the study to prove IBS diagnosis in participants. Only 3 studies (Bensoussan,
1998; Vejdani,et al., 2006; Hawrelak and Myers, 2010) used international accredited scale (Rome criteria scale)
for diagnosis and as an explicit inclusion /exclusion scale through studies. Despite the last 4 studies (Madisch, et
al., 2004; Zhang, et al., 2007; Reissenweber, 2008; Sahib, 2013) used a diagnosis scale. These scales are not
international accredited scales (see appendix 10).
Description of Intervention
Duration of intervention (see table 2).
(Micklefield, et al., 2000) did not mention any duration for the course of the study.
5 studies out of 10 were performed for short duration only (Madisch, et al., 2000; Madisch, et al., 2004; Vejdani,
et al., 2006; Zhang, et al., 2007; Sahib, 2013) for, 4, 4, 8, 2, 8 weeks respectively. Only 4 studies (Bensoussan,
1998; Brinkhaus, et al., 2008; Reissenweber, 2008; Hawrelak and Myers, 2010) were performed for longer
duration ranged from (12-18) weeks.
With the exception of (Sahib, A. S., 2013), which mentioned the duration of IBS symptoms in participants before
the study beginning, which ranged between 5 and 10 years as inclusion criteria, none of the other 9 studies pointed
to duration of IBS in participants.
Types of used herbs (see table 2).
45 types of herbs were evaluated as herbal mixtures or preparation in the 10 reviewed studies, however two studies
(Zhang, et al., 2007; Reissenweber, 2008) did not mention the composition of the herbal preparation, rather they
provided the generic name of the herbal product without explaining the ingredients. In 4 studies (Micklefield, et
11
al., 2000; Vejdani, et al., 2006; Brinkhaus, et al., 2008; Sahib, 2013) the herbal mixture was composed of 2 or 3
herbs only. While in the other last 4 studies (Bensoussan, 1998; Madisch, et al., 2000; Madisch, et al., 2004;
Hawrelak and Myers, 2010) the herbal mixture was higher in number of composing herbs, ranging from 4 herbs
to 20 herbs in each herbal mixture preparation (see table 2).
Study Duration Shape of herbs Type of herbs used

used
(Madisch, et al., 2000). 4 weeks. Extract. Bitter candyduft, matricaria
flower, peppermint leaves,
Benefit of an herbal preparation in caraway, licorice root and melissa
patients with irritable bowel balm.
syndrome: Results of a double blind,
randomized, placebo-controlled
multicenter trial.
(Micklefield, et al., 2000). Not Extracts Peppermint–caraway oil

mentioned. combination.
Effects of Peppermint Oil and entericcoated
Caraway Oil on Gastro duodenal
Motility. (Enteroplant and
nonentericcoated.
(Hawrelak and Myers, 2010). 12 weeks. Mixture of dried, Bilberry fruit, slippery elm bark,
powdered.
Effects of Two Natural Medicine Agrimony aerial parts, and
Formulations on Irritable Bowel cinnamon quills for IBS – D.
Syndrome Symptoms: A Pilot Study.
Slippery elm bark, lactulose, oat
bran, and licorice root for IBS – C.
(Brinkhaus, et al., 2008). 18 weeks. Dry herb. Curcuma xanthorriza 60 mg daily

(curcuma group) (n ¼ 24), 2.)
Is herbal medicine effective in Fumaria officinalis.
irritable bowel syndrome? Results of
a randomized, placebo controlled,
double blind clinical trial.
.(Madisch, et al., 2004) 4 weeks. Product of (STW5):

Treatment of irritable mixture of herbal
extract. Bitter candytuft, chamomile
bowel syndrome with
flower, peppermint leaves,
herbal preparations:
caraway fruit, licorice root, lemon
results of a double blind,
balm leaves, celandine herbs,
randomized, placebo-
angelica root and milk thistle
controlled multi-center
fruit.
.trial
(b) Research herbal preparation
(STW 5-II): bitter candytuft,
chamomile flower, peppermint
leaves, caraway fruit, licorice root
and lemon balm leaves.
12
(Sahib, 2013). 8 weeks. Dry power Mentha longifolia, Cyperus

capsules. rotundus and Zingiber officinale.
Treatment of irritable bowel
syndrome using a selected herbal
combination of Iraqi folk medicine.
(Bensoussan, 1998). 16 weeks. Capsules given 3
times a day in all
Chinese herbs calm irritable bowel. groups as dried
JAMA. 280, 1585–1590. powder.
(Reissenweber, 2008). 3 months Not mentioned

with 3 and the way of
Japanese phytotherapy (Kampo) in evaluations preparing herbs is Rikkunshi-to (TJ-43).
functional dyspepsia and diarrhea- at the end of not mentioned as
type irritable bowel syndrome month 1, 2 well.
and 3.
(Zhang, et al., 2007). 2 weeks. Capsule. Dinggui oil.

Dinggui Oil Capsule in treating
irritable bowel syndrome
(Vejdani, et al., 2006).The Efficacy 8 weeks. Total extract. Melissa officinalis,

of an Herbal Medicine, Carmint, on
Mentha spicata, and Coriandrum
the Relief of Abdominal Pain and
Bloating in Patients with Irritable sativum.
Bowel Syndrome: A Pilot Study.
Table (2): Description of Intervention: duration, types of used herbs, form of used herbs.
Some herbs were used in more than one study such as bitter candytuft which was used in two trials (Madisch, et
al., 2000; Madisch, et al., 2004); licorice used in 3 studies (Madisch, et al., 2000; Madisch, et al., 2004; Hawrelak
and Myers, 2010); peppermint and caraway used in 3 studies (Madisch, et al., 2000; Madisch, et al., 2004;
Micklefield, et al., 2000); mellisa in 2 studies (Madisch, et al., 2000; Vejdani, et al., 2006); and Zingiber officinale
in 2 studies (Bensoussan, 1998; Sahib, 2013). However none of the herbal mixture preparation in any of the studies
resembled the composition of the mixture of any of the other studies. The most important notice in the review that
there was no trial testing exactly the same herbal medicine combination in the active and even in the control group.
(See table 2).
Form of used herbs. (See table 2).
(Bensoussan, 1998; Vejdani, et al., 2006; Hawrelak and Myers, 2010; Sahib, 2013), mentioned the use of whole
13
herb or complete herbal extract (combinations). However, (Madisch, et al., 2000; Micklefield, et al., 2000;
Madisch, et al., 2004) mentioned the use of herbal extracts without specifying type of extracting (watery, oily or
alcoholic). Zhang, et al., (2007) used oily extract in a capsule, while Reissenweber (2008) did not mention the
shape of herbal mixture used in the trial. Brinkhaus et al (2008) used mixture of dry herbs but without information
about how delivered to participants; swallowing as a capsule, decoction (boiling in water) or any other method?
(Madisch, et al., 2000; Madisch, et al., 2004; Micklefield, 2000) used multiple herbs combination extract, without
specifying the dose or the concentration of the extract. (See table 2).
Outcomes
Evaluated outcomes (see table 3).
(Bensoussan, 1998; Madisch, et al., 2000; Madisch, et al., 2004; Vejdani, et al., 2006; Brinkhaus, et al., 2008;
Sahib, 2013) evaluated general scales of IBS symptoms and global assessments of changes in IBS symptoms such
as; severity and frequency of abdominal pain, discomfort and bloating, frequency of hard or loose/watery stool,
number of days without defecation, number of days with more than three bowel movements per day. However,
(Micklefield, et al., 2000; Hawrelak and Myers, 2010) evaluated only the gastrointestinal tract (GIT) motility and
bowel habits, where (Zhang, et al., 2007; Reissenweber, 2008) evaluated discrete variables not including all IBS
symptoms scale such as abdominal pain, epigastric fullness, epigastric pain, nausea, and diarrhea. Nonetheless,
Brinkhaus et al (2008) was the only study to proved evaluation for the extra (GIT) symptoms such as psychosocial
stress associated with IBS.
None of the reviewed studies stated a follow up of the participants after the study, reported relapse, evaluated
quality of life or evaluated the cost effectiveness of IBS.
Outcome in different range of symptoms;
The possibility of bias in the reviewed studies
Except for two studies (Madisch, et al., 2000; Madisch, et al., 2004), which were multi-center randomized trials;
all the remaining studies were reported as parallel group randomized trials. Only one study of the 10 (Madisch, et
al., 2004) specified the methods of generation of allocation randomization. From the 10 reviewed studies, only 2
trials (Bensoussan 1998; Madisch, et al., 2004) provided information about allocation concealment. They were
considered as adequate because they used sealed envelope or central control for the allocated treatment. However,
Madisch et al (2004) used random number table or computer-generated numbers.
Only two trials achieved double blinding (Bensoussan 1998; Madisch, et al., 2004). The same trials were the only
trial mentioned the reasons for loss of follow up, documented pre estimation of the sample size before starting the
study. Hence, these two randomized trials are considered of good quality. (Bensoussan 1998; Madisch, et al.,
2004)
Forms of interventions (see table 3).
Six trials out of 10, tested multiple herbs mixture preparations compared with placebo, (Bensoussan, 1998;
Madisch, et al., 2000; Madisch, et al., 2004; Vejdani,et al., 2006; Zhang, et al., 2007; Brinkhaus, et al., 2008).
The remaining trials, either used conventional medicine group comparative (Sahib, 2013), or compared the effect
of multiple herbs on different types of IBS (IBS-C/IBS- D) in the active groups (Hawrelak and Myers, 2010), or
did not use any control group but one active group, which was evaluated in chronological steps (Micklefield, et
14
al., 2000; Reissenweber, 2008).
Effects of interventions (see table 3).
All the reviewed studies showed that multiple herbs combination use was significant in controlling IBS different
symptoms, including Abdominal pain, bloating, flatulence, straining, bowel habits, stool frequency, colic and
global IBS GIT symptoms, however, (Vejdani, et al., 2006; Brinkhaus, et al., 2008) showed that the difference
between active group and control group was insignificant. It is noticed that number of used herbs in herbal
mixtures of these studies was dual or triple. Brinkhaus, et al., (2008) used only two herbs; Curcuma and Fumaria,
where Vejdani, et al (2006) used 3 herbs (Melissa officinalis, Mentha spicata and Coriandrum sativum). On the
other hand Sahib (2013) reported considerable success to treat different types of IBS using multiple herbs mixtures
with complete safety despite using only 3 herbs in the mixture preparation (Mentha longifolia, Cyperus rotundus
and Zingiber officinale).
Effect of multiple herbs mixture on each symptom: (see table 3).
9 out of 10 reviewed studies evaluated abdominal pain as a main symptom of IBS (Bensoussan, 1998; Madisch,
et al., 2000; Madisch, et al., 2004; Vejdani, et al., 2006; Zhang, et al., 2007; Brinkhaus, et al., 2008;
Reissenweber, 2008; Hawrelak and Myers, 2010; Sahib, 2013) 4 of these studies used specific abdominal pain
scale for evaluation the degree of abdominal pain before and after the intervention (Bensoussan, 1998; Madisch,
et al., 2004; Vejdani, et al., 2006; Zhang, et al., 2007). However, all the other 5 remaining studies evaluated
abdominal pain as a part of general scale of IBS symptoms evaluating scale. From all the nine studies evaluated
the effect of multiple herbs mixture preparation on abdominal pain, only Brinkhaus, et al., (2008) found that herbal
mixture intervention has no significant improvement on abdominal pain. However this study is the only study that
used two herbs mixture only (Curcuma and Fumaria), all remaining 8 studies used three or more herbal mixtures
and proved significant improvement in abdominal pain as a part of IBS.
Change in bowel habits such as related stool frequency and consistency was evaluated in 8 out of 10 studies, 3 of
them (Madisch, et al., 2000; Madisch, et al., 2004; Brinkhaus, et al., 2008) evaluated this symptom in general as
a part of general IBS symptoms, However, the other remaining five studies Vejdani, et al., 2006; Brinkhaus, et
al., 2008; Reissenweber, 2008; Hawrelak and Myers, 2010; Sahib, 2013) evaluated this symptom in details as a
significant individual measured parameter in the results.
All the eight mentioned studies except one (Brinkhaus, et al., 2008), documented improvement in bowel habits
symptoms in all types of IBS (constipation, diarrhoea or mixed).
Symptoms related to production of gas such as bloating, flatulence or abdominal distension were evaluated in 7
studies out of the 10 reviewed studies (Bensoussan, 1998; Madisch, et al., 2000; Vejdani, et al., 2006; Brinkhaus,
et al., 2008; Reissenweber, 2008; Hawrelak and Myers, 2010; Sahib, 2013), however, these studies did not
evaluate gas production symptoms using a specific scale, but through using the IBS general symptom scale. When
results were exhibited, only 4 of these studies (Bensoussan, 1998; Vejdani, et al., 2006; Reissenweber, 2008;
Hawrelak and Myers, 2010) mentioned the degree of improvement in gas production symptoms (bloating,
flatulence or abdominal distension) other studies, did not focus on that symptom individually, rather it was
evaluated altogether with other symptoms in general IBS symptoms scale.
Safety of multiple herbs mixture use in the reviewed studies (see table 3).
Two studies of the 10 reviewed trials (Madisch, et al, 2004; Vejdani, et al., 2006) stated presence of adverse effect
15
of using multiple herbs mixture. However, 5 studies including (Bensoussan, 1998; Madisch, et al., 2000;
Study What to evaluate Results Side effects of the
used herbs
(Madisch, et al., 2000). Abdominal pain Significant Not mentioned in
the study
Benefit of an herbal preparation Abdominal pain (p<0.0004)
in patients with irritable bowel
syndrome: Results of a double General score of General score of IBS
blind, randomized, placebo- IBS
(P<0.0004)
controlled multicenter trial.
(Micklefield, et al., 2000). Motility of GIT Significant for coated and non No side effect
coated capsules
Effects of Peppermint Oil and
Caraway Oil on Gastro
duodenal Motility.
(Hawrelak and Myers, 2010). Bowel habits Reductions in straining Not mentioned
Effects of Two Natural (P¼0.004), abdominal pain
Medicine Formulations on (p¼0.006), bloating (p<0.0001),
Irritable Bowel Syndrome flatulence (p¼0.0001), and global
Symptoms: A Pilot Study. IBS symptoms
(p¼0.002) During the treatment
phase of the trial. Subjects in the
C-IBS group experienced a 20%
increase in
Bowel movement frequency
(p¼0.016) and significant
reductions in straining (p<0.0001),
abdominal pain
(P¼0.032), bloating (p¼0.034),
and global IBS symptom severity
(p¼0.0005), as well as
improvements in stool
Consistency (p<0.0001). Both
formulas were well tolerated.
(Brinkhaus, et al., 2008). Changes in global Not significant Not mentioned
patient ratings of
Is herbal medicine effective in IBS-related pain Neither Curcuma nor Fumaria had
irritable bowel syndrome? and distension any therapeutic benefit over
Results of a randomized, placebo in patients with IBS. The
placebo controlled, double use of these herbs for the treatment
blind clinical trial. of IBS cannot be recommended
Additional
outcome
parameters
included global
assessments of
changes in IBS
symptoms and
psychosocial stress
16
caused by IBS.
Madisch, et al., ) Irritable bowel In abdominal pain sore first Side effect
.(2004 syndrome product of mixture of herbs mentioned
Treatment of symptom scale. showed STW 5, P <0.0009.
irritable bowel
Abdominal pain Second product showed STW 5-II,
syndrome with
scale.
herbal preparations: P < 0.0005) and the irritable bowel
results of a double Intensity of syndrome symptom score STW 5,
blind, randomized, discomfort caused P < 0.001; STW 5-II, P < 0.0003.
placebo-controlled by irritable bowel
.multi-center trial syndrome each day No statistically significant
on diary cards. differences between the bitter
candytuft mono-extract group and
the placebo group
(P< 0.1473, P< 0.1207).

(Sahib, 2013). All symptoms of Treatment with the herbal It was mentioned
IBS combination significantly that the tested
Treatment of irritable bowel (P≤0.05) reduced the mean herbs have no
syndrome using a selected Pain severity  Pain symptom severity in patients side effect on the
herbal combination of Iraqi folk frequency,   Stool initially classified as having mild, tested group
medicine. frequency,   Stool moderate or severe IBS symptoms,
consistency,
Abdominal
distension,
Incomplete
evacuation,
Urgency, Passing
of mucus
(Bensoussan, 1998). All symptoms of Dramatic improvement in the Not mentioned.

IBS. symptoms according to patients,
Chinese herbs calm irritable gastroenterologist
bowel. JAMA. 280, 1585–1590. Visual scales
related to each In-group 1, 2 with the group 1
symptom (pain improvement lasted longer.
/discomfort, According to total severity score.
bloating, No details related to degree of
constipation and improvement
diarrhea) and
general overall
severity scale.
(Reissenweber, 2008). Symptomatic A clinically meaningful Not mentioned.
functional upper improvement of symptoms by
Japanese phytotherapy and lower more than 50% was found after 3
(Kampo) in functional gastrointestinal months of treatment with
dyspepsia and diarrhea-type com- plaints Rikkunshi.
irritable bowel syndrome epigastric fullness,
epigastric pain, Each symptom was evaluated
nausea, abdominal individually.
pain, bloating and
diarrhea. Improvement in epigastric pain,
bloating and diarrhea was
remarkable.
17
(Zhang, et al., 2007). Efficacy of the Dinggui Oil Capsule showed a No adverse effect
Dinggui oil capsule higher efficacy than the placebo in was found.
Dinggui Oil Capsule in treating on abdominal pain relieving the abdominal pain (P <
irritable bowel syndrome of patients with 0 .01).
IBS, safety of
Dinggui oil
capsules.
(Vejdani, et al., 2006). Severity of There was not a significant 30.77%) of

The Efficacy of an Herbal abdominal difference between the two groups patients in the
Medicine, Carmint, on the pain/discomfort in overall relief of Carmint group
Relief of Abdominal Pain and using a 4-point and
IBS symptoms during the weeks of
Bloating in Patients with
• Severity of treatment. However, despite each (13.33%)of
Irritable Bowel Syndrome: A
bloating using a 4- symptom was evaluated patients in the
Pilot Study.
point scale (0= individually The results of the placebo group
none, study showed that the severity of reportedat least
pain and severity of bloating only one Adverse
1= mild, 2= started to differ from the beginning Event (AE)
moderate, 3= of the second week of treatment. during the course
severe) of the study.
• Frequency of There were two
abdominal During the treatment period, the discontinuations
pain/discomfort percentage of patients with overall from the placebo
relief increased notably in the group due to
• Frequency of Carmint group, while no such
bloating bloating and
improvement was observed in the palpitation.
• Frequency of placebo group.
hard or
loose/watery stool
• Number of days
without defecation
• Number of days
with more than
three bowel
movements per day
Table (3): Outcomes description: Forms of interventions, effects of interventions, safety of multiple herbs
mixture.
Brinkhaus, et al., 2008; Reissenweber, 2008; Hawrelak and Myers, 2010) did not reports any side effects or
adverse reactions on participants. The last three trials (Micklefield, 2000; Zhang, et al., 2007; Sahib, 2013)
claimed that there was no side
Discussion and Conclusions:
Factors to be considered during studying use of multiple herbs mixture on IBS patients.
These are specific factors, which may play an important role in pathogenicity, severity of symptoms, prognosis
and outcome of IBS trials. Some of these factors discussed later, can be considered as influencing variables affect
the methodology designs, data collection, data analysis and the expected outcomes. It is significant to put these
factors into consideration when performing replicable similar clinical trials using multiple herbs to control IBS
symptoms. Neglecting them may add hidden variables that may influence the design and implementation of these
18
replicable trials. However, some of these factors are unique for using multiple herbs mixture in treating IBS, others
can be generalized to include using multiple herbs mixture in any other different entity of diseases and syndromes
trials.
1-Gender.
In their study sampling, only 6 out of the ten reviewed trials (Bensoussan, 1998; Micklefield, et al., 2000; Madisch,
et al., 2004; Vejdani, et al., 2006; Zhang, et al., 2007; Brinkhaus, et al., 2008), reported male to female ratio.
These 6 studies reported that IBS prevalence was higher among females than males, which is compatible with the
international statistics related to IBS gender distribution. According to (Wilson, et al., 2004), females are more
affected with IBS than males. However, the other 4 reviewed trials (Madisch, et al, 2000; Reissenweber, 2008;
Hawrelak and Myers, 2010; Sahib, 2013) did not mention any information related to gender of participants or
whether female participants, if any, have the menstruation during the period of the study or not. These 4 trials did
not supply any information related to number of days of menstruation in female participants during the trial period
and if menstruation has an effect on severity of symptoms and total IBS-QOL evaluation.
These four trials can be criticized for neglecting the gender difference in sampling and outcome for the following
reasons:
1- It is evident that severity of symptoms such as bloating, gas, loose stool, and pain increase during menstruation
in IBS female patients (Adeyemo, et al, 2009). In a review of clinical and basic science studies, Martin, (2009)
revealed that most pain in IBS and other pain disorders were worsened during the late luteal and early follicular
phases of the menstrual cycle. Pain thresholds and tolerance times also varied during different phases of the
menstrual cycle in IBS female patients. Variation in severity of pain and tolerance during the menstrual cycle may
affect the quality of life evaluation using multiple herbs to control IBS symptoms, especially during the more
intense periods of pain of the menstrual cycle, mentioned earlier.
2- Naliboff, et al., (2003) revealed that higher prevalence of IBS in women than in men (2:1) is related to
physiologic sex-related differences in the autonomic and perceptual response to pain and stress. In addition,
female patients with IBS reported greater frequency of non-painful extra intestinal symptoms compared with IBS
male patients. Naliboff, et al., (2003) concluded that ovarian hormones in females have distinct effects on
inflammation, affective states, stress responses, modulatory pain systems, and afferent sensory systems—that
increase pain reactivity.
Since use of multiple herbs mixture intends to control multiple mechanisms of action, in which hormonal and
autonomic mechanisms are among the targeted mechanisms, it is significant to specify the response variation to
these herbal mixtures between males and menstruating females, especially in the light of presence of the evidence
that multiple herbs with other medications were used to control the hormonal mechanism in IBS patients (Ding
and Wang, 1997).
All the ten reviewed studies are criticized for not stating any information related to expected presence of difference
in response or outcome, if any, between males and females participants after using the multiple herbs mixtures.
Another criticism is directed for these trials, that all of them have no statement regarding the degree of response
in female participants during their menstruation periods along the trials time (Tilburg, et al, 2009). We suggest
that future studies evaluating the effect of multiple herbs mixture on IBS patients, should focus on the difference
between symptoms in both genders of participants carefully, should pay precise attention to severity of symptoms
in female participants during menstruation, late luteal and early follicular phase of the period and should measure
the degree of response to multiple herbs mixture on a fixed scale, including males, non menstruating females and
19
females during menstruation. The purpose of these suggestions is to evaluate whether multiple herbs mixture have
different effect between males and females, and between menstruating and non-menstruating women.
Factor 2: age.
Only Bensoussan has applied the intervention on 75 years old participants (Bensoussan, 1998). All other reviewed
trials, included participants aged from 18-60 years. According to (Minocha, et al, 2006), older patients suffer
different symptoms and poorer quality of life than younger patients of IBS. Prevalence of IBS among old patients
reaches 10% (Minocha, 2005).
Elderly age group is important to be considered during the study of using multiple herbs to control IBS in four
aspects;
1- Limited data related to IBS in elderly:
According to Bennett and Talley (2002), there has been very little research examining risk factors, diagnosis and
treatment of IBS in the elderly. They reported that there was reason to believe that IBS was a prevalent disorder
which may also behave differently in the elderly and that the approach to management needs to take age-related
issues into account. Nonetheless, Kurniawan and Kolopaking (2014), stated that management of IBS in the elderly
is more difficult and complicated, when compared to the management of IBS in the younger
populations. According to Wade, (2002), the possible reason behind this difficulty is related to that understanding
of age-related changes in the enteric nervous system (ENS) is extremely poor, compared with the rapid advances
in the neurobiology of aging in the central nervous system, According to Ohman and Simren (2007), enteric
nervous and visceral hypersensitivity mechanisms are among the most important pathogenicities of IBS.
We suggest that studying multiple herbs effect on symptoms of IBS should be accompanied by considering elderly
category as an important stratification during sampling, analysis of data, data interpretation and the conclusive
outcome. The literature is limited in evaluation of multiple herbs mixture effect on IBS patients older than 60. It
is important that future trials should perform studies focusing on this age category to fill this gap and to evaluate
the safety and response to multiple herbs mixture on this unique category symptoms and QOL especially in the
light of different pathophysiology and more difficult management on poorer outcome and QOL
2- Accompanying diseases with IBS in elderly may complicate IBS:
According to Kurniawan and Kolopaking (2014), several studies have shown a strong relationship of IBS with
psychiatric conditions in elderly; thus, psychological treatments by conventional or herbal medicines should also
be considered in the management of IBS in the elderly. Future studies evaluating multiple herbs effect on IBS
symptoms in elderly, should consider the role of multiple herbs toward the accompanying psychiatric conditions,
which may complicate the presentation of vague IBS symptoms and QOL in elderly category.
3- Increase the possibility of multiple herbs and drugs interaction:
In a systematic review Lin, et al., (2014), stated that elderly people, especially those with chronic conditions, and
have diminished body functions, are more prone to experiencing drug interactions with multiple herbs and are
more exposed to develop adverse drug reactions accordingly. The review stated that between 2% to 46% of
reviewed trials showed that elderly combined multiple herbs along with their medications. According to Lantz,
(1999), older adults are large consumers of both over-the-counter and prescription medications, they are
particularly vulnerable to interactions between medications and products sold as nutritional or herbal supplements
especially multiple herbs mixture where more ingested herbs increase the possibility of interactions with multiple
20
used medications. Lantz reported in this article a series of five cases of clinically diagnosed central serotonergic
syndrome among elderly patients who combined prescription antidepressants with St. John's herb. According to
(Saito, et al., 2010), St. John's herb with other multiple herbs are frequently used by elderly for IBS and associated
diseases such as, depression.
According to Fugh-Berman, (2000), concurrent use of herbs may mimic, magnify, or oppose the effect of drugs.
Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginger, decreased
bioavailability of digoxin, theophylline and cyclosporine, when these drugs are combined with St John's wort,
potentiation of oral and topical corticosteroids by liquorice and Liquorice and ginseng have been linked to
hypertension. Ginger and liquorice were among the herbs mixture used in our reviewed trials (Madisch, et al.,
2000; Madisch, et al., 2004; Hawrelak and Myers, 2010; Sahib, 2013).
4- Unexpected adverse reaction for multiple herbs in elderly:
Some herbs have unexpected adverse reactions in elderly that do not appear usually in younger population.
According to Hopkins, et al., (1988), ginseng may produce an oestrogen-like effect manifesting as mastalgia and
vaginal bleeding, as reported in elderly, postmenopausal women taking a modest oral dosage or with even topical
application.
Since the pathogenicity of IBS in elderly has some different mechanisms of those in younger population, since
elderly are more prone to have associated physical and psychiatric diseases that require using multiple medications
and multiple herbs combinations, which increases the possibility of herbal drug interaction and more possible
unexpected adverse reaction of using the multiple herbs. Future trials evaluating multiple herbs on IBS symptoms
in elderly, should consider all these aspects during performing their trial, which may complicate or change the
outcomes of the trials.
Factor 3: Criteria for IBS diagnosis.
During revising the inclusion criteria for the accredited diagnosis of IBS in the 10 reviewed trials. Only 3 of the
trials (Bensoussan, 1998; Vejdani, et al., 2006; Hawrelak and Myers, 2010) mentioned Rome criteria scale as an
accredited international scale to diagnose IBS. However all the other 7 trials, either did not use any scale at all,
(Madisch, et al., 2000; Micklefield, et al., 2000; Brinkhaus, et al., 2008) or used unknown scales (Madisch, et al.,
2004; Zhang, et al., 2007; Reissenweber, 2008; Sahib, 2013). Whether the authors invented these scales? Or
whether there is evidence that the used scales are accredited internationally is not explicit in these trials? Using
valid and reliable diagnostic scale is considered important in the light of high percentage of IBS misdiagnosis
(Longestreth and Yao, 2004). IBS diagnosis overlaps with multiple pathologic entities that mime IBS symptoms,
these entities include; chronic inflammatory pelvic disease, coronary artery disease, gall bladder problems, peptic
ulcer disease (Longestreth and Yao, 2004). All these diseases may be accompanied by real IBS symptoms or
present with similar IBS symptoms presentations, in the absence of true IBS diagnosis (Longestreth and Yao,
2004). Since the diagnosis of IBS is and must be clinical, where any objective confirmative diagnostic test for the
disorder is lacking. And since the history most often gives all necessary information for a positive working
diagnosis (Hatlebakk, and Hatlebakk, 2004), it is important to use accredited diagnostic scales, able to evaluate
the diagnostic criteria of IBS through the precise clinical history findings, The importance for accredited
diagnostic scales increases in the light of presence criticism against 3 out of 5 scales invented to evaluate the
severity of IBS symptoms. The criticized scales did not achieve the practical utility for IBS patients and did not
reflect the real severity of symptoms that may affect the outcome of the intended medical, herbal or natural
interventions (Bijkerk, et al, 2003). Using unaccredited, unreliable scales may include participants that do not
suffer from IBS, but from other conditions that may mime the symptoms of IBS, Hence applying of multiple herbs
mixture on those participants may lead to false negative outcome, which can affect the total outcome statistics and
21
figures of the study. It is suggested that future studies evaluating IBS, should depend on accredited high quality
accredited scales as a base for proper inclusion of true IBS patients, in order to achieve more reliable results and
more proper outcomes. Suggested accredited international scales to be used include Rome I, II, III or manning
criteria (Manning, 1978; Drossman, 1994; Thompson, 1999).
Factor 4: Duration of the study.
Related to the duration of each study, only 4 out of 10 trial (Bensoussan, 1998; Brinkhaus, et al., 2008;
Reissenweber, 2008; Hawrelak and Myers, 2010) extended from 12 to 18 weeks duration, all other studies were
short in duration. Short studies may be criticized because they may not reflect the real effect of using multiple
herbs mixture on the nature course of IBS in real life. According to Watson, IBS is a chronic disease with
frequently recurring symptoms (Watson, et al, 1998). Since IBS lives with the patient life long, and has chronic
continuous nature (Olafsdottir, et al, 2010), suggestion for the future trials to apply their implementation studies
for longer times, which are more compatible with the chronic course of IBS, provide more explicit view of the
true participant response to intervention and achieving many goals:
First: verifying the real efficacy of studied herbs mixture to alleviate the symptoms of IBS for longer time
duration, which is more compatible with the real life status and decrease the chance of placebo effect in short
duration studies.
Second: to explore whether using herbs for longer time duration, will develop tolerance against multiple herbs
mixture. There is increasing evidence that IBS symptoms, like pain, develop a decrease in response to treatment
with time (Stabell, et al., 2011). One of the most studied multiple herbs mixture preparations, to control IBS
symptom, is STW 5 (Iberogast). This product, which was reviewed in trial of (Madisch, et al., 2004), works on
opioid receptors, as a main mechanism of action (Simmen, et al, 2006). Opioid receptors active herbs usually
develop tolerance when used in gradual or fixed doses for long time duration, resulting in gradual decrease of the
efficacy of the active substances of herbs during the course time of their use and gradual decrease in response of
the affected symptom/s with higher doses of the treatment and longer duration of use (Qiu He, et al, 2013).
Third: The short duration of mentioned reviewed trials, without follow up, will arise queries around the duration
of effect of the claimed improvement after discontinuing the use of multiple herbs mixture. What will occur to
participants’ symptoms after stopping the herbal mixture? Will the proposed improvement stay life long, or just
for few months duration? If relapse occurred, will symptoms measure the same degree of severity on the same
evaluative scales, less degrees or more degrees than that of the primary symptoms?
Factor 5: Duration of IBS course before inclusion in the study trial
All the reviewed trials did not state the duration of IBS course in participants before enrolling into the trial except
one (Sahib, 2013). It is evident that type of symptoms, pain, pathology and outcome of IBS differs according to
chronicity of the disease (Rodero, et al, 2010). Olafsdottir, et al, (2010) proved that symptoms of IBS are
increasing in type and intensity after 10 years duration of IBS course to become more intense and reach highest
severity and resistance to intervention.
In the light of the previous evidences, we recommend to examine the role of herbs mixture on IBS symptoms
according chronicity of the disease. It is important to explore whether the use of herbal mixture should be modified
in types or doses during increasing of chronicity and aggravation of symptoms during the course of IBS.
Including participants with chronic IBS course >10 years (with severe symptoms) together with participants with
short duration IBS course < 10 years of mild to moderate severity symptoms in the same trial, may complicate the
outcome results and may add hidden variables that may affect the response to herbal mixture intervention. More
22
recommendations are directed toward dividing participants during sampling in the future studies according to their
chronicity of symptoms: to < 10 years and > 10 years of IBS course. More suggestions are directed to more
subdivision according to chronicity, such as classification to: 0-3 years, 3-6 years, 6-10 years, more than 0 years
to ease the ability to evaluate the effect of multiple herbs on IBS symptoms according to chronicity, severity of
the syndrome and intensity of symptoms more objectively.
Different herbal mixtures were used in the 10 reviewed trials, none of these mixture resemble in its composition
the used mixture of the other trial or even on the other control group of the same study. This is good for affirming
the concept itself, using (multiple herbs mixture) to control the symptoms of IBS. However, This may carry a
criticism toward these trials. Except for Sahib (2013), It was not explicit on what basis herbal combination were
chosen, whether choosing depended on previous research that prove effectiveness, or on proved precautions
related to side effect, interactions or toxicity. Or whether chosen mixture relied on folk tradition concept, such as
studies which used mixtures, based on traditional Chinese medicine (Bensoussan, 1998; Zhang, et al., 2007) or
Japanese traditional herbal medicine (Reissenweber, 2008), however, these studies did not explain on what basis
was the definition of traditional Chinese or Japanese medicine and choosing herbal mixture (traditionally)
identified.
Specifying the basis of choosing the types of herbs used in the mixture and on what basis they were chosen, will
establish a principle to develop more herbal mixture preparations according to explicit methodology of combining
herbal mixture in future trials. In addition this can establish for more explicit trials’ methodologies to develop
better choices of types and doses of the used herbs in the severe situations of IBS mentioned earlier, such as, IBS
patients over than 60 of age, chronic syndrome course over than 10 years duration, and complicated symptoms in
menstruating women.
Factor 6: Number and the type of herbs used in each mixture.
Number and the type of herbs used may affect the outcome. It is observed during the review that trials that used
low number of mixed herbs; 2 or 3 in each the mixture preparation, were associated with Insignificant outcome
between active groups and placebo (Vejdani, et al., 2006; Brinkhaus, et al., 2008) or were associated with
unexpected considerable success and complete safety (Sahib, 2013). However, all other 7 reviewed trials that used
higher number of herbs in each mixture (5-20), achieved more positive outcomes. These results can be interpreted
according to synergism principle that mixing plants extract is more than the sum of their parts, which will
substantiate the perception that natural medicines have something special to offer (Williamson, 2001). According
to Wagner (2006) multiple herbs mixture will provide multi-target action of compounds on a molecular level and
by an improved resorption rate and a change of pharmacokinetic. It is important for future trial to examine the
principle of increase synergism between the active substances of the mixed herbs when using more herbs in the
mixture or when examining new types of herbal mixtures effect on IBS- QOL. According to this observation,
future trials are advised to verify, whether increasing the number and types of herbs in the mixture will achieve
higher efficacy and more safety than using less number and different types of herbs in the mixture, or not?
The suggestion is to start combining two herbs in a mixture as a beginning. Choosing herbal mixture should
depend of the previous scientific evidence of the efficiency of single herb to control one or more of IBS symptoms.
This may fulfill the principle of synergism in the mixture aiming to achieve better response and fewer side effects
in comparison to using of solitary herb for the same purpose (Wagner and Ulrich-Merzenich, 2009). Should the
synergism between two herbs in multiple clinical trials proved, a third herb can be add to the mixture of two herbs
to verify the efficacy of 3 herbs mixture in comparison to two herbs mixture. Adding more herbs in the successive
steps of studies chain, should consider the previous scientific evidence evaluating safety of a single herb used in
23
previous studies. Proved toxic herbs or herbs with obvious adverse reaction or proved chemical interaction should
be excluded from the designed mixture.
Factor 7: Form of the herbal mixture used:
In 4 studies (Bensoussan, 1998; Vejdani, et al., 2006; Hawrelak and Myers, 2010; Sahib, 2013), a complete herb
extracts or whole herbal combination was used. This is the best evidence of the bioavailability of all active
materials inside the whole herb capsule. However, (Madisch, et al., 2000; Micklefield, et al., 2000; Madisch, et
al., 2004) used herbal combination extracts, however, It was not explicit in these trials whether these extracts were
watery, oily, alcoholic or complete extracts?
We suggest the future studies may benefit from specifying should the type of herbal mixture extract used in the
trials, whether these extracts are complete? Oily, watery or alcoholic extracts. The constituents of each extract
depend on type of solvent used to extract the herb constituents. Oily solvents will extract only the oil soluble
substances inside the extracted herbs, where watery solvents will extract only, the watery soluble constituents of
the extracted herb and the same for the alcoholic solvents, which will extract the alcoholic soluble substances of
the extracted herb. It is significant to realize that active substances ingredients differ in each extract, oily, watery,
and alcoholic or others. (Guimarães, et al, 2013).
Since the bioactive materials that produced the favored effect on IBS symptoms, was not specified in the reviewed
trials. It is important for future trials to specify type of herbal extracts mixture used to improve IBS symptoms.
This is significant to specify the group of ingredients (oily, watery or alcoholic) that produced the favored effect.
Unknowing the type of extract (type of ingredients) in previous trials may let the researcher use different type of
extracts (ingredients) in new studies, that may not have the desired effect and may carry misleading and
contradicting outcomes in further studies.
Brinkhaus et al (2008) used mixture of dry herbs. However, no information about how delivered to participants,
swallowing as a capsule, decoction (boiling in water) or using any other methods? The importance of form of herb
mixture gain more significance in the light of evidence that bioavailability of active substances inside each herb
differs according to herbal preparation methods or extraction (Guimarães, et al, 2013). It is significant to specify
and describe precisely the way of herbal mixture preparation during the trial, to obtain a series of dependent
studies that usually evaluate one measurable variable, not multiple and hidden variables where misleading and
contradicting results dominate.
Factor 8: Dose of herb mixture used.
Regarding using the form of mixture and the dose of each herb inside the mixture, 3 out of 10 studies (Madisch,
et al., 2000; Madisch, et al., 2004; Micklefield, 2000) used multiple herbs combination extract. The concentration
of extracts (the dose) was not mentioned in those 3 studies, and whether or not; it meets the standard criteria of
the recommended doses to fulfill the efficiency and avoiding overdose adverse effect. He, (2013) evaluated the
appropriate dose that guarantees Chinese herb's safety and effectiveness, according to adult dose criteria for
Chinese herbs in decoction in the Pharmacopoeia of the People's Republic of China (2010 Edition). In comparison
to the famous ancient literature, Bei Ji Qian Jin Yao Fang, He (2013) found that the dose criteria of Chinese herbal
medicines in the Pharmacopoeia of the People's Republic of China (2010 Edition) are not comprehensive enough
and requires more modifications and changing to achieve the comprehensive concept. However, two of our
reviewed studies (Reissenweber, 2008; Zhang, et al., 2007) evaluated Chinese multiple herbs mixture and Asian
multiple herbs mixture, respectively, No information in the two reviewed studies, related to the principle used for
specifying the proper dose in both studies, were mentioned.
24
Peldonen, et al., (2013), stated that side effect and toxicity to multiple herbs containing thujone such as sage and
Artemisia, which are used frequently in herbal mixture to control IBS, are dose dependent. The higher the dose
of the herb, the higher the possibility to develop adverse reaction and toxicity, such as neurotoxicity from single
dose, or repeated doses. They reported that the best estimates for allowable daily intakes of thujone via herbal
mixture preparations and diet are of the order of 3–7 mg/day. There are still important gaps in the knowledge
required to assess thujone containing herbal mixture toxicity, the most important ones being human dose-
concentration-effect relationships (Peldonen, et al., 2013).
Wiesner, (2014) stated that during the long-standing use of mixture of herbs, particular attention should be paid
to effects that are difficult or even impossible to detect clinically, such as toxicity to reproduction, genotoxicity
and carcinogenicity. However, Bae, et al., (2015), reviewed  233 studies comprising 105 single-herb and 128
multiple-herb studies performed on animals such as mice, rats, rabbits and dogs, this review verified the human
equivalent dose (HED) which were 322.7 mg/kg for single herb and 241.6 mg/kg for multiple herbs. And these
doses considered as a safe and effective dose of herbal medicines. Suggestions for future trials to specify the
concentration (dose) of the multiple herbs extracts, to control IBS symptoms according to recommendation of
Bae, et al., (2015), and in the light of avoiding the doses that cause considerable side effects or toxicity, so that
future trials are able to achieve through the proper dose, the highest efficiency and lowest side effect as a starting
point.
Factor 9: sample size.
It is observed that 3 trials (Micklefield, et al., 2000; Vejdani, et al., 2006; Sahib, 2013) were designed to perform
their study on these samples sizes (n: 6, 26 and 40 respectively), it is important to verify whether these sample
sizes were proper or not enough? Burmeister, and Aitken (2012) stated that Sample size is an element of research
design that significantly affects the validity and clinical relevance of the findings identified in research studies.
Nonetheless, The small sample size may reflect possible sample error, and is less likely to represent the true
population (Raudys and Jain, 1991), especially in the light of absence of explicit unbiased sampling methodology,
in these trials.
According to Green (1991): to perform proper regression analysis during studies for estimating the relationships
among variables such as the relationship between a dependent variable and one or more independent variables,
sample size as a rule-of-thumb should be N ≥ 50 for the multiple correlation and N ≥104 for the partial correlation.
However, according to Burmeister, and Aitken (2012), there is no specific number of participants to be considered
proper during clinical trials, however, there are multiple factors which may influence sample size including; the
effect size, or difference expected between groups or time points, the likelihood of finding an important result that
is both clinically and statistically meaningful and the homogeneity of the study participants (our review
highlighted the importance of homogeneity in gender and age factors). Haas (2012), added another factor that
may affect the sample size during the study, in considering that the size of the difference that the study seeks to
detect, is inversely related to sample size; the bigger the difference, the smaller the sample size needs to be.
Since trials related to multiple herbal mixture use, in general, are still in their beginnings, future trials are advised
for achieving more reliable and valid studies to preform their trials and choosing the size of their samples
according to these principles discussed earlier.
Among these principles:
• Choosing larger sample size to decrease the sampling error, and to increase the probability to represent the
25
targeted population.
• Identifying proper explicit sampling methodology.
• Focusing on the homogeneity of each group of participants that decrease the possibility of sampling error, to
elucidate the difference, which should be measured among the studied groups, for the sake to increase the
credibility of these inchoate phytotherapy studies.
Factor 10: methodology of multiple herbs mixture trials on the true efficiency of using multiple herbs
mixture to control IBS symptoms.
The 10 reviewed studies achieved the criteria of randomized trials, however only two fulfilled double blinding
and were of high quality (Bensoussan 1998; Madisch, et al., 2004). These two studies fulfilled allocation
concealment, used sealed envelope or central control for the allocated treatment. The remaining studies did not
fulfill blinding or any of the mentioned randomization.
Since IBS has a very high prevalence, high negative impact on its patients (Creed, et al., 2001; Hungin, et al.,
2003), carries high economical burden on its patients (Bergemann, et al., 2006), resistant for curative treatments
of conventional medicine (Chey, et al., 2011), prone to aggravate its symptoms through the adverse reaction
resulted from using conventional medicine drugs (Shah, et al., 2012), and patients of IBS are in high need to find
an alternative for the medications of IBS to relieve their symptoms(Yoon, et al., 2011), we recommend future
studies to adhere to highest standards of applying controlled trials, randomization and even double blinding. These
methodologies are accepted as a highest quality studies in credibility, and as prime studies are considered the best
to lead to proper systematic review (Jüni, et al., 2008) and meta-analysis (Moher, et al., 1998) outcomes,
compatible with highest degree of truth and actual practical findings results.
Factor 11: type of symptoms to evaluate in IBS.
Regarding type of IBS symptoms classification, 6 out of 10 trials (Bensoussan, 1998; Madisch, et al., 2000;
Madisch, et al., 2004; Vejdani, et al., 2006; Brinkhaus, et al., 2008; Sahib, 2013) evaluated general scales of IBS
symptoms, However all these studies focused on intra (GIT) symptoms, non of them focused on extra (GIT) such
as depression, sexual impairment, headache, sleep disturbances, tension, anxiety, urinary symptoms, dyspareunia,
lower back pain and fatigue. And non of them focused on other dimensions of IBS sequels such as lower quality
of life (Hahn, et al., 1999), reduced work productivity and low overall health status (Par, et al., 2006),
In the light of effect of IBS at different levels, physically, emotionally, socially, professionally, and sexually
(Creed, et al., 2001; Hungin, et al., 2003), it is significant for future studies to consider multiple herbs use in wider
evaluation of IBS aspects, inside, outside GIT symptoms in addition to use accredited scales to evaluate quality
of life in each aspect of IBS sequels; emotionally, socially and professionally, sexually quality of life and overall
health status.
Factor 12: Abdominal pain, the most common symptom of IBS?
Despite the 10 reviewed studies used general scales for evaluating IBS symptoms, some studies focused with their
outcomes on specific symptoms, the most evaluated specific symptom of IBS was abdominal pain which was
evaluated in 9 out of 10 studies (Bensoussan, 1998; Madisch, et al., 2000; Madisch, et al., 2004; Vejdani, et al.,
2006; Zhang, et al., 2007; Brinkhaus, et al., 2008; Reissenweber, 2008; Hawrelak and Myers, 2010; Sahib, 2013).
4 of the studies used specific evaluation for this symptoms individually regardless the general IBS symptoms
evaluation scale.
Since IBS is a complex syndrome with multiple symptoms and pathophysiologies (Koretz and Rotblatt, 2004),
26
We recommend evaluating each symptom of IBS and measuring the significance of its improvement, regardless
the general IBS scale. This procedure will enable further studies to direct their herbal combinations to specific
symptom according to previous proved studies. In addition, this procedure can establish the base for developing
the herbal combination according to primary findings in previous studies and to evaluated the impact of each
symptom improvement on the quality of life of the IBS patients as a whole.
In all 9 studies, abdominal pain responded significantly to multiple herb mixture except in one study (Brinkhaus,
et al., 2008) in which the response was not significant, however this study was the only study evaluated the effect
of multiple herbs mixture on abdominal pain, that used 2 herb in the herbal mixture only. All remaining 8 trials,
which used 3 or more herbs in the herbal mixture preparation, fulfilled significant outcome in relieving abdominal
pain. It seems that the more numbers of herbs used in the herbal combination, the more possible covering of the
mechanisms of action related to one symptom and the higher possibility to achieve better outcome in that symptom
through the synergism principle between used herbal mixture, as discussed earlier, However it is significant to
point that abdominal pain was not a part of diagnostic criteria of IBS in Rome criteria 1, luckily this was changed
when it was considered as a principal symptom in Rome criteria II (Moayyedi and Ford, 2011).
Presence of significant response to control abdominal pain (the most common symptoms of IBS) in 8 out of 9 of
the reviewed trials, is considered a promising result for IBS patients, However, with the previous weakness in the
review trials discussed earlier, We recommend to obtain more reliable outcomes with higher validity, to perform
further well-designed, randomized, double blind, placebo-controlled trials for longer duration, with bigger sample
size, using international diagnostic criteria, using validated scales, to evaluate multiple herbs preparation effect
on IBS symptoms.
Factor 13: Impact of each symptom on quality of life of IBS patients.
Bowel habits and related symptoms of stool frequency and consistency were the second symptom to be evaluated
in studies. 8 out of 10 studies evaluated bowel habits symptom, bowel habits change is considered one of the
principal criteria for diagnosis of IBS (Moayyedi and Ford, 2011).
Gas production symptoms (bloating, flatulence or abdominal distension) were the third evaluated symptom after
abdominal pain and bowel habits in all evaluated studies, 7 out of 10 reviewed trials evaluated this symptom. Only
4 studies evaluated the outcome of this symptom in their results, not hidden through the general IBS scale.
Except in 3 studies (Vejdani, et al., 2006; Reissenweber, 2008; Hawrelak and Myers, 2010), none of the remaining
studies evaluated the effect of each herbal mixture preparation, on each individual symptom and whether this
preparation has affected one of the evaluated symptoms more than the other. However in the 3 studies (Vejdani,
et al., 2006; Reissenweber, 2008; Hawrelak and Myers, 2010), each symptom responded in a different degree to
each one of the herbal mixture preparation, while in (Vejdani, et al., 2006) severity of bloating and abdominal
pain were among the highest symptoms improved significantly, (Reissenweber, 2008) found that improvement in
epigastric pain, bloating and diarrhoea was better than the improvement in other symptoms, however, (Hawrelak
and Myers, 2010) revealed that bloating and flatulence improved significantly better than abdominal pain using
the same mixture of herbal preparation despite the fact that all symptoms in this trial improved significantly.
Recommendation for future studies are to develop better mixtures that are able to cover most of IBS symptoms
and fulfilling the best quality of life for IBS patients. Suggestion is to add one herbal mixture composition, to
control one symptom (abdominal pain) from the best evident very well designed controlled trial, to another
27
different herbal mixture composition, to control another symptom (abdominal distention) in another best evident,
very will designed controlled trial.
We suggest inventing more accredited scales that can measure the impact of one symptom relief or one
complication disappearance on the total quality of life of IBS patients. This can specify the true weight for each
symptom impact on IBS patients. In addition, this can establish to direct studies to control the highest impact
symptom or complication in systemized arranged priorities order.
Despite low but presence of two main symptoms (abdominal pain and bloating), which did not respond in two
studies (Vejdani, et al., 2006: Brinkhaus, et al., 2008), should arise more questions related to herbal mixture in
these two trials. Is the failure of significant improvement of abdominal pain and bloating related to number of
herbs in each herbal combination used? Is it related to type of herbs used in these herbal combinations? Shall
repeating the trial in the same conditions but with different types or number of herbal combination achieve
different outcome? Suggestions for future studies to put these questions into consideration, while performing
multiple herbs mixture trials, to relieve the symptoms in IBS patients, using same herbal combination and number
in the mixture.
Factor 14: side effect and adverse reaction of multiple herbs mixture used to control IBS symptoms.
5 out of the 10 trials did not state the possible adverse effect of the multiple herbs mixture preparations
(Bensoussan, 1998; Madisch, et al., 2000; Brinkhaus, et al., 2008; Reissenweber, 2008; Hawrelak and Myers,
2010). Despite stating the possible adverse reaction, during the design, 3 out of 10 trials did not document any
side effect or adverse reaction on participants (Micklefield, 2000; Zhang, et al., 2007; Sahib, 2013).
Although the included trials did not report any serious adverse effect from using multiple herbs preparation to
control IBS symptoms for short period of time, two issues should be taken into consideration when verifying
safety using multiple herbs mixture to control IBS symptoms.
First: safety related to multiple herbs mixture use for long period of time.
IBS has a chronic nature, which lives with the patient life long (Olafsdottir, et al, 2010). The reviewed studies did
not show any evidence on humans that use multiple herbs mixture for long term is safe, the only evidence for
long-term use of multiple herbs was proved on dogs and rats, (Shin and Park, et al, 2010). However, we suggest
that safety of using multiple herbs on animals could not be generalized, except on the examined specific (multiple
herbs mixture), which used in that trial. More caution should be paid when using the same mixture on humans.
Recommendation that different multiple herbs mixture should be applied first on animal studies, then when safety
are proven, the same herbal mixture can be applied with cautions on trial performed on humans.
Second: Is all multiple herbs mixture safe?
A wide debate in literature, related the safety of multiple herbs mixture is present. (Wagner, 2006), suggested that
mixture of herbs would increase safety and decrease side effects and possible adverse reaction, via achieving the
principle of synergism through multiple herbs mixture. However (De Oliveira, et al., 2011) claimed that multiple
herbs carries toxicity on kidneys. Despite low, clinical symptoms of liver injury after using multiple herbs was
present, as well (Kim, et al., 2011). In one case report, it was reported occurrence of multi-organ toxicity following
ingestion of mixed herbal preparations (Nnbas ̧ et al., 2006). According to (Jordan, et al., 2010), there has been
more recognition of the potential risks associated with multiple herbs products. Potential harm can occur via
28
inherent toxicity of herbs, as well as from contamination, adulteration, plant misidentification, and interactions
with other herbal products or pharmaceutical drugs.
Presence of multiple contradicted proofs about the safety of herbs, with presence of dangerous adverse reaction,
should suggest the use of multiple herbs mixture with these recommendations
1- Each multiple herb mixture should be considered as a unique mixture, that if its safety is proved, the safety
should not be generalized on other multiple herbs mixtures, even if the contained some of similar herbs of the
proved mixture.
2- Choosing herbal mixture should depend of the previous scientific evidence, which evaluated the safety of a
single herb used in previous studies. Proved toxic herbs or herbs with obvious adverse reaction or proved chemical
interaction should be excluded from the mixture.
3-If scientific evidence of the efficiency and safety is not present, suggested herbs for mixture preparations might
be chosen depending on old proved tradition of herbal medicine in a specific region, which have been used for a
long time generation after generation with proved traditional efficiency and safety. This may need a survey study.
4-We suggests exploring the chemical studies of the ingredients and component of the intended herbs to be used
in the mixture. Knowing the chemical constituents and these possible interaction inside the human body will
exclude some herbs from the mixture combination, to decrease the danger of adverse reactions and possible side
effect due to chemical interaction between these constituents.
5- In vitro and in vivo animal studies are considered good basis to start with, using multiple herbs mixture before
application on humans, especially when little is known about the safety of the intended used herbal mixture.
6- To ensure more safety, suggested herbs to be used in the mixture preferred to be classified as GRAS (Generally
recognized As Safe). This may decrease interaction and possible adverse effects.
7- In previous trials, where herbs in the mixture are chosen according to explicit principles, will ease the mission
to exclude some ineffective or harmful herbs from the mixture, or to add more herbs to improve the response in
the same mixture, in future studies.
Final Conclusion
According to folk beliefs use of multiple herbs, provide more control upon the symptoms of IBS, and grant safer
effect (Wagner, 2006). Most of the people believe that herbs are safe (Myers and Cheras, 2004), if no benefit
gained through their use, no harm is expected. Many studies support this folk belief (Wagner, 2006; Madisch, et
al., 2004).
This review highlighted that multiple herbs preparation use may be effective and safe in relieving and improving
IBS symptoms. Since the combination of herbs mixtures was different in all reviewed studies, there is a lack of
replicable evidence because no more than one trial compared the same herbal mixture preparation and control
treatment. Thus, the benefit of herbal mixture of the same combinations may not be conclusive. Recommendations
for replicable longitudinal studies, using same mixture of herbs in many trials is required.
This review highlighted that multiple herbs mixture preparation might improve most of the symptoms of IBS,
such as abdominal pain, abdominal distention, flatulency, constipation and diarrhea, However, one herbal mixture
is not able to control all the symptoms of IBS and suggestion to invent more combination according to best results
of each herbal combinations on each symptom from previous trials, so that the new combination will consist of
more herbal combination that cover more symptoms according to reviewed or future evidences.
29
However, the findings of this review should be interpreted with caution due to many of the reviewed studies are
not well designed, in the light of small sample size, absence of unbiased sampling methods, short duration course
study, improper use of IBS diagnosis scales, lack of information about the bioavailability of active ingredient due
to ambiguous information related to herbal forms. Bias in some small studies may be noticed with exaggeration
of positive results (100% cure) and complete absence of adverse effects (0%).
References:
Adeyemo, M.A., Spiegel, B.M. and Chang, L., (2009). Do IBS Symptoms Vary Between Men and Women? A
Meta-Analysis. Gastroenterology. 136 (5), A374 -A374.
Bae, J.W., Kim, D.H., Lee, W.W., Kim, H.Y. and Son, C.G., (2015). Review  Characterizing the human
equivalent dose of herbal medicines . Journal of ethnopharmacology.162, 1-6.
Bennett, G. and Talley, N.J., (2002). Irritable bowel syndrome in the elderly. Best Practice & Research Clinical
Gastroenterology. 16 (1), 63–76.
Bergemann, S.M., Thielecke, F., Abel, F. and Bergemann, R., (2006). Costs of Irritable Bowel Syndrome in the
UK and US. Pharmacoeconomics. 24 (1), 21-37.
Berrin, Y., Ali, O., Umut, S., Meltem, E, Murat, B. and Barut, Y., (2006). Multi-organ toxicity following ingestion
of mixed herbal preparations: An unusual but dangerous adverse effect of phytotherapy. European Journal of
Internal Medicine. 17, 130 – 132.
Bijkerk, C. J., Wit, N. J. D., Muris, J. W. M., Jones, R. H., Knottnerus, J. A. and Hoes, A. W., (2003). Outcome
Measures in Irritable Bowel Syndrome: Comparison of Psychometric and Methodological Characteristics. The
American Journal of Gastroenterology. 98, 122–127.
Brinkhaus, B., Hentschel, C., Schindler, G., Lindner, H., Stutzer, R. and Kohnen, R., et al., (2008). Is herbal
medicine effective in irritable bowel syndrome? Results of a randomised, placebo controlled, double-blind clinical
trial. European Journal of Integrative Medicine. 8, 134.
Burmeister, E. and Aitken. L.M., (2012). Sample size: How many is enough? Australian Critical Care. 25, 271-
274.
30
Camilleri, M. and Andresen, V., (2009). Current and novel therapeutic options for irritable bowel syndrome
management. Digestive and Liver Disease. 41, 854–862.
Camilleri, M. and Choi, M.G., (1997). Review article: Irritable bowel syndrome. Alimentary Pharmacology
Therapy. 11, 3-15.
Chang, J. Y. and Tally, N. J., (2010). Current and emerging therapies in Irritable bowel syndrome: from
pathophysiology to treatment. Trends in Pharmacological Sciences. 31 (7), 326-334.
Chang, F.Y. and Ching, L.L., (2009). Treatment of Irritable Bowel Syndrome Using Complementary and
Alternative Medicine. Journal of the Chinese Medical Association. 72 (6), 294-300.
Chey, W.D., Maneerattaporn, M. and Saad, R., (2011). Pharmacologic and Complementary and Alternative
Medicine Therapies for Irritable Bowel Syndrome, Gut and Liver. 5 (3), 253-266.
Creed, F., Ratcliffe, J., Fernandez, L., Tomenson, B., Palmer, S., Rigby, C., et al., (2001). Health-Related
Quality of Life and Health Care Costs in Severe, Refractory Irritable Bowel Syndrome. Annals of Internal
Medicine. 134 (2), 860-868.
De Oliveira, R.B., De Paula, D.A.C., Rocha, B.A., Franco, J.J., Gobbo-Neto, L., Uyemura, S.A., et al, (2011).
Renal toxicity caused by oral use of medicinal plants: The yacon example. Journal of Ethnopharmacology. 133,
434–441.
Douglas, A.D., (2006). The Functional Gastrointestinal Disorders and the Rome III Process. Gastroenterology.
130, 1377–1390.
Drossman, D.A., Richter, J.E. and Talley, N.J., (1994). The functional gastrointestinal disorders,
pathophysiology, and treatment: a multinational consensus. 1st Ed. Boston: Little Brown.
Farthing, M.J.G., (2004). Treatment options in irritable bowel syndrome. Best Practice & Research Clinical
Gastroenterology. 18 (4), 773-786.
Fugh-Berman, A., (2000). Herb-drug interactions. The Lancet, 355 (9208), 1020.
Green, S.B., (1991). How Many Subjects Does It Take To Do A Regression Analysis. Multivariate Behavioral
Research. 26 (3). 499-510.
Guimarães, R., Barros, L., Dueñas, M., Calhelha, R., Carvalho, A.M and Buelga, C.S., et al, (2013). Nutrients,
phytochemicals and bioactivity of wild Roman chamomile: A comparison between the herb and its preparations.
Food Chemistry. 136, 718–725.
Hawrelak, J. A. and Myers, S. P., (2010). Effects of Two Natural Medicine Formulations on Irritable Bowel
Syndrome Symptoms: A Pilot Study. The Journal of Alternative and Complementary Medicine. 16 (10), 1065–
1071.
Hahn, B., Yan, S. and Strassels, S, (1999). Impact of irritable bowel syndrome on quality of life and resource use
31
in the United States and United Kingdom. Digestion. 60, 77–81.
Haas, J.P. (2012). Sample size and power. American Journal of Infection Control. 40 (8), 766–767.
Hatlebakk, J.G. And Hatlebakk, M.B., (2004). Diagnostic approach to suspected irritable bowel syndrome. Best
Practice & Research Clinical Gastroenterology. 18 (4), 735–746.
He, S., (2013). Chinese herbal dose in ancient and modern times: a comparative study. Journal of Traditional
Chinese Medicine. 33 (2), 268–271.
Heitkemper, M.M., Cain, K.C., Jarrett, M.E., Burr, R.L., Hertig, V., Bond, E.F., (2003). Symptoms across the
menstrual cycle in women with irritable bowel syndrome. The American Journal of Gastroenterology. 98 (2),
420-430.
Hopkins ,M.P., Androff, L. and Benninghoff, A.S., (1988). Ginseng face cream and unexplained vaginal bleeding.
American Journal of Obstetrics & Gynecology. 159, 1121–1122.
Hungin, A.P., Whorwell, P.J., Tack, J. and Mearin, F., (2003). The prevalence, patterns and impact of irritable
bowel syndrome: an international survey of 40,000 subjects. Alimentary Pharmacology and Therapeutics. 17,
643-650.
Jackson, N. and Waters, E., (2005). Criteria for the systematic review of health promotion and public health
interventions. Health Promotion International, 20 (4), 367-374.
Jadad, A.R., Moore, R.A., Carroll, D., Jenkinson, C., Reynolds D.J., Gavaghan, D.J., et al. (1996). Assessing the
quality of reports of randomized clinical trials: is blinding necessary? Controlled Clinical Trials. 17 (1), 1–12.
Johansson, P.A., Farup, P.G., Bracco, A. and Vandvik, P.O., (2010). How does comorbidity affect cost of health
care in patients with irritable bowel syndrome? A cohort study in general practice. PubMed Central
Gastroentrology. 10 (1), 31.
Jordan, S.A., Cunningham, D.G and Marles, R.J., (2010). Assessment of herbal medicinal products: Challenges,
and opportunities to increase the knowledge base for safety assessment. Toxicology and Applied Pharmacology.
243, 198-216.
Jüni, P., Altman, D.A. and Egger, M., (2008). Systematic reviews in health care Assessing the quality of controlled
clinical trials. British Medical Journal. 336, 601.
Kim, S-Y., Lee, H., Chae, Y., Park, H. and Lee, H., (2012). A systematic review of cost-effectiveness analyses
alongside randomized controlled trials of acupuncture. Acupuncture in Medicine. 30, 273-285.
Kiyohara, H., Matsumoto, T. and Yamada, H. (2004). Combination Effects of Herbs in a Multi-herbal Formula:
Expression of Juzen-taiho-to’s Immuno-modulatory Activity on the Intestinal Immune System. Evidence-Based
Complementary and Alternative Medicine. 1 (1), 83-91.
Koretz, R. L. and Rotblatt, M., (2004). Complementary and Alternative Medicine in Gastroenterology: The Good,
32
the Bad, and the Ugly. Clinical Gastroenterology and Hepatology. 2, 957–967.
Kurniawan, I. and Kolopaking, M.S., (2014). Management of Irritable Bowel Syndrome in the Elderly. The
Indonesian Journal of Internal Medicine. 46 (2), 138-147.
Lantz, M.S., (1999). St. John's Wort and Antidepressant Drug Interactions in the Elderly. Journal of Geriatric
Psychiatry and Neurology. 12, 7-10.
Lin, H.L., Tsai, H.H., Yu, I.W., Kumar, A. and Wu, M.P., (2014). Would It Matter to Expose Elderly Patients
Who Took Digoxin to Chinese Medications? Value in Health Regional Issues. 3, 211–221.
Liu, J.P., Yang, M., Liu, Y., Wei, M. L. and Grimsgaard, S., (2011). Herbal medicines for treatment of irritable
bowel syndrome (Review). The Cochrane Collaboration. 5, 1-120.
Longestreth, G.F. and Yao, J.F., (2004). Irritable Bowel Syndrome and Surgery: A Multivariable Analysis.
Gastroenterology. 126 (7), 1665–1673.
Manning, A.P., Thompson, W.G., Heaton, K.W. and Morris, A.F., (1978). Towards positive diagnosis of the
irritable bowel. British Medical Journal. 2, 653–654.
Madisch. A., Holtmann, G., Plein, K. and Hotz, J., (2004). Treatment of irritable bowel syndrome with herbal
preparations: results of a double blind, randomized, placebo-controlled, multi-center trial. Alimentary
Pharmacology & Therapeutics. 19, 271–279.
Madisch, A., Plein, K., Mayr, G. and Dagobert, D.B., (2000). Benefit of herbal preparation in patients with
irritable bowel syndrome: Results of a double-blind, randomized, placebo-controlled multicenter trial.
Gastroenterology. 118 (4), A846.
Martin, V.T., (2009). Ovarian Hormones and Pain Response: A Review of Clinical and Basic Science Studies.
Gender Medicine. 6, 168-192.
Melzer, J., Rosch, W., Reichling, J., Brignoli, R. and Saller, R., (2004). Meta-analysis: phytotherapy of functional
dyspepsia with the herbal drug preparation STW 5 (Iberogast). Alimentary Pharmacology & Therapeutics. 20,
1279-1287.
Micklefield, G.H., Greving, I., May, B., (2000). Effects of Peppermint Oil and Caraway Oil on Gastroduodenal
Motility. Phytotherapy Research. 14, 20–23.
Minocha, A., (2005). Irritable Bowel Syndrome in the Older Patient. Gastroenterology. 13, 19-24.
Minocha, A., Johnson, W.D., Abell, T.L. And Wigington, W.C., (2006). Prevalence, Sociodemography, and
Quality of Life of Older Versus Younger Patients with Irritable Bowel Syndrome: A Population-Based Study.
Digestive Diseases and Sciences, 51 (3), 446–453.
Moayyedi, P. and Ford, A.C., (2011). Symptom-Based Diagnostic Criteria for Irritable Bowel Syndrome: the
More Things Change, the More They Stay the Same. Gastroenterology Clinics of North America. 40, 87-103.
33
Moher, D., Pham, B., Jones, A., Cook, D.J., Jadad, A.R Moher, M., et al., (1998). Does quality of reports of
randomised trials affect estimates of intervention efficacy reported in meta-analyses. The Lancet. 352 (9128),
609–613.
Myers, S.P. and Cheras, P. A., (2004). The other side of the coin: safety of complementary and alternative
medicine. Medical Journal of Australia, 181 (4), 222-225.
Naliboff, B.D., Berman, S., Chang, L., Derbyshire, S.W.G., Suyenobu, B., Vogt, B.A., et al., (2003). Sex-Related
Differences in IBS Patients: Central Processing of Visceral Stimuli. Gastroentrerology. 124, 1738–1747.
Nnbas, Y., Berrin, O. Ali, Z. Umut, S., Meltem, E., Murat B., et al., (2006). Multi-organ toxicity following
ingestion of mixed herbal preparations: An unusual but dangerous adverse effect of phytotherapy. European
Journal of Internal Medicine. 17, 130 – 132.
Ohman, L. and Simren, M., (2007). New insights into the pathogenesis and pathophysiology of irritable bowel
syndrome. Digestive and Liver Disease. 39, 201–215.
Olafsdottir, L.B., Gudjonsson, H., Jonsdottir, H.H., Thjodleifsson, B., (2010). Stability of the irritable bowel
syndrome and subgroups as measured by three diagnostic criteria- a 10-year follow-up study. Alimentary
Pharmacology and Therapeutics. 32, 670–680.
Par, P., Gray, J., Lam, S., Balshaw, R., Khorasheh, S., Barbeau, M, et al., (2006). Health-Related Quality of Life,
Work Productivity, and Health Care Resource Utilization of Subjects with Irritable Bowel Syndrome: Baseline
Results from LOGIC (Longitudinal Outcomes Study of Gastrointestinal Symptoms in Canada), a Naturalistic
Study. Clinical Therapeutics. 35.
Pelkonen, O., Abass, K. and Wiesner, J., (2013). Thujone and thujone-containing herbal medicinal and botanical
products: Toxicological assessment. Regulatory Toxicology and Pharmacology. 65, 100–107.
Pittler, M.H. and Ernst, E.,(1998). Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis.
American Journal of Gastroenterology. 93 (7), 1131–1135.
Public Health Resource Unit, (2006). Critical Appraisal Skills Program (CASP) making sense of evidence.
England, 1-4.
Qiu-He, S., Yang, F., Perez, F.M., Xu, Q., Shechter, R., Cheong, Y.K., et al., (2013). Tolerance develops to the
antiallodynic effects of the peripherally acting opioid loperamide hydrochloride in nerve-injured rats. Pain. 154,
2477–2486.
Rahimi, R. and Abdollahi, M., (2012). Herbal medicines for the management of irritable bowel syndrome: A
comprehensive review. World Journal of Gastroenterology. 18 (7), 589-600.
Raudys, S.J. and Jain, A.K., (1991), Small Sample Size Effects in Statistical Pattern Recognition:
34
Recommendations for Practitioners. Pattern Analysis & Machine Intelligence. 3 (13), 252-264.
Reissenweber, H., (2008). Japanese phytotherapy (Kampo) in functional dyspepsia and diarrhea-type irritable
bowel syndrome: Clinical observation in German patients. European Journal of Integrative Medicine. 10, 1016.
Roasch, W., Liebregts, T., Gundermann, K.J., Vinson, B. and Holtmann, G., (2006). Phytotherapy for functional
dyspepsia: A review of the clinical evidence for the herbal preparation STW 5. Phytomedicine. 13, 114–121.
Rodero, B., Casanueva, B., Campayo, J. G., Roca, M., Magallón, R. and Hoyo Y.L.D., (2010). Stages of
chronicity in fibromyalgia and pain catastrophising: a cross-sectional study. BMC Musculoskeletal Disorders. 11,
251.
Rodgers, M., Sowden, A., Petticrew, M., Arai, L., Roberts, H., Britten, N., et al., (2009). Testing Methodological
Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. Effectiveness of Interventions to Promote
Smoke Alarm Ownership and Function, Evaluation, 15 (1), 49-73.
Shah, E., Kim, S., Chong, K., Lembo, A. and Pimentel, M., (2012). Evaluation of Harm in the Pharmacotherapy
of Irritable Bowel Syndrome. The American Journal of Medicine. 125, 381-393.
Sahib, A.S., (2013). Treatment of irritable bowel syndrome using a selected herbal combination of Iraqi folk
medicine. Journal of Ethnopharmacology. 148, 1008–1012.
Saito, Y.A., Rey, E., MD1, Almazar-Elder, A.E., Harmsen, S., Zinsmeister, A.R., Locke, R., et al., (2010).
Randomized, Double-Blind, Placebo-Controlled Trial of St John’s Wort for Treating Irritable Bowel Syndrome.
The American Journal of Gastroenterology – Nature. 105, 170–177.
Simmen, U., Kelber, O., Okpanyi, S.N., Jaeggi, R., Bueter, B. and Weiser, D., (2006). Binding of STW 5
(Iberogast) and its components to intestinal 5-HT, muscarinic M3, and opioid receptors. Phytomedicine. 13, 51–
55.
Snelling, N., (2006). Do any treatments work for irritable bowel syndrome? International Journal of Osteopathic
Medicine. 9, 137-142.
Stabell, N, Flægstad, T., Stubhaug, A. and Nielsen, C.S., (2011). Irritable Bowel Syndrome (IBS) is associated
with reduced pain tolerance: results from the 6th Tromso Study. Journal of Pain Supplements. 5 (1), 203.
Thompson, W.G., Longstreth, G.F., Drossman, D.A., Heaton, K.W., Irvine, E.J. and Muller-Lissner, S.A., (1999).
Functional bowel disorders and functional abdominal pain. Gut. 45, II43–II47.
Thompson, W.G., Hungin, A.P., Neri, M., Holtmann, G., Sofos, S., Delvaux, M., et al., (2001). The management
of irritable bowel syndrome: a European, primary and secondary care collaboration. European Journal of
Gastroenterology & Hepatology. 13, 933–939.
35
Tilburg, M. A., Turner, M. J., Palsson, O. S., Kanazawa, M. and Whitehead, W. E., (2009). Reduced Symptoms
and Visceral Sensitivity Is Related to Menstrual Cycle Changes in IBS. Gastroenterology. 136 (5), A162-A162.
Vejdani, R., Shalmani, H.R.M., Mir-Fattahi, M.M., Sajed-Nia. F., Abdollahi, M., Zali, M.Z., et al., (2006). The
Efficacy of an Herbal Medicine, Carmint, on the Relief of Abdominal Pain and Bloating in Patients with Irritable
Bowel Syndrome: A Pilot Study. Digestive Diseases and Science. 51, 1501–1507.
Wade, P.R., (2002). Age-related changes in the enteric nervous system. American Journal of Physiology -
Gastrointestinal and Liver Physiology. 283.
Wagner. H. and Ulrich-Merzenich, H., (2009) Synergy research: Approaching a new generation of
phytopharmaceuticals. Phytomedicine. 16, 97–110.
Wagner, H., (2006). Multi-target therapy- the future of treatment for more than just functional dyspepsia.
Phytomedicine. 13, 122–129.
Wang, Z., Li, H., Wang, J. and Zhang, F., (2008). Effect of Shugan Jianpi Granule on Gut Mucosal Serotonin-
positive Cells in Patients with Irritable Bowel Syndrome of Stagnated Gan-qi Attacking Pi Syndrome Type.
Chinese Journal of Integrative Medicine. 14 (3), 185-189.
Watson, M., Greenford, D.G., Zeist, H.J. and Yan, S., (1998). Frequency and duration of symptoms in patients
with irritable bowel syndrome (IBS). Gastroenterology. 114 (4), A760.
Wiesner, J., (2014). Challenges of safety evaluation. Journal of Ethno pharmacology. 158, 467–470.
Williamson, E.M., (2001). Synergy and other interactions in phytomedicines. Phytomedicine. 8 (5), 401–409.
Wilson, S., Roberts, L., Roalfe, A., Bridge, P. and Singh, S., (2004). Prevalence of irritable bowel syndrome: a
community survey. British Journal of General Practice. 54 (504), 495-502.
Yoon, S. L., Grundmann, O., Koepp, L. and Farrell, L., (2011). Management of Irritable Bowel Syndrome (IBS)
in Adults: Conventional and Complementary/Alternative Approaches. Alternative Medicine Review. 16 (2), 134-
151.
Zhang, R., Wang. L., Yang, X., Xia, Q., Jiang, Z., Fan, J., et al., (2007). Dinggui Oil Capsule in treating irritable
bowel syndrome with stagnation of qi and cold: a prospective, multicenter, randomized, placebo controlled,
double blind trial. Journal of Chinese Integrative Medicine, 5 (4), 392-397.
Appendix 1 CRITICAL APPRAISAL CHECKLIST FOR A SYSTEMATIC REVIEW. Adapted from: Critical
Appraisal Skills Programme (CASP), Public Health Resource Unit, Institute of Health Science, Oxford.
36
DOES THIS REVIEW ADDRESS A CLEAR QUESTION?
1. Did the review address a clearly focussed issue? Was there enough information on: yes Can't tell No
• The population studied
• The intervention given
• The outcomes considered
2. Did the authors look for the appropriate sort of papers?

The ‘best sort of studies’ would
• Address the review’s question
• Have an appropriate study design
ARE THE RESULTS OF THIS REVIEW VALID?
3. Do you think the important, relevant studies were included? Look for yes Can't tell No
• Which bibliographic databases were used
• Follow up from reference lists
• Personal contact with experts
• Search for unpublished as well as published studies
• Search for non-English language studies
4. Did the review’s authors do enough to assess the quality of the included studies?
The authors need to consider the rigour of the studies they have identified. Lack of
rigour may affect the studies results.
5. If the results of the review have been combined, was it reasonable to do so?
• The results were similar from study to study
• The results of all the included studies are clearly displayed
• The results of the different studies are similar
• The reasons for any variations are discussed
WHAT ARE THE RESULTS?
6. What is the overall result of the review? yes Can't tell No
• If you are clear about the reviews ‘bottom line’ results
• What these are (numerically if appropriate)
• How were the results expressed (NNT, odds ratio, etc)
. How precise are the results?

Are the results presented with confidence intervals?
WILL THE RESULTS HELP LOCALLY?
8. Can the results be applied to the local population? yes Can't tell No
• The patients covered by the review could be sufficiently different from your
37
population to cause concern
• Your local setting is likely to differ much from that of the review
9. Were all important outcomes considered?
10. Are the benefits worth the harms and costs?

Even if this is not addressed by the review, what do you think?
(Appendix 2) Table of the excluded studies.
Excluded studies. Cause of exclusion.

Using herbs with other complementary methods Or using conventional or complementary intervention
other than multiple herbs mixture.
Ducrotte, et al., (2005). Using mud as complementary medicine not
multiple herbs.
Symptomatic efficacy of beidellitic montmorillonite in irritable
bowel syndrome: a randomized, controlled trial.
Ko, et al., (2005). Using other ways ( probiotic with herbs).
Effect of herbal extract granules combined with probiotic mixture
on irritable bowel syndrome with diarrhea: study protocol for a
randomized controlled trial.
Astegiano, et al., (2006). Using vitamins and probiotic.

Treatment of irritable bowel syndrome. A case control experience.
Bittner, (2009). Using probiotics not multiple herbs.
Prescript-Assist probiotic-prebiotic treatment for irritable bowel
syndrome: a methodologically oriented, 2-week, randomized,
placebo-controlled, double-blind clinical study.
Magge, (2011). Evaluation complementary medicine
methods with herbs.
Complementary and alternative medicine for the irritable bowel
syndrome.
Yoon, et al., (2011). Evaluation complementary medicine

methods with herbs.
Management of irritable bowel syndrome (IBS) in adults:
conventional and complementary/alternative approaches.
Xing, et al., (2013). Evaluation complementary medicine

methods without using herbs.
A clinical observation of irritable bowel syndrome treated by
traditional Chinese spinal orthopedic manipulation.
Magge and Wolf, (2013). Evaluation complementary medicine

methods with herbs.
Complementary and alternative medicine and mind-body
therapies for treatment of irritable bowel syndrome in women.
Grundmann and Yoon, (2014). Evaluation complementary medicine

methods with herbs.
Complementary and alternative medicines in irritable bowel
syndrome: an integrative view.
38
Reme, et al., (2011) Evaluating cognitive therapy mediators.

Mediators of change in cognitive behaviour therapy and
mebeverine for irritable bowel syndrome.
Reme, et al., (2010) Evaluating cognitive therapy with

medication.
Predictors of treatment outcome after cognitive behavior therapy
and antispasmodic treatment for patients with irritable bowel
syndrome in primary care.
Kennedy, et al., (2006) Mixing herbs cognitive behavioral therapy.

Cognitive behavioural therapy in addition to antispasmodic
therapy for irritable bowel syndrome in primary care: randomised
controlled trial.
Using languages other than English
Gao, (2010). Despite fulfilling the multiple herbs effect

criteria on IBS. Article in chinese (not
Effect of jianpi tiaogan wenshen recipe in treating diarrhea-
english).
predominant irritable bowel syndrome.
[Article in Chinese].
Zhang, et al., (2012). Despite fulfilling the multiple herbs effect

A multi-center randomized controlled trial on treatment of
english).
diarrhea-predominant irritable bowel syndrome by Chinese
medicine syndrome-differentiation therapy.
Sun, et al., (2004). Despite fulfilling the use of multiple herbs

however , the evaluation was directed toward
Observation on intestinal flora in patients of irritable bowel
the colon flora not the symptoms of IBS.
syndrome after treatment of Chinese integrative medicine.
[Article in Chinese]. [Article in Chinese].
Wang, et al., (2008). Despite fulfilling the use of multiple herbs

however , the evaluation was directed toward
Effect of Shugan Jianpi Granule on gut mucosal serotonin-
gut mucosal serotonin positve cells in IBS
positive cells in patients with irritable bowel syndrome of
not the symptoms of Ibs. [Article in
stagnated Gan-qi attacking Pi syndrome type. [Article in
Chinese].
Chinese].
Gao, et al., (2010).

Despite fulfilling the multiple herbs effect
Effect of jianpi tiaogan wenshen recipe in treating diarrhea-
predominant irritable bowel syndrome.
english).
Gao, et al., (2011). Article in chinese.

Effects of Changjishu soft elastic capsule in treatment of diarrhea- using single herb.
predominant irritable bowel patients with liver-qi stagnation and
spleen deficiency syndrome: a randomized double-blinded
controlled trial. [Article in Chinese].
39
Yu, et al., (2005). Article in chinese.

Effect of modified Sinisan on anorectal manometry of the using single herb.
constipation predominant type of irritable bowel syndrome.
Using single herb as intervention instead of multiple herbs mixture.
Bortolotti, (2011). Using single herb.

Effect of red pepper on symptoms of irritable bowel syndrome:
preliminary study.
Van Tilburg, et al., (2014). Using single herb.
Is ginger effective for the treatment of irritable bowel syndrome?

A double blind randomized controlled pilot trial.
Using single herb.
Saito, et al., (2010).

A randomized, double blind, placebo-controlled trial of St John's
wort for treating irritable bowel syndrome.
Davis, et al., (2006). Using single herb.

Randomised double-blind placebo-controlled trial of aloe vera for
irritable bowel syndrome.
Studies related to diagnostic tools not evaluating intervention effect (multiple herbs) on IBS symptoms
outcome.
Stoicescu, et al., (2012). Evaluating tool through specific germs.

Microscopic colitis and small intestinal bacterial overgrowth--
diagnosis behind the irritable bowel syndrome?
Williams, et al., (2005). Differential diagnosis between IBS and

chronic pelvic pain.
Recognition and treatment of irritable bowel syndrome among
women with chronic pelvic pain.
Ohlsson, et al., (2009). Evaluating the diagnostic value of video

capsule endoscopy.
A prospective evaluation of the diagnostic value of video capsule
endoscopy in patients initially classified as irritable bowel
syndrome.
40
Cremonini and Talley (2004). Diagnostic strategy.

Diagnostic and therapeutic strategies in the irritable bowel
syndrome.
Studies not related to IBS despite their relation to herbs.
Roozbeh, et al., (2013). Not related to IBS but hemodialysis.

Use of herbal remedies among patients undergoing hemodialysis.
Seethapathy, (2012). Not related to I BS : comparing raw and

prepared herbs nr DNA sequence.
nrDNA ITS sequence based SCAR marker to authenticate

Aconitum heterophyllum and Cyperus rotundus in Ayurvedic raw
drug source and prepared herbal products.
Rösch, et al., (2006). Not related to IBS ,but evaluating of multiple

herbs role on functional dyspepsia.
Phytotherapy for functional dyspepsia: a review of the clinical
evidence for the herbal preparation STW 5.
[No authors listed], (2008). Not related to IBS ,but evaluating of

peppermint role on functional dyspepsia.
Herbal remedies for dyspepsia: peppermint seems effective.
Pieroni and Torry (2007). Related to different subject ( effect of taste of

herbs on their consuming) .
Does the taste matter? Taste and medicinal perceptions associated
with five selected herbal drugs among three ethnic groups in West
Yorkshire, Northern England.
Reviews: systematic – non systematic.
Shi, et al., (2008). systematic review evaluating single and

multiple herbs.
Effectiveness and safety of herbal medicines in the treatment of
irritable bowel syndrome: a systematic review.
Liu, et al., (2006). systematic review for single herbs and

multiple herbs.
Herbal medicines for treatment of irritable bowel syndrome.
Rahimi and Abdollahi, (2012). systematic review for single herbs.

Herbal medicines for the management of irritable bowel
syndrome: a comprehensive review.
Darvish-Damavandi, et al., (2010), systematic review for single herbs +

evaluating medication not a herb.
A systematic review of efficacy and tolerability of mebeverine in
irritable bowel syndrome.
41
Bian, (2006). systematic review for a chinese formula.

Effectiveness of the Chinese herbal formula TongXieYaoFang for
irritable bowel syndrome: a systematic review.
Ervin and Mangel (2013). Evaluation medical agents used in phase 2 &
3 to treat IBS: a review.
Clinical trials in irritable bowel syndrome: a review.
CAM: Complementary and Alternative Medicine, GIT: Gastrointestinal tract, IBS: Irritable Bowel Syndrome,
OTC: Over The Counter, RCT: Randomized Controlled Trials.
Appendix 3 (figure of included type of participants of the included studies) IBS: Irritable bowel Syndrome.
42
Appendix 4: inclusion criteria for IBS types and symptoms.
GIT: Gastrointestinal tract, IBS: Irritable Bowel Syndrome.
43
Appendix 5: Inclusion criteria for the intervention (multiple herbs mixture).
Appendix 6: Modified Critical Appraisal of the reviewed studies Program (CASP).
Clear statement of the aims. • Research goal.
• Importance of the research.
• Relevance of the research.
Appropriateness of the • How appropriate was the used methodology in achieving the aims of
research. the research.
Methodology: Sampling: • How participants chosen.
• Why chosen participants were the most appropriate for the sample.
• Why some participants did not continue the study.
Methodology: data collection • How data were collected.

1.
• Is the setting for data collection was justified?
• Did the researcher justify the used methods?
• Were the methods used explicit?
• Are there and modification to methods during the study? And why
modified?
• Are there clear data forms?
44
• Is saturation of data discussed?
Methodology: data collection • Did the research examine the possible participants bias, role?
2.
• Is there explicit formulation of research question?
• Was sample recruitment during data collection Explicit?
• Consideration for research design and possible changes.
.Ethical Issues • Details related to how research was explained to participants.
• How the researched handled the effects on participants during and after
the study.
• If approval has been sought from ethical committee.
Data analysis. • Presence of in depth analysis process.
• How categories and themes were obtained from data?
• How presented data were selected from original sample to demonstrate

the analysis process?
• Sufficiency of data to support the findings.
• Are there contradictory data? To what extent were they taken into
account?
• Any explicit tools to examine possible bias during analysis and

selection of data.
.Findings • Are findings explicit?
• Presence of adequate discussion around the evidence.
• For and against researcher arguments.
• How credible are the findings? Using more than one analysis or
validity.
• Are finding discussed in relation to original research question?
How valuable is the • Did the research add for the existing knowledge?
research?
• Are findings considered current practices or relevant research
literature?
• Is the study fill a literature gap?
• Are findings discussed how could be transferred to another population.
Critical Appraisal Skills Program (CASP)
45
Appendix 7: Data collection appraisal.
study Methods
(Madisch, et al., 2000).

Benefit of an herbal preparation in Multi-centre, placebo-controlled.
patients with irritable bowel
syndrome: Results of a double blind, Allocation concealment: not mentioned.
multicenter trial. Blinding: Yes in investigators and patients.
Loss to follow up: inadequate.
(Micklefield, et al., 2000). Methods Generation of allocation sequence: not mentioned

Effects of Peppermint Oil and Allocation concealment: not mentioned
Caraway Oil on Gastro duodenal
Motility. Blinding: investigators and patients, capsules were identical in size,
colour, taste and smell in both groups
(Hawrelak and Myers, 2010). Methods Generation of allocation sequence: open-label, uncontrolled
clinical trial.
Effects of Two Natural Medicine
Formulations on Irritable Bowel Allocation concealment: not mentioned.
Syndrome Symptoms: A Pilot Study.
Blinding: unclear and inadequate.
Loss to follow up: despite participant have the right to withdraw any
time, the trial did not show number of withdrawn participants and the
reason behind withdrawal (if any).
(Brinkhaus, et al., 2008). Methods Generation of allocation sequence: patients were randomly
assigned.
Is herbal medicine effective in
irritable bowel syndrome? Results of Allocation concealment: unclear.
a randomized, placebo controlled,
double blind clinical trial. Blinding: investigators and patients unclear for form of preparation in 3
groups.
Loss to follow up: unclear/ inadequate.
.(Madisch, et al., 2004) Multi-centre, placebo-controlled, four arms.

Generation of allocation sequence: Computer program.
syndrome with herbal preparations:
results of a double blind, randomized, Allocation concealment: sealed, coded envelope.
placebo-controlled multi-center trial.
Blinding: investigators and patients, similar appearance and taste of
tested medications.
Loss to follow up: number and reasons for loss to follow up were
46
reported, and intention to treat principle was applied.

(Sahib, 2013). Methods Generation of allocation sequence: Yes in two groups but not
mentioned how (inadequate).
syndrome using a selected herbal Allocation concealment: unclear.
combination of Iraqi folk medicine.
Blinding: inadequate.
(Bensoussan, 1998). Methods Generation of allocation sequence: unclear.
Chinese herbs calm irritable bowel. Allocation concealment: sealed envelope.

JAMA. 280, 1585–1590. Blinding: adequate double blinding.
Loss to follow up: yes, by intention-to-treat protocol.
(Reissenweber, 2008). Methods Generation of allocation sequence: inadequate.
Japanese phytotherapy (Kampo) in Allocation concealment: unclear, inadequate.

functional dyspepsia and diarrhea-
type irritable bowel syndrome Blinding: unclear/ inadequate.
Loss to follow up: not mentioned/ inadequate.
(Zhang, et al., 2007). Methods Generation of allocation sequence: Yes according to summary,
details in Chinese.
Dinggui Oil Capsule in treating
irritable bowel syndrome Allocation concealment: Yes according to summary, details in Chinese.
Blinding: Yes according to summary, details in Chinese.
(Vejdani, et al., 2006). Methods Generation of allocation sequence: participants from two
The Efficacy of an Herbal Medicine, private offices of two gastroenterologists but not mentioned how
Carmint, on the Relief of Abdominal allocation happened/ inadequate.
Pain and Bloating in Patients with
Irritable Bowel Syndrome: A Pilot Allocation concealment: inadequate.
Study.
Blinding: Yes for the intervention drops were used in groups with
similar color, odor, and taste.
Loss to follow up: 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 beginning of the study
because they did not start taking the study medication or were lost to
follow-up.
47
Appendix 8: table of data extraction
Categories of extracted data. Subcategories of extracted data.

Study and used methods. • Authors.
• Published years.
• Language (including language of abstracts and
summaries).
• Type of randomization and blinding (number
of centers used to collect participants (single,
multiple or unknown).
• Other methodological features:
1. Randomization of participants in
groups.
2. Non-compliant withdrawn
participants.
3. Reasons for non-compliance.
• Duration of the study.
• What are the symptom/s evaluated by the
study.
Participants • Age and average age.
• Gender, number of participant from each
gender.
• Ethnicity.
• Number of participants in each group.
• Participants’ inclusion and exclusion criteria in
each study.
Intervention (multiple herbs mixture). • Form herb mixture used (tablet, capsule,
extract, oily, watery, alcoholic).
• Composition of herbal mixture (type of mixed
herbs).
• Number of herbs in each mixture.
• Route of delivery.
• Dose and frequency to deliver the preparations
in each study.
• Details of intervention in the comparison group
or the placebo.
The outcome (irritable bowel syndrome). • Type of diagnostic criteria used.
48
Credibility of these diagnostic tools.

•
Type of evaluated IBS in the trial
•
(constipation- diarrheal or mixed).
• Explored symptoms of IBS inside GIT: Colic,
diarrhea, constipation, gases, bloating,
distension and passage of mucus per rectum.
• Explored symptoms of IBS outside GIT:
depression, sexual impairment, headache,
sleep disturbances, tension and anxiety.
• Significance of each symptom change in
comparison to control groups (results).
• Side effects and adverse reaction.
• Possible Interaction (if any).
• Measuring outcome end (time of intervention
end and follow up of the participant).
GIT: Gastrointestinal tract, IBS: Irritable Bowel Syndrome, RCT: Randomized Controlled Trials.
Male to female Age range Number of

Study participants /
ratio
number of groups
(Madisch, et al., 2000). Not given. Not given. 103.

Benefit of an herbal preparation in patients with 51-52 divided in
irritable bowel syndrome: Results of a double blind, two groups.
randomized, placebo-controlled multicenter trial.
(Micklefield, et al., 2000). 2/4. 24-40. 6.

Effects of Peppermint Oil and Caraway Oil on Average 32.
Gastro duodenal Motility.
(Hawrelak and Myers, 2010). Not given. 18–60. 31 participants:

Effects of Two Natural Medicine Formulations on Average 39. 21 IBS-D gr1.
Irritable Bowel Syndrome Symptoms: A Pilot
Study. 10 IBS-C gr2.
(Brinkhaus, et al., 2008). 63% F. 36-60 years. 106 patients

Is herbal medicine effective in irritable bowel 37% M. Average 48.
syndrome? Results of a randomized, placebo
controlled, double blind clinical trial.
49
.(Madisch, et al., 2004) 84 M/124 F. 30-56 years. 208 participants.

Treatment of irritable bowel syndrome
Average 43. STW 5 (n = 51),
with herbal preparations: results of a
double blind, randomized, placebo- STW 5-II (n = 52),
.controlled multi-center trial bitter candytuft
monoextract.
(N = 53) or placebo
(N = 52).
(Sahib, 2013). Not 25-60. 20/20.
mentioned.
Treatment of irritable bowel syndrome using a Average 42.5. Total 40.
selected herbal combination of Iraqi folk medicine.
M/F. 18-75 years. 116.
(Bensoussan, 1998).Chinese herbs calm irritable
Gr1 0.52. Average 46.5. Gr1 38.
bowel. JAMA. 280, 1585–1590.
Gr2 0.65. Gr2 43.
Gr3 (control). Gr3 (control) 35.
0.46.
(Reissenweber, 2008). M/F. 45-59 years. 22.
Japanese phytotherapy (Kampo) in functional Not Average 52. One group.

dyspepsia and diarrhea-type irritable bowel mentioned.
syndrome.
(Zhang, et al., 2007). Group 1 28-52 years. 191.

Dinggui Oil Capsule in treating irritable bowel 36/30. Average 40. Group 1 n=66.
syndrome.
Group 2 Group 2 n=61.
36/25. Placebo n=64.
Placebo
30/34.
(Vejdani, et al., 2006). The Efficacy of an Herbal Group 1 18–65 years. 26 participants.
Medicine, Carmint, on the Relief of Abdominal 64.3% Placebo
Pain and Bloating in Patients with Irritable Bowel 50% Average. Group 1/ 14.
Syndrome: A Pilot Study. 41.5. Placebo/ 18
Appendix 9: description or participants
Study Who diagnosed before the trial? Diagnosis scale
(Madisch, et al., 2000). Multicenter trial. (Not mentioned).

Benefit of an herbal preparation in patients with
50
irritable bowel syndrome: Results of a double

blind, randomized, placebo-controlled
multicenter trial.
(Micklefield, et al., 2000). Not mentioned. Yes mentioned.

Effects of Peppermint Oil and Caraway Oil on
Gastro duodenal Motility.
(Hawrelak and Myers, 2010). Mentioned. Yes fulfilled the Rome

II criteria for IBS.
Effects of Two Natural Medicine Formulations
on Irritable Bowel Syndrome Symptoms: A
Pilot Study.
(Brinkhaus, et al., 2008). Not mentioned. Not mentioned.

Is herbal medicine effective in irritable bowel
syndrome? Results of a randomized, placebo
controlled, double blind clinical trial.
.(Madisch, et al., 2004) Multicenter trial. Irritable bowel

Treatment of irritable bowel syndrome symptom
syndrome with herbal preparations: scale. +
results of a double blind,
Abdominal pain scale.
.multi-center trial
(Sahib, 2013). Outpatient clinic in al Kindy Present by not
College of Medicine. nominated or specified.
Treatment of irritable bowel syndrome using a
selected herbal combination of Iraqi folk
medicine.
(Bensoussan, 1998). Multicenter trials. Rome criteria I.
Chinese herbs calm irritable bowel. JAMA. 280,

1585–1590.
(Reissenweber, 2008). Not mentioned. A five-scale symptom

score before treatment,
Japanese phytotherapy (Kampo) in functional after 1 month, 2
dyspepsia and diarrhea-type irritable bowel months and 3 months
syndrome. of treatment.
(Zhang, et al., 2007). Not mentioned. No obvious scale.

Dinggui Oil Capsule in treating irritable bowel
51
syndrome.
(Vejdani, et al., 2006).The Efficacy of an Multicenter trials. Rome criteria scale.

Herbal Medicine, Carmint, on the Relief of
Abdominal Pain and Bloating in Patients with
Irritable Bowel Syndrome: A Pilot Study.
Appendix 10: description of diagnostic tools of IBS.
52
View publication stats

Multiple herbs mixture for IBS symptoms

Diunggah oleh

Informasi Dokumen

Deskripsi Asli:

Judul Asli

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Multiple herbs mixture for IBS symptoms

Diunggah oleh

Hak Cipta:

Format Tersedia

See discussions, stats, and author proﬁles for this publication at: https://www.researchgate.

Vital factors to be considered when studying multiple herbs mixture

Article · January 2018

The user has requested enhancement of the downloaded ﬁle.

Vital factors to be considered when studying multiple herbs mixture

Jamil Alqudsi, MD., Msc CAM.

Department of Complementary Medicine, University of Westminster

*Correspondence should be addressed to JA (Jamil.alqudsi@my.westminster.ac.uk)

CAM: Complementary and Alternative Medicine.

CASP: Critical Appraisal Skills Program.

GIT: Gastrointestinal tract.

IBS: Irritable Bowel Syndrome.

OTC: Over The Counter.

RCT: Randomized Controlled Trials.

Role of narrative approach

How CASP was used?

Systematic search: Data sources and search strategy

Inclusion/ Exclusion criteria for the review (see table 1).

Excluded from the review: (see appendix 2).

2. In vitro and In vivo studies.

3. Studies reported in abstracts presented in scientific conferences.

5. Single herbs studies

7. Conventional or complementary intervention studies without using herbs.

8. Studies evaluating diagnostic methods not herbal interventions for IBS.

Details of excluded studies (see appendix 2).

Table1: Inclusion/ Exclusion criteria

• Clinical utility for IBS symptoms.

• Inside GIT; Colic, diarrhea, constipation, gases, bloating,

• Outcomes supporting the active effect of the herbs on IBS

Symptoms of IBS outside (GIT.)

Inclusion criteria: (See table 1).

Type of included studies:

What outcome measures are acceptable?

Used critical tools (See Appendix 1& 6).

Data collection and analysis (see appendix 7).

Data extraction (see appendix 8)

Multiple herbs mixture groups were compared with placebo groups.

Trials with similar outcomes were analyzed together.

Participants: (see appendix 9).

Diagnosis tools description (see appendix 10).

Duration of intervention (see table 2).

Types of used herbs (see table 2).

Study Duration Shape of herbs Type of herbs used

(Micklefield, et al., 2000). Not Extracts Peppermint–caraway oil

(Brinkhaus, et al., 2008). 18 weeks. Dry herb. Curcuma xanthorriza 60 mg daily

.(Madisch, et al., 2004) 4 weeks. Product of (STW5):

(Sahib, 2013). 8 weeks. Dry power Mentha longifolia, Cyperus

(Reissenweber, 2008). 3 months Not mentioned

(Zhang, et al., 2007). 2 weeks. Capsule. Dinggui oil.

(Vejdani, et al., 2006).The Efficacy 8 weeks. Total extract. Melissa officinalis,

Form of used herbs. (See table 2).

Evaluated outcomes (see table 3).

Outcome in different range of symptoms;

The possibility of bias in the reviewed studies

Forms of interventions (see table 3).

al., 2000; Reissenweber, 2008).

Effects of interventions (see table 3).

Effect of multiple herbs mixture on each symptom: (see table 3).

(P< 0.1473, P< 0.1207).

(Bensoussan, 1998). All symptoms of Dramatic improvement in the Not mentioned.

(Vejdani, et al., 2006). Severity of There was not a significant 30.77%) of

Discussion and Conclusions: