Bensoussan A, Talley NJ, Hing M, Menzies R, Guo A, Ngu M. Treatment of Irritable Bowel Syndrome With Chinese Herbal MedicineA Randomized Controlled Trial. JAMA. 1998;280(18):1585-1589. doi:10.1001/jama.280.18.1585
From the Research Unit for Complementary Medicine, University of Western Sydney Macarthur (Mr Bensoussan), the Department of Medicine, Nepean Hospital (Dr Talley) and the Department of Behavioral Sciences (Dr Menzies). University of Sydney, Bondi Junction Endoscopy Centre (Dr Hing), Balmain Chinese Herbal Centre (Dr Guo), and Gastroenterology Unit, Concord Repatriation General Hospital (Dr Ngu), Sydney, Australia.
Context.— Irritable bowel syndrome (IBS) is a common functional bowel disorder
for which there is no reliable medical treatment.
Objective.— To determine whether Chinese herbal medicine (CHM) is of any benefit
in the treatment of IBS.
Design.— Randomized, double-blind, placebo-controlled trial conducted during
1996 through 1997.
Setting.— Patients were recruited through 2 teaching hospitals and 5 private practices
of gastroenterologists, and received CHM in 3 Chinese herbal clinics.
Patients.— A total of 116 patients who fulfilled the Rome criteria, an established
standard for diagnosis of IBS.
Intervention.— Patients were randomly allocated to 1 of 3 treatment groups: individualized
Chinese herbal formulations (n=38), a standard Chinese herbal formulation
(n=43), or placebo (n=35). Patients received 5 capsules 3 times daily for
16 weeks and were evaluated regularly by a traditional Chinese herbalist and
by a gastroenterologist. Patients, gastroenterologists, and herbalists were
all blinded to treatment group.
Main Outcome Measures.— Change in total bowel symptom scale scores and global improvement assessed
by patients and gastroenterologists and change in the degree of interference
in life caused by IBS symptoms assessed by patients.
Results.— Compared with patients in the placebo group, patients in the active
treatment groups (standard and individualized CHM) had significant improvement
in bowel symptom scores as rated by patients (P =
.03) and by gastroenterologists (P = .001), and significant
global improvement as rated by patients (P=.007)
and by gastroenterologists (P=.002). Patients reported
that treatment significantly reduced the degree of interference with life
caused by IBS symptoms (P=.03). Chinese herbal formulations
individually tailored to the patient proved no more effective than standard
CHM treatment. On follow-up 14 weeks after completion of treatment, only the
individualized CHM treatment group maintained improvement.
Conclusion.— Chinese herbal formulations appear to offer improvement in symptoms
for some patients with IBS.
IRRITABLE BOWEL syndrome (IBS) is a common functional bowel disorder
that accounts for a significant proportion of patients seen in gastroenterology
offices1 and is characterized by chronic or
recurrent abdominal pain and disturbed defecation. Studies in the United States
and Australia suggest that between 10% and 20% of the population have this
No single available treatment is reliably effective for this condition,6,7 and patients use a variety of approaches
for symptom management, including drugs, dietary modifications, and counseling.
To date, no strong scientific evidence available supports the use of
Chinese herbal agents in IBS.8 However, CHM
has been used for centuries in the treatment of functional bowel disorders
and is routinely used for this purpose in China. Several Chinese studies have
suggested the potential effectiveness of CHM for treatment of IBS, although
these have all lacked rigor in clinical trial protocol9- 13
and have had poor randomization techniques and lack of blinding.8
According to the fundamental principles of traditional Chinese medicine,
treatment should be tailored to the individual clinical presentation of patients,
even though they all may have the same medical diagnosis.8,14,15
Furthermore, treatment needs to be modified at different stages of the patient's
illness or recovery. In this study, we evaluated the effectiveness of CHM
in the treatment of IBS. We compared individualized therapy against a standard
Chinese herbal formulation for IBS and a placebo using a randomized, double-blind,
placebo-controlled study design.
Patients were recruited from gastroenterology units in 2 teaching hospitals
in Sydney, Australia, and through 5 private practices of gastroenterologists.
After patient screening and subsequent review in these centers, patients'
conditions were further diagnosed (according to Chinese medicine principles)
and treated in 3 Chinese herbal clinics by 3 Chinese medicine practitioners.
A clinical trial notification was filed with the Therapeutic Goods Administration,
Commonwealth Department of Health, Housing, Local Government and Community
Services, Canberra, Australia. All herbal substances used in this trial were
listed with the Australian Therapeutic Goods Administration, have been acknowledged
as suitable for human consumption, and were administered within standard dosage
levels. All herbs used in this trial are available over-the-counter throughout
Australia. No product used in this trial was a controlled substance, animal
product, or endangered species. The trial protocol was approved by the ethics
committee of the University of Western Sydney Macarthur and the ethics committees
of the 2 participating hospitals.
Patients between the ages of 18 and 75 years (inclusive) were screened
by a gastroenterologist. Screening involved a routine clinical workup for
IBS with diagnostic tests as determined appropriate by the specialist. Patients
were assessed according to the Rome criteria, an established standard for
diagnosis of IBS.16,17 If diarrhea
was a prominent symptom, lactose intolerance was excluded by hydrogen breath
testing or during a 2-week lactose exclusion period. The inclusion and exclusion
criteria are shown in Table 1.
Written informed consent was obtained from all patients before entering the
trial. Patients were free to withdraw from the study at any time.
After initial gastroenterological screening (week 0), all patients entered
a 2-week run-in period. A Bowel Symptom Scale (BSS) was completed at the beginning
and end of the 2-week period to assess measurement reliability and to account
for any degree of improvement based simply on admission to the trial. Patients
were seen on specified days by 1 of 3 herbalists during the trial period and
were not permitted to change herbalist during the course of the treatment.
The first consultation with the Chinese herbalist occurred at week 2, at which
time the patient was randomized (by an assistant) to placebo, standard CHM,
or individualized CHM treatment. The patient was reevaluated by the Chinese
herbalist at 2-week intervals for 2 occasions and then at monthly intervals
for 2 further occasions. Continuous treatment was administered for 16 weeks.
No special instructions were given to patients regarding diet, other than
to continue consumption of foods they felt comfortable with and to avoid foods
known to cause them gastrointestinal tract irritation. All patients were evaluated
by their gastroenterologist after 8 weeks of treatment and again at the end
of the 16-week treatment period. Patients were closely monitored for any adverse
effects or worsening of symptoms. Liver function tests were performed after
8 weeks of treatment. Follow-up questionnaires were sent to all patients 14
weeks after completion of the treatment period. Treatment codes were broken
and revealed to patients only after completion of the follow-up questionnaires.
Randomization was done by selection of a sealed envelope from a closed
bag. Seventy sealed envelopes were prepared for each of the standard and individualized
groups, and 60 envelopes were prepared for the placebo group. Patients were
aware that there was a greater chance of receiving active treatment. Success
in blinding was evaluated using a treatment credibility scale administered
during the trial.
All herbs were administered in the dried powdered form and encapsulated.
A period of preparation was required before commencement of the trial to develop
a suitable dispensary of 81 individual dried powdered Chinese herbs for dispensing
to patients in the individualized treatment group. The standard herbal formulation
was designed by Chinese herbalists and prepared by the principal supplier,
Mei Yu Imports, Sydney, Australia (Table
2).18 The placebo preparation was
prepared and encapsulated by a pharmaceutical contractor and was designed
to taste, smell, and look similar to a Chinese herb formula. After testing
on 5 independent volunteers, the placebo was deemed indistinguishable from
raw powdered Chinese herbs. All herbs and the placebo formulation were supplied
in the same opaque capsules. Patients in all 3 groups were required to take
5 capsules 3 times daily.
After consulting with the Chinese herbalist, all patients were required
to complete a series of questionnaires and wait 30 minutes for the preparation
of their capsules. The wait time was used to avoid patients identifying whether
they were receiving prepared capsules (standard or placebo) or individualized
formulations that were made at the treatment center. All medication preparation
occurred in a closed room by assistants who were restricted from contact with
the patients. Treatment codes were held by these assistants and by the chief
investigator (A.B.). A blinded primary research assistant managed all the
questionnaires and was responsible for giving the capsules to the patients.
All patients were treated in an equivalent fashion. Compliance was assessed
by an item included in the BSS and by pill count.
The BSS was used to assess change in IBS symptoms during the course
of the treatment. The BSS consists of 100-mm visual analog scales related
to each symptom of IBS (pain/discomfort, bloating, constipation, and diarrhea)
and an overall severity scale. Patients and gastroenterologists completed
this scale independently at the beginning and end of the treatment period.
Patients also were monitored during the course of the trial using this scale.
The BSS also included items for assessing rate of stool passage, rating the
degree to which IBS symptoms interfered with life activities, and recording
changes in medications usage and fiber consumption. To assess the success
of patient blinding, a brief questionnaire was administered to patients after
2, 4, 10, and 16 weeks of treatment. This 4-item scale has been used to test
credibility of different forms of psychological treatment19
but also has been successfully used in acupuncture trials and shown to have
good internal consistency and test-retest reliability.20,21
Pearson product moment correlation was used in the analysis of reliability
and validity data, and factor analysis was used to determine construct validity
of the credibility scale. Outcome measures with categorical responses were
analyzed using χ2 and Fisher exact tests. For the BSS, analysis
of variance was used to determine the differences among groups at baseline,
end of treatment, and follow-up. All P values were
2-tailed, unless otherwise indicated, and the α level of significance
was set at .05. Missing scale and item scores were not replaced. Data are
presented according to an intention-to-treat protocol, in which patients who
withdrew from the trial were recorded as having worsened (if appropriate)
for categorical items only. Data for all other outcome measures are presented
as per protocol analysis.
There were no reliable data that could be used to accurately predict
the anticipated effect size between placebo, standard, and individualized
treatment groups. We estimated that for adequate power (80%) to detect a 20%
difference on the BSS scores at the α=.05 level (1-tailed test), 35
patients were needed in each group.
A total of 116 subjects were recruited during an 18-month period: 35
were randomized into the placebo group, 43 into the standard group, and 38
into the individualized treatment group (Figure 1). Fifteen patients withdrew during the 4-month course
of the trial, and 2 patients were withdrawn from the trial for commencing
a variety of relevant medications during the treatment period. Patient data
on study entry are shown in Table 3.
Patient groups were similar in terms of age, weight, and sex distributions.
There were no significant differences among patients in the 3 groups in terms
of total severity of symptoms as judged independently by both the patient
and gastroenterologist, or in duration of the disease as reported by patients.
Patients allocated to the placebo group had a higher mean score for constipation,
while patients allocated to the standard treatment had a higher mean score
for diarrhea. Compliance with study medication was high as measured by a
questionnaire item and by random pill counts and did not differ between groups
(95% for standard CHM, 94% for individualized CHM, and 95% for placebo).
Fiber and nonstudy medication consumption did not change significantly for
any group during the treatment period.
The reliability of the BSS (ie, consistency of the measure) was determined
by a test-retest assessment during the run-in period prior to treatment commencing
(week 0-2). Correlation between the BSS completed during the initial interview
with the gastroenterologist and then 2 weeks later at the clinical treatment
centers was high for total score (r=0.7; P<.01, 2-tailed) and for each individual symptom (bloating [r=0.8], pain [r=0.6], diarrhea
[r=0.8], and constipation [r=0.7]).
The credibility scale also was examined for test-retest reliability.
Correlation between the first and second administration of this scale was
significant (r=0.6; P <.01,
2-tailed). The correlation coefficients for each of the 4 scale items were
in the range of 0.47 to 0.65. The internal consistency of the credibility
scale based on interitem correlations on both occasions were uniformly high
and Cronbach coefficient α (representing average interitem correlations)
was .87 and .86 for the first and second occasions, respectively.
The visual analog scales within the BSS had high face validity (100-mm
lines with severity marked at the extreme right and absence of symptom marked
at the extreme left) and have high content validity (ie, they incorporate
the key domains of interest—pain and discomfort, bloating, constipation,
and diarrhea). Testing items in the scale for concurrent validity at the commencement
and end of treatment showed that the gastroenterologist's assessment of the
patient correlated highly with the patient's own perception of severity of
symptoms. For both, Pearson correlation coefficient was in the range of r=0.63 to 0.84 for any 1 item (symptom) or for the total
symptom score (P<.01 on all occasions).
Assessment of the credibility scale for construct validity through a
principal components factor analysis based on the first administration revealed
only 1 factor with an eigenvalue greater than 1 (2.89). This factor accounted
for 72.2% of variance in this data set. All items had a high correlation with
this first factor, suggesting satisfactory construct validity.
For all 5 main outcome measures—total mean BSS scores and global
improvement as assessed by patients and gastroenterologists, and interference
with life as assessed by patients—patients receiving the standard CHM
formulation responded significantly better than patients in receiving placebo.
Patients receiving individualized CHM treatment also responded significantly
better on 4 of 5 scores than patients receiving placebo. Overall, patients
receiving individualized CHM fared slightly worse than those receiving standard
At the end of treatment, there was a significant difference between
the mean total BSS scores as assessed by patients, with patients in the standard
CHM group and those in the individualized CHM group responding significantly
better compared with placebo (Table 3).
No significant differences were noted between standard and individualized
CHM treatment groups.
The BSS scores completed by the gastroenterologist at the end of treatment
showed a significant difference between the mean total BSS scores for patients
in each group, with patients receiving standard and individualized CHM responding
significantly better compared with those taking placebo (P = .001). A post hoc Bonferroni test demonstrated that this difference
was significant for patients in the standard group (P=.001)
but not for those in the individualized group (P=.08).
Patients receiving standard herbal formulations improved by 44% (according
to patients) and 59% (according to gastroenterologists), in contrast to patients
in the placebo group who improved 22% (according to patients) and 19% (according
to gastroenterologists). Patients receiving individualized CHM improved by
42% (according to patients) and 40% (according to gastroenterologists).
There was a significant association between the treatment groups and
the change in the degree to which IBS symptoms caused interference with life
and activities by the end of treatment (P=.03). Of
patients receiving the standard formulation and of those receiving individual
formulations, 63% and 54%, respectively, stated that treatment resulted in
IBS causing less interference in their lives and activities, compared with
37% of patients in the placebo group.
At the end of the trial, the ratings of both gastroenterologists and
patients who believed that the IBS symptoms had improved, stayed the same,
or worsened (Table 4) showed
a significant association by treatment group (P=.007).
Of patients receiving standard CHM and of those receiving individual CHM,
76% and 64%, respectively, stated they had improved during treatment. In contrast,
only 33% of patients receiving placebo stated they had improved during treatment.
The gastroenterologists' responses also demonstrated a significant association
between the treatment group and how patients felt at the end of treatment
( χ24=17.1; P =.002). Seventy-eight
percent of patients receiving the standard CHM formulation, 50% of those receiving
individual CHM, and 30% of those receiving placebo were judged by the gastroenterologist
as having improved during treatment. There was significant correlation between
patients' and gastroenterologists' assessment of global improvement and of
total BSS scores at the beginning and end of the trial (all r>0.5, all significant to P≤.01 level,
Two patients withdrew from the trial because of discomfort associated
with the treatment. One patient developed upper gastrointestinal discomfort
while taking the standard CHM formulation. A second patient developed headaches
(although a history of headaches existed), which gradually subsided on discontinuation
of therapy. Recommencement of treatment caused gastrointestinal discomfort,
and the patient was subsequently withdrawn from the study. No other major
adverse effects were noted. Liver function tests obtained after 8 weeks of
treatment showed no abnormal values.
Results of the BSS administered to patients 14 weeks after completion
of the course of treatment (but before treatment codes were revealed) demonstrated
that the treatment effect weakened, with only the individualized CHM group
maintaining improvement (P<.10) (Table 3). However, there was significant association between the
treatment group and how patients felt at the 14-week follow-up (P=.02). Of patients who had received the standard CHM formulation and
of those who had received individual CHM formulations, 63% and 75%, respectively,
stated that they still felt an improvement compared with 32% of patients who
The success of blinding patients to treatment was tested at the beginning,
end, and on 2 other occasions during the course of treatment. At 2 weeks into
treatment, the overall mean on this 6-point scale was 4, indicating that patients
on average viewed CHM as only moderately credible and were not a self-selected
group with a bias in favor of complementary medicine. No significant difference
was noted between groups at outset and at end of treatment. However, the mean
credibility score decreased slightly with time for the placebo group and remained
strong within the standard CHM group. Since the standard CHM treatment proved
the most effective, the increased difference in credibility toward the end
of the treatment may be a reflection that this group of patients was receiving
the most benefit. There was a significant negative correlation between the
final mean credibility score and the final patient-rated BSS score (r=−0.43; P<.01) and the
final gastroenterologist-rated BSS score (r=−0.58; P <.01).
To our knowledge, this is the first clinical trial in CHM that fully
adheres to the traditional Chinese diagnostic and treatment processes while
using a strict and accepted methodological protocol. Our study demonstrated
that CHM is effective in the management of symptoms related to IBS with, in
some cases, effects lasting up to 14 weeks after completion of treatment.
Patients receiving standard or individualized CHM treatment demonstrated significantly
better outcomes (both clinically and statistically) than patients receiving
the placebo on all 5 key outcome measures. However, patients receiving individualized
CHM formulations had less improvement during treatment than patients receiving
the standard formula, although this difference was not statistically significant.
The first null hypothesis that CHM treatment of IBS with a standard
herbal formula is of no value is rejected. The second null hypothesis that
individualized treatment of IBS according to the principles of traditional
CHM is of no added value to treatment with a standard formula is partially
accepted. While there were no significant differences between patients receiving
standard or individualized treatment at the end of the treatment period, on
follow-up, patients in the individualized treatment group had maintained more
Three Chinese herbalists with contrasting Chinese medicine education
backgrounds participated in this trial. In theory, their degree of education
in Chinese herbalism should affect their ability to successfully tailor treatment
for patients. While outcome differences between practitioners were observable
for this cohort of patients, sample sizes were too small to make reliable
conclusions. Furthermore, the overall differences between standard and individualized
CHM may be relatively small (as both are active treatments) and require larger
sample sizes. This does not, however, account for the notable improvement
that was maintained in the individualized CHM group after cessation of treatment.
One plausible explanation may be that the standard CHM formulation was
suitably designed to treat the complex presentations of IBS but was incapable
of successfully dealing with underlying causes for most patients as viewed
by Chinese medicine. The tailored formulations may have permitted the herbalists
to individually address these underlying causes and deficiencies. Moreover,
there may be active ingredients in the CHM formulation with properties similar
to antispasmodic or anxiolytic drugs. Chinese herbal formulas are complex
and viewed as a number of active ingredients working together, rather than
1 specific active substance. The standard formulation used in this study is
not a sedative or anxiolytic preparation in traditional CHM terms but is a
formulation considered to regulate and strengthen bowel function.
In our study, all efforts were made for the approach in the 3 treatment
groups to be indistinguishable. The credibility scale was demonstrated to
be a reliable and valid instrument and presents strong evidence that blinding
was maintained throughout the trial. The slight decrease in credibility score
seen in the placebo group toward the end of the trial was accounted for by
its significant correlation with the actual treatment outcome. The authors
are convinced that patients, herbalists, and gastroenterologists were all
There were minimal adverse effects reported during the study. Liver
function screening was included as a precaution because liver dysfunction
associated with the use of Chinese herbs has been noted in other studies.8,22 Liver dysfunction was not expected
with the type and form of herbs used in this study. In our study, liver function
was reassessed after 8 weeks of treatment. We have no data on liver function
after that time, and therefore cannot comment on longer-term safety of these
CHM products. Raw herbs used as starting products are partly regulated in
We conclude that Chinese herbal formulations may offer symptom improvement
to some patients with IBS. In this randomized, double-blinded, placebo-controlled
trial CHM was shown to be effective in the management of IBS. Patients receiving
the standard CHM formulation fared best during the course of treatment, while
patients receiving the individualized treatments found that the benefit gained
lasted beyond the treatment period. Although not all patients responded to
this therapy, our findings support the consideration of further investigation
of Chinese herbal medicine as a treatment option for IBS.