ORIGINAL ARTICLE
Peppermint Oil for the Treatment of Irritable
Bowel Syndrome
A Systematic Review and Meta-analysis
Reena Khanna, MD,* John K. MacDonald, MA,* and Barrett G. Levesque, MD, MSw
Goals: The aim of this study was to assess the ecacy and safety of
enteric-coated peppermint oil capsules compared with placebo for
the treatment of active irritable bowel syndrome (IBS).
Background: IBS is a common disorder that is often encountered in
clinical practice. Medical interventions are limited and the focus is
on symptom control.
Study: Randomized placebo-controlled trials with a minimum
treatment duration of 2 weeks were considered for inclusion. Cross-
over studies that provided outcome data before the rst cross-over
were included. A literature search upto February 2013 identied all
applicable randomized-controlled trials. Study quality was eval-
uated using the Cochrane risk of bias tool. Outcomes included
global improvement of IBS symptoms, improvement in abdominal
pain, and adverse events. Outcomes were analyzed using an
intention-to-treat approach.
Results: Nine studies that evaluated 726 patients were identied.
The risk of bias was low for most of the factors assessed. Pepper-
mint oil was found to be signicantly superior to placebo for global
improvement of IBS symptoms (5 studies, 392 patients, relative risk
2.23; 95% condence interval, 1.78-2.81) and improvement in
abdominal pain (5 studies, 357 patients, relative risk 2.14; 95%
condence interval, 1.64-2.79). Although peppermint oil patients
were signicantly more likely to experience an adverse event, such
events were mild and transient in nature. The most commonly
reported adverse event was heartburn.
Conclusions: Peppermint oil is a safe and eective short-term
treatment for IBS. Future studies should assess the long-term e-
cacy and safety of peppermint oil and its ecacy relative to other
IBS treatments including antidepressants and antispasmodic drugs.
Key Words: irritable bowel syndrome, peppermint oil, meta-anal-
ysis, treatment
(J Clin Gastroenterol 2014;48:505512)
I rritable bowel syndrome (IBS) is a chronic gastro-
intestinal disorder characterized by abdominal dis-
comfort, bloating, and altered bowel habits. Diarrhea,
Received for publication April 3, 2013; accepted August 2, 2013.
From the *Robarts Clinical Trials, Robarts Research Institute, The
University of Western Ontario, London, ON, Canada; and wDivi-
sion of Gastroenterology, University of California San Diego, La
Jolla, CA.
J.K.M. has received fees for consultancy from Tillotts Pharma AG.
B.G.L. has received fees for consultancy from Santarus Inc. and
Prometheus Labs; speakers bureau payments from UCB Pharma,
Salix and Warner Chilcott; and payment for development of edu-
cational presentations from Curatio. The remaining author declares
that she has nothing to disclose.
Reprints: Barrett G. Levesque, MD, MS, Division of Gastro-
enterology, University of California San Diego, 9500 Gillman
Drive, La Jolla, CA 92093-0956 (e-mail: bglevesque@ucsd.edu).
Copyright r 2013 by Lippincott Williams & Wilkins
J Clin Gastroenterol  Volume 48, Number 6, July 2014
constipation, and mixed (alternating diarrhea and con-
stipation) predominant varieties have been described. IBS
aects 5% to 15% of the population in the western coun-
tries and is more common in women than in men. Although
the etiology of IBS is unknown, alterations in gastro-
intestinal motility, visceral perception, and psychosocial
factors have been implicated. As the exact cause of IBS
remains uncertain, current treatment of IBS is aimed at
symptomatic relief.
Peppermint oil is a naturally occurring carminative that
causes relaxation of the gastrointestinal smooth muscle through
blockade of Ca2 + channels. As such, this agent has been
evaluated for its role in the treatment of IBS.13 The ecacy
and safety of peppermint has been evaluated in numerous
clinical trials with placebo or active comparators. Many of
these trials, however, are small in size and may have lacked
sucient statistical power to arrive at denitive conclusions.
Pittler and Ernst4 performed a meta-analysis of 5
placebo-controlled trials of peppermint oil treatment for
IBS. The results of this meta-analysis suggested that pep-
permint oil was eective for the treatment of IBS. However,
the authors concluded that no denitive conclusions could
be drawn owing to the quality of the primary studies.4 The
methodological aws included a failure to dene inclusion
criteria for patients with IBS, short treatment duration (6 of
the 8 trials in the meta-analysis were r1 mo in length), and
the use of cross-over designs could lead to carry-over
eects. Pittler et al4 did not conduct a paired analysis for
the included cross-over trials. That introduces a unit of
analysis error. A more recent meta-analysis by Ford et al5
excluded cross-over studies. It included 4 placebo-con-
trolled trials assessing peppermint oil and concluded that
peppermint oil was more eective than placebo for the
treatment of IBS. In this systematic review, we will only
include cross-over studies that provide outcome data from
the rst period before any cross-over, thereby allowing the
trials to be treated as a parallel group study.
However, the Pittler and Ernst4 and Ford et al5 meta-
analyses did not include some applicable studies.6,7 In
addition, two new studies assessing the ecacy of pepper-
mint oil have been completed since these meta-analyses
were published.8,9 The main objective of this systematic
review and meta-analysis is to assess the ecacy and safety
of enteric-coated capsules of peppermint oil compared with
placebo for the treatment of active IBS.
MATERIALS AND METHODS
Eligibility
Randomized, placebo-controlled trials of enteric-
coated capsules of peppermint oil treatment of a minimum
duration of 2 weeks were considered for inclusion. Patients
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Khanna et al J Clin Gastroenterol  Volume 48, Number 6, July 2014

of any age with active IBS as dened by the Manning,
Rome I, or Rome II criteria or clinical symptoms with the
exclusion of organic disease were considered for inclu-
sion.1012 Cross-over studies that provided outcome data
before the rst cross-over were included.
Each study identied by the literature search was
independently reviewed by the authors. Relevant studies
were selected for analysis on the basis of the above inclu-
sion criteria. The reasons for exclusion indicated for each
study were deemed ineligible.

Search Strategy Outcomes

MEDLINE (Ovid), EMBASE (Ovid), PubMed, and
the Cochrane Library were searched from inception to
February 2013. No language or document type restrictions
were applied. Review articles and conference proceedings
were also searched to identify additional studies. The search
strategies are listed in Table 1.
The primary outcomes were the proportion of patients
with a global improvement of the IBS symptoms and the
proportion of patients with improvement in abdominal
pain, as dened by the authors of each study. The secon-
dary outcome was the proportion of patients who experi-
enced at least 1 adverse event.

TABLE 1. Search Strategies

MEDLINE and EMBASE (Ovid) Search Strategies:
1. random$.tw.
2. factorial$.tw.
3. (crossover$ or cross over$ or cross-over$).tw.
4. placebo$.tw.
5. single-blind.mp.
6. double-blind.mp.
7. triple-blind.mp.
8. (singl$ adj blind$).tw.
9. (double$ adj blind$).tw.
10. (tripl$ adj blind$).tw.
11. assign$.tw.
12. allocat$.tw.
13. cross-over procedure/
14. double-blind procedure/
15. single-blind procedure/
16. triple-blind procedure/
17. randomized-controlled trial/
18. or/1-17
19. (exp animal/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans).ti.)
20. 18 not 19
21. spastic colon.mp.
22. irritable colon.mp. or exp Irritable Bowel Syndrome/
23. irritable bowel.mp.
24. functional bowel.mp.
25. colonic disease.mp.
26. colonic diseases.mp.
27. IBS.mp.
28. gastrointestinal syndrome.mp.
29. gastrointestinal syndromes.mp.
30. 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29
31. 20 and 30
32. Peppermint oil .mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word,
protocol supplementary concept, rare disease supplementary concept, unique identier]
33. mintoil.mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol
supplementary concept, rare disease supplementary concept, unique identier]
34. colpermin.mp. [mp = title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol
supplementary concept, rare disease supplementary concept, unique identier]
35. 32 or 33 or 34
36. 31 and 35
PubMed Search Strategy:
#1. Search (randomized controlled) OR (controlled clinical) OR (random*) OR (single-blind* OR double-blind* OR triple-blind*) OR
(singl* OR doubl* OR tripl* OR trebl* OR blind* OR mask* OR placebo*)
#2. Search (spastic colon OR irritable colon OR functional bowel OR colonic disease OR colonic diseases OR IBS OR
gastrointestinal syndrome OR gastrointestinal syndromes)
#3. Search (#1 AND #2)
#4. Search (peppermint oil OR mintoil OR colpermin)
# 5. Search (#3 AND #4)
Cochrane Library Search Strategy:
#1. Spastic colon or irritable colon or irritable bowel or functional bowel or colonic disease or IBS or gastrointestinal syndrome
#2. Peppermint oil or mintoil or colpermin
#3. #1 and #2

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J Clin Gastroenterol  Volume 48, Number 6, July 2014
FIGURE 1. Flow diagram of assessment of studies identified by
the literature search. RCT indicates randomized-controlled trial.
Methods of the Review
Relevant studies were selected for analysis on the basis
of the listed inclusion criteria. The reasons for exclusion
were indicated for each study deemed ineligible.
The Cochrane risk of bias tool was utilized to assess
the methodological quality of the included studies.13 The
methodology of each study was assessed for sequence
generation and allocation concealment, blinding, complete,
or selective outcome data reporting. These items were rated
as low (eg, adequate methods were used for blinding), high
(eg, blinding was not used), or unclear risk of bias (eg,
procedures for blinding were not adequately described).
The overall quality of the primary outcomes was assessed
using the criteria of the Grading of Recommendations
Assessment, Development and Evaluation (GRADE)
working group.14 This instrument rates outcomes on a scale
ranging from high quality to very low quality on the basis
of risk of bias, consistency, directness, imprecision, and
reporting bias.
Statistical Analysis
Data were analyzed using the Cochrane Collaboration
software Review Manager (RevMan 5).15 Raw data for
each outcome were extracted and converted into individual
2  2 tables (enteric-coated peppermint oil capsules vs.
placebo). The relative risk (RR) and the 95% condence
intervals (95% CI) derived from each 2 2 table were
individually calculated and plotted. The results for each
comparison group were pooled to determine the RR and
the 95% CI for each outcome. The denitions of global
improvement and improvement in abdominal pain were set
by the authors of each paper, and the data were combined
for analysis only if these denitions were suciently similar.
r 2013 Lippincott Williams & Wilkins
Peppermint Oil for the Treatment of IBS
A xed-eect model was used to calculate the RR. Results
were recorded on an intention-to-treat (ITT) basis,
regardless of whether or not the original authors had per-
formed such an analysis. As such, dropouts or withdrawals
before the completion of the studies were considered
treatment failures.
The presence of heterogeneity among studies was
assessed using the w2 test. As the w2 test has low statistical
power when trials have a small sample size or are few in
number, a P-value of 0.10 was regarded as statistically
signicant. The I2 statistic was used to assess the degree of
inconsistency between the trails.16 This measure describes
the percentage of total variation across studies that is due
to heterogeneity rather than chance. A value of 50%
is considered to be moderate heterogeneity. Whenever
statistically signicant heterogeneity was detected, a ran-
dom-eects model was used to calculate the RR. Sensitivity
analyses were performed to investigate the statistically sig-
nicant heterogeneity.
RESULTS
Description of Studies
A literature search conducted on February 23, 2013
identied 161 studies (Fig. 1). An additional 8 studies were
identied by searching conference proceedings and the
references of review articles. After duplicates were removed,
a total of 100 studies remained for review of titles and
abstracts. A review of titles and abstracts identied 25 trials
that compared the ecacy of the enteric-coated peppermint
oil (marketed as Colpermin or Mintoil) with placebo or
active comparator for the treatment of IBS. Sixteen studies
were excluded. One study was excluded because it was not a
randomized-controlled trial.17 Five cross-over studies were
excluded because they did not report any outcome data
before the rst cross-over.1822 One study was a cross-over
trial with a placebo and active comparator arm. This study
did not provide any outcome data before the rst cross-
over.23 Four studies were excluded because they were
active-comparator studies.2427 One study was excluded
because it did not provide any usable outcome data.28 This
study reported median scores for outcomes and no other
statistics were provided.28 Two studies were excluded
because they were preliminary abstract reports of an
excluded study.29,30 Two studies were excluded because
they were pharmacokinetic studies.31,32
Nine randomized studies (726 patients) that met the
inclusion criteria were identied. Seven studies were double-
blind, placebo-controlled parallel group trials in adult
patients with active IBS.6,8,9,3336 Kline et al37 conducted a
double-blind, placebo-controlled parallel group trial in
pediatric patients with active IBS. Schneider and Otten7
conducted a double-blind, placebo-controlled cross-over
trial that provided outcome results before the rst cross-
over. These studies used various doses of peppermint oil.
Some studies used 0.2 mL of peppermint oil per capsule.7,8
The pediatric study used doses of 0.2 or 0.1 mL of pep-
permint oil per capsule depending on the patients weight.37
The capsules utilized in the Lech et al35 study contained
50 mg of peppermint oil. The capsules used in the Liu et al36
study contained 187 mg of peppermint oil. The capsules
used in the Cappello et al34 study contained 225 mg of
peppermint oil. Three studies did not specify the dose of
peppermint oil that was used.6,9,33 The characteristics of the
included studies are described in Table 2.
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Khanna et al J Clin Gastroenterol  Volume 48, Number 6, July 2014

TABLE 2. Characteristics of Included Studies

Country Duration of
References No. Patients No. Centers Interventions Therapy (wk) Methods
Alam et al9 74 1 country Peppermint oil (unspecied) or 6 Double-blind
1 center placebo
Capanni et al33 178 1 country Peppermint oil (Mintoil) 2 capsules 12 Double-blind
1 center tid or placebo
Cappello et al34 57 1 country Peppermint oil (Mintoil) 225 mg 4 Double-blind
1 center peppermint oil) 2 capsules bid or
placebo
Kline et al37 50 children 1 country Peppermint oil (Colpermin) 2 Double-blind
3 centers (0.2 mL or 0.1 mL/capsule) 2
capsules tid (patients weighing
>45 kg) or 1 capsule tid (weight
30-45 kg) or placebo
Lech et al35 47 1 country Peppermint oil (Mintoil) 50 mg 4 Double-blind
1 center capsules 4 capsules tid or placebo
Liu et al36 110 1 country Peppermint oil (Colpermin) 187 mg 4 Double-blind
1 center peppermint oil 1 capsule tid or
qid or placebo
Merat et al8 90 1 country Peppermint oil (Colpermin) 8 Double- blind
1 center capsules 0.2 mL/capsule 1
capsule tid or placebo
Schneider and Otten7 60 1 country Peppermint oil (Colpermin) 6 Double-blind
1 center capsules 0.2 mL/capsule (tid) Cross-over
or placebo
Weiss and Koelbl6 60 1 country Peppermint oil (Colpermin) 1 3 Double-blind
1 center capsule tid or placebo
bid indicates twice daily; qid, 4 times daily; tid, 3 times daily.

Most of the included studies seemed to be of high
methodological quality (Table 3). However, none of the
studies described the methods used for allocation concealment
and were rated as unclear for this item. Three studies descri-
bed adequate methods for randomization (eg, computer
generated) and were rated as low risk for this item. The other
studies did not describe the methods used for generating the
random sequence and were rated as unclear for this item. Five
studies reported adequate methods for double-blinding and
were rated as low risk for this item. Four studies reported as
double-blind did not describe the methods used for blinding
and were rated as unclear for this item.
Five studies reported treatment outcomes in terms of
global improvement of IBS symptoms.6,3335,37 The pooled
analysis for the ITT population included 392 patients. The
pooled RR showed a statistically signicant benet for
peppermint oil relative to placebo for global improvement
of IBS symptoms (Fig. 2). Sixty-nine percent of the patients
receiving peppermint oil had improved IBS symptoms
compared with 31% of placebo patients (RR 2.23; 95% CI,

TABLE 3. Methodological Quality of Included Studies

Sequence Allocation Incomplete Outcome Selective Outcome
References Generation Concealment Blinding Data Reporting
Alam et al9 Unclear* Unclear* Unclear* Unclear* Unclear*
Capanni et al33 Low riskw Unclear* Unclear* Low riskz Low risky
Cappello et al34 Low riskw Unclear* Low risk8 Low riskz Low risky
Kline et al37 Unclear* Unclear* Unclear* Low risk# Low risky
Lech et al35 Unclear* Unclear* Unclear* Low riskz Low risky
Liu et al36 Unclear* Unclear* Low risk8 Low riskz Low risky
Merat et al8 Low riskw Unclear* Low risk8 Unclear** Low risky
Schneider and Unclear* Unclear* Low risk8 Low riskz Low risky
Otten7
Weiss and Koelbl6 Unclear* Unclear* Low risk8 Low riskz Low risky
*Not described.
wComputer generated.
zFive patients did not complete the study.
yAll expected outcomes reported.
8Double-blind matching or identical placebo.
zDropouts balanced across intervention groups with similar reasons for withdrawal.
#Four patients dropped out from each group.
**Forty percent of the placebo group were lost to follow-up compared with 27% of the peppermint oil group.

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J Clin Gastroenterol  Volume 48, Number 6, July 2014
1.78-2.81). The number of patients that needed to be treated
with peppermint oil versus placebo to induce global
improvement in symptoms of IBS in 1 patient at 2 to 12
weeks was 3. No statistically signicant heterogeneity was
detected for this comparison (w2 = 2.91, df = 4, P = 0.57,
I2 = 0%).
Five studies reported treatment outcomes in terms of
improvement in abdominal pain.7,8,3537 The pooled anal-
ysis for the ITT population included 357 patients. The
pooled RR showed a statistically signicant benet for
peppermint oil relative to placebo for improvement in
abdominal pain (Fig. 3). Fifty-seven percent of the patients
receiving peppermint oil had an improvement in the
abdominal pain compared with 27% of placebo patients
(RR 2.14; 95% CI, 1.64-2.79). The number of patients that
needed to be treated with peppermint oil versus placebo to
induce an improvement in the abdominal pain in 1 patient
at 2 to 8 weeks was 4. No statistically signicant hetero-
geneity was detected for this comparison (w2 = 2.55, df = 4,
P = 0.64, I2 = 0%).
Alam et al9 reported abdominal pain as a continuous
outcome. After 6 weeks of therapy abdominal pain was
signicantly improved (mean SD) in the peppermint oil
group (4.94 1.30) compared with the placebo group
(6.09 1.93; P < 0.001).
Few adverse events were reported. Two studies
reported no adverse events.6,37 The adverse events that were
reported in the placebo-controlled studies were mild and
transient in nature. The adverse events included: heart-
burn,8,3436 dry mouth,8 belching,8 peppermint taste,35
peppermint smell,7 rash,36 dizziness,8 headache,8 increased
appetite,8 and a cold perianal sensation.7
A pooled analysis (7 studies, 474 patients) indicates
that patients receiving enteric-coated peppermint oil cap-
sules were signicantly more likely to experience an adverse
event than patients receiving placebo. Twenty-two percent
of the peppermint oil patients experienced at least 1 adverse
event compared with 13% of the placebo patients (RR 1.73;
95% CI, 1.27-2.36). No statistically signicant hetero-
geneity was identied for this comparison (w2 = 1.95,
df = 4, P = 0.75, I2 = 0%). The Schneider and Otten7
study reported an unusually high number of adverse events
in comparison with the other placebo-controlled studies.
When this study was removed from the pooled analysis, the
relative risk was no longer statistically signicant (RR 1.65;
95% CI, 0.97-2.81).
The GRADE criteria were used to assess the overall
quality of the evidence reported (Table 4). The outcome
FIGURE 2. Peppermint oil versus placebo: global improvement. CI indicates confidence interval.
r 2013 Lippincott Williams & Wilkins
Peppermint Oil for the Treatment of IBS
global improvement in IBS symptoms was downgraded to
moderate because of sparse data. The outcome improve-
ment in abdominal pain was downgraded to moderate
because of sparse data. The outcome adverse events was
downgraded to moderate quality because of sparse data.
DISCUSSION
The results of the meta-analysis provide moderate-
quality evidence that peppermint oil is a safe and eective
short-term therapy for active IBS. The overall quality of the
evidence for the placebo-controlled studies using the
GRADE approach was rated as moderate for the selected
primary and secondary outcomes of interest because of
sparse data (ie, fewer than 400 events). The meta-analysis of
placebo-controlled trials using an ITT population showed
statistically signicant global improvement of IBS symp-
toms (P < 0.00001) and improvement in abdominal pain
(P < 0.00001) in patients treated with peppermint oil rela-
tive to placebo. These results are similar to those found in
the earlier meta-analyses, which suggested a possible benet
with peppermint oil treatment.4,5,38,39 However, a more
denitive conclusion is now possible because of the inclu-
sion of more studies that provide better-quality evidence.
The Pittler and Ernst4 and Lesbros-Pantoickova et al38
meta-analyses included 5 placebo-controlled trials and
showed a signicant global improvement of IBS symptoms
in patients treated with peppermint oil compared with
placebo. Pittler and Ernst4 concluded that these results
needed to be interpreted with caution because of several
methodological aws in the included studies. Similarly,
Lesbros-Pantoickova et al38 concluded that the pepper-
mint oil trials were not conclusive because of poor quality
of the included studies. However, Lesbros-Pantoickova
et al38 incorrectly stated that the Pittler and Ernst4 meta-
analysis came to a negative result. Nonetheless, several
methodological dierences exist between the current and
the previous meta-analyses.
Four of the 5 studies included in the Pittler meta-
analysis were of cross-over design.1820,23 A cross-over
design leads to the possibility of carry-over eects, partic-
ularly in studies that do not include a washout period.
Furthermore, including paired comparison data in a meta-
analysis that assumes that all outcome observations are
independent produce a unit of analysis error. To avoid this
problem, cross-over studies were only included in the
present meta-analysis if they provided outcome data before
the rst cross-over.
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FIGURE 3. Peppermint oil versus placebo: improvement in abdominal pain. CI indicates confidence interval.

Three studies in the Pittler and Ernst4 review and
meta-analysis were criticized for failure to dene any
inclusion criteria for patients with IBS.7,19,20 Furthermore,
only 1 of the 8 studies included in the Pittler and Ernst4
review used validated inclusion criteria (eg, Manning).21
Lawson et al21 did not nd a benet for peppermint oil.
However, this study was methodologically awed because it
was a cross-over study that did not include a washout
period and was excluded from the present meta-analysis.
Several studies included in this meta-analysis used validated
inclusion criteria. Kline et al37 used Manning or Rome
criteria and found a statistically signicant benet for
peppermint oil relative to placebo for improvement in
abdominal pain in children. Cappello et al34 used Rome II
criteria and found a statistically signicant benet for
peppermint oil relative to placebo for global improvement
in IBS symptoms. Capanni et al33 utilized the Rome II
criteria and found a statistically signicant benet for
peppermint oil relative to placebo for global improvement
in IBS symptoms. Alam et al9 utilized the Rome II criteria
and found a statistically signicant benet for peppermint
oil relative to placebo for improvement in abdominal pain.
Merat et al8 also utilized the Rome II criteria as inclusion
criteria for patients with IBS.
It has been suggested that the duration of trials
assessing treatment for IBS should be 2 to 3 months.40 Six
of the 8 trials included in the Pittler and Ernst4 review had
treatment periods of r1 month. Two of the studies
included in the present meta-analysis had treatment periods
of 88 and 12 weeks33 and found a statistically signicant

TABLE 4. Summary of Findings Table

Peppermint Oil vs. Placebo for Treatment of IBS
Patient or Population: Patients With Active IBS
Settings: Outpatients
Intervention: Enteric-coated Peppermint oil Capsules vs. Placebo
Illustrative Comparative Risks*
(95% CI)
Assumed
Risk Corresponding Risk
Quality of the
Peppermint Oil vs. Relative Eect No. Participants Evidence
Outcomes Control Placebo (95% CI) (Studies) (GRADE)
Global improvement in IBS 308 per 687 per 1000 (548 to 866) RR 2.23 (1.78-2.81) 392 (5 studies) """~
symptoms 1000w moderatez
Improvement in abdominal 268 per 574 per 1000 (440 to 748) RR 2.14 (1.64-2.79) 357 (5 studies) """~
pain 1000w moderatey
Adverse events 126 per 218 per 1000 (160 to 297) RR 1.73 (1.27-2.36) 474 (7 studies) """~
1000w moderate8
GRADE Working Group grades of evidence. High quality: further research is very unlikely to change our condence in the estimate of eect. Moderate
quality: further research is likely to have an important impact on our condence in the estimate of eect and may change the estimate. Low quality: further
research is very likely to have an important impact on our condence in the estimate of eect and is likely to change the estimate. Very low quality: we are very
uncertain about the estimate.
*The basis for the assumed risk (eg, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based
on the assumed risk in the comparison group and the relative eect of the intervention (and its 95% CI).
wControl group risk estimates come from control arm of meta-analysis, based on included trials.
zSparse data (224 events).
ySparse data (150 events).
8Sparse data (83 events).
CI indicates condence interval; RR, Relative risk.

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J Clin Gastroenterol  Volume 48, Number 6, July 2014
benet for peppermint oil relative to placebo for improve-
ment in abdominal pain8 and global IBS symptoms.33 In
addition, most of the studies included in the present meta-
analysis specied that patients had to have active symptoms
of IBS as part of the inclusion criteria.7,8,3337 Thus, the
results of the present meta-analysis provide good quality
evidence of the short-term ecacy of peppermint oil for the
treatment of active IBS. Future studies should assess the
ecacy of longer-term treatment with peppermint oil.
Enteric-coated peppermint oil capsules seem to be a
safe treatment for IBS. Few adverse events were reported in
the placebo-controlled studies. Although the meta-analysis
indicated that patients treated with peppermint oil were
more likely than placebo patients to experience an adverse
event, the adverse events were mild and transient in nature.
Adverse events reported in the placebo-controlled trials
include: heartburn,8,3336 dry mouth,8 belching,8 peppermint
taste,35 peppermint smell,7 rash,36 dizziness,8 headache,8
increased appetite,8 and a cold perianal sensation.7 The most
common adverse event was heartburn, which in some cases
was caused by patients chewing the capsules36 or taking the
capsules with meals causing premature release of peppermint
oil in the stomach and relaxation of the lower esophageal
sphincter. Unblinding that may contribute to a placebo eect
in randomized-controlled trials of treatment interventions
for IBS is probably not a serious problem in the studies
included in this meta-analysis, as peppermint smell (n = 8
patients)7 and peppermint taste (n = 1 patient)35 were
reported by a small number of patients in only 2 studies.
Some studies have compared enteric-coated peppermint
oil with antispasmodic medications,2325 and 1 small study
compared peppermint oil with the combination of anti-
depressants and antispasmodics.26 All of these studies were
excluded from the present meta-analysis. No conclusions as
to the relative ecacy of enteric-coated peppermint oil
compared with antispasmodics can be drawn from these
studies because of the methodological aws and small study
sizes. It is interesting to note that Carling et al23 and Ahmad
et al24 reported that patients receiving peppermint oil cap-
sules were signicantly less likely to experience an adverse
event than patients receiving antispasmodic drugs. Patients
receiving antispasmodic drugs also experienced more severe
adverse events compared with patients receiving peppermint
oil. For example, in the Ahmad et al24 study, 16% of the
patients in the antispasmodic drug group reported unbear-
able side eects compared with no patients in the peppermint
oil group. This suggests that it might be a reasonable
approach for clinicians to treat IBS patients with peppermint
oil, which may be better tolerated than antispasmodic drugs
as a rst-line therapy. Large, well-designed studies are
required to determine the safety and ecacy of enteric-
coated peppermint oil capsules relative to antispasmodic and
antidepressant drugs that are commonly used to treat IBS.
In conclusion, the results from this meta-analysis
demonstrate that peppermint oil is a safe and eective
short-term therapy for active IBS. Future studies should be
conducted to assess the long-term ecacy and safety of
peppermint oil treatment and to determine whether pep-
permint oil is equivalent or superior to antispasmodic and
antidepressant drugs.
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