Digestive Diseases and Sciences
Dig Dis Sci (2012) 57:2379-2384
Peppermint Oil Solution Is Useful
as an Antispasmodic Drug for
for Elderly Patients
Atsushi Imagawa, Hidenori Hata,
Morihito Nakatsu, Yasunari Yoshida,
Keiko Takeuchi, Toshihiro Inokuchi,
Takayuki Imada, et al.
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Peppermint Oil Solution Is Useful as an Antispasmodic Drug
for Esophagogastroduodenoscopy, Especially for Elderly Patients
Atsushi Imagawa •Hidenori Hata •Morihito Nakatsu •Yasunari Yoshida •
Keiko Takeuchi •Toshihiro Inokuchi •Takayuki Imada •Yoshiyasu Kohno •
Masahiro Takahara •Kazuyuki Matsumoto •Hirokazu Miyatake •
Satoru Yagi •Masaharu Ando •Mamoru Hirohata •Shigeatsu Fujiki •
Received: 7 December 2011 / Accepted: 14 April 2012 / Published online: 6 May 2012
ÓSpringer Science+Business Media, LLC 2012
Background Although hyoscine butyl bromide (HB) and
glucagon (GL) are often used as antispasmodic drugs
during esophagogastroduodenoscopy (EGD), these agents
may cause adverse effects. Recently, it was reported that
peppermint oil solution (PO) was very effective and had
few side effects.
Aim We clariﬁed the efﬁcacy and usefulness of PO as an
antispasmodic during upper endoscopy, especially for
Methods This study was a non-randomized prospective
study. The antispasmodic score (1–5, where 5 represents no
spasm) was deﬁned according to the degree of spasms of the
antrum and difﬁculty of biopsy. We compared the anti-
spasmodic scores between non-elderly patients (younger
than 70) and elderly patients (70 years old or older)
according to the antispasmodic agent.
Results A total of 8,269 (Group PO: HB: GL: NO (no
antispasmodic) =1,893: 6,063: 157: 156) EGD procedures
were performed. There was no signiﬁcant difference in the
antispasmodic score between Group PO (mean score ±
standard deviation: 4.025 ±0.925) and Group HB (4.063 ±
0.887). Among the non-elderly patients, those in Group PO
(n=599, 3.923 ±0.935) had a worse antispasmodic score
than those in Group HB (n=4,583, 4.062 ±0.876,
P\0.001). However, among the elderly patients, those in
Group PO (n=1,294, 4.073 ±0.917) had similar scores
to those in Group HB (n=1,480, 4.064 ±0.921, P=
0.83), and signiﬁcantly better scores than those in Group
GL (n=69, 3.797 ±0.933, P\0.05).
Conclusion Peppermint oil was useful as an antispas-
modic during EGD, especially for elderly patients.
Keywords Antispasmodic drug
Esophagogastroduodenoscopy Peppermint oil
Hyoscine butyl bromide (HB) (Buscopan 20 mg; Nippon
Boehringer Ingelheim, Hyogo, Japan) and glucagon (GL)
(Glucagon G Novo 1 mg; Novo Nordisk Pharma, Tokyo,
Japan) are often used as antispasmodic drugs during eso-
phagogastroduodenoscopy (EGD) in Japan. However, HB
may cause adverse effects, for example palpitation, ische-
mic heart disease, dry mouth, and urinary retention. GL
may cause hyperglycemia and reactive hypoglycemia
[1,2]. Because the average lifespan of individuals is
increasing, the number of elderly patients undergoing
endoscopic procedures is also increasing. Endoscopists
should take into account a variety of underlying diseases in
elderly patients and should take steps during preparation
for the procedure to avoid the occurrence of adverse
events. Therefore, we feel it is crucial to maintain stable
conditions in the patient and reduce the risk of complica-
tions of the procedure, especially for elderly patients.
Peppermint oil has been used to treat irritable bowel
syndrome for hundreds of years as a digestive aid and
Clinical trial registration number: UMIN00000 4710.
A. Imagawa (&)H. Hata M. Nakatsu Y. Yoshida
K. Takeuchi T. Inokuchi T. Imada Y. Kohno
M. Takahara K. Matsumoto H. Miyatake S. Yagi
M. Ando M. Hirohata
Department of Gastroenterology, Mitoyo General Hospital,
708 Himehama, Toyohama, Kan-onji, Kagawa 769-1695, Japan
S. Fujiki R. Takenaka
Endoscopy Center, Tsuyama Central Hospital, Okayama, Japan
Dig Dis Sci (2012) 57:2379–2384
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carminative [3–7]. Peppermint oil relaxes the tone of
gastrointestinal tract sphincters and aids the passage of
gas. The active component in peppermint oil is menthol,
which blocks calcium channels of smooth muscle [8,9].
Recently, it was reported that peppermint oil solution (PO)
is highly effective and has few side effects as an anti-
spasmodic agent during upper endoscopy and endoscopic
retrograde cholangiopancreatography (ERCP) [10,11].
Moreover, the peculiar aroma of this solution may reduce
stress and anxiety in patients undergoing the procedure
The objective of this study was to clarify the efﬁcacy
and usefulness of peppermint oil solution as an antispas-
modic during EGD, especially for elderly patients.
Materials and Methods
Patients who were scheduled to undergo EGD were
recruited for this non-randomized prospective study. The
following patients were excluded from this study: patients
with clinical evidence of severe disease, for example
American Society of Anesthesiologists (ASA) classiﬁca-
tion of 4 or 5 at the time of EGD, patients with peppermint
allergy, and patients who were pregnant or lactating.
Patients with remnant stomach were also excluded because
it was impossible to evaluate movement of the antrum
The exclusion criteria for using HB and GL are as
described below. This study was approved by the Institu-
tional Review Boards of the Faculty of Mitoyo General
Hospital and Tsuyama Central Hospital. All patients pro-
vided written informed consent to participate in the study
and the EGD procedure.
Selection of the Antispasmodic Agent
All patients were asked about the presence of diseases
before the EGD procedure. The age of the patients, and
commonly-used medicines were also conﬁrmed. For each
patient, the antispasmodic agent was selected according to
the judgment of the endoscopist who took into consider-
ation the patient’s age and underlying diseases. As a gen-
eral rule, HB was avoided for patients with severe heart
disease, prostate hypertrophy, and narrow angle glaucoma.
GL was avoided for patients with severe diabetes mellitus
and phaeochromocytoma. HB and GL were administered
by intramuscular or intravenous injection 3–5 min before
the EGD procedure.
Peppermint Oil Solution
Peppermint oil solution was prepared by mixing pepper-
mint oil (Yoshida Pharmaceutical, Tokyo, Japan), distilled
water, and the catalyst sorbitan monostearate (Wako Pure
Chemical Industries, Osaka, Japan). Approximately 20 ml
1.6 % peppermint oil solution was administered directly to
the antrum of the stomach at the initial stage of the EGD
A total of 8,269 EGD procedures were carried out at
Mitoyo General Hospital, Kagawa Prefecture, and Tsuy-
ama Central Hospital, Okayama Prefecture, in Japan from
March 2007 to September 2010. Peppermint oil was
administered intraluminally during EGD to 1,893 patients
(Group PO) with heart disease, prostate hypertrophy, or
narrow angle glaucoma. HB was administered to 6,063
patients (Group HB) and GL was administered to 157
patients (Group GL) before EGD. For the remaining 156
patients (Group NO), EGD was carried out without anti-
Assessment of Antispasmodic Effect in EGD
The main outcome of this study was to compare the anti-
spasmodic scores for the non-elderly group (patients
younger than 70 years) and elderly group (patients
70 years or older) and their dependence on antispasmodic
agent. The secondary objective was to compare the anti-
spasmodic scores of Group PO patients who did or did not
have atrophy in the stomach as evaluated from the endo-
scopic ﬁndings. We also compared the scores for non-
elderly patients and elderly patients in Group PO.
We used a scale of 1–5 (where 5 represents no spasm) to
rate the degree of spasm of the antrum during EGD and the
degree of difﬁculty of the biopsy procedure, in accordance
with the previous report of Niwa et al. . In cases where
there was severe spasm of the antrum during EGD and
biopsy could not be performed, indicating that the medi-
cation was ineffective, an antispasmodic score of 1 was
assigned. An antispasmodic score of 2 meant there was
severe spasm of the antrum during EGD and biopsy
was difﬁcult to perform, indicating that the medication was
slightly effective. A score of 3 meant there was moderate
spasm of the antrum and biopsy was easy to perform,
indicating that the medication was moderately effective. A
score of 4 meant there was slight spasm of the antrum and
biopsy was easy to perform, indicating that the medication
was effective. A score of 5 meant that biopsy was easy to
perform in the absence of movement of the antrum, indi-
cating that the medication was very effective.
Twenty-nine endoscopists belonged to the endoscopy
centers where this study was conducted during the study
period. All endoscopists had more than three years’
2380 Dig Dis Sci (2012) 57:2379–2384
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experience in performing EGD. The endoscopists assigned
the score immediately after the EGD procedure. The scores
were entered in a database. If the EGD was conducted
without performing a biopsy, the endoscopists assigned the
score according to the degree of spasm of the antrum
during EGD. Because the number of patients who were
taking oral antithrombotic drugs has been increasing and
magniﬁed endoscopy has been developed, in fact, 60–70 %
of the patients underwent EGD without biopsy.
All eligible patients with evaluable data who underwent
EGD during the study period were enrolled. Continuous
data are expressed as mean ±standard deviation (SD). The
coefﬁcient of variation (CV: (SD/mean) 9100) of the
antispasmodic scores was assessed. Statistical analysis was
performed by use of JMP 6 software (SAS Institute, Cary,
NC, USA). Patient characteristics were compared among
the groups using Fisher’s exact test. For the antispasmodic
scores, the Wilcoxon rank sum test was used to assess the
signiﬁcance of differences in two independent groups and
the Kruskal–Wallis test was used to assess the signiﬁcance
of differences in more than two independent groups.
P\0.05 was considered statistically signiﬁcant.
A total of 8,269 subjects who underwent EGD were
enrolled in this study. The mean age of the 8,269 subjects
who underwent EGD was 62.4 years (range 13–99 years).
The male/female ratio was 4,788/3,481. HB, PO, GL, or no
antispasmodic drug was administered to 6,063, 1,893, 157,
and 156 subjects, respectively. Group HB was signiﬁcantly
younger than Groups PO, GL, and NO. In contrast, the
proportion of elderly patients over 70 years was signiﬁ-
cantly higher and the male/female ratio tended to be higher
in Group PO than in Group HB. Groups GL and NO
consisted of small numbers of cases, because there was a
tendency to choose peppermint oil in elderly patients who
had a variety of underlying conditions (Table 1).
The antispasmodic score of Group PO (n=1,893,
4.025 ±0.925) did not signiﬁcantly differ from that of
Groups HB (n=6,063, 4.063 ±0.887, P=0.23) and GL
(n=157, 3.924 ±0.895, P=0.12). The antispasmodic
score of Group HB was signiﬁcantly higher than that of
Groups NO (n=156, 3.846 ±1.073, P\0.05) and GL
(P\0.05) (Fig. 1). The overall CV for the antispasmodic
score was 22.2 %.
Table 1 Patient characteristics and comparison of antispasmodic score among the groups
Total Group HB Group PO Group GL Group NO
No. of cases 8,269 6,063 1,893 157 156
Age (years) 62 ±14 59 ±14 73 ±11* 67 ±11* 73 ±11*
M/F 1.38 1.25 1.74* 3.13* 1.79**
4,788/3,481 3,368/2,695 1,201/692 119/38 100/56
All patients 4.048 4.063 4.025 3.924 3.846
Under 70 years 4.044 4.062 3.923 4.023 3.778
(n) (5,315) (4,583) (599) (88) (45)
70 years and older 4.055 4.064 4.073 3.797 3.874
(n) (2,954) (1,480) (1,294) (69) (111)
HB hyoscine butyl bromide, PO peppermint oil solution, GL glucagon, NO no antispasmodic
*P\0.0001; ** P\0.05 compared with Group HB
4.063 4.025 3.924 3.846
HB PO GL NO
No. of cases 6063 1893 157 156
Fig. 1 Comparison of antispasmodic scores among the four groups
who received PO, HB, GL, or no antispasmodic agent. The antispas-
modic score of Group PO (n=1,893, mean score =4.025 ±0.925)
did not signiﬁcantly differ from that of Groups HB (n=6,063,
score =4.063 ±0.887, P=0.23) and GL (n=157, score =
3.924 ±0.895, P=0.12). Group HB had a signiﬁcantly higher
antispasmodic score than Groups NO (n=156, score =3.846 ±
1.073, P\0.05) and GL (P\0.05)
Dig Dis Sci (2012) 57:2379–2384 2381
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Next, the data were analyzed separately among the non-
elderly patients under age 70 years and among the elderly
patients 70 years and older. Among the patients younger
than 70 years, patients in Group PO (n=599, 3.923 ±
0.935) had a signiﬁcantly worse antispasmodic score than
those in Group HB (n=4,583, 4.062 ±0.876, P\
0.001). The antispasmodic score of Group PO did not
signiﬁcantly differ from that of Group GL (n=88,
4.023 ±0.857, P=0.42) or Group NO (n=45, 3.778 ±
0.974, P=0.34) (Fig. 2). In contrast, among the elderly
patients 70 years or older, Groups PO and HB had similar
antispasmodic scores (Group PO (n=1,294, 4.073 ±
0.917) vs. Group HB (n=1,480, 4.064 ±0.921, P=
0.83)). In addition, Group PO had a signiﬁcantly better
antispasmodic score than Group GL (n=69, 3.797 ±
0.932, P\0.05) (Fig. 3).
Among the patients in Group PO, we were able to
endoscopically evaluate whether or not there was atrophy
in the stomach in 437 patients. There was no signiﬁcant
difference in the antispasmodic score between those with
atrophy in the stomach (n=356, 4.213 ±0.894) and
those without atrophy (n=81, 4.086 ±0.977, P=0.33).
In contrast, peppermint oil had a stronger antispasmodic
effect in elderly patients (n=1,294, 4.073 ±0.917) than
in non-elderly patients (n=599, 3.923 ±0.935, P\
0.001) (Fig. 4). This result showed that peppermint oil had
a weak antispasmodic effect in non-elderly patients.
However, our results showed that peppermint oil in elderly
patients was not inferior to HB and GL, although there
were many high-risk patients with an underlying disease in
Group PO. There were no severe adverse effects including
severe heartburn in any patient during and after the EGD
procedure in this study.
This study showed that peppermint oil solution is effective
and useful as an antispasmodic drug for EGD, especially
for elderly patients. Endoscopists should always consider
the background of the patients in order to carry out a safe
procedure. For elderly patients, the risk of complications of
EGD is increased, and the general condition of the patients
becomes unstable during EGD, because of their underlying
Peppermint oil has been used for treatment of irritable
bowel syndrome and functional dyspepsia [3–7,14]. In
addition, it has been used as an herbal medicine since
ancient times and is used in many foods . Peppermint
oil is a safe medication for elderly people because there are
no severe side effects including allergic reaction if a nor-
mal volume is used, although heartburn, perianal burning,
blurred vision, nausea, and vomiting were common adverse
effects of peppermint oil reported in clinical trials .
When peppermint oil is administered orally, menthol, one
of its important constituents, is rapidly absorbed and
metabolized to its glucuronide salt, which is excreted
almost entirely in the urine . Peppermint oil has been
reported to reduce spasm during colonoscopy, ERCP, and
barium enema examination [10,11,16–22]. It can also be
expected to have an anti-anxiety and relaxing effect on
patients because of its unique aroma.
In addition, there were some advantages for patients
who received PO. For medical staff, by eliminating needle
4.062 3.923 4.023
HB PO GL NO
No. of cases 4583 599 88 45
Fig. 2 Comparison of antispasmodic scores for non-elderly patients
in the four groups who received PO, HB, GL, or no antispasmodic
agent. Patients in Group PO (n=599, score 3.923 ±0.935) had a
signiﬁcantly worse antispasmodic score than those in Group HB
(n=4,583, score 4.062 ±0.876, P\0.001). There were no signif-
icant differences in the antispasmodic score between Group PO versus
Group GL (n=88, score 4.023 ±0.857, P=0.42) or Group NO
(n=45, score 3.778 ±0.974, P=0.34)
HB PO GL NO
No.of cases 1480 1294 69 111
Fig. 3 Comparison of antispasmodic scores for elderly patients in the
four groups who received PO, HB, GL, or no antispasmodic agent.
Elderly patients in Group PO (n=1,294, score 4.073 ±0.917) had a
similar antispasmodic score to those in Group HB (n=1,480, score
4.064 ±0.921, P=0.83), and a signiﬁcantly better score than those
in Group GL (n=69, score =3.797 ±0.933, P\0.05)
2382 Dig Dis Sci (2012) 57:2379–2384
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injection, the risks and burdens of pre-medication were
reduced. For the patients, the probability of needle-stick
injury decreased and the length of time of the endoscopy
procedure was shortened.
The main objective of this study was to compare the
antispasmodic effect of PO with that of HB and GL.
Although an antispasmodic effect was observed at nearly
satisfactory levels for all patients, the antispasmodic effect
for non-elderly patients who received peppermint oil was
insufﬁcient. This study also demonstrated that peppermint
oil had a stronger antispasmodic effect in elderly patients
than in non-elderly patients; however, the antispasmodic
effect of peppermint oil was not affected by the presence of
atrophy of the gastric mucosa. The reason for this result is
This study has some limitations. First, there was bias with
higher percentages of males and elderly people in Group PO.
This bias may be regarded as acceptable because of the
background of the patients. The second limitation is that the
antispasmodic score was assigned mainly by subjective
assessment. The ideal study may be to randomly assign non-
risk patients to groups HB and PO, and high-risk patients to
groups PO and NO. The third limitation of this study is that
the endoscopists were not unaware of the drugs being
administered; making them unaware would have been dif-
ﬁcult because of the unique fragrance of peppermint oil. The
fourth limitation is that peppermint oil has the drawback that
it is necessary to use a catalyst to mix the water and menthol
and preparation of this solution is slightly complex. This
problem was resolved by assistance of pharmacists at the two
hospitals. Ingestion of PO has been suggested to increase
symptoms of gastro-esophageal reﬂux disease . However,
in our study, no patient who received peppermint oil devel-
oped heartburn and chest discomfort during or after the
Another unique characteristic of peppermint oil is its
long length of effectiveness. In our experience, although a
few minutes were required for the effect of peppermint oil
to appear, it was expected that the duration of the anti-
spasmodic effect of peppermint oil would be 20 min or
longer because no patient developed relapse of movement
during EGD. Therefore, it is thought that peppermint oil,
which can be administered at any time, would also be
suitable for procedures that take a long period of time, for
example complex endoscopic treatment.
In conclusion, because PO was effective as an anti-
spasmodic agent during EGD, for the elderly in particular,
its use was suitable and sufﬁcient for conventional EGD.
Acknowledgments The authors thank Ms Sachiyo Kondo, a
member of the Department of Pharmacy, Tsuyama Central Hospital,
and Mr Masashi Katagiri and Mr Eiji Mukai, members of the
Department of Pharmacy, Mitoyo General Hospital, for their coop-
eration and assistance in this study. The authors thank Dr Yasuhiro
Miyake for assistance in the preparation of this manuscript.
Conﬂict of interest No conﬂicts of interest exist.
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Fig. 4 Comparison of antispasmodic scores among patients who
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