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Short Communication
The effect of mastic gum on Helicobacter pylori: A randomized pilot study
K.J. Dabos
, E. Sfika, L.J. Vlatta, G. Giannikopoulos
Department of Gastroenterology, Chios General Hospital Skylitsion, Helenas Venizalou 2, 82100 Chios, Greece
article info
Keywords:
Herbal remedies
Monotherapy
Chios mastiha
abstract
Our aim was to study the effect of pure mastic gum on Helicobacter pylori (H. pylori) eradication in
patients suffering from an H. pylori infection
Fifty two patients were randomized to receive either 350 mg three times a day (tid) of pure mastic
gum for 14 days (Group A), or 1,05 g tid of pure mastic gum (Group B) for 14 days, or pantoprazole 20 mg
twice a day (bd) plus pure mastic gum 350 mg tid for 14 days (Group C) or pantoprazole 20 mg bd plus
amoxicillin 1 g bd plus clarithromycin 500 mg bd for 10 days (Group D). All patients harboured H. pylori
before entering the study and that was confirmed by a
13
C urea breath test (UBT). H. pylori eradication
was tested by a UBT 5 weeks after completion of the eradication regime.
Eradication of H. pylori was confirmed in 4/13 patients in Group A and in 5/13 in Grour B. No patient
in Group C achieved eradication whereas 10/13 patients in Group D had a negative UBT. There were no
statistically significant differences in mean UBT values in Groups A, B, C although there was a trend in
Group A (p= 0.08) and in Group B (p =0.064). The difference was significant in Group D (p= 0.01). All
patients tolerated mastic gum well and no serious adverse events were reported. Mastic gum has
bactericidal activity on H. pylori in vivo.
&2009 Elsevier GmbH. All rights reserved.
Introduction
Helicobacter pylori (H. pylori) is a Gram-negative spiral
bacterium that colonises the stomach. Its prevalence in Europe
is in the range of 10-25% and has been falling during the last
decades while in the developing world it is estimated that its
prevalence is much higher (Magalhaes-Queiroz and Luzza 2006).
Infection with H. pylori is etiologically linked to gastritis, peptic
ulcer disease, primary B cell gastric lymphoma and adenocarci-
noma of the stomach (Lai and Sung 2007;Eslick 2006). H. pylori
can be eradicated but this is difficult to achieve and at least two
antibiotics and an acid suppressant are required to achieve
eradication (Malfetrheiner et al. 2007). Side effects for these
regimes are common and a major concern is the development of
antimicrobial resistance. Development and testing of new safe
alternatives to those regimes is therefore warranted.
Mastic gum is a natural resin that is excreted from the trunk
and branches of the mastic bush (Pistacia Lentiscus var. Chia). This
excretion is produced by incising the bark with a sharp
instrument. Mastic gum appears in the incisions in the form of
tears and exudes in droplets onto the soil. While it is flowing, it is
a gummy, clear liquid; it solidifies in irregular shapes after 15-20
days.
Collection is completed in September. Then it is cleaned first by
hand and then with mechanized means. Finally mastic gum is
sorted, classified and graded according to the color and size of the
granule.
The clean mastic gum granules were milled to fine powder
(particle size o200
m
m) by using a Hosokawa Alpine Fine Impact
Mill 100 UP2 (Hosokawa Alpine, Augsburg, Germany). The
encapsulation of powder was performed using the Profill Capsule
Filling System (Torpac Inc, Mumbai, India). Capsule shells
(Capsulegel, V caps, size 0) were made of Hypromellose (Hydro-
xypropyl methylcellulose) and each contained 0.35 (70,002) g of
mastic powder.
There have been references to mastic gum as a medicinal
product since ancient times. It has successfully been used in
gastrointestinal upsets (Kaliora et al. 2007).
Previous studies have shown some effect of mastic gum on the
healing of peptic ulcers in humans (Al-Habbal et al. 1984;Al Said
et al. 1986). Those studies were conducted before the discovery of
H. pylori. A recent case study has shown no effect of mastic gum
on H. pylori (Bebb et al. 2003).
The aim of our randomised controlled trial was to assess the
efficacy of mastic gum monotherapy or in combination with a
proton pump inhibitor on H. pylori eradication and to compare this
efficacy with the standard treatment regime.
Patients and methods
This prospective randomized controlled trial study was con-
ducted at the Gastroenterology Department of Chios General
ARTICLE IN PRESS
Contents lists available at ScienceDirect
journal homepage: www.elsevier.de/phymed
Phytomedicine
0944-7113/$ - see front matter &2009 Elsevier GmbH. All rights reserved.
doi:10.1016/j.phymed.2009.09.010
Corresponding author. Tel.: +302651080738; fax: + 302651080642.
E-mail address: kostasophia@yahoo.com (K.J. Dabos).
Phytomedicine 17 (2010) 296–299
ARTICLE IN PRESS
Hospital Skylitsion. The study was approved by the Local Ethics
Committee and the Greek Medicines Agency.
All eligible patients had an upper gastrointestinal endoscopy
and were found to harbour H. pylori by a rapid urease test (CLO
test, Kimberky Clark, Draper, Utah, USA).They were then asked to
participate in the study and gave their written informed consent.
Patients were excluded if they had a gastric or duodenal ulcer,
were pregnant women or had used in the previous 4 weeks, non
steroidal anti-inflammatory drugs, anticoagulants, steroids, pro-
ton pump inhibitors or antibiotics. Patients who chewed mastic
gum more than once a week were also excluded from the study.
Patients had confirmation of their H. pylori infection by a
13
C
urea breath test (UBT) (INFAI, York, UK). They were then
randomized to receive either a low dose mastic gum monotherapy
350 mg three times a day (tid) for 14 days, a high dose mastic gum
monotherapy 1g tid for 14 days, a dual regime of mastic gum
350 mg tid and pantoprazole 20 mg bd for 14 days, or a standard
triple therapy which consisted of pantoprazole 20 mg bd,
amoxicillin 1 g bd and clarithromycin 500 mg bd for 10 days.
They were asked to keep a log of adverse events. One week into
the study patients received a telephone call, in which their
compliance was assessed and an enquiry on possible adverse
events was made. At the end of the study a physical examination
was performed as well as routine laboratory tests.
Five weeks after the end of treatment, eradication was tested
with a second UBT.
Pure mastic gum was dispensed in capsule form. It contained
no additives or flavourings that could have an effect on its activity.
The randomization was generated using Proc random (SAS
version 6.9). The randomization code was kept at the Central
Pharmacy of Chios General Hopsital Skylitsion. The technician
who performed the UBTs and the operator who analysed the UBTs
were blinded as to which treatment each patient had received.
Data record and statistical analysis
Data were recorded prospectively in case report forms for all
participating patients. All analysis was conducted by intention to
treat. Results are shown as mean and SEM.
Comparisons between UBT values before and after the
intervention were made using the paired t-test. A pvalue of
o0.05 was taken as significant (two-tail test of significance).
Results and discussion
We enrolled fifty two patients from the Endoscopy unit: 13
received low mastic gum monotherapy 350mg tid for 14 days
(Group A), 13 received high mastic gum monotherapy 1g tid for 14
days (Group B), 13 received mastic gum 350 mg tid and
pantoprazole 20 mg bd for 14 days (Group C) and 13 patients
received triple therapy with pantoprazole 20mg bd, amoxicillin
1 g bd and clarithromycin 500 mg bd for 10 days (Group D).
There were no statistically significant differences between
groups with regards to age, sex, previous use of antibiotics or
proton pump inhibitors.
One patient from Group A completed the study but did not
return for his follow up UBT 5 weeks later. Two patients from
Group C completed the study but did not return for their UBT 5
weeks later. One patient in Group D stopped because of side
effects (diarrhoea and abdominal cramps).
Table 1 shows an overview of the results. Four patients in
group A achieved eradication (30,8%), whereas five in Group B
(38,5%) none in Group C and ten patients in Group D (76,92%)
achieved eradication.
UBT was performed a mean of 8 days (4-14 days) before
starting treatment. It was repeated a mean of 39 days (33-61 days)
after completion of the study medication. Fig. 1 shows mean UBT
values before and after treatment. There was a trend towards
significance in Group A (28.8674.4 vs 18.7673.1) (p= 0.08), and
in Group B (27.1175.2 vs 17.6874.8)(p =0.064). Group C showed
no difference (25.5673.8 vs 23.67 74.7) (p =NS) There was a
statistically significant difference in UBT values in Group D
(26.7373.9 vs 7.8572.8) (p o0.01).In nine patients in Group A
and ten patients in Group B the UBT value post treatment
decreased compared with the UBT value before treatment.
Patients who received mastic gum tolerated it well. One
patient in Group A complained of diarrhoea and another in Group
B complained of nausea. Both completed the therapy as per
protocol. Three patients in Group D complained of abdominal
cramping and diarrhoea, one stopped the treatment on day 4.
This study was designed to evaluate the effect of Mastic gum
on H. pylori in vivo. Our results showed that mastic gum has some
effect on H. pylori in vivo. Nine patients in the monotherapy groups
achieved eradication while in ten more patients the UBT value
decreased compared to the pre-treatment reading. UBT values
have been shown to provide rather accurate estimation of the in
vivo H. pylori load (Perri et al. 1998).
We have also shown that the combination of mastic gum and
pantoprazole was ineffective in eradicating H. pylori but it had no
effect on bacterial load either. Our control group with standard
triple therapy achieved an acceptable eradication rate.
The constituents which might contribute to the therapeutic
effects of mastic gum belong to the class of mono- and
sesquiterpenoids (essential oils) (Barra et al. 2007) and triterpe-
noids (e.g. masticadienonic acid) (Assimopoulou and Papageor-
giou 2005). Previous in vitro studies have shown that crude mastic
gum possesses antibacterial properties against H. pylori (Huwez et
al. 1998;Marone et al. 2001). A recent study has shown that the
acid fraction of mastic gum which contains triterpenic acids and
constitutes about 50% of its total weight has bactrericidal activity
against H. pylori (Paraschos et al. 2007). In particular, moronic acid
seems to be a powerful antibiotic not only against H. pylori but
also other bacteria (Hostettmann-Kaldas and Nakanishi 1979).
The activity of mastic gum against H. pylori in vivo was the
subject of studies with conflicting results. Early studies showed
bactericidal activity on H. pylori in vitro and it was hypothesized
that mastic gum killed H. pylori and thus helped ulcer healing
(Huwez et al. 1998;Marone et al. 2001). Unfortunately, two recent
in vivo studies, one in mice and the other in humans showed no
eradication of H. pylori and only a modest antibacterial activity
(Bebb et al. 2003;Loughlin et al. 2003).
Mastic gum is a herbal remedy and all studies that used mastic
gum on patients showed minimal side effects (Al-Habbal et al.
1984;Al Said et al. 1986;Bebb et al. 2003). Also a recent study on
animals showed that long term use of mastic gum was not
Table 1
Patients in Group A received low dose mastic gum monotherapy for 14 days. Group
B patients received high dose mastic gum monotherapy for 14 days. Group C
patients received mastic gum and pantoprazole for 14 days. Group D received
triple therapy with pantoprazole, amoxicillin and clarithromycin for 10 days.
Results are shown as mean7SEM
Eradication UBT pre UBT post p
Group A 4/13 (30.8%) 28.8674.4 18,76 73.1 0.08
Group B 5/13(38.5%) 27.11 75.2 17.6874.8 0.064
Group C 0/13 25.56 73.8 23.6774.7 NS
Group D 10/13 (76,92%) 26.7373.9 7.8572.8 0.01
Abbreviations: UBT= Urea breath test values.
K.J. Dabos et al. / Phytomedicine 17 (2010) 296–299 297
ARTICLE IN PRESS
associated with serious side effects (Kang et al. 2007). As a
considerable fraction of patients harbouring the bacterium are
unable to tolerate triple therapy due to side effects mastic gum
might provide a reasonable alternative in the future.
The fact that the combination of mastic gum and pantoprazole
showed no effect on H. pylori is somewhat surprising. Most active
substances of mastic gum belong to its acidic fraction. They
possibly require an acidic environment in the stomach to
successfully kill H. pylori. Proton pump inhibitors block the
hydrogen – potassium ATP enzyme system on the gastric parietal
cells. In that way, they increase the intragastric pH. Buffering the
acidity of the stomach by the proton pump inhibitors could result
in a hostile environment for mastic gum. This hypothesis needs to
be tested in further studies.
We have used two doses of mastic gum in our study the main
reason being that a low dose mastic gum monotherapy has shown
some activity in a previous study (Al-Habbal et al. 1984) while a
high dose monotherapy has been shown to be ineffective in
another study (Bebb et al. 2003).
Our study has limitations, the main one being its small size. We
also did not use two different methods of confirming H. pylori status
after treatment as a second endoscopy was deemed inappropriate.
In conclusion, this proof of principle study showed that mastic
gum possesses antibacterial activity against H. pylori in vivo and is
able to eradicate it from patients. Although even the high dose
monotherapy did not achieve acceptable eradication rates it could
be used as an alternative regime in patients unwilling to undergo
eradication with the triple therapy regime.
Acknowledgements
The study was funded by the Chios Mastic Gum Growers
Association
Konstantinos John Dabos declares that he received a travel
bursary from the sponsor during the study period.
Ekaterini Sfika was an employee of the sponsor during the
study period
Lisa Jo Vlatta and Georgios Giannikopoulos have nothing to declare
The study is registered with Controlled Trials and its registra-
tion number is ISRCTN01756929 The URL of the trial register is
www.controlled-trials.com
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Fig. 1. Urea breath test (UBT) was reformed a mean of 8 days (4-14 days) before starting treatment. It was repeated a mean of 39 days (33-61 days) after completion of the
study medication. Mean values of UBT before and after treatment are shown There was a trend towards significance in Group A (28.8674.4 vs 18.7673.1) (p= 0.08), and in
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values in Group D (26.7373.9 vs 7.8572.8) (p o0.01).
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