Chios mastic treatment of patients with active Crohn's disease

Abstract

To evaluate the effectiveness of mastic administration on the clinical course and plasma inflammatory mediators of patients with active Crohn's disease (CD).
This pilot study was conducted in patients with established mild to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Activity Index (CDAI), Nutritional Risk Index (NRI), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values +/- SE and P < 0.05 was considered to indicate statistical significance.
Patients exhibited significant reduction of CDAI (222.9 +/- 18.7 vs 136.3 +/- 12.3, P = 0.05) as compared to pretreament values. Plasma IL-6 was significantly decreased (21.2 +/- 9.3 pg/mL vs 7.2 +/- 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 +/- 13.1 mg/mL vs 19.7 +/- 5.5, P = 0.028). TAP was significantly increased (0.15 +/- 0.09 vs 0.57 +/- 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects.
The results suggest that mastic significantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately active CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD.

Full text

PO Box 2345, Beijing 100023, China World J Gastroenterol 2007 February 7; 13(5): 748-753
www.wjgnet.com
World Journal of Gastroenterology
ISSN 1007-9327
wjg@wjgnet.com © 2007 The WJG Press. All rights reserved.
Chios mastic treatment of patients with active Crohn’s disease
Andriana C Kaliora, Maria G Stathopoulou, John K Triantafi llidis, George VZ Dedoussis, Nikolaos K Andrikopoulos
www.wjgnet.com
CLINICAL RESEARCH
Andriana C Kaliora, Maria G Stathopoulou, George VZ
Dedoussis, Nikolaos K Andrikopoulos,
Department of Science
of Dietetics-Nutrition, Harokopio University, Athens, Greece
John K Triantafillidis,
Department of Gastroenterology, Saint
Panteleimon General State Hospital, Nicea, Athens, Greece
Supported by
a grant from the Chios Gum Mastic Growers
Association
Correspondence to:
Dr. Andriana C Kaliora, Department of Sci-
ence of Dietetics-Nutrition, Harokopio University of Athens, 70 El.
Venizelou ave., Kallithea 17671, Athens, Greece. akaliora@hua.gr
Telephone:
+30-210-9549303
Received:
2006-11-02
Accepted:
2006-12-21
Abstract
AIM:
To evaluate the effectiveness of mastic administra-
tion on the clinical course and plasma infl ammatory me-
diators of patients with active Crohn’s disease (CD).
METHODS:
This pilot study was conducted in patients
with established mild to moderately active CD, attend-
ing the outpatient clinics of the hospital, and in healthy
controls. Ten patients and 8 controls were recruited for a
4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap).
All patients successfully completed the protocol. CD Ac-
tivity Index (CDAI), Nutritional Risk Index (NRI), C-re-
active protein (CRP), interleukin-6 (IL-6), tumor necrosis
factor-alpha (TNF-
α
), monocyte chemotactic protein-1
(MCP-1), and total antioxidant potential (TAP) were
evaluated in the plasma at baseline and at the end of
the treatment period. Results were expressed as mean
values ± SE and
P
< 0.05 was considered to indicate
statistical signifi cance.
RESULTS:
Patients exhibited significant reduction of
CDAI (222.9 ± 18.7
vs
136.3 ± 12.3,
P
= 0.05) as com-
pared to pretreament values. Plasma IL-6 was signifi-
cantly decreased (21.2 ± 9.3 pg/mL
vs
7.2 ± 2.8 pg/ mL,
P
= 0.027), and so did CRP (40.3 ± 13.1 mg/mL
vs
19.7
± 5.5,
P
= 0.028). TAP was signifi cantly increased (0.15
± 0.09
vs
0.57 ± 0.15 mmol/L uric acid,
P
= 0.036). No
patient or control exhibited any kind of side effects.
CONCLUSION:
The results suggest that mastic signifi -
cantly decreased the activity index and the plasma levels
of IL-6 and CRP in patients with mildly to moderately ac-
tive CD. Further double-blind, placebo-controlled studies
in a larger number of patients are required to clarify the
role of this natural product in the treatment of patients
with CD.
© 2007 The WJG Press. All rights reserved.
Key words:
Chios mastic; Crohn’s disease; C-reactive
protein; Cytokines; Antioxidant potential; Conservative
treatment
Kaliora AC, Stathopoulou MG, Triantafillidis JK, Dedoussis
GVZ, Andrikopoulos NK. Chios mastic treatment of patients
with active Crohn’s disease.
World J Gastroenterol
2007;
13(5): 748-753
http://www.wjgnet.com/1007-9327/13/748.asp
INTRODUCTION
Crohn’s disease (CD) is a chronic inflammatory
disease of unknown etiology that may affect any level
of the gastrointestinal tract
[1-3]
. It is well established
that immunological mechanisms are involved in the
pathogenesis of the disease. Infl ammatory cytokines, such
as interleukin-6 (IL-6) and tumor necrosis factor-alpha
(TNF-
α
), have a pivotal role in induction and amplifi cation
of the infl ammatory cascade. Particularly, IL-6 stimulates
T-cell and B-cell proliferation and differentiation
[4]
, while it
mediates the hepatic expression of acute phase proteins
[5]
.
Increased concentration of TNF-
α
and monocyte
chemoattractant protein-1 (MCP-1) have been reported
in patients with CD
[6]
. Additionally, during chronic
inflammation, when sustained production of reactive
oxygen and nitrogen species occurs, antioxidant defenses
may weaken, resulting in a situation termed oxidative
stress
[7]
. Thus, in patients with CD, elevated oxidized low-
density lipoprotein levels have been reported compared to
healthy controls
[6]
.
Despite the large number of therapeutic agents
available today, none can be considered as completely
satisfactory either due to resistant cases or because
of significant side effects. To our knowledge, there
are only scattered reports of natural compounds that
potentially reverse relapse in CD. Trebble and co-workers
[8]
demonstrated an anti-infl ammatory activity of fi sh oil and
antioxidant supplementation evaluated in mononuclear
cells of CD patients, while Lavy
et al
[9]
demonstrated the
effectiveness of the antioxidant
β
-carotene in a rat model
as a prophylactic dietary measure in reducing the effects
of acid induced enteritis, thus raising the possibility that
patients with CD may benefit from the consumption
of natural
β
-carotene. Also the flavonoid rutin, a well-
established antioxidant compound, has been suggested as a
therapeutic agent in CD. Rutin has been shown to attenuate
pro-inflammatory cytokine production in both colonic

Kaliora AC
et al
. Chios mastic in Crohn’s disease 749
www.wjgnet.com
mucosa and peritoneal macrophages of experimental
animals
[10]
. Treatment with food phytochemicals has been
shown to be safe, sustainable and practical and changes
of dietary habits have been advocated in the therapy of
CD
[11]
.
Pistacia lentiscus
var. Chia (Anacardiaceae), well known
as Chios mastic gum, is an evergreen shrub widely
distributed in the Mediterranean region. Many ancient
Greek authors, including Dioscurides and Theophrastus,
mentioned Chios mastic for its healing properties in
intestines, stomach and liver. Mastic has also been
reported to possess antioxidant
[12]
and antibacterial
[13]
activity. With reference to gastrointestinal disorders, the
effectiveness of the resin against peptic ulcers is evident
[14]
in most studies, while only in two reports there is no
effect on
H pylori
eradication
in vivo
[15,16]
. Furthermore,
regarding gastric mucosa, the plant has been shown to be
hepatoprotective in tetrachloride-intoxicated rats
[17]
and to
suppress the extent of iron-induced lipid peroxidation in
rat liver homogenates
[18]
, without any toxic effect. A major
constituent of mastic, namely oleanolic acid, is among the
best-known triterpenes with biological properties against
chemically induced liver injury in laboratory animals,
exerting anti-inflammatory and antitumor-promotion
effects
[19]
. This background information led us to examine
the effects of supplementation with mastic in patients with
active CD. This study is the fi rst ever reported to evaluate
mastic for possible clinical effectiveness in patients with
CD.
MATERIALS AND METHODS
Study population
Ten consecutive patients with established CD and eight
healthy controls were recruited to participate in the trial.
All patients were attending the outpatient clinic of the
Department of Gastroenterology, Saint Panteleimon
General State Hospital in Nicea, Athens. Clinical evidence
of mild to moderate Crohn’s disease exacerbation was
defi ned by a score of CD Activity Index (CDAI) higher
than 150. Patients with clinical evidence of recurrence
and CDAI higher than 400 were excluded from the study.
Patients receiving mesalazine or antibiotics during the
time of relapse were asked to continue treatment. None
was receiving elemental diet or parenteral nutrition or
antioxidant/mineral supplements and none was under
treatment with immunosuppressives, immunomodulators
and/or corticosteroids. Eight healthy volunteers with
normal serum concentrations of C-reactive protein (CRP)
(< 5 mg/L) and albumin (> 40 g/L) served as controls.
Assessed by Medical History questionnaires, controls
included in the study were healthy persons
without chronic
inflammatory disorder. Exclusion criteria for control
recruitment were a body mass index (BMI) higher than
30 and anti-inflammatory drug treatment or antioxidant
vitamin/mineral supplementation prior to trial. All
volunteers gave a written consent after having received
thourough information about the aims and procedure of
the study. The Ethical Committees of both Harokopio
University and Saint Panteleimon General State Hospital
approved the protocol. Table 1 shows some demographic
characteristics of patients and controls.
Preparation of mastic caps
A UV source device (Jost/Ba-ro, Type FDLT 250/-80 ×
2500) was used for sterilization of the Chios Mastic resin.
Then, the sterilized mastic granules were milled to fine
powder (particle size < 400
μ
m) by using a Hosokawa Al-
pine Mill (Fine Impact Mill 100 UP2). The encapsulation
of powder was performed using the Profi ll Capsule fi lling
System (Torpac Inc.). Capsule cells (capsugel, V caps, size
0) were made of Hpromellose (hydroxypropyl methylcellu-
lose) and each contained 0.37 (± 0.02) g of mastic powder.
Intervention trial protocol
Dissolution time was measured according to standard
methods
[20]
and was found to last approximately 7 min.
Patients and healthy controls were subjected to a 4-wk
supplementation with mastic caps (6 caps/d, 2.2 g in total)
over a period from June 2005 to January 2006. Dietary
assessment was accomplished applying Food Frequency
Questionnaire (FFQ) and 24 h recalls. Dietary instruc-
tions were given to both healthy controls and patients as to
maintain consumption of food rich in anti-infl ammatory
and antioxidant ingredients as poor as initially assessed by
FFQ and 24 h recall interviews. Assessment of compli-
ance during the trial was tested applying 24 h recalls twice
a week. Mastic, either in the form of gum or as a sweet or
bread ingredient, and fi sh oil, either crude or in the form
of supplement, was not allowed in either group. The daily
energy intake was evaluated by means of 24 h recalls.
Blood samples were obtained for plasma isolation and
subjected to CRP and albumin measurements prior and af-
ter the trial. At the same time points, plasma cytokine and
antioxidant potential measurements were performed. Body
weight was measured using electronic scales initially and at
the end of the trial.
Disease activity index evaluation
The Crohn’s Disease activity was evaluated by means
Table 1 Demographic characteristics and medications of
patients with CD and controls
Characteristic Patients Controls
Age (yr)
Mean 36.9 31.5
Range 18-73 25-45
Sex
Female 5 4
Male 5 4
Duration of disease (yr) 6.4 (± 3.9) -
Concomitant medication -
None 3
Mesalazine 3 -
Metronidazole 2
Azathioprine 2
Location of Crohn’s disease -
Small bowel 4 -
Small and large bowel 6 -
Fistulizing disease 3 -

of the CDAI
[21]
. The CDAI incorporates eight related
variables: the number of liquid or very soft stools per
day, the severity of abdominal pain or cramping, general
well being, the presence or absence of extraintestinal
manifestations of CD, the presence or absence of an
abdominal mass, the use of antidiarrheal drugs, hematocrit,
and body weight. Scores range from 0 to 600 with higher
scores indicating more severe disease activity. A score
of 151 to 200 corresponds with mild disease activity;
moderate disease has a score of 201 to 400, and scores of
401 or greater represent severe disease activity.
Biochemical measurements
CRP concentrations were analyzed immunoturbidimetrically
on a Beckman Synchron CX5 fully automated chemistry
analyzer. Albumin was measured by means of the
bromocresol green method on the same analyzer.
Cytokine assays
Plasma cytokines from patients with CD and controls were
assessed by quantitative enzyme-linked immunosorbent
assays (ELISA) (R & D Systems Abingdon, UK) according
to the manufacturer’s instructions. Sensitivity limits of
TNF-
α
, IL-6, and MCP-1 ELISAs are, respectively, 1.6
pg/mL, 0.70 pg/mL and 5.0 pg/mL. Plasma cytokines
from patients with CD and controls were assessed in
duplicate.
Plasma total antioxidant potential assay
Total antioxidant potential (TAP) in plasma was assessed
by a colorimetric, quantitative assay for TAP in aqueous
samples (OxisResearch Portland, USA) according to
the manufacturer’s instructions. The results of the assay
were expressed as mmol/L of uric acid equivalents. The
sensitivity of the assay is 30
μ
mol/L uric acid equivalents.
Statistical analysis
Results were expressed as mean ± SE. The Mann-Whitney
Test was used for comparing differences between patients
and controls prior the intervention. Differences reported
primarily and at the end of the study within individual
groups, were tested for signifi cance by the Wilcoxon signed
ranks test. Calculated
P
< 0.05 was considered to indicate
statistical signifi cance.
RESULTS
Alterations of CDAI and induction of remission
The CDAI score was assessed at baseline and after
the 4 wk treatment with mastic. All patients receiving
mastic showed a reduction of the CDAI as compared to
pretreatment values. The reduction of the mean CDAI
value was statistically significant (from 222.9 ± 18.7 to
136.3 ± 12.3,
P
= 0.05) (Figure 1). The two main elements
of CDAI showing the most striking improvement were the
number of liquid stools per day and the score of general
well being.
Nutritional risk index
One of the clinically useful measures of nutritional status
in CD is the Nutritional Risk Index (NRI), which is
calculated based on serum albumin levels and body weight
using the following equation: NRI = [1.519 × albumin
(g/L)] + [0.417 × (current weight/usual weight) × 100]. A
NRI > 100 denotes absence of nutritional risk. NRI values
between 97.5 and 99.9 correspond to a mild nutritional
risk, NRI values from 83.5 to 97.5 to moderate nutritional
risk, and NRI values lower than 83.5 to severe nutritional
risk.
The patients’ “usual weight” was the body weight at
the time of remission, as reported in medical records at
the hospital and confi rmed by each single patient. NRI of
healthy controls was normal at the start of the study and
remained unchanged after the mastic supplementation (data
not shown). The mean NRI value of CD patients increased
from 87.5 ± 3.7 before treatment to 91.5 ± 3.2 at the end
of treatment (
P
= 0.059). This increase was evident at the
end of the second week of mastic supplementation and
remained constant thereafter until the end of the trial.
CRP
Prior to mastic treatment, CRP levels were significantly
higher in CD patients (40.3 ± 13.1 mg/mL) than
in healthy controls (2.4 ± 0.7 mg/L) (
P
= 0.002).
Treatment with mastic caps of healthy controls resulted
in no modifications in CRP values (2.3 ± 0.6 mg/L),
which remained at concentrations
≤
5.0 mg/mL in
all individuals. In CD patients, mean CRP levels were
signifi cantly decreased after treatment (from 40.3 ± 13.1
mg/mL to 19.7 ± 5.5,
P
= 0.028) (Figure 2).
IL-6 plasma concentration
IL-6 was below detection in healthy controls prior to
therapy, while in patients it was significantly elevated
compared to controls (
P
= 0.034). As with CRP, IL-6 in
controls remained unaltered, while in patients it decreased
signifi cantly (from 21.2 ± 9.3 pg/mL to 7.2 ± 2.8 pg/mL,
P
= 0.027) (Figure 3).
TNF-
α
plasma concentration
Patients with active CD had TNF-
α
plasma concentrations
10-fold higher compared to controls before therapy
(27.1 ± 9.7 pg/mL
vs
2.6 ± 1.5 pg/mL,
P
= 0.009). After
CDAI
300
250
200
150
100
50
0
Before treatment After treatment
a
Figure 1 Crohn’s disease activity index (CDAI) was decreased in patients with
active Crohn’s disease (n = 10) after 4-wk treatment with mastic caps (
a
P < 0.05).
Horizontal bars represent the mean value (± SE).
750 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol February 7, 2007 Volume 13 Number 5
www.wjgnet.com

treatment, plasma TNF-
α
decreased in patients, although
this decrease did not reach statistical signifi cance (27.1 ± 9.7
pg/mL to 16.4 ± 4.7 pg/mL,
P
= 0.114).
MCP-1 plasma concentration
In the case of MCP-1, patients with active CD had MCP-1
plasma concentrations 2.5-fold higher compared to
controls (140.7 ± 43.9 pg/mL
vs
57.5 ± 11.8 pg/mL,
P
=
0.368). Although not statistically signifi cant, a decrease was
observed in MCP-1 in CD patients at the end of the trial
(76.6 ± 20.9 pg/ mL,
P
= 0.074).
Plasma TAP
TAP was significantly different between the two groups
before mastic treatment (healthy controls, 0.4 ± 0.06
vs
CD patients, 0.15 ± 0.09 mmol/L uric acid,
P
= 0.003).
As shown in Figure 4,
TAP was significantly increased
in individual groups after mastic treatment (controls, 0.4
± 0.06
vs
0.5 ± 0.05 mmol/L uric acid,
P
= 0.025; CD
patients, 0.15 ± 0.09
vs
0.57 ± 0.15 mmol/L uric acid,
P
=
0.036).
Side-effects
No patient exhibited any side effects. However, during
the third day of treatment, one female patient with CD
of the small and large bowel reported an abrupt onset of
constipation. She was advised to reduce the dose for two
days. After that, she continued treatment without further
complaints. No other untoward effect was reported.
DISCUSSION
Chios mastic has been previously shown to exert vari-
ous biological properties
in vitro
[12]
, in experimental animal
models
[18]
and in humans
[14]
. In the current study, we dem-
onstrated that mastic was effective in the regulation of
infl ammation, evaluated by CRP, IL-6, TNF-
α
and MCP-1
in plasma, as well as in the regulation of oxidative stress,
evaluated by TAP. In more details, mastic treatment sig-
nifi cantly decreased the CDAI, which probably occurred
through decrease of the pro-infl ammatory IL-6, inducing
remission in seven out of ten patients. Another important
observation was that mastic resulted in improvement of
the nutritional status, as shown by NRI.
Nutritional support in patients with CD has a primary
role in inducing remission and malnutrition is very com-
mon in CD. While several factors, such as malabsorption
and increased resting energy expenditure in underweight
patients, may contribute to malnutrition
[22]
, decreased oral
intake is the primary cause. The methods used to sup-
port patients with CD are enteral and parenteral nutri-
tion, in terms of protein-calorie intake. NRI is one of
the most useful measures of nutritional status and points
out severely malnourished patients when less than 83.5
[23]
.
Hereby we show that NRI in patients supplemented with
mastic was increased, however not significantly, perhaps
due to the limited number of subjects. Particularly, NRI
was increased in nine out of ten patients supplemented
with mastic, two of whom experienced no nutritional risk
(data not shown). The main element of NRI showing im-
provement was body weight gain. Based upon the fact that
daily energy intake was unchanged during the trial (data
not shown), increase in body weight and in NRI is due to
the fact that mastic treatment resulted in decrease of liquid
stools and therefore improvement in nutrient absorption.
TAP (mmol uric acid)
0.8
0.6
0.4
0.2
0.0
Before treatment After treatment
a
Figure 4 Plasma total antioxidant potential (TAP) was upregulated in patients with
active Crohn’s disease (n = 10) after 4-wk treatment with mastic caps (
a
P < 0.05),
indicating absorption of antioxidants and an improved in vivo antioxidant status.
Horizontal bars represent the mean value (± SE).
IL-6 (pg/mL)
30
25
20
15
10
5
0
Before treatment After treatment
a
Figure 3 Plasma concentrations of interleukin-6 (IL-6) were suppressed in
patients with active Crohn’s disease (n = 10) after 4-wk treatment with mastic caps
(
a
P < 0.05). Horizontal bars represent the mean value (± SE).
CRP (mg/L)
60
45
30
15
0
Before treatment After treatment
a
Figure 2 C-reactive protein (CRP) concentrations in patients with active Crohn’s
disease (n = 10) before and after 4-wk treatment with mastic caps (
a
P < 0.05).
Horizontal bars represent the mean value (± SE).
Kaliora AC
et al
. Chios mastic in Crohn’s disease 751
www.wjgnet.com

The observed decrease in NRI in one of the patients was
due to body weight loss, despite the fact that the number
of liquid stools decreased. The daily energy intake of this
young patient was gradually reduced and, according to her
statement long after the end of the protocol, she was on a
diet for weight loss.
The importance of IL-6 in patients with CD has been
well documented. In patients with active CD, mRNA for
IL-6 is overexpressed in the infl amed mucosa
[24]
and IL-6
is thought to play a crucial role in the pathogenesis of CD.
Elevated IL-6 in plasma of patients with CD has been pre-
viously described
[25]
. Accordingly, we report that in patients
with CD plasma concentration of IL-6 was significantly
higher versus the control group. Significant decrease in
IL-6 with mastic treatment was observed in patients fol-
lowing a decrease in plasma CRP (Figure 2). Because IL-6
is the main cytokine factor responsible for hepatic induc-
tion of acute phase proteins in CD, respective decrement
in CRP is reasonable. In view of the fact that (1) oleoresins
consist of triterpenes
[26]
with established anti-infl ammatory
and antioxidant effects
[19,27]
and
(2) mastic contains anti-
oxidant phenolic compounds
[28]
, it is more likely that the
plasma IL-6 decrease observed in CD patients was due to
these compounds.
TNF-
α
showed an unsignifi cant (
P
= 0.114) 1.6-fold
decrease in CD patients. On the other hand, the difference
in TNF-
α
concentrations between patients and controls at
baseline was signifi cant. The data reported about TNF-
α
in CD are somewhat contradictory. Whereas some groups
were able to demonstrate increased concentrations of
TNF-
α
in CD compared to healthy controls
[29]
, others
were not
[30]
. Because TNF-
α
induces MCP-1 secretion via
the activation of nuclear factor-kappa B
[31]
, it is likely that
the slight decrease in MCP-1 was due to the lower activa-
tion of the nuclear factor-kappa B pathway secondary to
the decrease in TNF-
α
.
Oxidative stress has been proven to upregulate IL-6
gene expression
[32]
. We show that mastic treatment resulted
in increase of plasma TAP in CD patients (Figure 4) as
well as in controls. Plasma is a heterogenous solution of di-
verse antioxidants and an increase in the antioxidant capac-
ity indicates absorption of antioxidants and an improved
in vivo
antioxidant status
[33]
. Whether the antioxidant trit-
erpenes and phenolics contained in mastic
[12]
are absorbed
or act on the exposed gastrointestinal mucosa, remains
uncertain. Generally, our knowledge on the absorption and
bioavailability of polyphenols is still limited, and the few
studies in humans show that some are well absorbed and
others hardly absorbed
[34]
. The unabsorbed may remain in
the lumen and become available for fermentation in the
colon. A substantial proportion of the gastrointestinal
mucosa is therefore exposed to these compounds, or to
their bacterial and systemic metabolites
[35]
. However, phe-
nolic compounds do not seem to be absorbed as well as
vitamins C and E, and hence their concentrations can be
much higher in the lumen of the gastrointestinal tract than
are ever achieved in plasma or other body tissues, making
the action in the gastrointestinal tract more likely. Even
less are the data on the absorption of triterpenes. Glycyr-
rhetinic acid, the triterpene derivative of glycyrrhizin, has
been shown to be bioactive in experimental gastric lesion
models
[36]
and has also been detected in the serum of ex-
perimental animals
[37]
.
In conclusion, subjecting CD patients with mild to
moderate activity to mastic treatment seems to improve
the clinical features of the disease and to regulate infl am-
mation and antioxidant status. The use of natural products
as primary treatment in CD should attract wider support
and research, with increasing awareness of the harm of
the long-term use of corticosteroids. Whether it is time
for gastroenterologists to embrace the concept that natural
products, such as mastic, may be benefi cial to CD needs
further research in larger cohorts.
ACKNOWLEDGMENTS
We wish to thank the Chios Mastic Growers Association,
especially Dr. Christos Kartalis, for the production and
kind donation of Chios mastic caps, exclusively for the
needs of the trial.
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S- Editor
Liu Y
L- Editor
Negro F
E- Editor
Bi L
Kaliora AC
et al
. Chios mastic in Crohn’s disease 753
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