Effect of Ginger and Chamomile on Nausea and Vomiting Caused by Chemotherapy in Iranian Women with Breast Cancer

Abstract

Background: Chemotherapy-induced nausea and vomiting (CINV) places a significant burden on the patient.
Herbal agents are the most commonly complementary therapies used among the public. This study was done
to determine the effect of ginger and chamomile capsules on nausea and vomiting in chemotherapy for breast
cnacer (BC). Materials and Methods: In a randomized, double-blind and clinical trial study, 65 women with
BC undergoing chemotherapy were referred to Breast Cancer Research Center, Tehran, Iran, between May
2013 to June 2014. Regimen for ginger group for 5 days before and 5 days after chemotherapy was: 2 times
a day and 500 mg capsules of powdered ginger root in addition to a routine antiemetic regimen consisting of
dexamethasone, metoclopramide and aprepitant (DMA) capsules. Chamomile group similarly was: 2 times a
day and 500 mg capsules of Matricaria chamomilla extract in addition to a routine antiemetic regimen consisting
of DMA capsules. Control group, routine antiemetic regimen consisting of DMA capsules. Results: There were
no significant differences between the ginger, chamomile and control groups regarding age. Drugs used for
chemotherapy were identical and duration of disease was also matched (1-4 months). Ginger and chamomile
were both significantly effective for reducing the frequency of vomiting, there being no significant difference
between the ginger and chamomile groups. Moreover, unlike the chamomile, ginger effected significantly the
frequency of nausea. Conclusions: According to the findings of this study, it should be declared that taking ginger
capsules (1 g/day) might relieve CINV safely. Nurses dealing directly with cancer patients should be responsible
for providing educational programs for patients and their families about how to deal with their drug regimens
and its side effects.

Full text

Asian Pacic Journal of Cancer Prevention, Vol 17, 2016 4127
DOI:http://dx.doi.org/10.7314/APJCP.2016.17.8.4127
Effect of Ginger and Chamomile on Nausea and Vomiting Caused by Chemotherapy in Women with Breast Cancer
Asian Pac J Cancer Prev, 17 (8), 4127-4131
Introduction
Breast cancer (BC) is a very common health problem in
Iranian women (Amirifard et al., 2016). Nowadays, cancer
therapy consists of surgery, radiotherapy, chemotherapy
and biological therapy as well as some other methods,
whereas in the locally advanced stage, chemotherapy such
as Trastuzumab therapy is often the only effective method
of cancer therapy (Payandeh et al., 2015). Chemotherapy-
induced nausea and vomiting (CINV) places a signicant
burden on the patient.
There are multiple classes of medications developed to
treat this symptom in a large number of patients (Carelle
et al., 2002; Sun et al., 2005). The incidence of vomiting
has been signicantly reduced through combinations of
anti-emetic medications, but efforts to control nausea
have been less successful. Affecting upwards of 60%
1Department of Nursing, University of Wefare and Rehabilitation Sciences, 2Breast Cancer Research Centre, Jahad Daneshgahi,
Tehran University of Medical Sciences, 3Department of Nursing, University of Welfare and Rehabilitation Sciences, Tehran, 4Medical
Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran *For correspondence: safa3n@yahoo.com
Abstract
Background: Chemotherapy-induced nausea and vomiting (CINV) places a signicant burden on the patient.
Herbal agents are the most commonly complementary therapies used among the public. This study was done
to determine the effect of ginger and chamomile capsules on nausea and vomiting in chemotherapy for breast
cnacer (BC). Materials and Methods: In a randomized, double-blind and clinical trial study, 65 women with
BC undergoing chemotherapy were referred to Breast Cancer Research Center, Tehran, Iran, between May
2013 to June 2014. Regimen for ginger group for 5 days before and 5 days after chemotherapy was: 2 times
a day and 500 mg capsules of powdered ginger root in addition to a routine antiemetic regimen consisting of
dexamethasone, metoclopramide and aprepitant (DMA) capsules. Chamomile group similarly was: 2 times a
day and 500 mg capsules of Matricaria chamomilla extract in addition to a routine antiemetic regimen consisting
of DMA capsules. Control group, routine antiemetic regimen consisting of DMA capsules. Results: There were
no signicant differences between the ginger, chamomile and control groups regarding age. Drugs used for
chemotherapy were identical and duration of disease was also matched (1-4 months). Ginger and chamomile
were both signicantly effective for reducing the frequency of vomiting, there being no signicant difference
between the ginger and chamomile groups. Moreover, unlike the chamomile, ginger effected signicantly the
frequency of nausea. Conclusions: According to the ndings of this study, it should be declared that taking ginger
capsules (1 g/day) might relieve CINV safely. Nurses dealing directly with cancer patients should be responsible
for providing educational programs for patients and their families about how to deal with their drug regimens
and its side effects.
Keywords: Breast cancer - chemotherapy - ginger - chamomile - vomiting - nausea
RESEARCH ARTICLE
Effect of Ginger and Chamomile on Nausea and Vomiting
Caused by Chemotherapy in Iranian Women with Breast
Cancer
Fateme Sanaati1, Safa Naja2*, Zahra Kashaninia3, Masoud Sadeghi4
of patients (Bloechl-Daum et al., 2006), CINV has also
been shown to signicantly impact on patient quality of
life. Moreover, although it happens rarely, CINV can be
so severe that it can lead to dose reduction or treatment is
continuation, and subsequently increase the risk of disease
progression (Bloechl et al., 2006; Ballatori et al., 2007;
Vidall et al., 2011). This is of particular concern as nausea
and vomiting in oncology patients can adversely affect
food intake, increasing the risk of malnutrition during
treatment. Previous studies report one in two patients in
this setting as malnourished (Carelle et al., 2002). The
cumulative effect of pretreatment and treatment-related
malnutrition can be one of compromised immune function,
decreased performance status, poor response to treatment,
and sometimes treatment discontinuation (Davidson et al.,
2012; Van Cutsem and Arends, 2005; Tong et al., 2009).
Herbal therapy is the most commonly complementary

Fateme Sanaati et al
Asian Pacic Journal of Cancer Prevention, Vol 17, 2016
4128
therapies used among the public (Olaku and White,2011).
Two of the roots of the plant are used as medicine, are
ginger and chamomile. Ginger (Zingiber ofcinale) has a
long history in many cultures as a folk-remedy for nausea
and gastrointestinal discomfort. Empirical research has
demonstrated that ginger may be effective as an anti-
nausea agent; in particular (Wu et al., 2008), it has been
proposed as a possible candidate for anti-CINV therapy
(Wu et al., 2008; Marx et al., 2014). Furthermore, animal
studies provide preliminary support for the role of ginger
supplementation in the prevention of cisplatin-induced
emesis ( Sharma et al.,1997; Sharma and Gupta,1998). Few
adverse effects from the ingestion of ginger are reported
in the literature ( Ernst and Pittler,2000). Chamomile is
also extensively consumed as a tea or tonic and is used
internally to treat anxiety, hysteria, nightmares, insomnia
and other sleep problems, convulsions, and even delirium
tremens (Martens D,1995). One of chamomile’s main roles
is as a multipurpose digestive aid to treat gastrointestinal
disturbances including atulence, indigestion, diarrhea,
anorexia, motion sickness, nausea, and vomiting.
Chamomile used in modern medicine primarily for their
spasmolytic, antiphlogistic, antibacterial properties,
and as a multipurpose digestive to treat gastrointestinal
disturbances including atulence, indigestion, diarrhea,
anorexia, motion sickness, nausea, and vomiting (Shikov
et al., 2008) .
This study was done to determine the effect of Ginger
and Chamomile capsules on nausea and vomiting in
chemotherapy.
Materials and Methods
Patients
This study was approved by Ethics Committee of
University of Social Welfare and Rehabilitation Sciences
and was registered in Iranian Registry of Clinical Trials
(IRCT) with code of IRCT2013020912404N1. In a
randomized, double-blind and clinical trial study, 65
women with BC undergoing chemotherapy referred to
Breast Cancer Research Center, Tehran, Iran, between
May 2013 to Jun 2014.
Criteria
Inclusion criteria: Patients between 20 and 60 years;
histological diagnosis of BC, history of receiving at least
one chemotherapy injection, receiving single-day cycles
of chemotherapy (each cycle separated from next by≥2
weeks); experiencing vomiting in previous sessions, and
having normal values of hematologic and biomedical
laboratory parameters.
Exclusion criteria: Patients with multiple-day
chemotherapy; receiving concurrent radiotherapy with
high risk of causing emesis (i.e., total body, hemi body,
upper abdomen, and craniospinal radiation); taking
therapeutic doses of warfarin, aspirin, or heparin;
had a history of bleeding disorder(s) like severe
thrombocytopenia; had an allergy to ginger or chamomile
or had taken it in the last week; had gastrointestinal
disorders and cancers; and had other emesis-inducing
diseases, such as hypertension, liver, and renal failure.
Also, patients who met the following criteria: forgotten
to take capsules ≥3 consecutive times; used other
antiemetic drugs or therapeutic methods except the routine
antiemetic; had severe gastrointestinal problems during
the study; and refusal to continue participating in trial.
Regimens
A. Intervention group 1 (ginger group) for 5 days
before and 5 days after chemotherapy was: 2 times a
day and 500 mg capsules of powdered ginger root in
addition to a routine antiemetic regimen consisting of
dexamethasone, metoclopramide and aprepitant (DMA)
capsule was consumed.
B. Intervention group 2 (chamomile group) for 5 days
before and 5 days after chemotherapy was: 2 times a day
and 500 mg capsules of Matricaria Chamomilla extract
in addition to a routine antiemetic regimen consisting of
DMA capsule was consumed.
C. Control group, routine antiemetic regimen
consisting of DMA capsule was consumed.
Method
The patients were randomly allocated to treatment
two experimental groups (ginger and chamomile) and
one control group using the 20 block random tables. The
treatment groups received white capsules of ginger or
chamomile manufactured by University Biochemistry
Laboratory Shahed, Tehran, Iran. Coding and blinding
of the 2 groups were performed privately by the
pharmacologist consultant, and all of the samples, data
analyzers, and all participants too, were unaware of the
real content of the capsules.
The dosage of capsules was selected based on the
results of clinical trials conducted by Sontakke et al.
(2003) and Ryan et al. (2009). A self-made, two-part self-
reporting instrument was used to measure the frequency
and severity of nausea and vomiting each member of three
groups, after checking the content validity. This instrument
was a reliable standard table that has been used in various
studies as well (Sontakke et al., 2003; Manusirivithaya
et al., 2004; Ozgoli et al., 2009; Zick et al., 2009). First
part contained two tables with a 10 cm visual analogue
scale (VAS) to record chemotherapy induced nausea and
vomiting (CINV), and the second section included 3
questions about the: (a) probable use of other antiemetics;
(b) missed cases of capsule taking; (c( probable side effects
due to capsules intake. The patients were asked to ll the
questionnaires out every night during the study and in any
cases of intolerable complications stop the consumption
and contact the researchers for more information.
Statistical Analysis
Professional blind interviewers collected and recorded
the information and then data entry and analysis, were
performed by a professional blind statistician. Data
were analyzed using SPSS software version 16 and the
application of descriptive and inferential statistics. The
Chi-squared test was applied to compare the 2 groups
regarding demographic characteristics, such as age
(continuous variable) and education (ranked qualitative
variance). To examine differences in the frequency and

Asian Pacic Journal of Cancer Prevention, Vol 17, 2016 4129
DOI:http://dx.doi.org/10.7314/APJCP.2016.17.8.4127
Effect of Ginger and Chamomile on Nausea and Vomiting Caused by Chemotherapy in Women with Breast Cancer
severity of nausea and vomiting, inferential statistics
of the linear logarithm model with Poison and paired
t-test function were applied. After completing the data
analysis the consultant pharmacologist broke the codes
and introduced the groups.
Results
Out of 65 patients, 20 patients (8 patients in the
intervention group with ginger; 7 patients in the
intervention group with chamomile; and 5 patients in the
control group) interrupted their participation (7 for general
weakness and canceling of the chemotherapy; 6 because
of unwillingness to continue the study; 6 for not lling
the tools; and 1 due to die). Sampling time was extended
to maintain the sample size (45 persons).
There were no signicant differences between the
ginger; chamomile and control groups regarding age
variable (P = 0.45). Most participants of all three groups
had Diploma and were homogenous (P = 0.19) according
to Table 1.
Used Drugs for chemotherapy were identical
(same severity of nausea) and duration of disease was
also matched (1-4 months). The ndings indicated no
signicant differences between the groups in terms of
state proles.
Table 2 indicates that ginger and chamomile are
ineffective on intensity of nausea (P=0.238) while both
are effective on the frequency of vomiting (P<0.0001),
though there is no signicant difference in the ginger and
chamomile groups (Table 3)
Moreover, unlike the chamomile (P=0.895) (Table
4), ginger effects on the frequency of nausea (P=0.006)
(Table 5).
Discussion
BC is the most frequent malignancy among females
and is a leading cause of death of middle-aged women
(Payandeh et al., 2015). Advances in our understanding of
the pathophysiology of CINV), the identication of patient
risk factors, and the development of new antiemetics
have led to signicant improvements in CINV prevention
(Jordan et al., 2014). In addition to controversial reports,
there are few studies about the effect of ginger extract on
the CINV. It seems that characteristics of those studies
could affect their results. For example, they have targeted
wide range and kind of cancers (Manusirivithaya et
al., 2004; Zick et al., 2009). Meanwhile, each of them
has special therapeutic protocol and each protocol has
also its own special emetogenicity in comparison to
the others. Hence, we can’t easily approve or refuse
the effectiveness of ginger plant on CINV and also we
Table 4. Paired Sample t-test Comparison of Number of Nausea
Group Mean difference Standard error of the coefcient Degree of freedom P-value
Ginger-Control 1.5845 0.5787 1 0.006
Chamomile-Control 0.0769 0.5851 10.895
Chamomile-Ginger 1.6615 0.5282 1 0.002
Table 3. Effects of the Groups on Nausea and Vomiting Using the Generalized Estimating Equations (GEE) Model
Component Model coefcient Standard error of the coefcient Statistics Degree of freedom P-value
Nausea
Ginger 0.746 0.2996 6.195 1 0.013
Chamomile 0.025 0.1932 0.017 1 0.896
Control Basic - - - -
Vomiting
Ginger 1.303 0.5597 16.924 1 <0.0001
Chamomile 1.145 0.4911 5.437 1 0.02
Control Basic - - - -
Table 5. Paired Sample t-test Comparison of Number of Vomiting
Group Mean difference Standard error of the coefcient Degree of freedom P-value
Ginger-Control 0.108 0.2474 1 <0.0001
Chamomile-Control 0.8394 0.2814 1 0.003
Chamomile-Ginger 0.2686 0.1989 1 0.177
Table 1. Baseline Characteristics of the Randomized
Groups
Variables Ginger Chamomile Control
N=15 N=15 N=15
Age, n(%)
20-30 1(6.7) 1(6.7) 1(6.7)
31-40 6(40) 1(6.7) 6(40)
41-50 7(46.7) 12(80) 7(46.7)
51-60 1(6.7) 1(6.7) 1(6.7)
Education
High school 1(6.7) 1(6.7) 1(6.7)
Diploma 10(66.7) 10(66.7) 9(60)
University 4(26.7) 4(26.7) 5(33.3)
There was no signicant different between groups and P-value was
considered signicant at P < 0.05 by Chi-square test
Table 2. Effects of the Groups on Components Using
the Generalized Estimating Equations (GEE) Model
Component Chi-square
statistics
Degree of
freedom P-value
Intensity of nauseaa2.867 20.238
Number of nausea 7.376 2 0.025
Number of vomiting 20.812 2<0.0001
aIntensity of nausea was evaluated by using Visual analog scale: (0 =
no nausea, 3-1 = mild, 6-4 = moderate 9-7 = severe, 10 = very severe)

Fateme Sanaati et al
Asian Pacic Journal of Cancer Prevention, Vol 17, 2016
4130
can’t generalize the results to other types of cancer. On
the other hand, no studies have examined the effect of
chamomile on the CINV. Therefore, this study was
carried out to address those issues that have been less
studied. Only women with BC were attended to increase
the accuracy and generalizability of the results because
BC is the most common type of cancer among women
in Iran and in the world (Sontakke et al., 2003; Ryan et
al., 2009) and almost the same chemotherapy protocol
is used to treat it. In this study, the results indicate that
ginger and chamomile are ineffective on intensity of
nausea while both inuence on the frequency of vomiting.
Moreover, unlike the chamomile (P>0.05), ginger effects
on the frequency of nausea signicantly. Similar to our
ndings, Zick et al. (2009) reported that in cancer patients
undergoing chemotherapy, ginger capsules could not
relieve the CINV in acute and delayed (P>0.05) phases
in comparison to the control group that could be probably
due to the use of cisplatin as a high cytotoxic agent.
Moreover, Manusirivithaya et al. (2004) expressed that
there was no signicant differences between ginger and
placebo groups related to the complete control of acute
and delayed vomiting that could be concerned using
cisplatin in chemotherapy protocol. In contrast, Ryan et
al. (2009) indicated that in cancer patients undergoing
chemotherapy the use of ginger (5.0, 1 and 5.1 g/day)
reduced the intensity of nausea in acute phase (P<0.05).
Sontakke et al. (2003) indicated that in cancer patients
undergoing chemotherapy the antiemetic effect of
metoclopramide was equivalent to ginger (1g/day) in
acute phase (58% versus 62%, respectively). Similar to our
ndings, Nanthakomon and Pongrojpaw (2006), reported
that in cancer patients undergoing chemotherapy, ginger
capsules reduced the frequency of nausea and vomiting
signicantly. The results of other studies about the effect
of ginger extract on pregnancy-induced vomiting (PINV)
are the same as ours. As Ozgoli et al. (2009) stated, the
use of ginger (1g/day ( signicantly reduced the cases of
PINV. In addition, Jenabi et al. (2009) revealed that taking
ginger powder (1 g/day) signicantly relieved PINV.
There is no published study about the effect of
chamomile on the CINV. This study was only performed
on women with BC undergoing single-day courses of
chemotherapy. This matter has its own privileges, but also
limitations. The most important limitation of this study
was that our results were only devoted and applicable for
patients with BC, and thus we cannot generalize the results
to other types of cancers. So, it should be suggested that to
conduct more widespread studies about the effect of ginger
and chamomile on the different types of cancers and also
to assess the effect of ginger and chamomile on patients
undergoing multiple-day chemotherapy to achieve more
accurate information about the efcacy of these herbs.
In conclusions, according to the ndings of this study,
it should be declared that taking ginger capsules (1 g/day)
might relieve the CINV safely. Nurses are dealing directly
with cancer patients and are responsible for providing
educational programs for patients and their families
about how to deal with their drug regimens and its side
effects. Therefore, nurses should introduce and teach those
patients to take these capsules, as the effectiveness and
safety of ginger are conrmed.
Acknowledgements
This study was carried out with the nancial support
of research deputy of University of Social Welfare and
Rehabilitation Sciences and with the favor of Breast
Cancer Research Center of University of Tehran. Hereby
we would like to express our appreciation to all the dear
participants and personnel of Breast Cancer Research
Center.
This study was registered at http://www.irct.ir
(registration number IRCT2013020912404N1).
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