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The effect of Ginger (Zingiber officinale) on chemotherapy-induced nausea

and vomiting in breast cancer patients: a systematic literature review of
Randomized Controlled Trials

Article  in  Phytotherapy Research · May 2019

DOI: 10.1002/ptr.6377

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Received: 25 December 2018 Revised: 29 March 2019 Accepted: 8 April 2019
DOI: 10.1002/ptr.6377

REVIEW

The effect of ginger (Zingiber officinale) on chemotherapy‐

induced nausea and vomiting in breast cancer patients: A
systematic literature review of randomized controlled trials

Ali Saneei Totmaj1 | Hadi Emamat2 | Farshad Jarrahi3 | Mitra Zarrati1

1
Nutrition Department, School of Public
Health, Iran University of Medical Sciences, Breast cancer is the most commonly diagnosed cancer and is the leading cause of
Tehran, Iran
mortality due to all types of cancers among the female population worldwide. Results
2
Student Research Committee, Department of
Clinical Nutrition and Dietetics, Faculty of of clinical trials investigating the effect of ginger on chemotherapy‐induced nausea
Nutrition and Food Technology, National and vomiting (CINV) in breast cancer patients are inconsistent. This study was aimed
Nutrition and Food Technology Research
Institute, Shahid Beheshti University of at obtaining a comprehensive overview of the current evidence regarding the effec-
Medical Sciences, Tehran, Iran tiveness of ginger as an antiemetic modality for controlling CINV in breast cancer
3
Department of Nutrition, Science and
patients. All published randomized controlled trials in English were systematically
Research Branch, Islamic Azad University,
Tehran, Iran searched on Google Scholar, PubMed, Scopus, and Cochrane search databases up
to June 2018. The outcome variable of interest was severity and the frequency of
Correspondence
Mitra Zarrati, Assistant Professor, Nutrition nausea and vomiting in patients. A total of 50 studies were found through search
Department, School of Public Health, Iran
databases. After excluding duplicates, the 42 remaining studies were screened, and
University of Medical Sciences, Tehran, Iran.
Email: zarrati_ms@yahoo.com; zarrati.m@iums. finally, nine trials were included, which were published between 2012 and 2017.
ac.ir
Two studies have examined the effect of ginger on the frequency of nausea, five
studies on the frequency of vomiting, seven studies on the severity of nausea, and
three studies on severity of vomiting. A study evaluated the effectiveness of ginger
in improving dietary intake in CINV. Our investigation suggests that ginger may
reduce nausea in the acute phase of chemotherapy in patients with breast cancer.
The effect of ginger on nausea and vomiting in other conditions requires more
high‐quality clinical trials.

K E Y W OR D S

breast cancer, chemotherapy, CINV, ginger, herbal therapy, nausea, vomiting, Zingiber officinale

1 | I N T RO D U CT I O N some other procedures; however, in the advanced stages, chemother-

Breast cancer is the most commonly diagnosed cancer with 25% of
cases of cancer and is the leading cause of cancer mortality with
15% of all cancer deaths in the female population (Torre et al.,
2015). The most common causes of breast cancer are genetic factors
and also environmental and lifestyle risk factors such as early menar-
che, late menopause, low parity, giving birth at an advanced age, alco-
hol consumption, and obesity (Dossus & Benusiglio, 2015). Nowadays,
cancer treatment includes surgery, chemotherapy, radiotherapy, and
apy is often the only effective method of cancer treatment (Payandeh,
Sadeghi, Sadeghi, & Aeinfar, 2015). Although, in recent years, chemo-
therapy agents and antiemetic drugs have had significant advance-
ment, chemotherapy‐induced nausea and vomiting (CINV) has
remained as one of the worst side effects of cancer therapy (Palatty,
Haniadka, Valder, Arora, & Baliga, 2013).
In addition to causing an unpleasant feeling in the patient, CINV
may cause malnourishment and thus, influence the immune system,
electrolyte balance, performance, and the quality of life. Moreover,

Phytotherapy Research. 2019;1–9. wileyonlinelibrary.com/journal/ptr © 2019 John Wiley & Sons, Ltd. 1
2 SANEEI TOTMAJ
CINV may hinder the treatment procedure or necessitate reducing the
dosage of the drugs, thus might demote the treatment success rates
(Navari & Aapro, 2016; Shankar1, Shankar, Roy, Malik, Julka, & Rath,
2015). Although CINV is decreased by using multiple classes of anti-
emetic drugs, CINV is observed in 60% to 80% of patients under che-
motherapy (Ryan et al., 2012; Wang, Yang, Zhang, & Zhang, 2014).
These antiemetic agents may have significant side effects such as diar-
rhea, headache, sedation, dizziness, and asthenia (Palatty et al., 2013).
As a result, despite pharmacologic treatment, patients often chose
complementary and alternative medicine (CAM; Harris, Cooper,
Relton, & Thomas, 2012).
Herbal therapy is the most popular CAM in the world, especially in
patients with cancer (Saghatchian et al., 2014). One of the most fre-
quently used plant derivatives is ginger (Zingiber officinale; Konuklugil
& Özçelikay, 2004) that has been known as an antiemetic drug for
years (Jiyeon Lee, 2013). The antiemetic activities of ginger could be
mainly attributed to its active compounds, gingerol, and shogaol (Wil-
kinson, 2003; Zick et al., 2009).
The efficacy of ginger in preventing nausea and vomiting has been
assessed in a number of clinical trials in patients with various condi-
tions, such as pregnancy and postoperative nausea and vomiting
(Chaiyakunapruk, Kitikannakorn, Nathisuwan, Leeprakobboon, &
Leelasettagool, 2006a; Thomson, Corbin, & Leung, 2014; Viljoen,
Visser, Koen, & Musekiwa, 2014). Studies on the efficacy of ginger
on the number and severity of nausea and vomiting episodes in differ-
ent phases of chemotherapy in breast cancer patients have shown
conflicting results (Arslan & Ozdemir, 2015; Panahi et al., 2012;
Sanaati, Najafi, Kashaninia, & Sadeghi, 2016; Thamlikitkul et al.,
2017). A systematic review and meta‐analysis study have reviewed
this relationship in all types of cancers and concluded that there is
no evidence that supports the use of ginger to prevent CINV (Jiyeon
Lee, 2013).
Taking all these facts into account, this systematic review was
aimed at conducting a comprehensive overview of the current evi-
dence regarding the effectiveness of ginger as an antiemetic modality
for controlling CINV in breast cancer patients.
2 | MATERIALS AND METHODS
2.1 | Data source and search strategy
A systematic review of studies was conducted based on the Preferred
Reporting Items for Systematic Reviews and Meta‐analyses guidelines
(Brown et al., 2003). Comprehensive search strategies were used to
identify reports of randomized controlled trials (RCTs) indexed in Goo-
gle Scholar, PubMed, Scopus, and Cochrane search databases up to
February 2019. The keywords that were used to search studies rele-
vant to this review included the following: [“Ginger” OR “Asarum”
OR “Zingiber officinale”] AND [“Breast Neoplasms” OR “breast cancer”
OR “Mastectomy” OR “axillary dissection”] AND [“Nausea” OR
“Vomiting” OR “emesis” OR “vomit*” OR CINV] AND [“randomized
controlled trial” OR “controlled clinical trial” OR “placebo” OR
ET AL.
“randomized” OR “trial” OR “randomly” OR “group” OR “Double blind”
OR “Single blind”]. Moreover, the bibliographies of selected studies
were verified to find additional related trials. The language of studies
was not limited.
2.2 | Study selection
The published RCTs in English that verified the impact of ginger on
CINV in breast cancer patients were included. Determined exposure
and outcome were ginger intake and the severity of nausea and the
frequency of vomiting, respectively. If the results of a study were
reported in more than one publication, the one with the most com-
plete results was included.
Articles that did not meet our criteria, reviews, experimental stud-
ies, in vitro studies, conference papers, editorials, nonresearch letters,
case reports or case series, and observational studies were excluded.
Having pooled the retrieved papers and removing duplicates, two
reviewers (A. S. T. and H. E.) independently skimmed the title and
abstracts of each paper to detect potentially eligible papers. Then, all
selected studies were scrutinized to exclude noneligible ones and
include qualified RCTs based on the defined criteria.
2.3 | Data extraction
A data extraction form was prepared, and the outcomes of interest
were extracted from the selected articles. General information
(authors, title, journal, and date of publication), the study population
characteristics (age, sex, race, and health condition), and the type of
exposure (ginger) and outcomes (nausea and vomiting degree) were
extracted.
2.4 | Risk of bias assessment
Using the Cochrane collaboration tool (Higgins et al., 2011), two
reviewers (A. S. T. and H. E.) independently evaluated risks of bias
for each study in seven areas: random sequence generation, allocation
concealment, blinding of patients and personnel, blinding of outcome
assessment, incomplete outcome data, selective reporting, and other
sources of bias. For each study, the overall risk of bias was considered
“high” if (1) the risk of bias was high in any domain and (2) if the risk of
bias was unclear in any domain (and was not high in other areas). On
the other hand, the overall risk of bias was considered low if the risk
of bias was low across all domains. The reviewers resolved uncertainty
and disagreement by discussion and consensus.
3 | RESULTS
3.1 | Search results
A total of 50 studies were found through search databases as depicted
in Figure 1. After excluding duplicates, the 42 remaining studies were
screened by their title and abstract of which 33 were excluded due to
SANEEI TOTMAJ ET AL.
the following reasons: (a) 16 studies were review articles, (b) 13 of
them were not relevant in exposure or outcome, (c) one study was ani-
mal based, (d) one study was a conference paper, and (e) two papers
were commentary or editorial. Finally, nine trials (Ansari et al., 2016;
Arslan & Ozdemir, 2015; Lua, Salihah, & Mazlan, 2015; Panahi et al.,
2012; Ryan et al., 2012; Salihah, Mazlan, & Lua, 2016; Sanaati et al.,
2016; Thamlikitkul et al., 2017; Yekta et al., 2012) were included in
this review, which were published between 2012 and 2017
(Table 1). Included studies were conducted in Turkey (one study),
Malaysia (two studies), Iran (four studies), United States (one study),
and Thailand (one study).
The five studies included in this systematic review were double
blinded randomized controlled trials (Ansari et al., 2016; Ryan et al.,
2012; Sanaati et al., 2016; Thamlikitkul et al., 2017; Yekta et al.,
2012). A cross‐over design was applied in three studies (Lua et al.,
2015; Salihah et al., 2016; Thamlikitkul et al., 2017). One study was
open label (Panahi et al., 2012), and two studies were single‐blind ran-
domized controlled trials (Lua et al., 2015; Salihah et al., 2016). One
study compared different doses of ginger on CINV management (Ryan
et al., 2012). Among the studies, two studies had examined the effect
of intervention on the frequency of nausea, five studies on the fre-
quency of vomiting, seven studies on the severity of nausea, and three
studies on the severity of vomiting. One study evaluated the effec-
tiveness of ginger in improving dietary intake in patients with CINV.
FIGURE 1 Flowchart of identification of
included trials [Colour figure can be viewed at
wileyonlinelibrary.com]
3
3.2 | Participant characteristics
In total, nine studies were included in this systematic review. The
mean age of these participants ranged from 41.8 to 53 years.
Experiencing nausea and/or vomiting caused by chemotherapy were
the main inclusion criteria. Exclusion criteria were presence of condi-
tions that may cause nausea or vomiting (e.g., brain metastasis, bowel
obstruction, hepatitis, or recent abdominal or pelvic irradiation) and
having a history of bleeding disorder(s).
3.3 | Chemotherapy regimens
Most of the participants were under combination chemotherapy
regimens, such as those based on doxorubicin (Ansari et al., 2016)
and adriamycin–cyclophosphamide (Thamlikitkul et al., 2017),
which are moderate to highly emetogenic (Arslan & Ozdemir,
2015; Panahi et al., 2012; Thamlikitkul et al., 2017). Three studies
did not provide information about chemotherapy regimens,
although the administration of antiemetic drugs implied that the
chemotherapy regimens applied induced a moderate to high degree
of nausea in patients (Ryan et al., 2012; Sanaati et al., 2016; Yekta
et al., 2012).
 4

TABLE 1 Characteristics of the studies in this systematic review

Age of participants
intervention
Author Country RCT type Journal (control) Sample Intervention/dose Duration Main results Side effects

Arslan & Turkey RT without control Clinical Journal of 48.5 60 500 mg powdered ginger Twice a day for 3 days ↓ Nausea severity No side effects
Ozdemir, Oncology Nursing ↓ Number of vomiting
2015 episodes
↔ Number of retching
episodes

Lua et al., Malaysia Single‐blind, Complementary 45.9 (48.7) 60 Two drops of ginger 5 days, breath at least ↓ Nausea score during Very mild
2015 cross‐over RCT Therapies in Medicine essential oil or ginger three times a day for acute phase dizziness only
fragrance oil (placebo) at least three periods ↔ Overall treatment in one person
of 2‐min duration effect
on nausea
↔ Aromatherapy on
vomiting incidence
↑ Global health
↑ Role functioning
↑ Appetite

Ansari et al., Iran RCT Asian Pacific Journal of 48.6 119 250 mg ginger powder Two capsules every ↔ Nausea score No side effects
2016 Cancer Prevention or starch 12 hr for 3 days (intensity)
↔ Vomiting scores
(intensity)

Panahi et al., Iran Open‐label RCT Integrative Cancer 51.8 100 1.5 g/d in three divided 4 days ↓ Acute nausea (6–24 hr Heartburn,
2012 Therapies doses every 8 hr post chemotherapy) headache,
↔ Prevalence or and vertigo
severity of acute or
delayed vomiting and
retching episodes

Author Country RCT type Journal Age of participants Sample Intervention/dose Duration Main results Side effects
intervention
(control)

Ryan et al., USA Double‐blind RCT Support Care Cancer 53 576 0.5, 1.0, and 1.5 g 6 days ↓ Acute nausea severity Heartburn,
2012 ginger capsule (all doses) bruising/
Largest reduction flushing, and
occurred with 0.5 and rash
1.0 g

Salihah et al., Malaysia Single‐blind, Focus on Alternative 47.3 60 Two drops of ginger EO or 5 days ↑ Energy intake at Day 3 No side effects
2016 cross‐over RCT and Complementary ginger fragrance oil (FO) and Day 5
Therapies (fragrance‐matched
placebo)

Iran Double‐blind RCT 40–50 65 No side effects

SANEEI TOTMAJ

(Continues)
ET AL.
 SANEEI TOTMAJ

TABLE 1 (Continued)
ET AL.

Age of participants
intervention
Author Country RCT type Journal (control) Sample Intervention/dose Duration Main results Side effects

Sanaati et al., Asian Pacific Journal of 500 mg capsules of 5 days before and ↓ Frequency of vomiting
2016 Cancer Prevention powdered 5 days after (ginger)
ginger and 500 mg chemotherapy: two ↓ Frequency of vomiting
capsules of Matricaria times a day (chamomile)
chamomilla extract ↓ Frequency of nausea
(ginger)
↔ Frequency of nausea
(chamomile)

Thamlikitkul Thailand Double‐blind, Support Care Cancer 49 34 500‐mg ginger capsule twice a day for 5 days ↔ Nausea scores No side effects
et al., cross‐over RCT ↔ Vomiting incidence
2017 and severity
↔ Rescue medication
use
↔ Chemotherapy
compliance
↔ Adverse events

Yekta et al., Iran Double‐blind RCT Iranian Journal of 41.8 (45.1) 80 250 mg ginger powder 6 days since 3 days ↓ Vomiting cases Heartburn
2012 Nursing and capsules (Zintoma) and before chemotherapy (anticipatory phases)
Midwifery Research placebo group 250 mg ↓ Vomiting cases (acute
starch capsules four phases)
times a day (1 g/day) ↓ Vomiting cases
(delayed phases)
heartburn was the
only and venial
reported side effect

Abbreviation: RCT, randomized controlled trial.

↔ = No significant difference compared with control.
↓ = significantly decreased compared with control.
↑ = significantly increased compared with control.
5
6 SANEEI TOTMAJ
3.4 | Antiemetic control
Arsalan et al. used 5‐HT3 receptor antagonists (dexamethasone), an
antihistamine (ranitidine), and aprepitant to manage CINV (Arslan &
Ozdemir, 2015). Aromatherapy was used in two studies (Lua et al.,
2015; Salihah et al., 2016). Aromatherapy (Essential Oil Vapor Inhala-
tion [EO]) is a special form of complementary and alternative therapy
that is widely used to treat or reduce physical and emotional symp-
toms (Price & Price, 2011). Clinical studies suggest that aromatherapy
as a complementary therapy has beneficial effects in reducing nausea
(Steflitsch & Steflitsch, 2008). In five studies, subjects received a 5‐
HT3 receptor antagonist and dexamethasone to prevent CINV (Ansari
et al., 2016; Panahi et al., 2012; Ryan et al., 2012; Thamlikitkul et al.,
2017; Yekta et al., 2012). Sanaati et al. used dexamethasone,
metoclopramide and aprepitant as a routine antiemetic regimen
(Sanaati et al., 2016).
3.5 | Ginger administration
Ginger capsules that were used as an intervention contained pow-
dered ginger root (0.25 or 0.5 g; Ansari et al., 2016; Sanaati et al.,
2016), dry powdered ginger root containing 5.38 mg (2.15%) 6‐
gingerol, 1.8 mg (0.72%) 8‐gingerol, 4.19 mg (1.78%) 10‐gingerol,
and 0.92 mg (0.37%) 6‐shagaol (Panahi et al., 2012; Thamlikitkul et al.,
2017; Yekta et al., 2012), or purified liquid extract of ginger root con-
taining gingerols, zingerone, and shogoal (Ryan et al., 2012). In two
studies, patients were asked to wear an aromatherapy necklace con-
taining two drops of ginger EO (Lua et al., 2015; Salihah et al.,
2016). In one study, 500 mg powdered ginger mixed with a spoonful
of yogurt to make swallowing easier was administered to patients
(Arslan & Ozdemir, 2015). Daily ginger doses varied from 0.5 to
1.5 g, and the intervention duration ranged from 3 to 10 days. Admin-
istration of ginger initiated from 5 days before to 30 min after the
beginning of chemotherapy.
3.6 | Measurements
The CINV experience was evaluated by the participants. Visual ana-
log scale (Lua et al., 2015; Salihah et al., 2016; Sanaati et al., 2016;
Thamlikitkul et al., 2017; Yekta et al., 2012) and semantic scales
(Arslan & Ozdemir, 2015; Ryan et al., 2012) were the main tools used
to record CINV. One study used a simplified form of the Rhodes
Index of Nausea, Vomiting, and Retching (RINVR) to record symp-
toms (Panahi et al., 2012). The RINVR is a self‐reporting eight‐item,
5‐point Likert‐type tool that measures the frequency and duration
of nausea, vomiting, and retching. Five studies investigated acute as
well as delayed CINV (Arslan & Ozdemir, 2015; Lua et al., 2015;
Panahi et al., 2012; Ryan et al., 2012; Thamlikitkul et al., 2017).
One study measured only vomiting in acute and delayed phase
(Yekta et al., 2012).
ET AL.
3.7 | Findings
The findings of four studies support the effect of ginger in controlling
acute nausea (Arslan & Ozdemir, 2015; Lua et al., 2015; Panahi et al.,
2012; Ryan et al., 2012). Lua et al. and Salihah et al. reported that the
use of inhaled ginger EO for CINV could possibly help patients
improve overall health status (p < .001), role functioning (0.002), appe-
tite loss (p < .001), and dietary intake over time (p < .001). Sanaati et al.
observed that ginger and chamomile were both significantly effective
in reducing the frequency of vomiting (p < .0001), and there was no
significant difference between the ginger and chamomile groups in
this regard. Unlike chamomile (0.8), ginger significantly influenced
the frequency of nausea (0.006). Ryan et al. did not provide informa-
tion regarding the incidence of CINV, but the final analysis showed
that all doses of ginger significantly reduced the severity of acute nau-
sea compared with the placebo on Day 1 of chemotherapy (0.003).
The largest reduction in nausea intensity was observed with doses
of 0.5 g (0.01) and 1 g (0.03) of ginger. The results of Ryan et al. did
not support ginger's effect in controlling acute and delayed vomiting
or delayed nausea (Ryan et al., 2012). Two studies did not support
the effect of ginger in reducing the severity of nausea (Ansari et al.,
2016; Thamlikitkul et al., 2017). Three studies were able to demon-
strate ginger's impact on chemotherapy‐induced vomiting (Arslan &
Ozdemir, 2015; Sanaati et al., 2016; Yekta et al., 2012), whereas four
other studies showed that ginger intake had no significant effect in
controlling acute and delayed vomiting (Ansari et al., 2016; Lua et al.,
2015; Panahi et al., 2012; Thamlikitkul et al., 2017).
3.8 | Side effects
Lua et al. (2015) reported that only one person was withdrawn from
the study after complaining of having very mild dizziness or light
headedness on Day 5 of aromatherapy treatment with ginger essential
oil (Lua et al., 2015). Panahi et al. (2012) reported ginger‐related
adverse effects such as heartburn, headache, and vertigo (Panahi
et al., 2012). Ryan et al. reported adverse effects including gastrointes-
tinal symptoms, like grade 2 heartburn, bruising/flushing, and rash
(Ryan et al., 2012). Yekta et al. reported heartburn as the main com-
plaint after taking ginger capsules (Yekta et al., 2012). Other five stud-
ies found no side effects that were attributable to ginger.
3.9 | Risk of bias
Risk of bias within the individual studies is depicted in Figure 2. Six
studies were judged to be at high risk of bias out of which three stud-
ies were prone to selection bias. Two studies were regarded as having
a low risk of bias. Risk of bias was unclear for the remaining study.
4 | DISCUSSION
Systematic reviews and meta‐analyses are at the top in the hierarchy
of the clinical evidence (Izzo, Hoon‐Kim, Radhakrishnan, & Williamson,
SANEEI TOTMAJ ET AL.
FIGURE 2 Risk of bias summary: review authors' judgements about
each risk of bias item for each included study. Risk of bias levels:
low (green), unclear (yellow), high (red) [Colour figure can be viewed at
wileyonlinelibrary.com]
2016). The current systematic review provides the first comprehen-
sive summary of the clinical trials evaluating the effect of ginger on
chemotherapy‐induced nausea and vomiting in breast cancer patients.
Evidence suggests that ginger may have a positive effect on the sever-
ity of acute nausea. There was not enough evidence to support the
effect of ginger on other clinical manifestations relevant to this
review. Chemotherapy regimens, antiemetic agents use, preparation
of ginger capsules, dose of the administered ginger, and the duration
of ginger treatment could have influenced the results of the studies.
In these studies, the use of antiemetic drugs was not adjusted in
patients; therefore, drawing any conclusion about the benefits of non-
drug interventions, such as ginger, more difficult. Common antiemetic
drugs include 5‐HT3 receptor antagonists, NK1 receptor antagonist,
7
dopamine antagonist, steroids, cannabinoids, and antihistamines
(Palatty et al., 2013).
The effects of ginger are attributed to the presence of its active
compounds, including gingerols, shogaols, zingerone, and paradol
(Palatty et al., 2013). Ginger has been shown to have antinausea
and antivomiting effects through systematic and gastrointestinal‐
related effects (Chaiyakunapruk, Kitikannakorn, Nathisuwan,
Leeprakobboon, & Leelasettagool, 2006b). The main mechanism of
the effect of ginger on the reduction of nausea and vomiting is
unknown; it may be due to the dose‐dependent effect on 5‐HT3
and NK‐1 receptors and substance P (Marx et al., 2014; Palatty
et al., 2013). Current antiemetic medication, such as 5‐HT3 antago-
nists, prevent the binding of neurotransmitters to their receptors in
the gastrointestinal tract (Herrstedt & Dombernowsky, 2007). Like-
wise, ginger can increase the antiemetic effects of medications by
binding to 5‐HT3 receptors and promote detoxification enzymes to
prevent oxidative damage to the tissues (Geiger, 2005). Animal stud-
ies have shown that ginger increases gastric emptying and intestinal
motility (Giacosa et al., 2015). Contradictory results of ginger on
vomiting may be due to the fact that the administration of 5‐HT3
receptor antagonists significantly reduces the vomiting frequency to
the lowest possible degree. It is reported that these antiemetic
agents will act more preferably against vomiting than nausea (Aapro,
2005; Grunberg et al., 2005; Hickok et al., 2005). Therefore, patients
receiving this kind of medication may not have been experiencing
vomiting at a sufficiently high level of frequency to have responded
to ginger intervention.
Previous studies have shown that patients who experienced a dif-
ferent degree of nausea and vomiting undergoing each cycle of che-
motherapy, regardless of the emetogenicity of chemotherapy
regimen, experienced significantly a higher and more‐difficult‐to‐treat
vomiting; even under standard antiemetic medication (Roscoe, Mor-
row, Aapro, Molassiotis, & Olver, 2011). In the studies reviewed in
this article, patients were included in the study after experiencing
nausea and vomiting in a previous chemotherapy cycle. In addition,
delayed symptoms increase with highly emetogenic chemotherapy
and respond less to treatment and intervention than to prevention
(Schnell, 2003). One of the possible reasons for the lack of effect
of ginger on delayed symptoms in these studies might be the inclu-
sion of patients receiving highly emetogenic regimens. Another rea-
son could be the use of aprepitant as an antiemetic drug, which is
usually Ca‐a Cancer Journal for Clinicians. Zick et al. (2009) observed
that the use of aprepitant with ginger increases the severity of nau-
sea, which indicates a possible interaction between ginger and pre-
scribed antiemetic drugs, especially aprepitant; this matter requires
further investigation. In another study (Ansari et al., 2016), chemo-
therapy with AC (doxorubicin + cyclophosphamide) and ginger intake
induced less vomiting than in the control group. The interaction of
chemotherapy with ginger has not yet been thoroughly investigated.
Ginger may be more effective in patients under specific chemother-
apy regimens.
Yekta and Ryan (Ryan et al., 2012; Yekta et al., 2012) used ginger
capsules with a specific active compound, whereas the other studies
8 SANEEI TOTMAJ
used powdered ginger root or ginger essential oil. This makes it diffi-
cult to decide if the amount of the active compounds causes changes
in the results.
Ryan, Yekta, and Sanaati (Ryan et al., 2012; Sanaati et al., 2016;
Yekta et al., 2012) began the intervention before chemotherapy. Ryan
et al. speculated that the onset of ginger intake before the start of
chemotherapy may prepare the intestine for the emetic response by
binding to the 5‐HT3 receptors and inducing detoxification enzymes
(Ryan et al., 2012). It seems that starting treatment with ginger before
chemotherapy may elicit better results. Further studies are needed to
ensure this claim.
Ryan et al. reported that a dose of 0.5 to 1 g of ginger effectively
controlled acute nausea, whereas a dose of 1.5 g was not effective
(Ryan et al., 2012). Lien et al. found that a dose of 1 g/d of ginger
was more effective against motion sickness than a dose of 2.0 g (Lien
et al., 2003). It seems that a dose of 1 g of ginger saturates all recep-
tors, rendering further doses ineffective.
In a systematic review and meta‐analysis by Lee et al. (Jiyeon Lee,
2013), the effect of ginger on CINV of all cancers was investigated.
Each cancer has a specific therapeutic protocol, and each protocol
may exert a different rate of nausea.
The present study examined the effect of ginger on CINV in women
with breast cancer. This review has some limitations as well as some
strength. Some limitations are listed as below: (a) the results of this
study cannot be generalized to other populations, (b) a meta‐analysis
cannot be performed due to the use of various tools and cross‐over
studies; the meta‐analysis of cross‐over studies can be too complicated
and thus incomprehensible (Atkinson, Douglas, & Stensel, 2014). Poor
reporting of cross‐over trials will often impede attempts to perform a
meta‐analysis using the available methods (Elbourne et al., 2002). There-
fore, in our study, due to existence of cross‐over trials and lack of final
reports, performing a meta‐analysis was impossible. To conduct a meta‐
analysis, we needed more parallel clinical trials in this field.
More methodologically rigorous studies investigating the effect of
ginger on the management of CINV in breast cancer patients are
required. Controlling the chemotherapy regimen, antiemetic use, risk
factors of CINV development, preparation of ginger capsules, dose
of the ginger administered, and duration of ginger treatment in future
trials would improve our understanding of the effect of ginger in CINV
management.
In conclusion, the findings of this review suggest that ginger may
reduce nausea in the acute phase of chemotherapy in patients with
breast cancer. The effect of ginger on nausea and vomiting in other
conditions requires more controlled trials. Further high‐quality studies
are needed to firmly establish the clinical efficacy of ginger.
FUND ING INF OR MATI ON
This research did not receive any specific grant from funding agencies
in the public, commercial, or not‐for‐profit sectors.
CONF LICT OF INT E RE ST
There is no conflict of interest.
ET AL.
ORCID
Mitra Zarrati https://orcid.org/0000-0002-2123-3319
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How to cite this article: Saneei Totmaj A, Emamat H, Jarrahi
F, Zarrati M. The effect of ginger (Zingiber officinale) on chemo-
therapy‐induced nausea and vomiting in breast cancer
patients: A systematic literature review of randomized con-
trolled trials. Phytotherapy Research. 2019;1–9. https://doi.
org/10.1002/ptr.6377