The Effects of Ginger Extract on Chemotherapy- induced
Nausea and Vomiting
Adam Aguilera & Joanna Bundros
NFSC 345: Fall 2013
Introduction
Chemotherapy patients experience many distressing side effects that decrease their quality of
life, including a high prevalence of chemotherapy-induced nausea and vomiting (CINV).
Besides physiological discomfort, CINV is concerning due to decreased nutrient intake,
hydration status, depression, and decreased likelihood of following the therapy regimen. 1
Although general chemotherapy treatment involves use of antiemetic medications, a large
majority of patients still suffer from various forms of nausea and vomiting, including acute,
delayed and anticipatory.1,2 Acute nausea is nausea occurring in the first 24 hours of treatment,
whereas delayed nausea occurs after 24 hours and may persist for a week. Anticipatory nausea
occurs before patients receive chemotherapy, in those patients who have received previous
chemotherapy treatments. 1,3 About a third of chemotherapy patients being given traditional
antiemetics still experience acute nausea and vomiting, and up to 70% of patients still experience
delayed and anticipatory CINV.1 The high prevalence of CINV chemotherapy patients shows
that the current medication regimen is not alleviating these symptoms for the majority of
patients. It is clear that additional treatments for CINV are needed, which provided motivation
to research additional supplements that are being explored as possible treatments to better
manage these symptoms. There have been studies conducted looking at the ability of ginger
supplementation to reduce the prevalence of CINV in chemotherapy patients who are
concurrently receiving the standard antiemetic medications.
Ginger (zingiber officinale) has been used for thousands of years by many cultures as a
treatment for digestive problems such as nausea and vomiting. Ginger can be used fresh, dried
or as an extract. The active components of ginger that appear to alleviate digestive problems are
gingerols found in the root and shogaols found in dried ginger .3
Ginger has been studied in relation to alleviating the frequency and severity of CINV,
and has produced varying results that both support and negate the efficacy of the use of ginger
for CINV management. A randomized trial done on cancer patients undergoing chemotherapy
and taking a standard 5-HT3 receptor antagonist antiemetic drug, showed a significant reduction
in severity of nausea symptoms with the addition of ginger extract.2 On the contrary, another
randomized trial of chemotherapy patients given ginger supplementation while also taking an 5HT3 receptor antagonist and/or aprepitant drugs for CINV, showed no significant difference in
occurrence of CINV or in severity of symptoms. 3 Additionally, patients receiving both the
aprepitant anti-emetic drug and the highest dose of ginger supplementation had more severe
nausea symptoms than those just receiving the aprepitant. While these trials show that the
current research is mixed on the specific role of ginger extract in relation to CINV, the
conclusion of ginger supplementation significantly reducing in the severity and prevalence of
symptoms when partnered with the established protocols is best supported by the studies we
examined.1, 2 Ginger appears to be a helpful anti-emetic agent for patients undergoing
chemotherapy and is deserving of further investigation in additional clinical trials to better
understand its efficacy in treating CINV.
Discussion of Studies
Study Objectives, Design, and Methods
The objective of the study by Ryan et al was to determine if ginger supplementation could be an
effective treatment for reducing severity of CINV in patients receiving standard antiemetics. The
study design was a randomized, double-blind, placebo-controlled dose-finding clinical trial.
Patients were included if they currently had cancer, were over 18, had received at least one round
of chemotherapy, and were planning to receive additional chemotherapy. They had to be
receiving a 5-HT3 receptor antagonist drug and have experienced nausea during treatment. The
intervention was done in 23 oncology clinics on the 744 patients meeting the inclusion criteria,
and patients were randomly assigned to receive either a placebo 6 times daily (extra virgin olive
oil capsules), or purified ginger capsules 6 times daily totaling 0.5 grams, 1.0 grams, or 1.5
grams of ginger. All subjects took their assigned treatment twice a day for six days, beginning
three days prior to when their chemotherapy began. Patients used validated reporting
questionnaires to record the prevalence and severity of any nausea experienced, as well as
quality of life. Statistical analysis was done on the 576 patients who both completed baseline
measures prior to the intervention, and gave needed data during the following rounds of
receiving the medication.
Results and Conclusions by the Researchers
Patients were most commonly female, white, around 50 years of age, with breast, lung, or a form
of GI cancer. Statistical results showed that all doses of ginger significantly reduced the
occurrence of acute CINV compared to the placebo (p=0.013 and 0.003). The most effective
doses in reducing prevalence of acute CINV were 0.5 g and 1.0 g of ginger per day. Other forms
of nausea did not show a significant relationship to ginger supplementation. The authors
concluded that ginger supplementation in moderate doses during chemotherapy had a beneficial
effect of reducing the prevalence of acute CINV, in patients also taking a standard anti-emetic,
making it a valuable additional treatment for CINV.
Study Strengths and Weaknesses
Strengths included the randomized, double-blind, placebo-controlled study design, because this
removes possible bias from either the patient or the administrator knowing whether the ginger or
placebo has been taken. The randomization also reduces potential confounding variables
associated with participants had they not been randomized. The large sample size, as well as
including only subjects with complete information were also strengths. Having a large sample
size better reflects the population sampled from, and decreases the chance that what was
observed was due to chance. Additional strengths were the use of standardized ginger and
placebo capsules all manufactured from the same company, made in ways that made them look
and smell the same. This eliminated potential confounding variables and bias that would exist
had there been variation in how the capsules were made, or appeared to the participant taking
them. Counts of capsules were also done at the end of each round of ginger or placebo given to
subjects, which is a strength because it better ensures compliance with the intervention. The use
of validated questionnaires for determining nausea severity and quality of life were also study
strengths, since these tools have previously been determined to accurately measure these
variables in previous studies. Another study strength regarding accurately examining acute
nausea was excluding nausea reported on days/times when it was not likely patients received
prior chemotherapy treatment. This was a strength because it more strongly identified only acute
nausea occurrence, and reduced the chance of accidentally including delayed or anticipatory
nausea in the analysis. Authors also offered explanations from previous literature as to why the
highest dose of ginger may not have been as effective, which confirmed the validity of their
findings.
One possible weakness is that the majority of subjects were white women around 50
years old, who most commonly had breast, lung, or GI cancer. This is a possible weakness
because this may introduce unknown confounding variables due to the subjects being similar in
these ways. Additionally, it may limit the generalizability of the study results, since these
demographics are very similar. An additional weakness is the occurrence of nine reported
adverse events such as rashes, flushing and heartburn from patients taking the ginger. Although
this number is not very high, we felt it was a weakness because it was discussed very little in the
paper. Another weakness was that they did not control for how strong of a chemotherapy
treatment was received, or how severe nausea was before the intervention began. This is a
weakness because perhaps patients receiving different chemotherapy doses would show a
significant difference in relation to ginger effectiveness, and this was not explored. There was
also a small effect size for severity of nausea between treatment and control (even though the pvalue was significant), which is a weakness because it questions the power of the findings.
However, the authors point out that this would probably had changed had they limited
enrollment just to patients with moderate or severe nausea.
After analysis of the study conclusions, strengths and weaknesses we support the
researcher’s conclusions of ginger supplementation having a significant role in treating acute
CINV. We support this conclusion because there were extremely significant p-values for all
analyses relating to acute CINV (p=0.013 and 0.003) from a large sample size, and findings were
in line with previous studies which adds validity to findings. Additionally, researchers were very
careful in their identification of acute nausea episodes in their analysis, and we feel the small
effect size was probably due to how the data was organized for analysis, and not due to the
findings not being significant.
Study Objectives, Design, and Methods
The second study, written by Suzanna M. Zick and colleagues, was designed to research the
effect of multiple doses of powdered ginger extract versus a placebo for reducing the occurrence
and severity of delayed and acute CINV. The main objective focused on delayed CINV since
previous studies had only shown significance with acute stages. The study also wanted to assess
the safety of varying ginger doses. A randomized, double-blind, placebo-controlled trial was
initiated to study the use of ginger on patients recruited from oncology clinics and other sites
affiliated with the National Cancer Institute’s oncology center. 162 participants were recruited,
who were 18 or older, diagnosed with cancer, receiving chemotherapy, and had experienced
CINV during one or more prior rounds of treatment.
Patients were excluded if they were
receiving more than one dose of chemotherapy daily, also receiving radiation that may cause
nausea or vomiting, using medications like Coumadin or aspirin, or if they were pregnant or
nursing. All patients were randomized to receive 1.0g ginger (4 capsules ginger, 4 capsules
placebo), 2.0g ginger (8 capsules ginger) or a placebo (8 capsules placebo) daily for 3 days.
Each capsule contained a standardized 250 mg of dry ginger extract. Subjects were also
randomized to concurrently receive either a 5-HT3 receptor antagonist and/or aprepitant to help
manage CINV. Validated questionnaires and Likert scales were used to separately determine
occurrence and severity of both acute and delayed CINV experienced by patients. Safety was
determined by both talking with subjects, and looking through hospital records or documented
adverse events relating to the ginger supplementation.
Results and Conclusions by the Researchers
Researchers saw no significant difference between any of the ginger doses in severity or
prevalence of either acute or delayed CINV, compared to the placebo. This lack of significance
remained, even when data was analyzed by whether or not the participant had received the
aprepitant drug.
However, researchers did observe that for patients receiving the aprepitant
drug, the highest dose treatment group (2 g ginger/day) showed a trend of higher severity of
delayed nausea compared to the low dose and placebo group, although not statistically
significant (p=0.07). Authors concluded that ginger extract has no benefit on either the
occurrence or severity of acute and delayed CINV for patients receiving chemotherapy, when
taken concurrently with standard antiemetic drugs. They also concluded that high doses of
ginger extract may exacerbate delayed CINV when taken with an aprepitant medication.
Study Strengths and Weaknesses
Study strength included the use of standardized ginger capsules from the same manufacturer, as
well as using dosages based on previous clinical trials. These are strengths because using
capsules from the same manufacturer eliminates possible confounding variables had they been
made differently, and using dosages based on previous clinical trials increases validity and
generalizability of findings. Additional strengths included use of validated questionnaires to
determine occurrence and severity of CINV, because these tools have been previously shown to
accurately measure these variables. The extensive assessment of safety of ginger
supplementation was also a strength, and was done by use of talking to participants, and
checking hospital adverse event documentation. This is a strength because they took safety of
participants very seriously, and also were able to statistically show there was not a difference in
occurrence of adverse events between placebo and ginger groups. An additional strength was the
equal distribution of the aprepitant drug between all treatment groups. This is a strength because
it increases the significance of any findings involving this drug and ginger. Many covariates
were also controlled for in statistical analysis, including presence of baseline CINV, how strong
of a chemotherapy treatment was being received, and whether an aprepitant was being taken.
Controlling for these covariates is a strength because it increases the likelihood that any observed
outcomes are due to ginger, and not to these factors. There was also a high retention rate, and
strong adherence to following the medication dosages, which increases validity of the results.
Weaknesses included that the intervention only lasted for 3 days. This is a weakness
because perhaps a longer time is needed to examine CINV, and especially delayed CINV. A
major weakness was also that participants were significantly able to guess which treatment group
they were in, based in part on the flavor. This is a weakness because it introduces bias from the
patient knowing they are getting either the placebo or the treatment. When patients can correctly
identify their treatment, the study is no longer really a “double-blind” trial. An additional
weakness is the researchers asking participants to return all capsules not taken to them at their
third day visit. This is a weakness because perhaps participants would not actually return all
capsules they had not taken, if they were concerned administrators would be upset that they had
not taken them all. This could skew results, if patients were believed to have consumed all their
dosages. A more accurate method would have been to observe the capsules being taken by each
patient. Lastly, a weakness was that they point out several published studies with results in
contrast to theirs, which may call into question the validity of their findings.
After analysis of the study conclusions, strengths and weaknesses we do not support the
researcher’s conclusions of ginger supplementation having no effect on severity or occurrence of
acute or delayed CINV. We do not support this conclusion because this was a very short trial,
and we don’t feel it was long enough to significantly analyze both acute and delayed CINV
occurrence. We also decided this due to participants being mostly aware of which treatment
group they were in, as well as multiple studies reporting the opposite of the results of this study.
Conclusion and Recommendations
Based on our analysis of this literature relating to ginger supplementation for treatment of
chemotherapy-induced nausea and vomiting, we conclude that ginger is an effective treatment
for reducing occurrence and severity of acute CINV. Due to the significant p-values associated
with ginger as a treatment, the large sample size, as well as the careful process of identifying
acute nausea episodes for analysis, we feel these strongly support this conclusion. Additionally,
although the second study did not show an association between ginger supplementation and
CINV, due to the short study duration and the issues with the double-blind portion of the study
sample, we feel it is more likely that in fact ginger does have an association with CINV. Our
recommendations for further research include randomized double-blind clinical trials of longer
duration, to better examine an association between ginger and delayed CINV. We also
recommend additional in-vitro and in-vivo studies examining the safety of taking ginger
supplements in high doses concurrently with aprepitant medications. Lastly, we recommend
further trials regarding anticipatory nausea, as it appears to be the least understood form,
although it is highly prevalent among chemotherapy patients.
References:
1. Panahi Y, Saadat A, Sahebkar A, et al. Effect of ginger on acute and delayed
chemotherapy-induced nausea and vomiting: a pilot, randomized, open-label clinical trial.
Integr Cancer Ther. 2012; 11: 204-211.
2. Ryan JL, Heckler CE, Roscoe JA, et al. Ginger (Zingiber officinale) reduces acute
chemotherapy-induced nausea: A URCC CCOP study of 576 patients. Support Care
Cancer. 2012; 20: 1479-1489.
3. Zick SM, Ruffin MT, Lee J, et al. Phase II trial of encapsulated ginger as a treatment for
chemotherapy-induced nausea and vomiting. Support Care Cancer. 2009; 17: 563-572.