THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE

Volume 14, Number 5, 2008, pp. 545–551

© Mary Ann Liebert, Inc.
DOI: 10.1089/acm.2007.0817

Protein and Ginger for the Treatment of Chemotherapy-Induced

Delayed Nausea

MAX E. LEVINE, Ph.D.,1 MARCUM G. GILLIS, B.S.,2 SARA YANCHIS KOCH, B.S.,3
ANNE C. VOSS, Ph.D.,4 ROBERT M. STERN, Ph.D.,5 and KENNETH L. KOCH, M.D.3

ABSTRACT

Background: Nausea that develops during the period that begins 24 hours after the administration of
chemotherapy is called delayed nausea, and occurs in many patients with cancer. Meals high in protein de-
crease the nausea of motion sickness and pregnancy, possibly by reducing gastric dysrhythmias. Ginger also
has antinausea properties.
Objectives: To explore the use of protein meals with ginger for the treatment of the delayed nausea of
chemotherapy.
Design: Twenty-eight (28) patients with cancer receiving chemotherapy for the first time were assigned to
1 of 3 groups. For 3 days beginning the day after their chemotherapy, Control Group patients continued with
their normal diet, Protein Group patients consumed a protein drink and ginger twice daily, and High Protein
Group patients consumed a protein drink with additional protein and ginger twice daily.
Outcome measures: Patients recorded in a diary each day whether they had experienced nausea, whether
their nausea had been frequent, whether their nausea had been bothersome, and whether they had needed any
antiemetic medication. Gastric myoelectrical activity was assessed in 5 patients before and after ingestion of a
high protein meal and ginger.
Results: Reports of nausea, frequent nausea, and bothersome nausea were significantly less common among
High Protein Group patients than among Control and Protein Group patients. Furthermore, significantly fewer
patients in the High Protein Group used antiemetic medication. Differences between the Protein and Control
groups were not statistically significant. In the 5 patients who had tests of gastric myoelectrical activity per-
formed, a significant decrease in gastric dysrhythmia occurred after ingestion of the protein and ginger.
Conclusions: High protein meals with ginger reduced the delayed nausea of chemotherapy and reduced use
of antiemetic medications. Protein with ginger holds the potential of representing a novel, nutritionally based
treatment for the delayed nausea of chemotherapy.

INTRODUCTION of their chemotherapy,1 and are sometimes intense enough

to compel a patient to withdraw from treatment.2 Despite

N ausea is a frequent and debilitating side-effect of can-

cer chemotherapy. Nausea and vomiting are reported
by patients to be among the most bothersome side-effects
efforts to reduce chemotherapy-induced nausea and vomit-
ing through the administration of various antiemetic agents,
nausea remains a significant problem.3 The incidence of

1Department of Psychology, Siena College, Loudonville, NY.

2Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
3Department of Internal Medicine, Section of Gastroenterology, Wake Forest University School of Medicine, Winston-Salem, NC.
4Ross Products Division, Abbott Laboratories, Columbus, OH.
5Department of Psychology, The Pennsylvania State University, University Park, PA.

545
546 LEVINE ET AL.

vomiting has been significantly diminished in recent years
with the introduction of serotonin and neurokinin-1 antago-
nist antiemetics, but patients continue to suffer from
chemotherapy-induced nausea.4
Protein meals and ginger represent potentially effective
novel treatments for nausea. Jednak et al.5 compared the ef-
fect of protein, carbohydrate, and fat meals on nausea ex-
perienced during the first trimester of pregnancy. Protein-
predominant meals reduced nausea significantly more than
isocaloric carbohydrate and fat meals. Levine et al.6 demon-
strated that liquid protein meals reduced nausea and other
motion sickness symptoms during exposure to provocative
motion significantly more than liquid carbohydrate meals
and when no meal was given. The physiologic mechanism
by which protein offers protection against the development
of nausea remains unclear, but the reduction of gastric dys-
rhythmias represents one possibility. Reports of nausea tend
to be accompanied by abnormalities in gastric myoelectri-
cal activity, as measured by electrogastrography.7 Interven-
tions that have been effective for the reduction of the sever-
ity of nausea have tended to diminish the dysrhythmic stom-
ach activity that accompanies nausea (e.g., Muth et al.8). In-
deed, the antinausea effects referred to earlier of protein
meals in the context of pregnancy and motion sickness were
accompanied by significant reductions in gastric dysrhyth-
mias.5,6
Lien et al.9 showed that ginger reduces nausea, gastric
dysrhythmia, and plasma vasopressin, a hormone that has
been shown to increase along with nausea. Ginger also pro-
longed latency before nausea onset and shortened recovery
time after exposure to a rotating optokinetic drum, a stimu-
lus that often induces symptoms of motion sickness.
Gonlachanvit et al.10 reported that one gram of ginger re-
duced the gastric dysrhythmia and nausea resulting from the
infusion of dextrose to produce hyperglycemia in healthy
humans. In addition, it has been shown that ginger reduces
postoperative nausea and vomiting.11
The aim of the present study was to determine the extent
to which protein meals with ginger, used as adjuvant thera-
pies for standard antiemetic treatment, would reduce the de-

TABLE 1. DEMOGRAPHIC VARIABLES, CANCER TYPES, CYTOTOXIC AGENTS, AND ANTIEMETIC

MEDICATIONS AS A FUNCTION OF EXPERIMENTAL GROUP

Experimental Group
Control Protein High Protein

Demographics
Patients (n) 9 9 10
Sex (no. female) 5 5 9
Age (mean years) 56.1 55.0 52.1
Cancer type
Breast 5 5 7
Hodgkin’s lymphoma 1 0 1
Non-Hodgkin’s lymphoma 1 2 0
Bladder 1 0 1
Lung 1 0 1
Gastric 0 1 0
Prostate 0 1 0
Cytotoxic agent
Cyclophosphamide/doxorubicin 6 5 5
Cyclophosphamide/epirubicin 0 0 1
Cyclophosphamide/doxorubicin/rituximab 0 1 0
Doxorubicin/dacarbazine 1 0 0
Doxorubicin/docetaxel 0 1 0
Doxorubicin 0 1 0
Paclitaxel/gemcitabine 0 0 1
Paclitaxel 0 0 1
Gemcitabine/navalbine 0 0 1
Etoposide (VP-16) 0 0 1
Cisplatin 1 0 0
Oxaliplatin 0 1 0
Carboplatin 1 0 0
Antiemetic medication
Promethazine 4 3 1
Prochlorperazine 6 8 4
Lorazepam 9 11 6
Ondansetron 3 4 2
Dexamethasone 0 2 1
Aprepitant 1 3 1

Note: None of the group differences in any of the variables displayed was statistically significant.
PROTEIN, GINGER, AND NAUSEA OF CHEMOTHERAPY 547

layed nausea that often develops at least 24 hours after the
administration of chemotherapy, and can continue for sev-
eral days. In addition, electrogastrograms (EGGs) were
recorded from a small sample of the patients to examine the
effects of the test meal on gastric myoelectrical activity.
MATERIALS AND METHODS
Participants
Twenty-eight (28) patients with cancer (19 women) aged
29–83 years (mean age  54.3 years) scheduled for their
first chemotherapy treatment with a moderately or highly
nauseogenic cytotoxic drug completed the study. To be con-
sidered eligible, patients must also have been at least 18
years old at the time of their enrollment, and must not have
had a history of gastrointestinal disorders involving nausea,
undergone gastrointestinal surgery, or been diagnosed with
gastrointestinal obstruction. A history of adverse reactions
to any proteins or ginger also excluded patients from the
study. The characteristics of the patients in each experi-
mental group are displayed in Table 1. The table highlights
the great variability among the study sample in terms of the
type of cancer that had been diagnosed, the cytotoxic agent
that was administered, and the antiemetic drug that was pre-
scribed. However, no difference between groups on any of
these characteristics was statistically significant, nor were
there significant correlations between these characteristics
and any outcome measure. All patients provided written in-
formed consent prior to their participation in the study.
Procedure
Recruitment and assignment to test meal groups. Patients
with cancer scheduled for their first chemotherapy treatment
were invited to participate. Patients were told that the pro-
tein meals with ginger were test products that may or may
not relieve delayed nausea with any more success than stan-
dard antiemetic treatment would alone. As patients were en-
rolled in the study, they were randomly assigned to 1 of 3
experimental groups: Protein Group, High Protein Group,
or Control Group. This was not a blinded study; both the in-
vestigators and the patient were aware of the group to which
the patient had been assigned, but not until after the patient
had provided consent to participate. There was no system-
atic bias in group membership in terms of sex, age, cancer
type, cytotoxic agent administered, or antiemetic medication
prescribed (Table 1). The Protein and High Protein Groups
received test meals of varying protein content and ginger in
the form of dried powdered ginger root in addition to stan-
dard antiemetic medication; the Control Group received only
standard antiemetic medication. Patients assigned to the Pro-
tein and High Protein groups were asked to consume 2 test
meals each day: 1 at breakfast (8:00 AM) and 1 in the late af-
ternoon before dinner (4:00 PM) for 3 days beginning 24 hours
after their first chemotherapy session had ended; patients in
the Control Group were asked to continue with their normal
diet. The composition of the test meals for each group is de-
noted in Table 2. Patients in all groups were asked not to
modify their intake of protein and ginger during the study
period unless dictated by the study protocol.
Symptom diary. At the end of each day of the 3-day study
period, patients completed a Symptom Diary before bedtime
to indicate whether or not they had experienced symptoms
of nausea that day. Reports of the incidence of nausea, of
nausea being a frequent occurrence, and of nausea being
bothersome were made in the diary. All patients had been
prescribed antiemetic medication to take as needed over the
3-day period; they also recorded in the diary the use of any
such medication each day. Patients were instructed not to
refer in their diaries to their nausea or use of antiemetic med-
ication during the first 24 hours after the administration of
their chemotherapy.
Adverse event monitoring. Patients were instructed to
contact the investigators in the event of any adverse inci-
dent related to their participation in the study. Patients also
received a phone call each evening during the 3-day study
period from 1 of the investigators to monitor the occurrence
of any adverse events. The phone call also represented an
opportunity to remind patients to continue with their test

TABLE 2. TEST MEAL COMPOSITION

Protein Group meal:

• One 237-mL ProSure® beveragea
• - 300 kcal (23% whey protein (17 g), 21% fat, 57% carbohydrates)
• Four 250-mg capsules of dried powdered ginger root (Zintona®)b
High Protein Group meal:
• One 237-mL ProSure beverage
• - 300 kcal (23% whey protein (17 g), 21% fat, 57% carbohydrates)
• Three 6.6-g scoops of ProMod® protein powdera (added to ProSure)
• - 84 calories (71% whey protein (15 g), 19% fat, 10% carbohydrate)
• Four 250-mg capsules of dried powdered ginger root (Zintona)
aAbbott Laboratories, Abbott Park, IL.
bHerbalist & Ooc GmbH, Berlin, Germany.
548 LEVINE ET AL.

meals and diaries, and to answer any questions patients may
have had.
Electrogastrography
Electrogastrograms (EGGs) were collected from 5 of the
High Protein Group patients in a manner identical to that
described in Levine et al.12 For 15 minutes before and 30
minutes after ingestion of their test meal, estimates of the
percentage of EGG power within the normal range
(2.50–3.75 cpm) and within the gastric tachyarrhythmia fre-
quency bandwidth (3.75–9.75 cpm) were obtained by di-
viding power in those frequency ranges by estimates of to-
tal EGG power.
Data analysis
Chi-square analyses were performed to determine
whether the percentage of reports of the incidence of nau-
sea differed among the three groups. Similar analyses were
conducted for the percentage of reports of nausea being fre-
quent, the percentage of reports of nausea being bothersome,
and the number of patients in each group who used
antiemetic medication at any time during the 3-day study
period. Alpha levels were set at 0.05 for each of these tests.
The percentage of normal EGG activity before the test meal
was compared to the percentage after the meal by paired t-
tests with the  level set at 0.05. Similarly, the percentage
of gastric tachyarrhythmia was compared before and after
the test meal. Preprandial and postprandial ratings of nau-
sea that corresponded to those changes were also assessed.
RESULTS
Of 178 screened patients, 50 were deemed eligible to par-
ticipate, and 36 were enrolled. Most of the screen failures
were based on the administration of chemotherapy that was
only mildly, if at all, nauseogenic. Eight (8) of the enrolled

A B

C D

FIG. 1. Nausea data obtained from the symptom diaries of patients assigned to the Control, Protein, and High Protein Groups. (A)
Reports of nausea were significantly less common among High Protein Group patients (p  0.01). (B) Reports of nausea being frequent
were significantly less common among High Protein Group patients (p  0.01). (C) Reports of nausea being bothersome were signifi-
cantly less common among High Protein Group patients (p  0.01). (D) The use of prescribed antiemetic medication was significantly
less common among High Protein Group patients (p  0.05). Asterisks represent significant differences between the High Protein Group
and the other 2 groups; none of the differences between the Protein Group and Control Group were statistically significant.
PROTEIN, GINGER, AND NAUSEA OF CHEMOTHERAPY 549

patients failed to return their symptom diaries to the inves-
tigators; 3 of these patients had been assigned to the Protein
Group, 2 to the High Protein Group, and 3 to the Control
Group. No adverse events were reported by patients who
had either completed or not completed the study.
Among the 28 patients who completed the study, signif-
icantly fewer reports of nausea were made by patients in the
High Protein Group than by patients in the other 2 groups,
2(2)  12.7, p  0.01. The difference between the Protein
and Control Groups was not statistically significant. Only 6
of 24 ratings made by High Protein Group patients indicated
that nausea had been experienced during the preceding day,
while 15 of 25 ratings made by Control Group patients and
20 of 27 ratings made by Protein Group patients indicated
the incidence of nausea (Fig. 1A).
Significantly fewer reports of nausea being a frequent
symptom were made by patients in the High Protein Group
than by patients in the other 2 groups, 2(2)  19.9, p 
0.01. The difference between the Protein and Control Groups
was not statistically significant. Only 3 of 23 ratings made
by High Protein Group patients indicated that frequent nau-
sea had been experienced during the preceding day, while
15 of 25 ratings made by Control Group patients and 20 of
27 ratings made by Protein Group patients indicated frequent
bouts of nausea (Fig. 1B).
Significantly fewer reports of nausea being bothersome
were made by patients in the High Protein Group than by
patients in the other 2 groups, 2(2)  14.0, p  0.01. The
difference between the Protein and Control Groups was not
statistically significant. Only 6 of 23 ratings made by High
Protein Group patients indicated that nausea had been both-
ersome during the preceding day, while 11 of 25 ratings
made by Control Group patients and 21 of 27 ratings made
by Protein Group patients indicated that their nausea had
been bothersome (Fig. 1C).
Significantly fewer patients in the High Protein Group
elected to use antiemetic medication than patients in the
other 2 groups, 2(2)  6.4, p  0.05. The difference be-
tween the Protein and Control Groups was not statistically
significant. Only 5 of 10 patients in the High Protein Group
used a prescribed antiemetic drug at any time during the 3-
day test period, while all 9 patients in the Control Group
and 7 of 9 patients in the Protein Group used an antiemetic
drug (Fig. 1D).
For the 5 High Protein Group patients who had their
EGGs recorded before and after ingestion of their first test
meal, their mean baseline nausea rating was 8.0 (out of 10).
The rating decreased to 4.6 after the test meals, but the dif-
ference was not statistically significant for this small group
of patients. Gastric tachyarrhythmia decreased significantly
from before to after ingestion of the test meal, t(4)  3.13,
p  0.05 (Fig. 2A). Normal gastric activity increased sig-
nificantly over this same time period, t(4)  2.70, p  0.05
(Fig. 2B).

A B

FIG. 2. Gastric myoelectrical activity before and after the test meals in 5 patients. (A). Gastric tachyarrhythmia decreased signifi-
cantly from before to 20 minutes after ingestion of the test meal (p  0.05). (B) Normal gastric activity increased significantly from
before to 20 minutes after the test meal (p  0.05). Error bars represent standard errors of the means.
550
DISCUSSION
Reports of nausea were significantly less common among
patients treated with high protein meals with ginger for 3
days following their initial chemotherapy treatment. Fur-
thermore, the use of antiemetic medication among the same
patients was significantly reduced, and indicates that the use
of protein and ginger holds the potential for being an ef-
fective alternative for managing delayed nausea. That the
ingestion of high protein meals with ginger was associated
with fewer reports of frequent nausea and fewer reports of
nausea being bothersome reinforces the notion that these nu-
tritional supplements can provide relief for patients as they
recover from a chemotherapy treatment.
Five (5) nauseated patients, all of whom had been as-
signed to the High Protein Group, consumed their first test
meal as their gastric myoelectrical activity was monitored.
Though the physiologic mechanism responsible for any pur-
ported beneficial effect of this nutritional intervention re-
mains unknown, it is noteworthy that a consistent decrease
in gastric dysrhythmia and a concurrent increase in normal,
rhythmic gastric activity were evident after ingestion of the
test meal. Each of the patients reported a relief from nausea
with the meal’s ingestion. The ability of protein meals to re-
duce the nausea of pregnancy5 and the nausea of motion
sickness6 has been attributed to their reduction of gastric
dysrhythmias. The suggestion that protein’s value is based
upon its ability to reduce gastric dysrhythmia and/or enhance
normal gastric activity should be regarded only as conjec-
ture at this point, given that these data reflect the responses
of only 5 patients, but more research in this area seems war-
ranted.
Ginger has been used in Asian countries for hundreds of
years to relieve nausea, and many studies have demonstrated
the potential value of ginger in preventing or reducing the
nausea of pregnancy,13 postoperative nausea,11 and the nau-
sea of motion sickness.9 Many of the studies have tried to
determine the mechanism by which ginger relieves nausea.
For example, Sharma and Gupta14 demonstrated in a rat
study that ginger reversed a cisplatin-induced delay in gas-
tric emptying. That the Protein Group was not different from
the Control Group in terms of the symptoms reported in the
diary while the High Protein Group reported less nausea sug-
gests that ginger was not critical to the high protein meal’s
beneficial effects. However, the present study’s design does
not allow for such a conclusion to be firmly drawn. For in-
stance, there may have been a unique interaction effect of
high doses of protein and ginger on nausea.
CONCLUSIONS
Additional studies are needed to confirm the present re-
sults. There are several limitations of the study. The sample
of patients was small and widely variable in terms of can-
LEVINE ET AL.
cer types, the cytotoxic agents administered, and the
antiemetic medications prescribed. There was not an ade-
quate control group for the ginger component of the test
meals. In addition, a placebo meal that contained neither
protein nor ginger was not included in the design. Future
studies using randomized designs should aim to reduce the
impact of these limitations. Nevertheless, the present results
do suggest a therapeutic effect of this nutritionally based in-
tervention for the delayed nausea of cancer chemotherapy.
ACKNOWLEDGMENTS
This study was sponsored by Ross Products Division of
Abbott Laboratories, Columbus, OH. The authors wish to
thank the patients who participated in the study, and Drs.
Denise Levitan, Mebea Aklilu, Istvan Molnar, and Susan
Melin of the Comprehensive Cancer Center at Wake Forest
University Health Sciences for their assistance with the com-
pletion of this study.
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