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Complementary Therapies in Medicine (2015) xxx, xxxxxx

Available online at www.sciencedirect.com

ScienceDirect
journal homepage: www.elsevierhealth.com/journals/ctim

Effects of inhaled ginger aromatherapy on

chemotherapy-induced nausea and
vomiting and health-related quality of life
in women with breast cancer
Pei Lin Lua a,, Noor Salihah b, Nik Mazlan c
a

Community Health Research Cluster, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA),
Kampus Gong Badak, 21300 Kuala Nerus, Terengganu, Malaysia
b
Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA) , Kampus Gong Badak, 21300 Kuala
Nerus, Terengganu, Malaysia
c
Kulliyyah of Allied Health Sciences, International Islamic University Malaysia (IIUM), Kuantan Campus,
25710 Kuantan, Pahang, Malaysia
Received 18 September 2014; received in revised form 31 December 2014; accepted 27 March 2015

KEYWORDS
Aromatherapy;
Chemotherapyinduced nausea
vomiting;
Ginger;
Zingiber ofcinale;
Essential oil

Summary
Objective: To assess the efcacy of inhaled ginger aromatherapy on nausea, vomiting and
health-related quality of life (HRQoL) in chemotherapy breast cancer patients.
Design: Single-blind, controlled, randomized cross-over study. Patients received 5-day aromatherapy treatment using either ginger essential oil or fragrance-matched articial placebo
(ginger fragrance oil) which was instilled in a necklace in an order dictated by the treatment
group sequence.
Setting: Two oncology clinics in the East Coast of Peninsular Malaysia.
Main outcome measures: VAS nausea score, frequency of vomiting and HRQoL prole (EORTC
QLQ-C30 scores).
Results: Sixty female patients completed the study (age = 47.3 9.26 years; Malay = 98.3%; on
highly emetogenic chemotherapy = 86.7%). The VAS nausea score was signicantly lower after
ginger essential oil inhalation compared to placebo during acute phase (P = 0.040) but not sustained for overall treatment effect (treatment effect: F = 1.82, P = 0.183; time effect: F = 43.98,
P < 0.001; treatment time effect: F = 2.04; P = 0.102). Similarly, there was no signicant effect
of aromatherapy on vomiting [F(1, 58) = 0.29, P = 0.594]. However, a statistically signicant
change from baseline for global health status (P < 0.001) was detected after ginger essential
oil inhalation. A clinically relevant 10 points improvement on role functioning (P = 0.002) and
appetite loss (P < 0.001) were also documented while patients were on ginger essential oil.

Corresponding author. Tel.: +60 9 6688520; fax: +60 9 6687896; mobile: +60 17 6228430.
E-mail addresses: peilinlua@unisza.edu.my, peilinlua@hotmail.com (P.L. Lua).

http://dx.doi.org/10.1016/j.ctim.2015.03.009
0965-2299/ 2015 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

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P.L. Lua et al.

Conclusion: At present time, the evidence derived from this study is not sufciently convincing
that inhaled ginger aromatherapy is an effective complementary therapy for CINV. The ndings
for HRQoL were however encouraging with signicant improvement in several domains.
2015 Elsevier Ltd. All rights reserved.

Introduction
Despite dramatic improvements in antiemetic control conferred by 5-HT3 receptor antagonist, chemotherapy-induced
nausea and vomiting (CINV) remains the most worrisome adverse effects of anti-neoplastic treatment.1,2 As
many as 80% of patients who received anthracycline-based
chemotherapy and cyclophosphamide; a commonly prescribed adjuvant regimens for breast cancer, did experience
some degree of nausea and vomiting.3,4 Poorly controlled
CINV symptoms may result in multiple physiologic consequences, pose impact on patients quality of life (QoL) and
alter patients compliance with treatment.57
In view of the gaps in the current practices, attention
given to the use of complementary and alternative medicine
(CAM) as an adjuvant treatment has recently been escalating. Aromatherapy is a particular kind of CAM widely used for
the purposes of inhalation of the vapors or absorption of the
oil into the skin, to treat or alleviate physical and emotional
symptoms.8 Early clinical trials suggest that aromatherapy
may have some benet as a complementary treatment in
reducing stress, pain, nausea, and depression.9 In cancer
populations, a recent study had stipulated that 47% (n = 21)
of nauseous oncology patients had settled the symptom
by using personalized aromatherapy inhalation device.10
A compilation of available scientic evidence related to
inhaled aromatherapy had also suggested that the inhaled
vapor of peppermint or ginger essential oil not only reduced
the incidence and severity of nausea and vomiting but also
decreased antiemetic requirements and improved patient
satisfaction.11 However, the therapeutic use of aromatherapy remains controversial possibly due to lack of scientic
effectiveness and safety.
On the other side, ginger, the rhizome of Zingiber
ofcinale historically has been used in Asian countries, particularly in China and India for hundreds of years as a
remedy for conditions such as headaches, nausea, rheumatism and colds. Primarily, gingerol is the pungent ketones
that is accountable for the strong aroma of ginger.12 Previous
studies have reported gingers effectiveness against nausea
in various conditions including motion sickness; pregnancyinduced and post-operative nausea.12 In relation to CINV,
most studies demonstrated favorable results but a few have
been contradictory.13 Although a rm conclusion cannot be
drawn from previous clinical studies, it is hypothesized that
the direct effect of ginger on the gastrointestinal tract
may be due to the aromatic, spasmolytic carminative and
absorbent properties of ginger.14 While the ingestion of
ginger was associated with minimal toxicity, it was not
without adverse effects. Mild gastrointestinal effects like
heart burn, diarrhea, and irritation of mouth were among
the uncommon side effects. Despite these minimal invasive
properties of ginger, previous studies have used the ingested
formulation of powdered or extract of ginger rather than

aromatherapy. If the ingested form of ginger is safe and

lacks toxicity, the inhaled form has greater likelihood of
safety, but the efcacy has not been determined. This study,
therefore aims to determine the impact of aromatherapy
using ginger essential oil in alleviating CINV in breast cancer patients. Additionally, patients health-related quality
of life (HRQoL) prole following aromatherapy treatment
was also assessed.

Methods
Study design and sample selection
A single-blind, randomized, controlled, cross-over study was
conducted in two oncology clinics whereby the study participants were recruited from Hospital Sultanah Nur Zahirah
(HSNZ), Kuala Terengganu and Hospital Raja Perempuan
Zainab II (HRPZ II), Kota Bharu, Kelantan, Malaysia. At each
center, standard procedures for nausea and emesis prevention and management were conducted in accordance with
the standard chemotherapy protocol and patients clinical
condition. Patients were eligible for this study if they met
the following selection criteria: (1) women aged 18 years
and above, with a normal sense of smell; (2) were diagnosed with breast cancer; (3) were receiving chemotherapy
and experienced nausea and/or vomiting of any severity;
(4) had at least two remaining chemotherapy courses using
similar chemotherapeutic agents; (5) consenting to participate in the study. Excluded from this study included those
with other malignancies, being allergic to ginger, perfumes
or cosmetics or patients undergoing concurrent radiotherapy. Patients were randomized using permuted block four
randomization with an allocation ratio 1:1. Permission to
conduct this study was obtained from Malaysia Ministry of
Healths (MOH) Research and Ethics Committee (MREC) (Ref.
no: (2) dlm.KKM/NIHSEC/08/0804/P11-42).

Intervention procedures
In addition to standard care, an aromatherapy necklace
(Murano glass, Mizitco Sdn. Bhd. Sungai Petani, Kedah,
Malaysia) was given to the patients to wear it for ve days
during day and night. The aromatherapy necklace was a crystal chamber like a small bottle pendant which was made
from glass which was hang around their neck, and placed
approximately 20 cm from their nose. On each day, patients
were asked to hold the necklace just under their nose and
breathe in deeply at least 3 times a day for at least 3 periods
of 2 min duration, even if they did not have symptoms. This
aromatherapy necklace was lled with either two drops
of ginger essential oil or ginger fragrance oil (fragrancematched articial placebo) depending on the randomization

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

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Effects of inhaled ginger aromatherapy

Figure 1

CONSORT ow diagram.

allocation sequence (Fig. 1). Patients in Group 1 was

provided with ginger fragrance oil (placebo) on their rst
chemotherapy course, followed by ginger essential oil on
the next chemotherapy course. In contrary, patients who
were randomized into the Group 2 were rst supplied with
ginger essential oil on their rst chemotherapy course,
and then were given placebo (ginger fragrance oil) for the
next treatment course. The wash-out period was estimated
around two weeks; the time gap between two consecutive
chemotherapy courses. Patients were instructed to remove
the necklace after the treatments were ended. Both ginger
essential oil and fragrance oil were obtained from Take It
Global Sdn. Bhd. Butterworth, Penang, Malaysia; an authorized essential oil dealer for Ungerer Australia PTY LTD.
While ginger essential oil is a naturally-occurring substance
found in ginger rhizome, the fragrance oil (placebo) is a
blend of aroma components that contains ginger oil extract
(a concentrated product) and synthetic materials (typically
the esters, aldehydes and ketones of various aromatics).
Basically, both oils were identical in appearance and texture but the therapeutic values of fragrance oil may have
decreased substantially due to changes in the chemical
structure of the concentrated product (extract) and mixture
of synthetic components.15 In terms of odor characteristics,
fragrance oil nearly always mimics those of natural essential
oil product yet it usually smells inferior when compared to
the pure essential oil.

Data collection
Every patient needed to complete two phases of study
periods (phase 1 and phase 2). One phase encompassed
ve days of aromatherapy intervention starting from the
rst day of chemotherapy treatment. Day-1 was denoted

as the day of chemotherapy administration. For every study

phase, data were collected at baseline (prior to chemotherapy administration), during ve days intervention period
(Day-1 till Day-5) as well as on Day-8 post-chemotherapy.
Questionnaires were distributed during the study visit and
collected and checked for missing data at the subsequent
visit.

Outcome measures
Baseline demographic, disease characteristics and treatment information were collected from patient medical records. Blinding assessment with three categorical
responses (believed had ginger essential, believed had
ginger fragrance or did not know either ginger essential or fragrance oil) was also completed by the patients.
Patients were asked to report any adverse events that
occurred during aromatherapy intervention period. The
following major outcomes were collected throughout the
study:
Severity of nausea and incidence of vomiting
A 100 mm visual analog scale (VAS) has been used to measure
the severity of nausea with the left end corresponding to no
nausea and the right to severe nausea.16 No nausea was
dened as VAS < 5 mm and a 10 mm difference was generally
considered clinically important.17 A total of three marks per
day were required as this instrument was to be completed
upon the administration of aromatherapy at 9am, 3pm and
lastly 9pm. This VAS was incorporated in the patients diary
card, complimented with the self-report on the frequency
of vomiting within 24 hour. Vomiting was dened as one or
more emetic episode. Episodes were considered different if
they were separated by at least one minute. The patients

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

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Table 1

Patients baseline data at the time of enrolment.

Characteristics

Ginger FO/ginger
EO (n = 30),
Group 1

Ginger EO/ginger
FO (n = 30),
Group 2

All patients
(n = 60)

Age
2039 years
4059 years
6079 years
Race
Malay
Other
Years after diagnosis (month)
1 years
>1 years
Family history of malignancy
Yes
No
Unsure
Breast cancer stage
Stage I
Stage II
Stage III
Stage IV
Chemotherapy cycle
2
3
4
5
Chemotherapeutic agentsa
High (>90%) emetic risk
5-Flouracil + epirubicin + cyclophosphamide (FEC)
Docetaxel + doxorubicin and cyclophosphamide (TAC)
Low (1030%) emetic risk
Docetaxel
Severity of nausea (averaged over time)
Baseline HRQoL (Global health status of EORTC-30)

45.9 9.5
10 (33.3)
17 (56.7)
3 (10.0)

48.7 8.9
4 (13.3)
23 (76.7)
3 (10.0)

47.3 9.3
14 (23.3)
40 (66.7)
6 (10.0)

29 (96.7)
1 (3.3)
11.6 12.7
24 (80.0)
6 (20.0)

30 (100)

12.0 12.6
23 (76.7)
7 (23.3)

59 (98.3)
1 (1.7)
11.8 12.5
47 (78.3)
13 (21.7)

7 (23.3)
21 (70.0)
2 (6.7)

15 (50.0)
14 (46.7)
1 (3.3)

22 (36.7)
35 (58.3)
3 (5.0)

3 (10.0)
18 (60.0)
7 (23.3)
2 (6.7)

2 (6.7)
17 (56.7)
8 (26.6)
3 (10.0)

5 (8.3)
35 (58.3)
15 (25.0)
5 (8.4)

11 (36.6)
8 (26.7)
8 (26.7)
3 (10.0)

7 (23.3)
7 (23.3)
8 (26.7)
8 (26.7)

18 (30.0)
15 (25.0)
16 (26.7)
11 (18.3)

24 (80.0)
5 (16.7)

21 (70.0)
2 (6.7)

45 (75.0)
7 (11.7)

1 (3.3)
27.8 18.1
52.5 8.8

7 (23.3)
26.4 16.7
51.1 9.5

8 (13.3)
27.1 17.3
51.8 9.1

Data are presented as number and percentage (%) or mean SD, unless otherwise indicated.
a American Society of Clinical Oncology (ASCO) guidelines.20

reported the nausea and emetic events in this diary card up

to Day-5 post-chemotherapy.

Health-related quality of life (HRQoL)

The impact of CINV on patients HRQoL was assessed at
baseline (before chemotherapy administration) and Day8 post-chemotherapy using the European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).18 The translated and validated
version of EORTC QLQ C-30 in the Malay language was
adapted in this study.19 This questionnaire contains 30 items
including ve functional scales (physical, emotional, cognitive, social and role), three symptom scales (fatigue, pain,
nausea and vomiting), a global health/HRQoL scale and six
single items assessing symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea) and nancial
impact of disease. The scoring of the EORTC QLQ-C30 was
performed in accordance with the EORTC scoring manual.
The raw scores were linearly transformed to obtain standard

scores in the range of 0100 for each of the scales and single items. A high scale score represented a higher response
level.

Statistical analysis
The planned sample size was 60 patients (30 per sequence)
which was considered large enough to detect a 10 mm difference (common SD = 1920) using VAS between the two
treatments with 90% power at the 5% signicant level. The
Statistical Package for the Social Science (SPSS) Version 16.0
(SPSS Inc., Chicago, IL, USA) was used for data compilation
and statistical analysis. Descriptive statistics and parametric
test were applied. The modied intention-to-treat approach
was applied for all efcacy analysis whereby only patients
who had completed all study phases and received both
inhaled ginger essential oil and ginger fragrance oil were
included in the analysis. Two-factor (group and time) analyses of variance with repeated measures were performed

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

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0.736
0.440
0.760
0.709
0.083
0.34)
0.13)
0.18)
0.07)
0.01)
(0.24,
(0.29,
(0.25,
(0.11,
(0.11,
0.05
0.08
0.03
0.02
0.05
3.59
2.87
2.53
1.58
0.91

2.08
1.42
0.78
0.28
0.13
3.22
3.01
2.34
1.38
1.05

2.03
1.50
0.82
0.30
0.18
2.77
2.66
2.02
0.40
0.18

2.07
1.43
0.73
0.10
0.03

Data are mean SD, unless otherwise indicated. Bold values shows the signicant difference, P < 0.05.
a Independent t-test; signicant at P < 0.05.
b Paired t-test; signicant at P < 0.05.

2.59
2.69
1.73
0.53
0.31

2.07
1.33
0.60
0.17
0.10
4.30
3.10
2.98
2.20
1.28

2.10
1.40
0.83
0.47
0.23

(7.76,
(2.44,
(1.87,
(2.57,
(2.56,
3.97
0.21
0.46
0.80
1.07
21.65
24.60
20.58
14.58
10.68

38.98
36.09
27.34
17.16
11.24
38.83
34.44
28.04
17.77
10.63

22.83
24.70
21.26
15.94
11.12

40.82
35.88
25.98
18.17
12.76

22.69
25.42
20.79
17.16
13.74

42.95
36.30
26.88
17.96
12.31

24.82
23.98
20.92
16.49
13.34

60
60
30
30

0.343
0.869
0.832
0.754
0.994
20.79
24.81
20.21
13.32
10.37

0.938
0.766
0.638
0.348
0.389

0.17) 0.040
2.03)
0.851
2.79)
0.696
0.97)
0.370
0.41)
0.157

Pb
Mean diff. (95%CI)
Ginger EO (group 1)

Ginger FO (group 2)

Ginger FO

Ginger EO

Treatment effect

P
30

39.13
37.74
26.64
16.54
11.84

When looking at the trend of symptoms, nausea level

was mostly a little bit lower over ve days of treatment
period when treated with ginger EO as compared to ginger
FO (Table 2). However, based on univariate analyses, the
treatment effect was only predominantly observed during
acute phase as signicant difference in VAS nausea score
between two treatment groups was only detected on Day-1
(P = 0.040). If between-group comparison was made, the VAS
nausea score on Day-1 was lower in ginger essential oil group
than ginger fragrance oil group as being observed during
phase 1 of the study, but the difference was not signicant.
During delayed phase (Day-2 till Day-5), VAS nausea scores
were comparable in both treatment groups. Also, there was

n
30
Nausea, VAS score (mm)
Day-1 45.08 27.01
Day-2 36.72 22.87
Day-3 27.79 21.36
Day-4 17.74 16.07
Day-5 11.87 13.14
Vomiting, (frequency)
Day-1
2.00 3.79
1.67 3.34
Day-2
1.03 2.83
Day-3
0.43 1.89
Day-4
0.27 1.46
Day-5

Severity of nausea and incidence of vomiting

Ginger EO (group 2)

The baseline characteristics were equivalent across treatment groups (Table 1). The majority of patients were Malay
with a mean age of 47 years. Patients were predominantly
in early stage of disease (stage I and II) (66.6%) and were
receiving highly emetogenic chemotherapy (anthracycline
and cyclophosphamide combinations) (86.7%). At baseline,
no statistically signicant mean difference between the two
groups for severity of nausea and HRQoL prole (data not
shown in tabular form). The attempt to blind the patients
was almost 100% effective except for four patients (6.7%)
in each treatment group who could somehow detect which
type of treatment they have actually received.
On the days of chemotherapy, all patients were prescribed the standard antiemetics; intravenous granisetron
(3 mg) and dexamethasone (8 mg) before treatment. After
chemotherapy, medication home treatment for CINV
included anti-emetic prophylaxis containing oral granisetron
(1 mg twice a day from Day-1 to Day-2), oral dexamethasone
(4 mg three times a day from Day-1 to Day-4) and oral metoclopramide (10 mg three times a day from Day-3 to Day-6).

Ginger FO (group 1)

Socio-demographic and clinical characteristics

Treatment mode

From December 2011 to January 2014, a total of 145 of

breast cancer patients undergoing chemotherapy treatment
were screened, of whom 99 met all eligibility criteria. Of
these 99 patients, 24 refused to participate and 75 patients
were enrolled and randomized: 37 to the Group 1 and 38
to the Group 2. Fig. 1 depicts the recruitment process of
potential participants and reasons for exclusions and discontinuing the participation. Overall, 30 patients from each
groups completed all study visits providing a total of 60
evaluable patients for data analysis.

Phase 2

Screening, enrolment, and withdrawals

Results

Phase 1

on the continuous outcome variables (VAS nausea score,

frequency of vomiting and HRQoL prole) comparing differences between ginger essential oil (study group) and ginger
fragrance oil (placebo group) taking treatment sequence
into account. The Bonferroni adjustment was used when
necessary and signicant level was xed at 0.05.

5
Table 2 Comparison of VAS nausea score and frequency of vomiting between ginger essential oil (EO) and ginger fragrance oil (FO) at each study phase (phase 1 and 2) and
treatment effect.

Effects of inhaled ginger aromatherapy

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

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Table 3 Two-factor analyses of variance with repeated measure on VAS nausea score and frequency of vomiting comparing
differences between ginger essential oil (EO) and ginger fragrance oil (FO).
F stat.a (df)

Adjusted mean (95% CI)

Ginger FO
Nausea, VAS score (mm)
Day 1
45.08 (36.27, 53.89)
Day 2
36.72 (28.00, 45.44)
Day 3
27.79 (20.19, 35.39)
Day 4
17.75 (12.35, 23.14)
Day 5
11.87 (7.54, 16.19)
Vomiting, (frequency)
Day 1
Day 2
Day 3
Day 4
Day 5

2.03
1.50
0.82
0.30
0.18

(1.19, 2.87)
(0.72, 2.28)
(0.21, 1.42)
(0.06, 0.66)
(0.09, 0.46)

P valuea

Ginger EO
38.98
36.09
27.34
17.16
11.24

2.08
1.42
0.78
0.28
0.13

(33.34, 44.63)
(29.69, 42.49)
(21.98, 32.71)
(13.36, 20.95)
(8.46, 14.02)

(1.15, 3.02)
(0.67, 2.16)
(0.13, 1.44)
(0.13, 0.69)
(0.10, 0.37)

Time (T):
43.98 (1)
G* T
2.04 (4)
Group (G):
1.82 (1)
Time (T):
9.58 (1)
G* T
0.19 (4)
Group (G):
0.29 (1)

<0.001
0.102
0.183

<0.001
0.942
0.594

Bold values shows the signicant difference, P < 0.05.

a Repeated measure ANOVA.

no signicant difference in vomiting occurrences detected

during any days of aromatherapy treatment period.

Effects of aromatherapy on severity of nausea and

incidence of vomiting
Analyses of data using repeated measure ANOVA showed
that there was no signicant mean difference of VAS nausea scores between ginger essential oil and ginger fragrance
oil [F(1, 58) = 1.82, P = 0.183] indicating that there was
no signicant effect of aromatherapy on nausea severity
(Table 3). However, there were signicant reduction in VAS
nausea score with time with ginger essential oil inhalation
[F(1, 58) = 43.98, P < 0.001]. Similarly, there was no significant effect of aromatherapy treatment on vomiting [F(1,
58) = 0.29, P = 0.594]. There were signicant differences in
the incidence of vomiting over ve days treatment period
[F(4, 55) = 9.58, P < 0.001]. For all the aforementioned analyses, there was no signicant interaction between time
and treatment groups as well as between time and treatment sequence. Overall, no signicant mean difference by
treatment sequence was detected. No major adverse events
from the aromatherapy intervention were reported during
the study. Only one person withdrew after complaining of
having very mild dizziness or light-headedness on Day-5 of
aromatherapy treatment with ginger essential oil.

Effects of aromatherapy on HRQoL prole

Table 4 shows EORTC QLQ-30 subscale scores at baseline and
after inhaled ginger aromatherapy treatment. There were
signicant changes in the following HRQoL subscales score
over three time-points (baseline, after ginger essential oil
and after ginger fragrance oil namely global health status
(P < 0.001), role functioning (P = 0.001), fatigue (P = 0.002),
nausea and vomiting (P < 0.001), pain (P = 0.017), appetite

loss (P < 0.001) and constipation (P = 0.046) (Table 4). There

was no evidence of a sequence by time interaction for any
of the HRQoL domains; hence the change from the baseline for each domain was assessed. Post hoc tests using
the Bonferroni correction showed that a statistically significant change from baseline for global health status (95%
CI mean difference; 4.12, 9.77, P < 0.001) was detected
after ginger essential oil inhalation. Conversely, signicant
improvements from baseline for role functioning were noted
in both groups; ginger essential oil (95% CI mean difference; 3.08, 16.92, P = 0.002) and ginger fragrance oil (95%
CI mean difference; 1.96, 14.15, P = 0.006). Even so, better
score increment was noted with ginger essential oil applications. For symptom scale scores, fatigue (95% CI mean
difference; 10.98, 2.35, P = 0.001), nausea and vomiting (95% CI mean difference; 9.07, 2.59, P < 0.001),
pain (95% CI mean difference; 10.16, 0.95, P = 0.013)
and appetite loss (95% CI mean difference; 16.87, 5.36,
P < 0.001) were signicantly reported to have been reduced
while patients were on ginger essential oil. Interestingly, two
domains managed to acquire the level considered clinically
relevant of 10 points difference for EORTC QLQ-30, which
were role functioning and appetite loss. Unexpectedly, the
symptom score of constipation was reported higher than the
baseline value for both groups but the difference in the score
was signicant between baseline and after the use of ginger
fragrance oil (95% CI mean difference; 0.12, 6.55, P = 0.040).

Discussions
To the best of our knowledge, this is the rst clinical aromatherapy investigation using a randomized clinical trial
of crossover design to elucidate the effect of inhaled ginger essential oil on alleviating CINV in an Asian population.
The results of this study demonstrated that aromatherapy
administered as inhaled ginger essential oil for ve days

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

Treatment mode

Treatment effect

Ginger FO
Post-8 day score
Global health status
Functioning
Physical functioning
Role functioning
Emotional functioning
Cognitive functioning
Social functioning

Symptoms/items
Fatigue
Nausea and Vomiting
Pain
Dyspnea
Insomnia
Appetite loss
Constipation
Diarrhea
Financial difculties

51.81 9.09

54.31 10.68

Change from baseline

Change from baseline

2.5 10.21

58.75 9.76

6.94 8.84a

4.44 (1.13, 7.76)

Pb

ARTICLE IN PRESS

Post-8 day score

Adjusted for
treatment
sequence

Ginger EO

<0.001

76.00
49.17
69.72
90.83
97.50

16.93
2.14
18.73
18.77
10.55

45.56 19.91
6.67 10.27
36.39 17.49
5.00 13.48
20.56 28.85
25.00 26.49
7.22 16.34
1.67 7.33
16.67 30.38

16.83
23.24
29.21
19.46
12.08

0.78
8.06
3.19
0.83
0.56

9.36
19.04a
21.97
12.44
3.02

75.11
59.17
68.19
91.11
97.50

19.32
24.82
24.04
18.53
10.55

0.89 10.52
10.00 21.74a
1.53 19.13
0.28 12.08

0.11 (2.99, 2.77)

1.94 (5.35, 9.24)
1.67 (7.28, 10.61)
1.11 (2.13, 4.35)
0.56 (0.41, 1.52)

42.04 22.32
4.44 12.22
33.61 18.28
5.56 13.95
25.00 30.45
20.56 26.10
10.56 18.91
2.22 8.38
14.44 29.02

3.52
2.22
2.78
0.56
4.44
4.44
3.33
0.56
2.22

14.39
9.44
10.70
9.69
19.86
14.35
10.08
7.49
16.08

38.89
0.83
30.83
5.00
21.67
13.89
8.89
1.67
17.78

23.28
3.66
18.87
14.81
28.67
24.77
18.27
7.33
29.73

6.67 13.45 a
5.83 10.09a
5.56 14.61a
3.33 15.89
1.11 20.32
11.11 18.07a
1.67 15.56

1.11 20.32

3.15 (8.06, 1.77)

3.61 (7.51, 0. 29)
2.78 (6.59, 1.03)
0.56 (2.96, 1.84)
3.33 (10.07, 3.40)
6.67 (12.50, 0.83)
1.67 (6.25, 2.92)
0.56 (2.96, 1.84)
3.33 (2.12, 8.79)

75.22
57.22
66.53
90.00
96.94

+Model

Baseline score

YCTIM-1440; No. of Pages 9

Scale/item

Effects of inhaled ginger aromatherapy

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

Table 4 Mean score changes in the EORTC QLQ-C30 subscale between ginger essential oil (EO) and ginger fragrance oil (FO) from post-8 day treatment to baseline and overall
treatment effect.

0.764
0.001
0.471
0.697
0.163
0.002
<0.001
0.017
0.839
0.222
<0.001
0.046
0.570
0.265

Data are mean SD, unless otherwise indicated. Bold values shows the signicant difference, P < 0.05.
* Score range 0100 = higher score indicates better HRQoL.
Score range 0100 = higher score indicates worse HRQoL.
Data for treatment effect are mean differences (95% CI) adjusted for treatment sequence assuming no carry over.
a P < 0.05 for change from baseline.
b Two-way mixed design repeated measure ANOVA was applied. No signicant interaction between treatment sequence and time (P > 0.05). Overall, no signicant mean difference by
treatment sequence was detected.

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P.L. Lua et al.

had limited effects in reducing CINV except for alleviating

acute nausea. Despite frequent reports on aromatherapy
intervention, limited literature was available to make
explicit comparisons. The only study involving the test of
ginger aromatherapy alone was reported by Geiger,21 using
combined applications (naso-cutaneous) to treat nausea
and vomiting induced by anesthesia exposure. Contrary to
the present ndings, positive effects of ginger aromatherapy was denoted in reducing post-operative nausea and
vomiting (PONV) using naso-cutaneous application. Geiger21
reported that 80% of high-risk patients had no complaints
of PONV after treated with 5% ginger essential oil in the
post-anesthesia recovery unit. Difference in condition and
methods of application could be the reason for these different ndings.
On the other hand, the lack of benets from ginger
essential oil treatment for vomiting occurrences may be
explained by the fact that the administration of 5-HT3 receptor antagonist class of anti-emetic may have signicantly
decreased the episode of vomiting as it was rated as low
at all-time points. These anti-emetics are also reported to
be more clinically effective against emesis than they are
against nausea.2224 Thus, this may have indicated that the
patients within the study may not have been experiencing vomiting at a sufciently high level of frequency to
have responded to the aromatherapy intervention. Previous literatures have also demonstrated that once a patient
undergoing chemotherapy experienced any form of nausea and vomiting (whether anticipatory, acute or delayed),
regardless of the emetogenicity of the antineoplastic regimen, the likelihood of that patient experiencing nausea
for the next chemotherapy cycle was signicantly higher
and more difcult to treat even with standard anti-emetic
medication.25 Since this study only included patients who
had previously experienced CINV, they might have had
an increased resistance to the intervention due to preconditioning. This is of particular concern since this study
adopted a crossover design, patients who were initially
in the control group could have established resistance to
the aromatherapy intervention before being subsequently
crossed over. Moreover, delayed symptoms also occur more
frequently with highly emetogenic chemotherapy and are
less responsive to treatment than prevention26 suggesting
possible reasons on the lack of treatment efcacy using ginger essential oil upon delayed symptoms especially in a study
that include a major proportion of patients receiving highly
emetogenic regimens.
It is of interest that Global HRQoL and several subscales of EORTC QLQ-30 (i.e. role functioning, fatigue,
nausea and vomiting, pain and appetite loss) did show statistically signicant improvements from baseline following
ginger essential oil inhalation even after limited decrease
of VAS nausea scores (except for acute phase). This result
is congruent with most previous works27,28 related to aromatherapy which indicated that although aromatherapy
did not produce detectable effect using objective measurements (i.e. numeric rating scores in pain), positive
subjective outcomes (i.e. patient satisfaction, HRQoL, experience of pain) were commonly reported by the patients.
Thus, it is possible to suggest that even a relatively low
amount of reduction on the severity of nausea may exert
benecial impacts on patient reported outcomes measures

such as HRQoL prole. Positive feedbacks by patients themselves could be of particular concern and seemed to be of
more importance as they came directly from the patients,
without peripheral interpretation from clinician or anyone
else.29 Moreover, two domains reached a minimal clinically signicant change of 10 points from the baseline
scores after application of ginger essential oil i.e. role
functioning (increased) and appetite loss (more markedly
reduced). A reduction in chemotherapy-induced nausea may
play a role in the reported improvements in these two
domains as patients would feel better to perform their
individual works or responsibilities and help them to enjoy
their foods. It is also possible that, as the chemotherapy
session progressed, patients experienced better HRQoL following their psychological adjustment as the ability to cope
with disease, treatment and effects of treatment would
have been improved after completing several chemotherapy
cycles.30,31
Additionally, there was an increase in constipation after
both ginger essential oil and FO interventions. The most
likely explanation of the increase might be due to the common side effect of 5TH3 anti-emetics. Since all patients
were prescribed with this prophylaxis medication before
chemotherapy and some received it as maintenance antiemetic therapy at home, this symptom may have manifested
within the limited HRQoL assessment period as this side
effect was unlikely to change in the rst week after
chemotherapy.
Several limitations of this study deserve mention,
nonetheless. First, the severity of nausea before enrolment was not evaluated. We assumed that the severity of
nausea was almost similar across the groups as patients
were only enrolled after they reported nausea from a previous chemotherapy cycle. Second, although the patients
were blinded, the possibility of a placebo effect cannot
be ignored. Because of the distinct odor of ginger essential oil, some of the patients who had experienced using
aromatherapy may have recognized the ginger essential oil
perfume. However, the attempt to blind the patients was
quite successful, achieving 93.3% effectiveness. Anyhow,
further exploration on how un-blinded patients detected
treatment allocation either through special characterization
of the oils or probably occurred by chance could additionally
provide better insight.

Conclusions
At the present time, the evidence derived from this study is
not sufciently convincing that inhaled ginger aromatherapy
is an effective complementary therapy for CINV. The ndings for HRQoL were however encouraging with signicant
improvement in several domains following this intervention.
The conduct of future studies with an additional control arm
(no treatment) would permit a more accurate comparison of
aromatherapy treatment for the prevention of CINV.

Conict of interest statement

None declared.

Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009

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Effects of inhaled ginger aromatherapy

Acknowledgements
The authors are grateful to the Director General of Health,
staff, respondents and patients of HSNZ and HRPZ II as
well as those who have helped facilitate the process of
this study. Financial support for this project was provided by the Universiti Sultan Zainal Abidin (Grant number:
UniSZA.B/2/KP9/628).

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Please cite this article in press as: Lua PL, et al. Effects of inhaled ginger aromatherapy on chemotherapy-induced
nausea and vomiting and health-related quality of life in women with breast cancer. Complement Ther Med (2015),
http://dx.doi.org/10.1016/j.ctim.2015.03.009