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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),

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ARTICLE IN PRESS+Model

YCTIM-1440; No.of Pages9

Complementary Therapies in Medicine (2015) xxx, xxx—xxx

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Effects of inhaled ginger aromatherapy onchemotherapy-induced nausea andvomiting and health-related quality of lifein women with breast cancer

Pei Lin Luaa,∗

, Noor Salihahb

, Nik Mazlanc

a Community Health Research Cluster, Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA),

Kampus Gong Badak, 21300 Kuala Nerus, Terengganu, Malaysiab Faculty of Health Sciences, Universiti Sultan Zainal Abidin (UniSZA) , Kampus Gong Badak, 21300 Kuala

Nerus, Terengganu, Malaysiac 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

KEYWORDSAromatherapy;

Chemotherapy-

induced nausea

vomiting;

Ginger;

Zingiber officinale;

Essential oil

Summary

Objective: To assess the efficacy 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 aro-

matherapy treatment using either ginger essential oil or fragrance-matched artificial 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 profile (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 significantly lower after

ginger essential oil inhalation compared to placebo during acute phase (P = 0.040) but not sus-tained 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 significant effect

of aromatherapy on vomiting [F (1, 58) = 0.29, P = 0.594]. However, a statistically significant

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:[email protected], [email protected] (P.L. Lua).


0965-2299/© 2015 Elsevier Ltd. All rights reserved.

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2 P.L. Lua et al.

Conclusion: At present time, the evidence derived from this study is not sufficiently convincing

that inhaled ginger aromatherapy is an effective complementary therapy for CINV. The findings

for HRQoL were however encouraging with significant improvement in several domains.

© 2015 Elsevier Ltd. All rights reserved.

Introduction

Despite dramatic improvements in antiemetic control con-

ferred by 5-HT3 receptor antagonist, chemotherapy-induced

nausea and vomiting (CINV) remains the most worri-

some adverse effects of anti-neoplastic treatment.1,2 As

many as 80% of patients who received anthracycline-based

chemotherapy and cyclophosphamide; a commonly pre-

scribed adjuvant regimens for breast cancer, did experience

some degree of nausea and vomiting.3,4 Poorly controlled

CINV symptoms may result in multiple physiologic conse-

quences, pose impact on patient’s quality of life (QoL) and

alter patient’s compliance with treatment.5—7

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 escalat-

ing. 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 benefit 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 scientific 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 aromather-

apy remains controversial possibly due to lack of scientific

effectiveness and safety.

On the other side, ginger, the rhizome of Zingiber

officinale historically has been used in Asian countries, par-

ticularly in China and India for hundreds of years as a

remedy for conditions such as headaches, nausea, rheuma-

tism and colds. Primarily, gingerol is the pungent ketones

that is accountable for the strong aroma of ginger.12 Previous

studies have reported ginger’s effectiveness against nausea

in various conditions including motion sickness; pregnancy-

induced and post-operative nausea.12 In relation to CINV,most studies demonstrated favorable results but a few have

been contradictory.13 Although a firm 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 andlacks toxicity, the inhaled form has greater likelihood of

safety, but the efficacy has not been determined. This study,

therefore aims to determine the impact of aromatherapy

using ginger essential oil in alleviating CINV in breast can-

cer patients. Additionally, patients’ health-related quality

of life (HRQoL) profile 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 partic-

ipants 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 preven-

tion and management were conducted in accordance with

the standard chemotherapy protocol and patient’s 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 diag-

nosed with breast cancer; (3) were receiving chemotherapy

and experienced nausea and/or vomiting of any severity;

(4) had at least two remaining chemotherapy courses usingsimilar chemotherapeutic agents; (5) consenting to partici-

pate in the study. Excluded from this study included those

with other malignancies, being allergic to ginger, perfumes

or cosmetics or patients undergoing concurrent radiothe-

rapy. 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

Health’s (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 five days

during day and night. The aromatherapy necklace was a crys-

tal 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 filled with either two drops

of ginger essential oil or ginger fragrance oil (fragrance-

matched artificial placebo) depending on the randomization

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Effects of inhaled ginger aromatherapy 3

• •

• •

• •

Figure 1 CONSORT flow diagram.

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

provided with ginger fragrance oil (placebo) on their first

chemotherapy course, followed by ginger essential oil on

the next chemotherapy course. In contrary, patients who

were randomized into the Group 2 were first supplied with

ginger essential oil on their first 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 consecutivechemotherapy 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 autho-

rized 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 tex-

ture but the therapeutic values of fragrance oil may have

decreased substantially due to changes in the chemical

structure of the concentrated product (extract) and mixtureof 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

five days of aromatherapy intervention starting from the

first 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 chemother-

apy administration), during five 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 treat-

ment information were collected from patient medi-

cal records. Blinding assessment with three categorical

responses (‘believed had ginger essential’, ‘believed had

ginger fragrance’ or ‘did not know either ginger essen-

tial 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 vomitingA 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

defined 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 patient’s diary

card, complimented with the self-report on the frequency

of vomiting within 24 hour. Vomiting was defined as one or

more emetic episode. Episodes were considered different if

they were separated by at least one minute. The patients



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4 P.L. Lua et al.

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 45.9± 9.5 48.7± 8.9 47.3± 9.3

20—39 years 10 (33.3) 4 (13.3) 14 (23.3)

40—59 years 17 (56.7) 23 (76.7) 40 (66.7)60—79 years 3 (10.0) 3 (10.0) 6 (10.0)

Race

Malay 29 (96.7) 30 (100) 59 (98.3)

Other 1 (3.3) — 1 (1.7)

Years after diagnosis (month) 11.6± 12.7 12.0± 12.6 11.8± 12.5

≤1 years 24 (80.0) 23 (76.7) 47 (78.3)

>1 years 6 (20.0) 7 (23.3) 13 (21.7)

Family history of malignancy

Yes 7 (23.3) 15 (50.0) 22 (36.7)

No 21 (70.0) 14 (46.7) 35 (58.3)

Unsure 2 (6.7) 1 (3.3) 3 (5.0)

Breast cancer stage

Stage I 3 (10.0) 2 (6.7) 5 (8.3)

Stage II 18 (60.0) 17 (56.7) 35 (58.3)Stage III 7 (23.3) 8 (26.6) 15 (25.0)

Stage IV 2 (6.7) 3 (10.0) 5 (8.4)

Chemotherapy cycle

2 11 (36.6) 7 (23.3) 18 (30.0)

3 8 (26.7) 7 (23.3) 15 (25.0)

4 8 (26.7) 8 (26.7) 16 (26.7)

5 3 (10.0) 8 (26.7) 11 (18.3)

Chemotherapeutic agentsa

High (>90%) emetic risk

5-Flouracil + epirubicin + cyclophosphamide (FEC) 24 (80.0) 21 (70.0) 45 (75.0)

Docetaxel + doxorubicin and cyclophosphamide (TAC) 5 (16.7) 2 (6.7) 7 (11.7)

Low (10—30%) emetic risk

Docetaxel 1 (3.3) 7 (23.3) 8 (13.3)

Severity of nausea (averaged over time) 27.8± 18.1 26.4± 16.7 27.1± 17.3

Baseline HRQoL (Global health status of EORTC-30) 52.5± 8.8 51.1± 9.5 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 Day-

8 post-chemotherapy using the European Organization for

Research and Treatment of Cancer Quality of Life Ques-

tionnaire (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 five functional scales ( physical, emotional, cogni-

tive, social and role), three symptom scales ( fatigue, pain,

nausea and vomiting), a global health/HRQoL scale and six

single items assessing symptoms (dyspnea, sleep disturb-

ance, appetite loss, constipation, diarrhea) and financial

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 0—100 for each of the scales and sin-

gle 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 dif-

ference (common SD = 19—20) using VAS between the two

treatments with 90% power at the 5% significant 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 modified intention-to-treat approach

was applied for all efficacy 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) anal-

yses of variance with repeated measures were performed



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6 P.L. Lua et al.

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).

Adjusted mean (95% CI) F stat.a (df) P valuea

Ginger FO Ginger EO

Nausea, VAS score (mm)

Day 1 45.08 (36.27, 53.89) 38.98 (33.34, 44.63) Time (T):

Day 2 36.72 (28.00, 45.44) 36.09 (29.69, 42.49) 43.98 (1)


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8 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 findings, positive effects of ginger aromather-

apy was denoted in reducing post-operative nausea andvomiting (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 differ-

ent findings.

On the other hand, the lack of benefits from ginger

essential oil treatment for vomiting occurrences may be

explained by the fact that the administration of 5-HT3 recep-

tor antagonist class of anti-emetic may have significantly

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.22—24 Thus, this may have indicated that the

patients within the study may not have been experienc-

ing vomiting at a sufficiently high level of frequency to

have responded to the aromatherapy intervention. Previ-

ous literatures have also demonstrated that once a patient

undergoing chemotherapy experienced any form of nau-

sea and vomiting (whether anticipatory, acute or delayed),

regardless of the emetogenicity of the antineoplastic reg-

imen, the likelihood of that patient experiencing nausea

for the next chemotherapy cycle was significantly higher

and more difficult 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 pre-conditioning. 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 efficacy using gin-

ger 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 sub-

scales of EORTC QLQ-30 (i.e. role functioning, fatigue,

nausea and vomiting, pain and appetite loss) did show sta-tistically significant 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 aro-

matherapy which indicated that although aromatherapy

did not produce detectable effect using objective mea-

surements (i.e. numeric rating scores in pain), positive

subjective outcomes (i.e. patient satisfaction, HRQoL, expe-

rience 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

beneficial impacts on patient reported outcomes measures

such as HRQoL profile. Positive feedbacks by patients them-

selves 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 clini-

cally significant 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 mayplay 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 fol-

lowing 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 com-

mon side effect of 5TH3 anti-emetics. Since all patients

were prescribed with this prophylaxis medication before

chemotherapy and some received it as maintenance anti-

emetic therapy at home, this symptom may have manifested

within the limited HRQoL assessment period as this side

effect was unlikely to change in the first week after

chemotherapy.

Several limitations of this study deserve mention,

nonetheless. First, the severity of nausea before enrol-

ment 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 pre-

vious chemotherapy cycle. Second, although the patients

were blinded, the possibility of a placebo effect cannot

be ignored. Because of the distinct odor of ginger essen-tial 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 isnot sufficiently convincing that inhaled ginger aromatherapy

is an effective complementary therapy for CINV. The find-

ings for HRQoL were however encouraging with significant

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.

Conflict of interest statement

None declared.



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Effects of inhaled ginger aromatherapy 9

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 pro-

vided by the Universiti Sultan Zainal Abidin (Grant number:

UniSZA.B/2/KP9/628).

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