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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
Available online 21 April 2015
KEYWORDS Summary
Objective: To assess the efcacy of inhaled ginger aromatherapy on nausea, vomiting and
Aromatherapy;
health-related quality of life (HRQoL) in chemotherapy breast cancer patients.
Chemotherapy-
Design: Single-blind, controlled, randomized cross-over study. Patients received 5-day aro-
induced nausea
matherapy treatment using either ginger essential oil or fragrance-matched articial placebo
vomiting;
(ginger fragrance oil) which was instilled in a necklace in an order dictated by the treatment
Ginger;
group sequence.
Zingiber ofcinale;
Setting: Two oncology clinics in the East Coast of Peninsular Malaysia.
Essential oil
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 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 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.
Effects of inhaled ginger aromatherapy 397
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
aromatherapy. If the ingested form of ginger is safe and
Despite dramatic improvements in antiemetic control con- lacks toxicity, the inhaled form has greater likelihood of
ferred by 5-HT3 receptor antagonist, chemotherapy-induced safety, but the efcacy has not been determined. This study,
nausea and vomiting (CINV) remains the most worri- therefore aims to determine the impact of aromatherapy
some adverse effects of anti-neoplastic treatment.1,2 As using ginger essential oil in alleviating CINV in breast can-
many as 80% of patients who received anthracycline-based cer patients. Additionally, patients health-related quality
chemotherapy and cyclophosphamide; a commonly pre- of life (HRQoL) prole following aromatherapy treatment
scribed adjuvant regimens for breast cancer, did experience was also assessed.
some degree of nausea and vomiting.3,4 Poorly controlled
CINV symptoms may result in multiple physiologic conse- Methods
quences, pose impact on patients quality of life (QoL) and
alter patients compliance with treatment.57 Study design and sample selection
In view of the gaps in the current practices, attention
given to the use of complementary and alternative medicine
A single-blind, randomized, controlled, cross-over study was
(CAM) as an adjuvant treatment has recently been escalat-
conducted in two oncology clinics whereby the study partic-
ing. Aromatherapy is a particular kind of CAM widely used for
ipants were recruited from Hospital Sultanah Nur Zahirah
the purposes of inhalation of the vapors or absorption of the
(HSNZ), Kuala Terengganu and Hospital Raja Perempuan
oil into the skin, to treat or alleviate physical and emotional
Zainab II (HRPZ II), Kota Bharu, Kelantan, Malaysia. At each
symptoms.8 Early clinical trials suggest that aromatherapy
center, standard procedures for nausea and emesis preven-
may have some benet as a complementary treatment in
tion and management were conducted in accordance with
reducing stress, pain, nausea, and depression.9 In cancer
the standard chemotherapy protocol and patients clinical
populations, a recent study had stipulated that 47% (n = 21)
condition. Patients were eligible for this study if they met
of nauseous oncology patients had settled the symptom
the following selection criteria: (1) women aged 18 years
by using personalized aromatherapy inhalation device.10
and above, with a normal sense of smell; (2) were diag-
A compilation of available scientic evidence related to
nosed with breast cancer; (3) were receiving chemotherapy
inhaled aromatherapy had also suggested that the inhaled
and experienced nausea and/or vomiting of any severity;
vapor of peppermint or ginger essential oil not only reduced
(4) had at least two remaining chemotherapy courses using
the incidence and severity of nausea and vomiting but also
similar chemotherapeutic agents; (5) consenting to partici-
decreased antiemetic requirements and improved patient
pate in the study. Excluded from this study included those
satisfaction.11 However, the therapeutic use of aromather-
with other malignancies, being allergic to ginger, perfumes
apy remains controversial possibly due to lack of scientic
or cosmetics or patients undergoing concurrent radiothe-
effectiveness and safety.
rapy. Patients were randomized using permuted block four
On the other side, ginger, the rhizome of Zingiber
randomization with an allocation ratio 1:1. Permission to
ofcinale historically has been used in Asian countries, par-
conduct this study was obtained from Malaysia Ministry of
ticularly in China and India for hundreds of years as a
Healths (MOH) Research and Ethics Committee (MREC) (Ref.
remedy for conditions such as headaches, nausea, rheuma-
no: (2) dlm.KKM/NIHSEC/08/0804/P11-42).
tism 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 Intervention procedures
in various conditions including motion sickness; pregnancy-
induced and post-operative nausea.12 In relation to CINV, In addition to standard care, an aromatherapy necklace
most studies demonstrated favorable results but a few have (Murano glass, Mizitco Sdn. Bhd. Sungai Petani, Kedah,
been contradictory.13 Although a rm conclusion cannot be Malaysia) was given to the patients to wear it for ve days
drawn from previous clinical studies, it is hypothesized that during day and night. The aromatherapy necklace was a crys-
the direct effect of ginger on the gastrointestinal tract tal chamber like a small bottle pendant which was made
may be due to the aromatic, spasmolytic carminative and from glass which was hang around their neck, and placed
absorbent properties of ginger.14 While the ingestion of approximately 20 cm from their nose. On each day, patients
ginger was associated with minimal toxicity, it was not were asked to hold the necklace just under their nose and
without adverse effects. Mild gastrointestinal effects like breathe in deeply at least 3 times a day for at least 3 periods
heart burn, diarrhea, and irritation of mouth were among of 2 min duration, even if they did not have symptoms. This
the uncommon side effects. Despite these minimal invasive aromatherapy necklace was lled with either two drops
properties of ginger, previous studies have used the ingested of ginger essential oil or ginger fragrance oil (fragrance-
formulation of powdered or extract of ginger rather than matched articial placebo) depending on the randomization
398 P.L. Lua et al.
allocation sequence (Fig. 1). Patients in Group 1 was as the day of chemotherapy administration. For every study
provided with ginger fragrance oil (placebo) on their rst phase, data were collected at baseline (prior to chemother-
chemotherapy course, followed by ginger essential oil on apy administration), during ve days intervention period
the next chemotherapy course. In contrary, patients who (Day-1 till Day-5) as well as on Day-8 post-chemotherapy.
were randomized into the Group 2 were rst supplied with Questionnaires were distributed during the study visit and
ginger essential oil on their rst chemotherapy course, collected and checked for missing data at the subsequent
and then were given placebo (ginger fragrance oil) for the visit.
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
Outcome measures
the necklace after the treatments were ended. Both ginger
essential oil and fragrance oil were obtained from Take It Baseline demographic, disease characteristics and treat-
Global Sdn. Bhd. Butterworth, Penang, Malaysia; an autho- ment information were collected from patient medi-
rized essential oil dealer for Ungerer Australia PTY LTD. cal records. Blinding assessment with three categorical
While ginger essential oil is a naturally-occurring substance responses (believed had ginger essential, believed had
found in ginger rhizome, the fragrance oil (placebo) is a ginger fragrance or did not know either ginger essen-
blend of aroma components that contains ginger oil extract tial or fragrance oil) was also completed by the patients.
(a concentrated product) and synthetic materials (typically Patients were asked to report any adverse events that
the esters, aldehydes and ketones of various aromatics). occurred during aromatherapy intervention period. The
Basically, both oils were identical in appearance and tex- following major outcomes were collected throughout the
ture but the therapeutic values of fragrance oil may have study:
decreased substantially due to changes in the chemical
structure of the concentrated product (extract) and mixture Severity of nausea and incidence of vomiting
of synthetic components.15 In terms of odor characteristics, A 100 mm visual analog scale (VAS) has been used to measure
fragrance oil nearly always mimics those of natural essential the severity of nausea with the left end corresponding to no
oil product yet it usually smells inferior when compared to nausea and the right to severe nausea.16 No nausea was
the pure essential oil. 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
Data collection upon the administration of aromatherapy at 9am, 3pm and
lastly 9pm. This VAS was incorporated in the patients diary
Every patient needed to complete two phases of study card, complimented with the self-report on the frequency
periods (phase 1 and phase 2). One phase encompassed of vomiting within 24 hour. Vomiting was dened as one or
ve days of aromatherapy intervention starting from the more emetic episode. Episodes were considered different if
rst day of chemotherapy treatment. Day-1 was denoted they were separated by at least one minute. The patients
Effects of inhaled ginger aromatherapy 399
reported the nausea and emetic events in this diary card up scores in the range of 0100 for each of the scales and sin-
to Day-5 post-chemotherapy. gle items. A high scale score represented a higher response
level.
0.17) 0.040
0.851
0.696
0.370
0.157
0.736
0.440
0.760
0.709
0.083
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
frequency of vomiting and HRQoL prole) comparing differ-
Pb
ences between ginger essential oil (study group) and ginger
fragrance oil (placebo group) taking treatment sequence
2.03)
2.79)
0.97)
0.41)
0.34)
0.13)
0.18)
0.07)
0.01)
into account. The Bonferroni adjustment was used when
(7.76,
(2.44,
(1.87,
(2.57,
(2.56,
(0.24,
(0.29,
(0.25,
(0.11,
(0.11,
Results
3.97
0.21
0.46
0.80
1.07
0.05
0.08
0.03
0.02
0.05
Screening, enrolment, and withdrawals
21.65
24.60
20.58
14.58
10.68
From December 2011 to January 2014, a total of 145 of
3.59
2.87
2.53
1.58
0.91
breast cancer patients undergoing chemotherapy treatment
Ginger EO
were screened, of whom 99 met all eligibility criteria. Of
60
38.98
36.09
27.34
17.16
11.24
2.08
1.42
0.78
0.28
0.13
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
Treatment mode
24.82
23.98
20.92
16.49
13.34
potential participants and reasons for exclusions and dis-
3.22
3.01
2.34
1.38
1.05
continuing the participation. Overall, 30 patients from each
Ginger FO
groups completed all study visits providing a total of 60
60
42.95
36.30
26.88
17.96
12.31
2.03
1.50
0.82
0.30
0.18
evaluable patients for data analysis.
Ginger FO (group 2)
The baseline characteristics were equivalent across treat-
22.69
25.42
20.79
17.16
13.74
2.59
2.69
1.73
0.53
0.31
ment groups (Table 1). The majority of patients were Malay
with a mean age of 47 years. Patients were predominantly
Data are mean SD, unless otherwise indicated. Bold values shows the signicant difference, P < 0.05.
in early stage of disease (stage I and II) (66.6%) and were
30
40.82
35.88
25.98
18.17
12.76
2.07
1.33
0.60
0.17
0.10
receiving highly emetogenic chemotherapy (anthracycline
and cyclophosphamide combinations) (86.7%). At baseline,
no statistically signicant mean difference between the two
Ginger EO (group 1)
4.30
3.10
2.98
2.20
1.28
was almost 100% effective except for four patients (6.7%)
in each treatment group who could somehow detect which
Phase 2
30
2.10
1.40
0.83
0.47
0.23
On the days of chemotherapy, all patients were pre-
scribed the standard antiemetics; intravenous granisetron
(3 mg) and dexamethasone (8 mg) before treatment. After
0.343
0.869
0.832
0.754
0.994
0.938
0.766
0.638
0.348
0.389
chemotherapy, medication home treatment for CINV
a
P
39.13
37.74
26.64
16.54
11.84
2.07
1.43
0.73
0.10
0.03
2.00 3.79
1.67 3.34
1.03 2.83
0.43 1.89
0.27 1.46
Nausea, VAS score (mm)
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).
Ginger FO Ginger EO
no signicant difference in vomiting occurrences detected loss (P < 0.001) and constipation (P = 0.046) (Table 4). There
during any days of aromatherapy treatment period. was no evidence of a sequence by time interaction for any
of the HRQoL domains; hence the change from the base-
line for each domain was assessed. Post hoc tests using
Effects of aromatherapy on severity of nausea and
the Bonferroni correction showed that a statistically signif-
incidence of vomiting icant change from baseline for global health status (95%
CI mean difference; 4.12, 9.77, P < 0.001) was detected
Analyses of data using repeated measure ANOVA showed after ginger essential oil inhalation. Conversely, signicant
that there was no signicant mean difference of VAS nau- improvements from baseline for role functioning were noted
sea scores between ginger essential oil and ginger fragrance in both groups; ginger essential oil (95% CI mean differ-
oil [F(1, 58) = 1.82, P = 0.183] indicating that there was ence; 3.08, 16.92, P = 0.002) and ginger fragrance oil (95%
no signicant effect of aromatherapy on nausea severity CI mean difference; 1.96, 14.15, P = 0.006). Even so, better
(Table 3). However, there were signicant reduction in VAS score increment was noted with ginger essential oil appli-
nausea score with time with ginger essential oil inhalation cations. For symptom scale scores, fatigue (95% CI mean
[F(1, 58) = 43.98, P < 0.001]. Similarly, there was no signif- difference; 10.98, 2.35, P = 0.001), nausea and vomi-
icant effect of aromatherapy treatment on vomiting [F(1, ting (95% CI mean difference; 9.07, 2.59, P < 0.001),
58) = 0.29, P = 0.594]. There were signicant differences in pain (95% CI mean difference; 10.16, 0.95, P = 0.013)
the incidence of vomiting over ve days treatment period and appetite loss (95% CI mean difference; 16.87, 5.36,
[F(4, 55) = 9.58, P < 0.001]. For all the aforementioned anal- P < 0.001) were signicantly reported to have been reduced
yses, there was no signicant interaction between time while patients were on ginger essential oil. Interestingly, two
and treatment groups as well as between time and treat- domains managed to acquire the level considered clinically
ment sequence. Overall, no signicant mean difference by relevant of 10 points difference for EORTC QLQ-30, which
treatment sequence was detected. No major adverse events were role functioning and appetite loss. Unexpectedly, the
from the aromatherapy intervention were reported during symptom score of constipation was reported higher than the
the study. Only one person withdrew after complaining of baseline value for both groups but the difference in the score
having very mild dizziness or light-headedness on Day-5 of was signicant between baseline and after the use of ginger
aromatherapy treatment with ginger essential oil. fragrance oil (95% CI mean difference; 0.12, 6.55, P = 0.040).
Symptoms/items
Fatigue 45.56 19.91 42.04 22.32 3.52 14.39 38.89 23.28 6.67 13.45 a 3.15 (8.06, 1.77) 0.002
Nausea and Vomiting 6.67 10.27 4.44 12.22 2.22 9.44 0.83 3.66 5.83 10.09a 3.61 (7.51, 0. 29) <0.001
Pain 36.39 17.49 33.61 18.28 2.78 10.70 30.83 18.87 5.56 14.61a 2.78 (6.59, 1.03) 0.017
Dyspnea 5.00 13.48 5.56 13.95 0.56 9.69 5.00 14.81 3.33 15.89 0.56 (2.96, 1.84) 0.839
Insomnia 20.56 28.85 25.00 30.45 4.44 19.86 21.67 28.67 1.11 20.32 3.33 (10.07, 3.40) 0.222
Appetite loss 25.00 26.49 20.56 26.10 4.44 14.35 13.89 24.77 11.11 18.07a 6.67 (12.50, 0.83) <0.001
Constipation 7.22 16.34 10.56 18.91 3.33 10.08 a
8.89 18.27 1.67 15.56 1.67 (6.25, 2.92) 0.046
Diarrhea 1.67 7.33 2.22 8.38 0.56 7.49 1.67 7.33 0.56 (2.96, 1.84) 0.570
Financial difculties 16.67 30.38 14.44 29.02 2.22 16.08 17.78 29.73 1.11 20.32 3.33 (2.12, 8.79) 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
had limited effects in reducing CINV except for alleviating such as HRQoL prole. Positive feedbacks by patients them-
acute nausea. Despite frequent reports on aromatherapy selves could be of particular concern and seemed to be of
intervention, limited literature was available to make more importance as they came directly from the patients,
explicit comparisons. The only study involving the test of without peripheral interpretation from clinician or anyone
ginger aromatherapy alone was reported by Geiger,21 using else.29 Moreover, two domains reached a minimal clini-
combined applications (naso-cutaneous) to treat nausea cally signicant change of 10 points from the baseline
and vomiting induced by anesthesia exposure. Contrary to scores after application of ginger essential oil i.e. role
the present ndings, positive effects of ginger aromather- functioning (increased) and appetite loss (more markedly
apy was denoted in reducing post-operative nausea and reduced). A reduction in chemotherapy-induced nausea may
vomiting (PONV) using naso-cutaneous application. Geiger21 play a role in the reported improvements in these two
reported that 80% of high-risk patients had no complaints domains as patients would feel better to perform their
of PONV after treated with 5% ginger essential oil in the individual works or responsibilities and help them to enjoy
post-anesthesia recovery unit. Difference in condition and their foods. It is also possible that, as the chemotherapy
methods of application could be the reason for these differ- session progressed, patients experienced better HRQoL fol-
ent ndings. lowing their psychological adjustment as the ability to cope
On the other hand, the lack of benets from ginger with disease, treatment and effects of treatment would
essential oil treatment for vomiting occurrences may be have been improved after completing several chemotherapy
explained by the fact that the administration of 5-HT3 recep- cycles.30,31
tor antagonist class of anti-emetic may have signicantly Additionally, there was an increase in constipation after
decreased the episode of vomiting as it was rated as low both ginger essential oil and FO interventions. The most
at all-time points. These anti-emetics are also reported to likely explanation of the increase might be due to the com-
be more clinically effective against emesis than they are mon side effect of 5TH3 anti-emetics. Since all patients
against nausea.2224 Thus, this may have indicated that the were prescribed with this prophylaxis medication before
patients within the study may not have been experienc- chemotherapy and some received it as maintenance anti-
ing vomiting at a sufciently high level of frequency to emetic therapy at home, this symptom may have manifested
have responded to the aromatherapy intervention. Previ- within the limited HRQoL assessment period as this side
ous literatures have also demonstrated that once a patient effect was unlikely to change in the rst week after
undergoing chemotherapy experienced any form of nau- chemotherapy.
sea and vomiting (whether anticipatory, acute or delayed), Several limitations of this study deserve mention,
regardless of the emetogenicity of the antineoplastic reg- nonetheless. First, the severity of nausea before enrol-
imen, the likelihood of that patient experiencing nausea ment was not evaluated. We assumed that the severity of
for the next chemotherapy cycle was signicantly higher nausea was almost similar across the groups as patients
and more difcult to treat even with standard anti-emetic were only enrolled after they reported nausea from a pre-
medication.25 Since this study only included patients who vious chemotherapy cycle. Second, although the patients
had previously experienced CINV, they might have had were blinded, the possibility of a placebo effect cannot
an increased resistance to the intervention due to pre- be ignored. Because of the distinct odor of ginger essen-
conditioning. This is of particular concern since this study tial oil, some of the patients who had experienced using
adopted a crossover design, patients who were initially aromatherapy may have recognized the ginger essential oil
in the control group could have established resistance to perfume. However, the attempt to blind the patients was
the aromatherapy intervention before being subsequently quite successful, achieving 93.3% effectiveness. Anyhow,
crossed over. Moreover, delayed symptoms also occur more further exploration on how un-blinded patients detected
frequently with highly emetogenic chemotherapy and are treatment allocation either through special characterization
less responsive to treatment than prevention26 suggesting of the oils or probably occurred by chance could additionally
possible reasons on the lack of treatment efcacy using gin- provide better insight.
ger essential oil upon delayed symptoms especially in a study
that include a major proportion of patients receiving highly
emetogenic regimens. Conclusions
It is of interest that Global HRQoL and several sub-
scales of EORTC QLQ-30 (i.e. role functioning, fatigue,
At the present time, the evidence derived from this study is
nausea and vomiting, pain and appetite loss) did show sta-
not sufciently convincing that inhaled ginger aromatherapy
tistically signicant improvements from baseline following
is an effective complementary therapy for CINV. The nd-
ginger essential oil inhalation even after limited decrease
ings for HRQoL were however encouraging with signicant
of VAS nausea scores (except for acute phase). This result
improvement in several domains following this intervention.
is congruent with most previous works27,28 related to aro-
The conduct of future studies with an additional control arm
matherapy which indicated that although aromatherapy
(no treatment) would permit a more accurate comparison of
did not produce detectable effect using objective mea-
aromatherapy treatment for the prevention of CINV.
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 Conict of interest statement
amount of reduction on the severity of nausea may exert
benecial impacts on patient reported outcomes measures None declared.
404 P.L. Lua et al.