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ORIGINAL RESEARCH
Effects of Ginger for Nausea and Vomiting in Early
Pregnancy: A Meta-Analysis
Maggie Thomson, MD, Renee Corbin, MSc, and Lawrence Leung, MBBChir, MFM(Clin)
Background: Nausea and vomiting in early pregnancy (NVEP) is commonly encountered in family medi-
cine. Ginger (Zingiber officinale) is a popular nonpharmacological treatment but consensus of its use
is lacking.
Methods: We conducted a meta-analysis of clinical trials using ginger for NVEP as published in
PubMed and EMBASE, CINAHL, Cochrane Library, and all EBM reviews. Studies satisfying 3 criteria were
selected: (1) randomized placebo-controlled design; (2) use of ginger or Z. officinale; and (3) extract-
able data on improvement in NVEP. Data were synthesized into pooled odd ratios based on the random
effects model, and results were tabulated with the aid of Forest plots.
Results: We identified 135 potentially relevant records; only 6 studies met the final criteria. Of the
total 508 subjects, 256 and 252 subjects were randomly assigned to receive ginger and placebo, respec-
tively. The use of ginger (⬃1 g daily) for at least 4 days is associated with a 5-fold likelihood of im-
provement in NVEP. Heterogeneity among the clinical studies were acknowledged in the final interpreta-
tion of results.
Conclusions: Despite the widespread use of ginger in the diet, its clinic value and safety profile in
treating NVEP is still unknown. Our meta-analysis suggests that ginger is an effective nonpharmacologi-
cal treatment for NVEP. (J Am Board Fam Med 2014;27:115–122.)
Keywords: Alternative Medicine, Complementary Medicine, Pregnancy, Prenatal Care, Primary Health Care
Pregnancy-induced nausea and vomiting is com-
monly seen in family medicine, and 50% to 90% of
pregnancies are affected by nausea with or without
vomiting. According to a recent study, up to 63%
of women experience nausea and vomiting up to 24
weeks’ gestation.
1
While only 0.3% to 2% of these
cases are considered severe (called hyperemesis
gravidarum, leading to a loss of ⬎5% of prepreg-
nancy body weight), all forms of pregnancy-related
nausea can affect quality of life.
2
Compared with
the volume of literature regarding the pathogenesis
and treatment of pregnancy-induced nausea and
vomiting in general, few studies look at nausea and
vomiting in early pregnancy (NVEP).
Epidemiology, Risk Factors, and Pathogenesis
of NVEP
Nausea and vomiting during pregnancy is known to
be more common in younger primigravid women,
as well as in Western countries and urban areas.
2
Risk factors for its development include history of
estrogen-based medication causing nausea and mo-
tion or migraine causing nausea. Multiple gestation
pregnancies,
3
women who did not take multivita-
mins before conception,
4
those with acid reflux,
5
and those with a hydatidiform mole
6
also are known
be at increased risk. There seems to be a genetic
component to developing hyperemesis gravidarum;
several studies demonstrate that daughters of women
who experienced the condition are at increased
risks.
7,8
It is interesting that alcohol consumption
and cigarette smoking have both been demon-
strated to be protective.
9
The exact pathogenesis of
NVEP remains unclear; however, hormonal changes
including elevated serum human chorionic gonado-
This article was externally peer reviewed.
Submitted 29 May 2013; revised 17 July 2013; accepted 22
July 2013.
From the Department of Family Medicine (MT, LL) and
the Centre of Studies in Primary Care (RC, LL), Queen’s
University, Kingston, Ontario, Canada.
Funding: none.
Conflict of interest: none declared.
Corresponding author: Lawrence Leung, MBBChir,
MFM(Clin), Department of Family Medicine, Queen’s
University, 220 Bagot St, PO Bag 8888, Kingston ON
K7L 5E9, Canada (E-mail: leungl@queensu.ca).
doi: 10.3122/jabfm.2014.01.130167 Ginger for Nausea and Vomiting in Early Pregnancy 115
tropin have been implicated,
2
as have psychological
factors and stress response.
10
Delayed or dysrhythmic
gastric motility also has been postulated as a likely
cause of NVEP.
2
Diagnosis and Treatment of NVEP
Diagnosis of NVEP is purely clinical. There exists
no defined diagnostic criteria for the condition.
Mean onset is known to be between 5 to 6 weeks of
gestation, with the majority of symptoms resolving
by 20 weeks.
2
Approximately 20% of women con-
tinue to have symptoms into their second and third
trimesters.
2
Contrary to popular belief, symptoms
occur throughout the day and are often not limited
to the morning as the term morning sickness would
imply.
2
Goals of treatment include reducing maternal
symptoms and complications and mitigating any
effects on the fetus. Antiemetics for NVEP that
have been studied include Diclectin (Duchesnay
Inc., Blainville, QC, Canada), ondansetron, ginger,
various antihistamines, vitamin B
6
, metoclopra-
mide, and phenothiazines.
2
A recent randomized,
double-blind, placebo-controlled trial
11
demon-
strated that Diclectin was effective for nausea and
vomiting during pregnancy, and this drug is cur-
rently recommended as first-line pharmacological
treatment for NVEP in Canada. Ondansetron is
commonly used as an antiemetic during chemo-
therapy, with good evidence.
12
However, it has
been used for some time in the United States as
a first-line (albeit off-label) treatment for preg-
nancy-related nausea and vomiting.
13
While ev-
idence exists for other pharmacological and nonphar-
macological treatments (eg, dietary adjustments,
acupressure, and acupuncture), they are beyond
the scope of this article. Our study aimed to
critically examine the efficacy of ginger in the
treatment of NVEP through meta-analysis of
published clinical trials.
Ginger and Its Medicinal Effects
The antinausea effect of ginger was first described
in one of the canons of traditional Chinese medi-
cine—the Synopsis of the Prescriptions of Golden
Chamber
14
—in 200 AD. Ginger is the under-
ground stem (or rhizome) of the perennial plant
Zingiber officinale, which is indigenous to China and
India but is cultivated all over the world. From the
body of ginger sprouts the peudostems, which
branch off to leaves that can reach 2 feet in
height.
15
Analysis of ginger reveals 2 major classes
of phytochemicals: volatile oils, which give ginger
its pleasant smell,
16
and the nonvolatile compounds
(eg, gingerols and zingerones), which account for
its piquant taste and its pharmacological effects.
17
Many studies of the antiemetic nature of ginger for
various conditions have been published but with
mixed results. While evidence supports benefits of
ginger for seasickness,
18
motion sickness,
19
and
postoperative nausea and vomiting,
20
its use in pre-
venting chemotherapy-induced nausea and vomit-
ing is still conflicting.
21,22
Ginger also has been
demonstrated to be effective in treating nausea and
vomiting in pregnancy to the extent that it is as
effective as vitamin B
6
alone.
23–27
The exact anti-
emetic mechanisms of ginger are still unknown, but
in vitro studies revealed antagonistic effects of gin-
gerols on serotonergic 5-HT
328,29
and cholinergic
M receptors.
29
So far, no direct adverse effects on
human fetuses or the course of pregnancy have
been demonstrated.
24–27
However, there had been
concerns about interfering with fetal development,
which led to the issuance within Finland and Den-
mark of warning labels for all supplements contain-
ing ginger.
30
It is also recognized that ginger has
potent anticoagulant effects, which may enhance
bleeding and miscarriages and interact with other
medications.
30
At present, there are no large-scale
studies ascertaining the safety of ginger. That said,
in Europe and North America the current consen-
sus for the maximum safe dose of ginger is 2 g/day
in divided doses of 250 mg, even during preg-
nancy.
30
Methods
Study Aim
NVEP is a commonly encountered condition in
family medicine, and ginger has been used as a
nonpharmacological remedy. Our meta-analysis
aimed to critically examine and synthesize available
data from good-quality randomized clinical trials to
evaluate the efficacy of ginger in treating NVEP.
Eligibility Criteria
Our primary interest was the treatment of NVEP
using ginger as the therapeutic intervention. To
minimize heterogeneity, we limited our scope to
randomized, placebo-controlled trials with a satis-
116 JABFM January–February 2014 Vol. 27 No. 1 http://www.jabfm.org
factory score on the Cochrane Risk of Bias assess-
ment tool.
Search Strategy
A literature search of published medical reports
was performed in all languages using PubMed,
EMBASE, CINAHL, the Cochrane Library, and
all evidence-based medicine reviews using the
OVID Portal of Queen’s University, Kingston,
Ontario. Abstracts were initially obtained using
MeSH keywords of early pregnancy,nausea,vomit-
ing, and ginger. Manual searches of references and
review articles supplemented the computerized
search.
Study Selection, Data Extraction, and Quality
Assessment
Two reviewers (MT and RC) went through the
initial abstracts. A simple form was adopted to
select trials that satisfied the eligibility criteria
stated above. Selected studies were evaluated ac-
cording to the Cochrane Risk of Bias tool with
regard to quality of the study, randomization pro-
tocol, adequacy of concealment and blinding, and
rigor of follow-up for drop-outs. Information re-
garding the demography of the study population,
duration of the study, the number of affected sub-
jects who improved with treatment and placebo,
and finally a numeric score for the Cochrane risk of
bias was extracted and tabulated in spreadsheets. Of
note, we found only 6 randomized, placebo-con-
trolled trials of ginger that displayed data required
for our meta-analysis (see Table 1). The primary
outcome was improvement of pregnancy-related
nausea and vomiting.
Statistical Analysis
All data from the 6 appropriate studies of ginger
were synthesized in a meta-analysis, and odds ratios
(ORs) were calculated with appropriate confidence
intervals (CIs) based on the number of subjects
reporting improvement in both the intervention
and control groups. Where necessary, the value of
1 was added to any arm with zero outcome events
according to the Sheele ⫹1 rule. To assess heter-
ogeneity, we used the Cochrane Q-statistic with
95% confidence CIs. We assumed a Pvalue of
⬍.05 for the Cochran Q-statistic. Forest plots were
generated with ORs for each ginger study. Statis-
tical advice was provided by our data analyst at our
Centre of Studies in Primary Care.
Results
We initially identified 135 records using the MeSH
keywords of early pregnancy,ginger,nausea, and
vomiting. After removing duplicates and further
screening, 8 full articles were retrieved. Two of
them were excluded because of irrelevance. Con-
sensus was reached among the reviewers to include
the final 6 studies. The 2009 PRISMA checklist was
used; the PRISMA flow diagram is given in the
Appendix.
In our meta-analysis, a total of 256 patients were
randomly assigned to receive ginger, and 252 pa-
tients were randomly assigned to receive placebo.
Total sample size per study ranged from 23 to 235.
The period of intervention lasted from 4 days to 3
weeks. Dose and method of administration of gin-
ger also varied among studies: Basirat et al
31
used 5
biscuits per day, each containing 500 mg of ginger,
Table 1. Brief Description of the 6 Studies Included in the Meta-Analysis
Study Intervention Placebo
Duration of
Study
Gestation
Stage
Outcome Measure (Nausea
and Vomiting)
Basirat et al.
31
500-mg ginger powder in
biscuit, 5 biscuits/day
Placebo biscuit 4 days ⬍17 weeks Nausea scale (VAS) ⫹
frequency of vomiting
Ozgoli et al.
35
250-mg ginger capsules QID Lactose capsules 4 days ⬍20 weeks Nausea scale (VAS) ⫹
frequency of vomiting
Smith et al.
26
350-mg ginger capsules TID Vitamin B
6
(25-
mg capsules)
3 weeks ⬍16 weeks Nausea and vomiting scales
(Rhodes Index)
Keating et al.
32
250-mg ginger syrup QID Plain syrup 2 weeks ⬍12 weeks 4-point nausea scale ⫹
frequency of vomiting
Vutyavanich et al.
34
250-mg ginger capsules QID Placebo capsules 4 days ⬍17 weeks VAS ⫹Likert scale
Fischer-Rasmussen
et al.
33
250-mg ginger capsules QID Lactose capsules 4 days ⬍20 weeks Unique scoring system
QID, four times per day; TID, three times per day; VAS, visual analogue scale.
doi: 10.3122/jabfm.2014.01.130167 Ginger for Nausea and Vomiting in Early Pregnancy 117
whereas the others used either capsules or syrup
containing approximately1gofginger daily
26,32–35
(Table 1).
We applied the Cochrane Risk of Bias assessment
to the 6 studies; they achieved a score of at least 3 of
6 and were deemed to be of satisfactory quality.
Our primary outcome was the improvement of
pregnancy-related nausea and vomiting, which was
reported in all 6 studies: 180 of the 256 subjects in the
ginger group and 126 of the 252 subjects in the
placebo group reported improvement in symptoms of
nausea and vomiting. In view of the interstudy varia-
tion in the duration and form of intervention, a ran-
dom effects model was adopted. The pooled OR was
4.89, with a 95% CI of 1.88 to 12.73 (see Table 2).
The Cochrane Q-statistic was significant at 33.72,
with a degree of freedom of 5 (P⬍.0001) (Table 3).
A synthesis Forest plot was generated (Figure 1), and
the corresponding funnel plot is included for refer-
ence (Figure 2). Relative risk was calculated at 1.76
(95% CI, 1.18–2.65), and the number needed to treat
for a positive effect was calculated to be 5.
Discussion
Our meta-analysis demonstrated that ginger (Z.
officinale) is better than placebo in improving
NVEP when administered at a dosage of approxi-
mately 1 g/day for a duration of at least 4 days.
Despite the common intake of ginger in our
diet, no large-scale studies have directly assessed
the safety profile of ginger during human preg-
nancy. In the early 1990s, Backon
36
commented on
a theoretical possibility of ginger affecting testos-
terone receptor binding and sex steroid differenti-
ation in the fetal brain. An antiplatelet effect of
ginger through inhibition of thromboxane synthe-
tase has been reported in vitro.
37
However, there
have been no reports of increased risk of antenatal
or postpartum hemorrhage with ginger use during
pregnancy. Increased levels of early embryonic loss
due to ginger intake
38
were reported in rats; how-
ever, the dosage was far greater than those rou-
tinely used in humans. Subsequent study of rats
using human-compatible doses of ginger showed
no similar adverse effects.
39
A commonly observed side effect of ginger is
reflux. In a study by Willets et al,
24
4 of the 120
subjects withdrew because of symptoms consistent
with reflux. Reflux has been commonly reported
with ginger use outside pregnancy. In a study of the
prevention of postoperative nausea and vomiting,
8% of subjects had heartburn after taking 1 g gin-
ger.
40
Another study of photopheresis-induced
nausea demonstrated that 27% of subjects has re-
flux as a result of ginger use.
41
Apart from gastric
discomfort, the side effect of reflux poses no long-
term harm or damage, and patients should be
warned of this side effect before beginning ginger
therapy.
There are a few limitations to our meta-analysis.
First, there is variability in the dosage and formu-
lation of ginger. While 4 studies administered gin-
ger in capsules,
26,33–35
one study administered gin-
ger in syrup
32
and the other in the form of
biscuits.
31
Moreover, the durations of intervention
also differed. Four studies administered interven-
tion for 4 days,
31,33–35
while Keating and Chez
32
gave ginger for 2 weeks and Smith et al
26
for 3
Table 2. Results from Meta-Analysis Comparing Ginger to Placebo in Improvement of Nausea and Vomiting in
Early Pregnancy
Study Intervention Group Control Group Odds Ratio 95% CI
Basirat et al.
31
28/32 21/30 3.00 0.81–11.1
Fischer-Rasmussen et al.
33
19/27 4/27 13.66 3.56–52.43
Keating et al.
32
10/13 2/10 13.33 1.78–100.14
Vutyavanich et al.
34
28/32 10/35 17.50 4.87–62.87
Ozgoli et al.
35
27/32 20/35 4.05 1.26–12.99
Smith et al.
26
68/120 69/115 0.87 0.52–1.47
Total (random effects) 180/256 126/252 4.89 1.88–12.73
CI, confidence interval.
Table 3. Test for Heterogeneity of Studies
Q-statistic 33.72
Degree of freedom 5
Significance level P⬍.0001
118 JABFM January–February 2014 Vol. 27 No. 1 http://www.jabfm.org
weeks. There was also variation in the combined
sample size in the studies, which ranged from 23 to
235 (see Table 2). All these translated to a level of
heterogeneity that was reflected in the Cochrane
Q-statistic, with a significance of P⬍.0001. A final
limitation of our study is the variability of scores
Figure 1. Forest plot for 6 studies using a random effects model. CI, confidence interval.
Figure 2. Funnel plot displaying the heterogeneity of studies. OR, odds ratio.
doi: 10.3122/jabfm.2014.01.130167 Ginger for Nausea and Vomiting in Early Pregnancy 119
used to qualify and quantify outcome measures in
NVEP. Vutyavanich et al,
34
Ozgoli et al,
35
and
Basirat et al
31
used a visual analog scale, whereas
Fischer-Rasmussen et al
33
developed a unique scor-
ing system. Keating and Chez used a symptoms
diary and a 4-point scale and Smith et al used the
Rhode’s index. While this does add heterogeneity
to our meta-analysis, the primary endpoint chosen
remained the same (ie, improvement of NVEP).
Given its limitations, our meta-analysis demon-
strated that ginger is better than placebo in improv-
ing NVEP, with an approximate number needed to
treat of 5. Further large-scale, multicenter trials
should be undertaken to further examine the effi-
cacies of ginger and detail its safety profiles when
treating NVEP.
Conclusions
Ginger is commonly consumed in our diet as an
additive in cooking. In traditional Chinese medi-
cine, ginger is indicated specifically as a remedy for
NVEP. Based on our meta-analysis, we conclude
that ginger is an effective nonpharmacological op-
tion for treating NVEP with respect to the inher-
ent heterogeneity of the available studies. Family
physicians and other medical professionals should
be cognizant of the value of ginger as they contem-
plate pharmacological options for suitable patients
with NVEP.
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Appendix: PRISMA Flow Diagram
133 records idenfied through
database searching
(
n =133
)
ScreeningIncluded Eligibility Idenficaon
17 addional records idenfied
through other sources
(
n=17
)
135 records aer duplicates removed
(n = 135 )
135 records screened
(n =135 )
129 records excluded
(n = 129 )
8 full-text arcles assessed
for eligibility
(
n=8
)
2 full-text arcles excluded due
to irrelevance
(
n=2
)
6 studies included in
quantave synthesis
(meta-analysis)
(n = 6 )
122 JABFM January–February 2014 Vol. 27 No. 1 http://www.jabfm.org