Viljoen et al.

Nutrition Journal 2014, 13:20

http://www.nutritionj.com/content/13/1/20

REVIEW Open Access

A systematic review and meta-analysis of the

effect and safety of ginger in the treatment of
pregnancy-associated nausea and vomiting
Estelle Viljoen1,3*, Janicke Visser1, Nelene Koen1 and Alfred Musekiwa2

Abstract
Background and objectives: Nausea and vomiting during pregnancy (NVP) occur commonly. Possible harmful
side-effects of conventional medicine to the fetus create the need for alternative options to relieve NVP. This systematic
review (SR) investigated current evidence regarding orally administered ginger for the treatment of NVP. The primary
objective was to assess the effectiveness of ginger in treating NVP. The secondary objective was to assess the safety of
ginger during pregnancy.
Methods: A comprehensive electronic bibliographic database search was carried out. Randomized controlled trials
(RCTs) of the efficacy of orally administered ginger, as treatment for NVP in pregnant women at any stage of pregnancy,
published in English, were included. Two researchers independently extracted data and assessed trial quality. RevMan5
software (Cochrane Collaboration) was used for data analysis. p < 0.05 was considered statistically significant.
Results: Twelve RCTs involving 1278 pregnant women were included. Ginger significantly improved the symptoms of
nausea when compared to placebo (MD 1.20, 95% CI 0.56-1.84, p = 0.0002, I2 = 0%). Ginger did not significantly reduce
the number of vomiting episodes during NVP, when compared to placebo, although there was a trend towards
improvement (MD 0.72, 95% CI −0.03-1.46, p = 0.06, I2 = 71%). Subgroup analyses seemed to favor the lower daily
dosage of <1500 mg ginger for nausea relief. Ginger did not pose a significant risk for spontaneous abortion compared
to placebo (RR 3.14, 95% CI 0.65-15.11, p = 0.15; I2 = 0%), or to vitamin B6 (RR 0.49, 95% CI 0.17-1.42, p = 0.19, I2 = 40%).
Similarly, ginger did not pose a significant risk for the side-effects of heartburn or drowsiness.
Conclusions: This review suggests potential benefits of ginger in reducing nausea symptoms in pregnancy (bearing in
mind the limited number of studies, variable outcome reporting and low quality of evidence). Ginger did not significantly
affect vomiting episodes, nor pose a risk for side-effects or adverse events during pregnancy. Based on evidence from
this SR, ginger could be considered a harmless and possibly effective alternative option for women suffering from NVP.
International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42011001237.
Keywords: Pregnancy, Ginger, Nausea, Vomiting, Systematic review

* Correspondence: [email protected]
1
Division of Human Nutrition, Faculty of Medicine and Health Sciences,
Stellenbosch University and Tygerberg Academic Hospital, Cape Town,
South Africa
3
Current affiliation: Discipline of Human Nutrition and Dietetics, School of
Health Care Sciences, University of Limpopo, MEDUNSA Campus, Garankuwa,
South Africa
Full list of author information is available at the end of the article

© 2014 Viljoen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain
Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,
unless otherwise stated.
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Introduction & rationale for the review There is mixed scientific evidence for the use of ginger
Nausea and vomiting are very common complaints dur- in NVP [8,10]. It should be noted that high doses of
ing the early weeks of pregnancy. Due to the possible concentrated ginger in the form of powder or herbal
harmful side-effects that conventional medicine may tinctures can increase bleeding risk by decreasing platelet-
pose to the unborn fetus, many mothers choose not to aggregation, and also increase stomach acid production,
use it, and are left helpless against this burden. Nausea especially if taken with other herbs or medicines with
and vomiting of pregnancy (NVP) is commonly referred the same effect [8,9,13]. Thus, ginger supplementation
to as morning sickness (although it can occur at any can have additive or competitive interactions with some
time of the day or night), and affects about 80-90% of medicines.
pregnant women in varying degrees [1,2]. Most of these Several studies have been performed on the use of
women will experience both nausea and vomiting, and ginger as an anti-emetic for use with post-operative
some only nausea without vomiting or retching, but nausea and vomiting, motion sickness and vertigo and
vomiting alone is rare [2]. Symptoms usually appear at chemotherapy-induced nausea and vomiting [8,9,11,14].
4–9 weeks of gestation, reaching a peak at 7–12 weeks, The ingestion of oral ginger in a fasting state or after
and subsiding by week 16. About 15-30% of pregnant food intake results in an increase in gastro-duodenal
women’s symptoms will persist beyond 20 weeks, or motility [15], which could be a possible mechanism of
even up to the time of delivery [1,2]. Hyperemesis gravi- action for the reduction in nausea and vomiting.
darum (HG) is severe and persistent vomiting during Currently no clear guidelines are available for ginger’s
pregnancy, which can lead to dehydration, electrolyte use in the treatment of NVP, despite some literature
disturbances and liver damage, possible fetal damage and available on the subject [10,16,17]. A systematic review of
in extreme cases, the death of the mother [1,3-5]. Women the available literature (also focusing on safety aspects)
with HG usually need to be hospitalized [1] and it occurs can provide the best current evidence regarding possible
in approximately 2% of pregnancies [1,2]. benefits or risks for the clinical use of ginger to treat NVP.
The exact cause of NVP remains unclear, and is prob-
ably multifactorial. Theories include the rapid increase Objectives
in hormones such as estrogen and human chorionic go- The primary objective of this systematic review (SR) was
nadotropin (hCG), [6] or Helicobacter pylori (H.pylori) to assess the effectiveness of ginger in the treatment of
infection, as well as psychological and genetic predispos- NVP. The secondary objective was to assess the safety of
ition [2,6]. Severe NVP and HG can lead to maternal orally administered ginger in the treatment of NVP, by
malnourishment and weight loss, leading to negative identifying adverse events or side-effects (if any), and
fetal outcomes including low birth weight and preterm to classify them as major (serious complications detri-
birth [1]. Maternal complications include acute renal mental to the mother or fetus), or minor (discomfort,
failure, esophageal rupture, coagulopathy and on rare but manageable side-effects).
occasions, Wernicke’s encephalopathy [2]. The negative
effects of NVP described clearly show the importance of
managing and treating NVP and HG as early as possible, Methods
and not considering NVP as merely an unpleasant part of Ethics and protocol registration
pregnancy that has to be endured and suffered through. As this SR utilizes data available in the public domain, it
Pharmacological treatment of NVP is complicated due was exempt from ethical review by the Health Research
to the fact that during pregnancy, many physiological Ethics Committee at Stellenbosch University (N11/04/127).
changes occur, including gastro-intestinal motility, plasma The protocol was registered on the PROSPERO Register
volume and glomerular filtration [7]. These factors all in- and can be viewed at http://www.crd.york.ac.uk/prospero/.
fluence the distribution, absorption and excretion of drugs Registration number CRD42011001237.
and due to this reason, not all drugs are safe during preg-
nancy. Many drugs cross the placenta by simple diffusion Criteria for considering studies for this review
and can affect the fetus directly [7]. Non-pharmacological Types of studies and participants
treatment of NVP includes ginger and simple lifestyle Randomized controlled trials (RCTs) involving human
changes that have been described in the literature [1]. participants, and investigating ginger for the treatment
Acupressure is also a safe and non-invasive treatment for of NVP were included in this SR. Only studies that were
NVP, although there is a lack of evidence of efficacy [1,6]. published in English were included. Trials were included
Ginger (Zingiber officinale Roscoe) is widely used, with despite lack of blinding or placebo treatment. Women
the most common ailments currently being treated with suffering from NVP were included, with no restriction
ginger including nausea, vomiting, pregnancy-associated on their age or stage of pregnancy (as included in the
morning sickness, motion sickness and indigestion [8-12]. various trials).
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Types of interventions excluded were listed in a table of excluded studies with

Any form of orally administered ginger intervention reasons for their exclusion.
(fresh root, dried root, powder, tablets, capsules, liquid
extract, and tea) compared with an inert (placebo) or Data extraction and management
active ingredient, was included. Data extraction was carried out in duplicate, independ-
ently, and differences were resolved by discussion and
Types of outcome measures consensus. Data extraction forms were designed to tabu-
late the characteristics of the included studies. Where
 Symptom scores on the subjective feeling of nausea, missing information was detected or clarity was needed,
measured by standardized scales or methods the authors of the primary studies were contacted via
[e.g. Visual Analogue Scale (VAS)]. e-mail. Variables for which data were sought included
 The incidence of vomiting episodes, measured by study design, treatment and comparator, total number of
daily recording. participants at beginning and end of trial in intervention
 The general response to the treatment, measured by and control groups, length of treatment in days, out-
standardized scales or methods (e.g. the 5-point comes, main results and adverse events reported.
Likert-type scale).
 The occurrence of adverse events and side-effects. Assessment of quality of evidence
Two reviewers independently assessed the components
Search methods for identification of studies of each trial for risk of bias, at study level. The Cochrane
Literature searches were conducted in computerized da- “risk of bias” assessment tool [18] was used to assess the
tabases from 1966 until 12 July 2013, with the help of a potential sources of bias in the methodology of the
qualified medical librarian. Databases searched included included trials. The domains assessed were sequence
Medline (accessed via Pubmed); EBSCO host, including generation, allocation concealment, blinding, incomplete
Academic Search Premier, CINAHL (nursing & allied outcome data, selective outcome reporting, and other
health research database), and CAB abstracts; CENTRAL potential threats to validity. Assessment was done by an-
(Cochrane Central Register of Controlled Trials); Science swering a pre-specified question about the adequacy of
Direct; ISI Web of Science, ISAP (Index to South African each individual study in relation to the entry, in such a
Periodicals – National Library of South Africa); Proquest; way that the judgment of ‘yes’ was indicative of low risk
Scopus Abstracts; Africa Wide; SABINET (South African of bias, ‘no’ was indicative of high risk of bias, and
Bibliographic Information Network); Current Controlled ‘unclear’ was indicative of uncertain risk of bias. Disagree-
Trials (www.controlled-trials.com) and Clinical trials.gov ments were resolved with discussion and consensus.
(www.clinicaltrials.gov). The author team also searched
for additional studies by searching the reference lists of Measures of treatment effect and data synthesis
the included trials and other articles identified by the Dichotomous outcomes (including adverse events, nausea
electronic search. The final complete search word and vomiting) were expressed as risk ratios (RR) with 95%
string was: Pregnan* AND (nausea OR vomit* OR confidence intervals (CI). Continuous outcomes such as
morning sickness OR hyperemesis gravidarum) AND symptom scores (for example, as measured by a VAS), were
(ginger OR zingiber officinale roscoe) AND (clinical trial* expressed as mean differences (MD) with 95% CI’s.
OR randomized control trial* OR random allocation Heterogeneity was assessed by both the visual inspection of
OR placebo* OR random research OR comparative OR the forest plots (where non-overlapping of confidence inter-
“evaluation stud*” OR follow up OR prospective* OR control* vals indicated the likelihood of heterogeneity) and by using
OR volunteer* OR single mask* OR double mask* OR treble the Chi2-test for heterogeneity (differences at the level
mask* OR tripl* mask* OR single-blind OR double-blind of p < 0.05 were considered to be statistically signifi-
OR treble blind OR tripl* blind*). cant). Heterogeneity was also expressed as the I2 statis-
tic, [18] with a value of 0% indicating no heterogeneity.
Selection of studies The investigators undertook to assess funnel plots to
Two reviewers independently assessed titles and ab- explore the possibility of small study and other bias
stracts of references retrieved from the searches and se- where at least ten studies were included per meta-
lected all potentially relevant studies. These potentially analysis [18].
relevant articles were retrieved as full text in hard copy The Review Manager 5.0 (RevMan 5) computer pro-
and assessed independently by the reviewers against the gram (developed by the Cochrane Collaboration) was
eligibility criteria, as described earlier. Disagreements used for data entry and statistical analysis of the data. A
were resolved with discussion and consensus. Studies that random effects model of meta-analysis was used in the
initially appeared to be relevant but were subsequently presence of moderate heterogeneity of treatment effects,
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and a fixed effect model in the absence of heterogeneity.

The Mantel-Haenszel (M-H) method of meta-analysis Records identified through
database searching
was used for dichotomous outcomes and the Inverse- (N=302)
Variance (IV) method was used for continuous outcomes.
All statistical methods used were confirmed by a statisti- Duplicates removed
cian trained in meta-analyses and systematic reviews. (N=117)

Subgroup and sensitivity analyses

The planned subgroup analyses to explore possible Records screened
(N=185)
sources of heterogeneity included different dosages ad-
ministered in the various studies [low (<1500 mg ginger/
day) vs. high (≥ 1500 mg ginger/day)] and different dura- Records excluded
tions of intervention in the various studies [short treat- (N=131)
ment (<7 days) vs. long treatment (≥7 days)]. Sensitivity
analyses were planned to explore the influence of study -Study type (N=100)
quality and source of funding on effect size, should - Brief items/letters/comment (N=7)
- Intervention (not ginger) (N=5)
sufficient studies exist.
- Participants (not pregnant) (N=16)
-Animal research (N=3)
Results
Study selection Full-text articles assessed
The process followed in the selection of studies and the eligibility
(N=54)
results obtained from the search are shown in Figure 1.
Across all searched databases (and reference lists
reviewed) 302 abstracts were identified as potentially Full-text articles excluded,
with reasons
relevant. Of these, 117 studies were identified as dupli- (N=42)
cates. In the case of duplicate publications, the original
paper (or the oldest version) was used. A further 173 - Study type (N=30)
were excluded, in 2 phases, for various reasons (Figure 1). - Brief items/letters/comment (N=9)
- Intervention (not ginger) (N=1)
Finally, twelve studies [19-30] met the aforementioned
- Foreign language (N=2)
criteria and were included. Although foreign language
studies were excluded from this review, all potentially
eligible studies reported in languages other than English Included studies
were documented for future assessment [31,32]. (N=12)

Figure 1 Diagrammatic representation of the process followed

Study characteristics in the selection of studies.
Included studies were published from 1991 to 2011. Key
characteristics of the included studies are presented in
Table 1 and arranged alphabetically. Eleven (91.6%) of dissolved in water; one study [30] (8.3%) used 1000 mg
the twelve included trials were designed as parallel group ginger extract per day, in capsule form; and one study
studies. Only one study [22] had a cross-over design. A [24] used a total of 600 mg ginger essence per day. The
total of 1278 participants were included in the respective comparator was clearly described in most of the in-
studies, ranging from 26 in the smallest trial [23] to 291 cluded studies [20-23,25-28,30]. A placebo was used as
participants in the largest trial [27]. Only 2 trials [26,27] the control in 7 studies. Two studies [22,25] used lactose
recruited more than 150 participants. Eleven of the as the placebo, one used lemon oil [23], one used flour
twelve included studies [19-21,23-30] (91.6%), included [24], and one used soy bean oil [30]. One study [19] used
women suffering from NVP, and one study [22] (8.3%) placebo biscuits but did not specify the content of the
included women suffering from HG. The study interven- biscuit, and one study [29] did not specify the content of
tion (ginger) was clearly described in each included the placebo capsule. Four studies used Vitamin B6 as
study. Most of the studies (n = 8) (66.7%) [20-22,25-29] active comparator. Two studies [20,27] used 70 mg per
used ginger powder capsules as intervention, ranging day, one [21] used 40 mg per day and one [28] used
from 1000 mg to 1950 mg ginger per day. One study 30 mg Vitamin B6 per day. One study [24] used 30 mg
[19] (8.3%) used ginger biscuits as intervention, with a Metoclopramide as comparator, as well as placebo. The
total dose of 2500 mg ginger per day. One study [23] remaining study [26] used 100 mg Dimenhydrinate per
(8.3%) used a total of 1000 mg ginger syrup per day, day as active comparator (Table 1).
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Viljoen et al. Nutrition Journal 2014, 13:20
Table 1 Characteristics of included studies
Study ID Risk of NPB/NME Intervention Comparator* L of T Main outcome measures Main results
bias (treatment) (ginger dose/day) (dose per day) (days)
Basirat [19] High 65/62 Ginger biscuits Placebo biscuit (5 biscuits 4 Severity of nausea (VAS 0–10); number Ginger biscuits provided significantly
(32G, 30C) (500 mg 5 times per day, dose not specified) of vomiting episodes; general response greater relief from the severity of nausea
daily = 2500 mg/day) to treatment (5-item Likert scale) (p = 0.01), and to some extent vomiting
(p = 0.24).
Chittumma [20] High 126/123 Ginger powder Vitamin B6 capsules 4 Change in nausea and vomiting scores Results showed that ginger is
(61G, 62C) capsules (325 mg ×2, (12.5 mg ×2, three times (3 symptoms on Rhodes index); significantly more effective in relieving
three times daily, = daily =75 mg/day) occurrence of side-effects NVP than vitamin B6 (p < 0.05).
1950 mg/day)
Ensiyeh [21] High 70/69 Ginger powder Vitamin B6 capsules (20 mg 4 Severity of nausea (VAS 0–10); number The results showed that the ginger is
(35G, 34C) capsules (500 mg twice per day =40 mg/day) of vomiting episodes; general response significantly more effective than vitamin
2×/d =1000 mg/day) to treatment (5-item Likert scale); B6 for relieving the severity of nausea
occurrence of side-effects or adverse (p < 0.024), and equally effective for
pregnancy outcome reducing the number of vomiting
episodes.
Fischer- Mode-rate 30/27 Ginger powder Placebo capsules (lactose) 4 Preference of treatment period; relief The results showed that ginger was
Rassmussen [22] (27G, 27C) capsules (250 mg (250 mg 4 times per day = scores (4-point scoring system); significantly more effective than the
(cross-over**) 4 times per day = 1000 mg/day) outcome of pregnancy placebo in eliminating or minimizing
1000 mg/day) HG (p = 0.035).
Keating [23] High 26/21 Ginger syrup in Placebo syrup (lemon oil) 14 Level of nausea (numerical scale 1–10); Ginger had a greater effect on the
(12G, 9C) water (250 mg 4x/day (dose not specified) number of vomiting episodes relieving of NVP, but due to the small
4 times per day = study sample the results were not
1000 mg/day) statistically analyzed. The authors
concluded that ginger syrup may be
more effective than placebo syrup in
treatment of NVP.
Mohammadbeigi High 102/102 Ginger essence 1. Metoclopramide capsules 5 Used RINVR to measure severity of Ginger was less effective than
[24] (34G, 34C1, capsules (200 mg (10 mg 3×/day = 30 mg/day) nausea and vomiting. metoclopramide in reducing nausea
34C2) 3×/day = 600 and vomiting during pregnancy, but
mg/day) 2. Placebo capsules (flour) the difference was not statistically
(200 mg 3×/day = 600 mg/day)
significant (p = 0.509).
Ozgoli [25] Mode-rate 70/67 Ginger powder Placebo capsules (lactose) 4 Nausea intensity (VAS 0–10); number The results showed that ginger was
(32G, 53C) capsules (250 mg (250 mg 4 ×/d 1000 mg/day) of vomiting incidences significantly more effective than the
4 times per day = placebo in improving symptoms of
1000 mg/day) NVP (p < 0.05).
Pongrojpaw [26] High 170/151 Ginger powder Dimenhydrinate capsules 7 Degree of nausea (VAS 0–10); number There was no significant difference in
(77G, 74C) capsules (500 mg (50 mg 2x/d = 100 mg/day) of vomiting incidences; occurrence the visual analogue nausea scores
2x/d =1000 mg/day) of side-effects between the two groups. Ginger
was as effective as dimenhydrinate in
the treatment of NVP, and has fewer
side-effects.
Smith [27] High 291/235 Ginger capsules Vitamin B6 capsules (25 mg 21 Nausea, vomiting and dry retching The results indicated that ginger is

Page 5 of 14
(120G, 115C) (350 mg 3times per 3x/d =75 mg/day) on days 0,7,14,21 (Rhodes Index of equivalent to vitamin B6 in improving
day = 1050 mg/day) Nausea and Vomiting Form2) (5-point nausea, dry retching and vomiting in
Likert scale); change in health status pregnancy. All p-values were <0.001.
on day 0,21 (MOS 36 Short Form Health
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Viljoen et al. Nutrition Journal 2014, 13:20
Table 1 Characteristics of included studies (Continued)
Survey, 8-multi-item scale, higher
core = better outcome); occurrence of
side-effects and adverse pregnancy
outcomes
Sripramote [28] High 138/128 Ginger powder Vitamin B6 capsules (10 mg 3 Severity of nausea (VAS 0–10); number Both ginger and vitamin B6 were
(64G, 64C) capsules (500 mg 3×/d =30 mg/day) of vomiting incidences; occurrence of effective for treating NVP (p < 0.001).
3×/d 1500 mg/day) side-effects There were no significant differences
between the two treatments’ efficacy.
Vutyavanich [29] High 70/67 Ginger powder Placebo capsules 4 Severity of nausea (VAS 0–10); number Ginger was significantly more effective
(32G, 35C) capsules (250 mg (not specified) (250 mg of vomiting episodes; general response than the placebo in relieving the
4x/day =1000 4x/day = 1000 mg/day) to treatment after 1 week (5-item Likert severity of nausea in pregnancy
mg/day) scale); occurrence of side-effects and (p = 0.014).
adverse pregnancy outcomes
Willetts [30] Mode-rate 120/99 Ginger extract Placebo capsules (soy bean 4 Used RINVR to measure frequency, Ginger was more effective than placebo
(48G, 51C) capsules (125 mg oil 4x/d) (dose not specified) duration, distress caused by nausea, for improving nausea and retching
4x/d =1000 mg/day) vomiting and retching; long term during pregnancy, but no difference
follow-up for birth outcome in the vomiting episodes were observed.
No p-values were provided.
*Comparator: includes placebo and active ingredients. **Cross-over design RCT. All the other studies were parallel design RCT’s.
RCT: Randomized controlled trial; NVP: Nausea and vomiting of pregnancy; HG: Hyperemesis gravidarum; NPB: Number of patients at beginning of trial; NPE: Number of patients at end of trial; L of T: Length of
treatment; G: patients in Ginger group; C: patients in comparator group C1: control group nr 1; C2: control group nr 2; VAS: Visual analogue scale; MOS: Medical outcome study; RINVR: Rhodes Index of Nausea,
Vomiting and Retching. 5-point Likert type tool with 8 items.

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Characteristics of outcome measures demonstrated in Figure 2, and indicate high risk of bias
Nausea (the feeling of being about to vomit) is a subject- in especially the “blinding” and “other bias” categories.
ive feeling, and several tools have been developed to reli- All included studies were concluded to be either at high
ably measure it. In contrast to nausea, vomiting is a [19-21,23,24,26-29] or moderate [22,25,30] risk of bias.
readily observable occurrence that can be measured or Only one [19] of the twelve studies (8.3%) had no risk
reported without information from the patient. Still, the of other bias. Six [22-25,27,30] of the studies (50%) had
distress caused by vomiting cannot be observed by an- an unclear risk of other bias, and five [19,21,26,28,29]
other person, and remains a subjective feeling. The in- studies (41.6%) had a high risk of other bias. The high
cluded studies used a variety of tools to measure nausea risk studies all included dietary counseling as part of
severity and vomiting incidences. Six of the studies their treatment in both the experimental and the control
[19,21,25,26,28,29] used a visual analogue scale (VAS) of groups. The authors considered this as a possible con-
0–10 centimeters to score nausea severity, and partici- founding factor, since change in outcome scores could
pants recorded the number of vomiting episodes daily. be affected by the dietary adjustments made, rather than
One study [23] used a numerical scale of 1–10 for scor- the intervention itself. No reporting was done on the
ing nausea severity, as well as daily recording of vomit- dietary measures in any of these mentioned studies.
ing episodes. Four studies [20,24,27,30], used the Rhodes
Index of Nausea and Vomiting, or parts of this index, to Effect of interventions
measure both nausea and vomiting, and the remaining The included studies were split into four groups, accord-
study [22] used a 4 point system to score nausea and ing to the comparison substance used. Placebo was used
vomiting symptoms. in seven studies (considered a control substance). Four
studies used Vitamin B6, one study used Dimenhydrinate,
General response to treatment and one study used Metoclopramide as comparator (these
The tools used in the included studies to measure the three substances were considered active ingredients, and
general response to treatment outcome were Likert not controls). The Metoclopramide study compared gin-
scales [19,21,29], a point-system instrument [22] and the ger to both Metoclopramide and placebo.
Medical outcome survey (MOS) Short form-36 Health The analyses for the different active ingredients were
Survey [27,33]. done separately as these were different comparisons and
they could not be pooled in one meta-analysis. Subgroup
Adverse events and side-effects analyses addressing dosage and duration aspects were
The judgments made on the seriousness of the reported performed for the primary objectives, namely the effect-
side-effects or adverse events are the author team’s own iveness of ginger for reduction in nausea and vomiting.
subjective judgments, also taking into account the fact No sensitivity analyses were performed as a result of an
that some of these events can occur in a normal preg- insufficient number of studies per comparison group.
nancy, without any interventions. Adverse events and There were insufficient studies per comparison and
side effects were classified as major when it was consid- outcome to permit the use of funnel plots to assess
ered a serious complication, possibly being detrimental publication bias.
to the mother or fetus. Major events reported across the
studies were allergic reaction [30], arrhythmia [20], de- Comparison 1: Ginger versus Placebo
hydration [30], and spontaneous abortion [21,22,29]. Seven studies assessed the effect of ginger versus
Events were classified as minor when considered a dis- placebo [19,22-25,29,30].
comfort, but manageable side-effects. Minor events re-
ported across the studies included abdominal discomfort Improvement in nausea symptoms
[29], belching [27], burning sensation after capsule in- All seven studies assessing the effect of ginger versus
gestion [27], diarrhea [29], dry retching or vomiting after placebo reported this outcome but their results could
capsule ingestion [27], headaches [20,29], drowsiness not all be pooled in a meta-analysis. Two studies [19,29]
[19,20,26,28] and heartburn [19,20,26,28-30]. reported the reduction in the visual analogue scale of
post-therapy minus baseline nausea as mean and standard
Methodological quality deviation (SD) and results were pooled in a meta-analysis.
All included trials were RCT’s. The Cochrane “risk of Ginger significantly decreased nausea symptoms when
bias” assessment tool [18] was completed for each of the compared to placebo (MD 1.20, 95% CI: 0.56 to 1.84,
included studies to assess methodological quality and p = 0.0002) (Figure 3) and there was no significant hetero-
to enable data entry into the RevMan 5 program. The geneity detected between the two studies (Chi2 = 0.00,
author team’s judgments about each methodological p = 1.00, I2 = 0%). There were no significant subgroup
quality assessment factor across all included studies are differences between the higher dose (≥1500 mg daily) and
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Figure 2 Methodological quality graph: judgments about each methodological quality item presented as percentages for all included
studies (n = 12).

the lower dose (<1500 mg daily) with respect to the im- and SD values could be extracted. No treatment effect
provement in nausea symptoms (change in VAS scores) could therefore be calculated.
(Chi2 = 0.00, p = 1.00, I2 = 0%). No subgroup analysis with The remaining study [22] was a crossover study which
respect to duration was undertaken, as the two studies reported the relief scores on symptoms of a combination
had the same duration of 4 days. of nausea, vomiting, change in body weight, and patient’s
One study [24] reported improvement in nausea sever- opinion about the treatment. The observed values for
ity using a Rhodes Index questionnaire during days 1–5. the relief scores were reported for each patient during
The observed trend showed a significant reduction in the two periods of the crossover study in the form of a
nausea severity in favor of ginger compared to the pla- table. These values were used in calculating the mean
cebo group (p = 0.003) at the second to fifth day of treat- difference (MD) and its standard error (SE) using a
ment compared to the first day. paired analysis and the 95% CIs were calculated using
Two studies [23,25] reported this outcome in terms of the generic-inverse variance method in RevMan 5. A sig-
the number of women showing improvement in nausea nificantly greater relief of the symptoms was found after
symptoms (again measured by VAS scores). Meta-analysis ginger treatment compared to the placebo (MD 3.52,
of the results from these two studies shows that ginger 95% CI: 0.27 to 6.77).
failed to decrease nausea symptoms when compared to
the placebo (RR 2.00, 95% CI: 0.77 to 5.19, p = 0.15) and Reduction in the number of vomiting episodes
there may be moderate heterogeneity between the two All seven studies in this comparison reported a reduc-
studies (Chi2 = 2.42, p = 0.12, I2 = 59%). There were tion in the number of vomiting episodes, but not all
no subgroup differences between the longer duration their results could be pooled in a meta-analysis. Two
(≥7 days) and the shorter duration (<7 days) with studies [19,29] reported this outcome in the form of
respect to the improvement in nausea symptoms mean and SD, and their results could be pooled in a
(number showing significant improvement) (Chi2 = 2.04, meta-analysis. According to the meta-analysis, ginger
p = 0.15, I2 = 50.9%). No subgroup analysis with respect to failed to significantly reduce the number of vomiting
dose was undertaken, as the two studies had the same episodes compared to the placebo, although it did ap-
dosage of 1000 mg/day. proach significance (MD 0.72, 95% CI: −0.03 to 1.46,
One study [30] reported the trend in mean nausea p = 0.06) and statistically significant heterogeneity was
experience scores for both the ginger and placebo detected between the two studies (Chi2 = 3.44, p = 0.06,
groups in the form of a figure only, from which no mean I2 = 71%). There were no significant subgroup differences

Ginger Placebo Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI IV, Fixed, 95% CI
Basirat 2009 2.6 1.77 32 1.4 1.62 30 57.5% 1.20 [0.36, 2.04]
Vutyavanich 2001 2.1 1.9 32 0.9 2.2 35 42.5% 1.20 [0.22, 2.18]

Total (95% CI) 64 65 100.0% 1.20 [0.56, 1.84]

Heterogeneity: Chi² = 0.00, df = 1 (P = 1.00); I² = 0%
-10 -5 0 5 10
Test for overall effect: Z = 3.67 (P = 0.0002)
Favours placebo Favours ginger

Figure 3 Forest plot of the improvement in nausea symptoms measured by change in VAS scores (ginger versus placebo).
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between the higher dose (≥1500 mg daily) and the lower Comparison 2: Ginger versus Vitamin B6
dose (<1500 mg daily) with respect to the reduction in Four of the included studies assessed the effect of ginger
the number of vomiting episodes (Chi2 = 3.44, p = 0.06, versus vitamin B6 [20,21,27,28].
I2 = 71%). No dose–response effect was found for this
outcome. Improvement in nausea symptoms
One study [24] reported improvement in vomiting se- All four studies assessing the effect of ginger versus vita-
verity using a Rhodes Index questionnaire during days min B6 reported this outcome, but their results could
1–5. The observed trend showed a significant reduction not all be pooled in a meta-analysis. Two studies [21,28]
in vomiting severity in favor of ginger compared to the reported the reduction in the VAS scores of post-therapy
placebo group (p = 0.046) at the second to fifth day of minus baseline nausea as mean and SD and their results
treatment compared to the first day. were pooled in a meta-analysis. According to this meta-
One study [22] reported vomiting in conjunction analysis, ginger failed to significantly decrease nausea
with nausea scores (as discussed in previous section). symptoms when compared to vitamin B6 (MD 0.34, 95%
One study [23] reported the number of women who CI: −1.52 to 2.20, p = 0.72) and significant heterogeneity
stopped vomiting by day 6 of treatment. Treatment was detected between the two studies (Chi2 = 10.64,
with ginger failed to reduce the number of women who p = 0.001, I2 = 91%). There were significant subgroup
stopped vomiting by day 6, when compared to the differences between the higher dose (≥1500 mg daily)
placebo treatment (RR 3.33, 95% CI: 0.91 to 12.26). and the lower dose (<1500 mg daily) with respect to
One study [25] reported that incidence of vomiting the improvement in nausea symptoms (change in VAS
decreased by 50% in the ginger group and 9% in the scores) (Chi2 = 10.64, p = 0.001, I2 = 90.6%) (Figure 4).
placebo group, but this information is insufficient for This implies a dose–response effect for this outcome in
calculation of a treatment effect. One study [30] only favour of the lower dosage. The different dosages between
reported that there was no significant difference be- the two studies may be the source of heterogeneity detected
tween ginger extract and placebo groups for any of the in this meta-analysis.
vomiting symptoms but failed to give any values for No subgroup analysis with respect to duration was
the calculation of a treatment effect, as mentioned undertaken, as the two studies had the similar short du-
earlier. rations of 4 days and 3 days.
One study [27] reported the reduction in nausea
symptoms from baseline using the Rhodes Index of
General response to treatment Nausea (ranging from 0 to 12, with larger scores indi-
Only 3 of the 12 studies included in this SR reported on cating more symptoms). The results were reported in
this outcome. One study [19] reported that ginger did the form of mean and standard error (SE) and these
not significantly result in better responses to the treat- values were used in calculating the SDs. The means
ment, when compared to the placebo. and SDs were used in calculating the mean difference
(MD) and its 95% CIs. There was no statistically sig-
nificant improvement of nausea symptoms with ginger
The occurrence of adverse events and side effects treatment compared to vitamin B6 treatment (MD −0.3,
Four studies [19,23,25,29] reported that none of the par- 95% CI: −0.85 to 0.25).
ticipants experienced any adverse events from ginger The remaining study [20] reported the reduction in
during the treatment period. nausea vomiting scales (episodes of nausea, duration of
One study [22] reported that one patient had a spon- nausea, and number of vomits) using a modified Rhodes’
taneous abortion and one patient asked for a legal abor- score. The results were reported in form of mean and
tion. Because this trial had a crossover design and all SD and were used in calculating the MD which showed
patients received both treatments, no treatment effect that ginger treatment significantly improved the nausea
could be calculated for the occurrence of spontaneous and vomiting symptoms compared to vitamin B6 treat-
abortion after the treatment period. ment (MD 0.70, 95% CI: 0.20 to 1.20).
For all reported adverse events and side-effects in the
various studies [including allergic reaction [30], dehydra- Reduction in the number of vomiting episodes
tion [30], spontaneous abortions [29,30], abdominal dis- All four studies in this comparison group reported a re-
comfort [29], diarrhea [29], drowsiness [19], headache duction in the number of vomiting episodes, but not all
[29], heartburn [19,29,30], worsening of symptoms re- the results could be pooled in a meta-analysis. Results
quiring pharmaceutical treatment [30] there were no from three studies [21,27,28] were reported in the form
significant differences between the ginger and placebo of mean and SD which were pooled in a meta-analysis.
treated groups (Table 2). According to this meta-analysis, ginger failed to reduce
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Table 2 Pooled estimates of effect size (95% confidence intervals) expressed as weighted relative risk for adverse
events and side-effects of ginger versus control group (Placebo, Vitamin B6, Dimenhydrinate)
Outcome Number of studies RR 95% CI Heterogeneity
Chi2 I2 (%)
Ginger versus placebo
#
Allergic reaction [30] 1 3.00 0.12 to 72.20
#
Dehydration [30] 1 3.00 0.12 to 72.20
#
Spontaneous abortions [29,30] 2 3.14 0.65 to 15.11 0.00 0
Abdominal discomfort [29] 1 3.27 0.14 to 77.57
Diarrhea [29] 1 3.27 0.14 to 77.57
Drowsiness [29] 1 2.82 0.12 to 66.62
Headache [29] 1 1.31 0.44 to 3.89
Heartburn[19,29,30] 3 5.03 0.89 to 28.61 0.35 0
Worsening of symptoms requiring pharmaceutical treatment [30] 1 0.33 0.01 to 8.02
Ginger versus vitamin B6
#
Arrhythmia [20] 1 0.51 0.05 to 5.46
#
Spontaneous abortions [21,27] 2 0.49 0.17 to 1.42 1.67 40
Belching [27] 1 27.18 1.63 to 453.06*
Burning sensation after capsule ingestion [27] 1 1.01 0.21 to 4.91
Drowsiness [20,28] 2 0.75 0.48 to 1.19 0.18 0
Dry retching [27] 1 0.93 0.76 to 1.15
Heartburn [20,28] 2 2.35 0.93 to 5.93 1.03 3
Vomiting [27] 1 1.51 0.26 to 8.91
Ginger versus Dimenhydrinate
Drowsiness [26] 1 0.08 0.03 to 0.18**
Heartburn [26] 1 1.44 0.65 to 3.20
#
Major adverse events (serious complications, possibly detrimental to the mother or fetus) (authors’ judgement); rest considered minor (discomfort, but
manageable side effects) - sorted alphabetically, first major then minor events.
*Indicates significant finding: Ginger significantly increased the risk of belching compared to vitamin B6.
**Indicates significant finding: Dimenhydrinate significantly increased the risk of drowsiness compared to ginger.
RR, Relative risk; CI, confidence interval.

the number of vomiting episodes when compared to The occurrence of adverse events and side-effects
vitamin B6 (MD −0.07, 95% CI: −0.48 to 0.35, p = 0.76) Two studies [20,28] reported that none of the partici-
and there may have been moderate heterogeneity be- pants experienced any adverse events from either ginger
tween the three studies (Chi2 = 3.58, p = 0.17, I2 = 44%). or vitamin B6 during the treatment period.
There were no significant subgroup differences between Ginger significantly increased the risk of belching com-
the higher dose (>1500 mg daily) and the lower dose pared to vitamin B6 (RR 27.18, 95% CI: 1.63 to 453.06) in
(<1500 mg daily) with respect to the reduction in the num- one study [27]. For all other adverse events and
ber of vomiting episodes (Chi2 = 0.72, p = 0.40, I2 = 0%). side-effects reported in the various studies [including
Similarly there were no significant subgroup differences arrhythmia [20], spontaneous abortions [21,27], burning
between the longer duration (≥7 days) and the shorter dur- sensation after capsule ingestion [27], drowsiness [20,28],
ation (<7 days) with respect to the reduction in the number dry retching [27], heartburn [20,28], vomiting [27]] there
of vomiting episodes (Chi2 = 3.51, p = 0.06, I2 = 71.5%). were no significant differences between the ginger and
The remaining one study [20] reported vomiting in Vitamin B6 treated groups (Table 2).
conjunction with nausea as mentioned above.
Comparison 3: Ginger versus Dimenhydrinate
General response to treatment Only one included study [26] assessed the effect of gin-
A meta-analysis of two studies [21,27] showed that gin- ger versus dimenhydrinate. This study reported a reduc-
ger did not significantly increase the number reporting tion in the VAS scores of post-therapy minus baseline
improvement when compared to vitamin B6. nausea, as well as reduction in the number of vomiting
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Ginger Vitamin B6 Mean Difference Mean Difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Random, 95% CI IV, Random, 95% CI
2.1.1 Higher dose (>=1500mg daily)
Sripramote 2003 1.4 2.21 64 2 2.19 64 50.5% -0.60 [-1.36, 0.16]
Subtotal (95% CI) 64 64 50.5% -0.60 [-1.36, 0.16]
Heterogeneity: Not applicable
Test for overall effect: Z = 1.54 (P = 0.12)

2.1.2 Lower dose (<1500mg daily)

Ensiyeh 2009 2.2 1.9 35 0.9 1.7 34 49.5% 1.30 [0.45, 2.15]
Subtotal (95% CI) 35 34 49.5% 1.30 [0.45, 2.15]
Heterogeneity: Not applicable
Test for overall effect: Z = 3.00 (P = 0.003)

Total (95% CI) 99 98 100.0% 0.34 [-1.52, 2.20]

Heterogeneity: Tau² = 1.64; Chi² = 10.64, df = 1 (P = 0.001); I² = 91%
-4 -2 0 2 4
Test for overall effect: Z = 0.36 (P = 0.72)
Favours vitamin B6 Favours ginger
Test for subgroup differences: Chi² = 10.64, df = 1 (P = 0.001), I² = 90.6%
Figure 4 Forest plot of the improvement in nausea symptoms as measured by the change in VAS scores (ginger versus Vitamin B6):
subgroup analysis regarding dose (≥1500 mg versus < 1500 mg).

episodes in the form of a figure only, from which no Discussion

mean and SD values could be extracted. No treatment Literature indicate that the exact cause and treatment of
effect could therefore be calculated. NVP is still unclear [2,6,17,34-37]. Mothers and health
No adverse events were reported. The study reported practitioners often investigate alternative options to alle-
results on drowsiness (minor side effect), with dimenhy- viate symptoms of NVP, due to the possible harmful side
drinate significantly increasing the risk of drowsiness effects that conventional medicine may pose to the un-
compared to ginger (RR 0.08, 95% CI: 0.03 to 0.18). The born fetus. In this regard, ginger is considered by many
study also reported results on heartburn (minor side as a possible non-pharmacological treatment option for
effect) and there was no statistically significant difference NVP. This updated systematic review has investigated
found between the ginger and dimenhydrinate treated the current evidence-base and supports and strengthen
groups (Table 2). previous findings that ginger could be considered a harm-
less and possibly effective alternative option for women
Comparison 4: Ginger versus Metoclopramide suffering from the symptoms of NVP.
Only one included study [24] assessed the effect of
ginger versus metoclopramide. Primary outcomes
Symptomatic relief of nausea, number of vomiting episodes
Improvement in nausea symptoms and general response to treatment
One study [24] reported improvement in nausea severity Ginger versus placebo was assessed in seven of the in-
using a Rhodes Index questionnaire during days 1 to 5. cluded studies [19,22-25,29,30]. Individually, all seven
There was no significant difference in the observed studies concluded that ginger was more effective than
trend in nausea severity between the ginger and meto- the placebo in relieving the intensity of nausea, or NVP
clopramide groups (p = 0.683) at the second to fifth day in general. One meta-analysis of two studies [19,29] in
of treatment compared to the first day. this SR showed that ginger significantly decreased nau-
sea symptoms when compared to placebo. When taking
Improvement in vomiting into account that other SRs [10,16,17,35,36] as well as
One study [24] reported improvement in vomiting sever- the above-mentioned 7 concluded that ginger had bene-
ity using a Rhodes Index questionnaire during days 1 to ficial effects on nausea during pregnancy (together with
5. There was no significant difference in the observed the findings of this SR), it is probably safe to assume that
trend in vomiting severity between the ginger and meto- ginger has potential as a possible anti-emetic drug-
clopramide groups (p = 0.718) at the second to fifth day alternative during pregnancy. The theoretical physio-
of treatment compared to the first day. No adverse logical mechanism by which ginger affects the digestive
events were reported in this study. system also supports this theory. Ginger can increase
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gastric contractility, speeding up gastric emptying, and included 4 RCTs [23,25,27,30], all of which were also
therefore increasing the gastro-intestinal transit time of included in the current SR. This group reported that
meals, which can decrease the feeling of nausea [15]. ginger was more effective than placebo, and as effective
Although three [22,25,29] of the seven studies that as Vitamin B6 in improving NVP. They concluded that
assessed ginger versus placebo concluded individually ginger use for NVP were safe, but highlighted the need
that ginger was more effective than placebo in reducing for further studies with longer duration, to establish the
the number of vomiting episodes, the remaining evi- long term safety and effectiveness of ginger.
dence and meta-analysis performed lead to the conclu- The SR by Thomson et al. [36] was published early in
sion that ginger did not significantly reduce the number 2014 and included six studies [19,22,23,25,27,29], all of
of vomiting episodes during NVP when compared to the which were also included in the current SR. This meta-
placebo. A meta-analysis of three studies [21,27,28] analysis indicated that ginger is better than placebo in
showed that ginger did not significantly reduce vomiting improving NVP (RR 1.76, 95% CI: 1.18 to 2.65).
episodes when compared to vitamin B6. Based on this Both these recent systematic reviews used the ap-
currently available evidence, the author team concludes proach of comparing ginger to placebo (both also in-
that ginger does not seem to reduce the number of vomit- cluding one study comparing ginger to Vitamin B6 [27]).
ing episodes significantly when compared to vitamin B6. This current updated SR builds substantially on previous
Due to the small number of studies reporting on the reviews by including a recent literature search and
outcome of general response to treatment, no conclu- grouping all comparators into four groups (placebo,
sions can be drawn in this regard. Vitamin B6, dimenhydrinate and metoclopramide), as
any other treatment than placebo was considered an
Secondary outcomes active ingredient.
Adverse events and side-effects
The author team made subjective judgments to classify Practice points
the occurring adverse events and side-effects as major From a practice point of view, the subgroup analysis per-
(serious complications detrimental to the mother or formed indicated that the lower dosage of <1500 mg gin-
fetus, including arrhythmia, spontaneous abortion, aller- ger per day could possibly be more effective than the
gic reaction to treatment, and dehydration), or minor higher dosage of ≥1500 mg (again, bearing in mind the
(discomfort, but manageable side-effects). According to limited value of the small subgroup analyses). Most
the available evidence (Table 2), ginger significantly in- studies provided 1000 mg of ginger powder for a period
creased the risk of belching compared to vitamin B6 of 4 days to women suffering from NVP (with no
(bearing in mind the very large CI indicating poor preci- apparent side-effects or adverse events). The litera-
sion and thus limiting firm conclusions). Dimenhydrinate ture suggests taking the total dose in three to four
significantly increased the risk of drowsiness compared to divided doses during the day, irrespective of meal-
ginger. Ginger therefore does not seem to pose a risk for times [21-23,25,26,29,30]. Mothers can be advised to
any major side-effects or adverse events occurring, and use ginger freely in their cooking, to drink ginger tea and
thus no risk for any serious complications detrimental to soft drinks, and to have dry ginger biscuits as needed.
the mother or fetus.
Strengths and limitations
Comparisons with other studies This updated SR includes the latest trials related to the
The findings of this updated SR compare well with the find- topic, with the last search for studies performed in July
ings of previously conducted reviews [10,14,16,17,34-36] 2013. The small sample sizes and few study numbers
on the same topic. Limited meta-analysis could be per- analyzed per outcome, as well as differences in dosage
formed, often due to the heterogeneity in participants, and duration of treatment lead to high levels of incon-
interventions, outcome measures and comparison groups sistency and heterogeneity in the results of the review.
encountered. This clearly shows the need for more re- Unfortunately, many of the included studies did not
search on the topic, with larger studies and standardization present data in a usable form for inclusion in meta-
of methods and materials. All these reviews suggest that analysis, or similar outcomes were reported differently
ginger may be effective for the treatment of NVP, but data and could not be pooled together. These factors limit
is insufficient to draw firm conclusions regarding the the strength of evidence and cause some degree of
dosage and duration of treatment. uncertainty when interpreting the results. None of the
Two recently published systematic reviews on the twelve studies included in this SR described any form of
same topic support the potential of ginger as a possible chemical or chromatographic tests to verify the exact
treatment option for NVP [35,36]. The SR by Ding et al. composition of the active compounds in the ginger prep-
[35] included studies published from 2000–2009 and arations. Another limitation of this SR is the inclusion of
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only English language studies, although foreign language Author details

1
studies were documented for possible future inclusion. Division of Human Nutrition, Faculty of Medicine and Health Sciences,
Stellenbosch University and Tygerberg Academic Hospital, Cape Town,
As with many nutrition-related research studies, it is South Africa. 2Centre for Evidence Based Health Care, Faculty of Medicine
difficult to control every exposure and it is almost and Health Sciences, Stellenbosch University, Cape Town, South Africa.
3
impossible to keep all dietary exposures identical for Current affiliation: Discipline of Human Nutrition and Dietetics, School of
Health Care Sciences, University of Limpopo, MEDUNSA Campus,
all participants. Ginger has a very characteristic and Garankuwa, South Africa.
recognizable taste, which makes it difficult to mask dur-
ing trials. This could act as a potential confounder, as it Received: 9 December 2013 Accepted: 13 March 2014
Published: 19 March 2014
can be considered “unblinding” in some cases. A pos-
sible solution to this problem is to do pre-trial testing,
as was done in the study by Vutyavanich et al., [29] to References
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doi:10.1186/1475-2891-13-20
Cite this article as: Viljoen et al.: A systematic review and meta-analysis of
the effect and safety of ginger in the treatment of pregnancy-associated
nausea and vomiting. Nutrition Journal 2014 13:20.

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