Effectiveness and Safety of Ginger in the Treatment of Pregnancy-Induced Nausea and Vomiting

Article (PDF Available)inObstetrics and Gynecology 105(4):849-56 · May 2005with802 Reads
DOI: 10.1097/01.AOG.0000154890.47642.23 · Source: PubMed
Abstract
Conventional antiemetics are burdened with the potential of teratogenic effects during the critical embryogenic period of pregnancy. Thus, a safe and effective medication would be a welcome addition to the therapeutic repertoire. This systematic review was aimed at assessing the evidence for or against the efficacy and safety of ginger (Zingiber officinale) therapy for nausea and vomiting during pregnancy. Systematic literature searches were conducted in 3 computerized databases (MEDLINE, EMBASE, and Cochrane Library), and the reference lists of all papers located were checked for further relevant publications. For the evaluation of efficacy, only double-blind, randomized controlled trials (RCTs) were included. All retrieved clinical data, including uncontrolled trials, case reports, observational studies, and RCTs, were included in the review of safety. Six double-blind RCTs with a total of 675 participants and a prospective observational cohort study (n = 187) met all inclusion criteria. The methodological quality of 4 of 5 RCTs was high. Four of the 6 RCTs (n = 246) showed superiority of ginger over placebo; the other 2 RCTs (n = 429) indicated that ginger was as effective as the reference drug (vitamin B6) in relieving the severity of nausea and vomiting episodes. The observational study retrieved and RCTs (including follow-up periods) showed the absence of significant side effects or adverse effects on pregnancy outcomes. There were no spontaneous or case reports of adverse events during ginger treatment in pregnancy. Ginger may be an effective treatment for nausea and vomiting in pregnancy. However, more observational studies, with a larger sample size, are needed to confirm the encouraging preliminary data on ginger safety. I.

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REVIEW
Effectiveness and Safety of Ginger in the Treatment
of Pregnancy-Induced Nausea and Vomiting
Francesca Borrelli,
PhD
, Raffaele Capasso,
PharmD
, Gabriella Aviello,
PharmD
,
Max H. Pittler,
MD
,
PhD
, and Angelo A. Izzo,
PhD
OBJECTIVE: Conventional antiemetics are burdened with
the potential of teratogenic effects during the critical em-
bryogenic period of pregnancy. Thus, a safe and effective
medication would be a welcome addition to the therapeutic
repertoire. This systematic review was aimed at assessing
the evidence for or against the efficacy and safety of ginger
(Zingiber officinale) therapy for nausea and vomiting dur-
ing pregnancy.
DATA SOURCES: Systematic literature searches were con-
ducted in 3 computerized databases (MEDLINE, EMBASE,
and Cochrane Library), and the reference lists of all papers
located were checked for further relevant publications.
METHODS OF STUDY SELECTION: For the evaluation of effi-
cacy, only double-blind, randomized controlled trials
(RCTs) were included. All retrieved clinical data, includ-
ing uncontrolled trials, case reports, observational studies,
and RCTs, were included in the review of safety.
TABULATION, INTEGRATION, AND RESULTS: Six double-blind
RCTs with a total of 675 participants and a prospective
observational cohort study (n 187) met all inclusion
criteria. The methodological quality of 4 of 5 RCTs was
high. Four of the 6 RCTs (n 246) showed superiority of
ginger over placebo; the other 2 RCTs (n 429) indicated
that ginger was as effective as the reference drug (vitamin
B6) in relieving the severity of nausea and vomiting epi-
sodes. The observational study retrieved and RCTs (in-
cluding follow-up periods) showed the absence of signifi-
cant side effects or adverse effects on pregnancy outcomes.
There were no spontaneous or case reports of adverse
events during ginger treatment in pregnancy.
CONCLUSION: Ginger may be an effective treatment for
nausea and vomiting in pregnancy. However, more obser-
vational studies, with a larger sample size, are needed to
confirm the encouraging preliminary data on ginger safety
(Obstet Gynecol 2005;105:849–56. © 2005 by The Amer-
ican College of Obstetricians and Gynecologists.)
LEVEL OF EVIDENCE: I
Nausea and vomiting (commonly referred to as morning
sickness) are very common symptoms in pregnancy,
affecting 70 85% and 40–50% of pregnant women,
respectively.
1,2
It has been estimated that the financial
burden of morning sickness on the American health
system is more than 130 million dollars per year.
3,4
Usually morning sickness begins between the first and
second missed menstrual period and may last until the end
of the third month of pregnancy. However, approximately
20% of women experience nausea and vomiting for a
longer period of time, and 2% of this group suffers until the
end of the pregnancy. Moreover, a small number (0.3–3%)
of all pregnant women experience a more severe form of
morning sickness, namely hyperemesis gravidarum.
5
Many medications are currently available for the treat-
ment of morning sickness.
3,6
However, concerns about
the potential teratogenic effects of drugs administered
during the critical embryogenic period of pregnancy
drastically limit their use. Consequently, many pregnant
women use complementary and alternative therapies.
These include vitamins, herbal products, homeopathic
preparation, acupressure, and acupuncture.
7–9
A recent
literature survey reports that the most commonly used
natural drugs for the treatment of morning sickness are
ginger, chamomile, peppermint, and raspberry leaf.
10
Among these, only ginger has been evaluated in con-
trolled trials for the treatment of morning sickness.
Ginger, a rhizome of Zingiber officinale Roscoe (Fam.
Zingiberaceae), has been widely used as a spice to enhance
the flavor of food and beverage and for medical pur-
poses, particularly to treat ailments such stomachache,
diarrhea, and nausea.
11,12
Ginger is among the 20 top-
selling herbal supplements in the United States, and its
retail sales in the mainstream U.S. market in 2001
amounted to 1.2 million dollars.
13
German and Euro-
pean monographs are available, and both list nausea/
vomiting as indications. Moreover, in 1997 the U.S.
Pharmacopoeia approved ginger and powdered ginger
monographs for inclusion in the National Formulary.
From the Department of Experimental Pharmacology, University of Naples Fed-
erico II, Naples, Italy; and Complementary Medicine, Peninsula Medical School,
Universities of Exeter and Plymouth, Exeter, United Kingdom.
VOL. 105, NO. 4, APRIL 2005
849© 2005 by The American College of Obstetricians and Gynecologists. 0029-7844/05/$30.00
Published by Lippincott Williams & Wilkins. doi:10.1097/01.AOG.0000154890.47642.23
Given the widespread use of ginger as an antiemetic drug,
we systematically assessed the efficacy and safety of this herbal
product in the treatment of nausea and vomiting in pregnancy.
SOURCES
Literature searches were performed to identify all clinical
reports regarding the efficacy and safety of ginger in
pregnancy. Three electronic databases, MEDLINE,
EMBASE, and Cochrane Library, were searched (all
from their respective inceptions to June 2004) using the
search terms “ginger” and Zingiber officinale.” No lan-
guage restrictions were imposed. Citations and bibliog-
raphies of all retrieved papers were reviewed for further
relevant publications not found in the electronic
searches. Additionally, several manufacturers of ginger-
containing preparations were asked to contribute pub-
lished or unpublished material, and web sites devoted to
providing information for pregnant women were visited.
STUDY SELECTION
For the evaluation of efficacy, only double-blind, ran-
domized controlled trials (RCTs) of the oral administra-
tion of a monopreparation of ginger for the treatment of
the symptoms of pregnancy-related nausea and vomiting
(morning sickness and hyperemesis gravidarum) were in-
cluded. All retrieved clinical data, including uncontrolled
trials, case reports, and observational studies, were in-
cluded in the review of safety. For papers not reporting
enough information, the authors were contacted to provide
additional data. The methodological quality of each study
was assessed using the scoring system developed by Jadad
and colleagues (Box: Jadad Score: Instrument Used to
Assess Methodological Quality of Clinical Trials”).
14
All
reviewers independently performed the screening of stud-
ies, selection, validation, data extraction, and the assess-
ment of methodological quality. Disagreements about the
assessment of data were resolved by discussion, and con-
sensus was reached in all cases. A meta-analysis was con-
sidered but proved to be not feasible. Because of the differ-
ent measures used to assess the outcomes and because of
the different control groups in the trials, a clinically mean-
ingful pooling of the data was not possible.
RESULTS
The searches identified 33 potentially relevant tri-
als,
15–47
but only 6 double-blind RCTs
15–20
met the
aforementioned inclusion criteria and were included in
this systematic review. The flow chart provides an over-
view of all included and excluded trials (Fig. 1). The
assessment of their methodological quality revealed a
maximal score for 5 of 6 studies. Four RCTs
15–17,19
compared the efficacy of ginger to placebo, whereas 2
trials
18,20
compared the efficacy of ginger to vitamin B6
(used as a reference compound). Key data are summa-
Fig. 1. Flowchart of studies included and excluded. RCTs,
randomized controlled trials.
Borrelli. Ginger and Pregnancy. Obstet Gynecol 2005.
Jadad Score: Instrument Used to Assess
Methodological Quality of Clinical Trials
Each “yes” scores 1 point; each “no” 0 points:
x Study described as randomized (this includes the
use of words such as random, randomly, and ran-
domization)?
x Study described as double-blind?
x Description of withdrawals and dropouts?
x Method to generate the sequence of randomiza-
tion described and appropriate (table of random
numbers, computer generated, etc.)?
x Method of double-blinding described and appro-
priate (identical placebo, active placebo, dummy,
etc.)?
Deduct 1 point if:
x Method to generate the sequence of randomiza-
tion described and inappropriate (patients were
allocated alternately, or according to their date of
birth, hospital number, etc.)?
x Method of double-blinding described and inap-
propriate (comparison of tablet versus injection
with no double dummy, etc.)?
850 Borrelli et al Ginger and Pregnancy OBSTETRICS & GYNECOLOGY
rized in Table 1, while the main results are described
below.
The first double-blind, crossover RCT included 30
pregnant women who needed hospitalization for hy-
peremesis gravidarum before the 20th week of gesta-
tion.
15
Twenty-seven woman completed the trial. Pa
-
tients received either ginger (250 mg) or placebo (lactose,
250 mg) 4 times a day for 4 days; the washout period was
2 days. No indication on the source of the ginger pow-
dered root was reported. Other antiemetic medications
Table 1. Clinical Trials Reporting the Effectiveness of Ginger in Treatment of Pregnancy-Related Nausea and Vomiting
Study JS Design
NPS/NPE
(Patient
Treatment)
Period of
Gestation
(wk)
Ginger
Dosage
Control
Treatment
(Dosage) LT
Main Outcome
Measures Main Results
Fischer-
Rasmussen,
1991
15
3 Randomized
double-blind
cross-over
trial
30/27
(14G, 13C)
20 250 mg 4
times
daily
Placebo 4 d Severity and relief
of nausea and
vomiting (4-point
scoring system);
change in body
weight
Ginger was better
than placebo in
diminishing or
eliminating the
symptoms of
hyperemesis
Vutyavanich,
2001
16
5 Randomized
double-blind
trial
70/67
(32G, 35C)
17 250 mg 4
times
daily
Placebo 4 d Severity of nausea
and vomiting
(visual analogue
scale and Likert
scale); number of
vomiting
episodes;
occurrence of side
and adverse
effects on
pregnancy
Ginger was more
effective than
placebo in
reducing the
severity of nausea
and vomiting; no
adverse effect was
detected
Keating,
2002
17
5 Randomized
double-blind
trial
26/23
(13G, 10C)
12 250 mg 4
times
daily
Placebo 2 wk Duration and
severity of nausea
and vomiting (10-
point scale)
Ginger was more
effective than
placebo in
reducing nausea
and stopping
vomiting
Sripramote,
2003
18
5 Randomized
double-blind
trial
138/128
(64G, 64C)
17 500 mg 3
times
daily
Vitamin B6
(10 mg; 3
times a
day) (30
mg)
3 d Severity of nausea
(visual analogue
scale), number of
vomiting
episodes, and
occurrence of
adverse effects
Significant
reductions of
nausea score and
vomiting episodes
were observed in
ginger and
vitamin B6
groups
Willetts,
2003
19
5 Randomized
double-blind
trial
120
(60G, 60C)
20 125 mg
of
ginger
extract
4 times
daily
Placebo
(soy bean
oil)
4 d Nausea, vomiting,
and retching
(Rhodes Index);
occurrence of side
and adverse
effects on
pregnancy.
Ginger was more
effective than
placebo in
reducing nausea
and retching; no
effects on
vomiting
symptoms
Smith,
2004
20
5 Randomized
double-blind
trial
291/235
(120G,
115C)
8,
16
350 mg 3
times
daily
Vitamin B6
(25 mg; 3
times a
day) (75
mg)
3 wk Nausea, retching,
and vomiting at
days 7, 14, 21
(Rhodes Index,
Form 2
9
); change
in health status
(MOS 36-Item
Short Form
Health Survey)
Ginger was as
effective as
vitamin B6 in
reducing nausea,
dry retching, and
vomiting
compared with
baseline
JS, Jadad Score; NPS/NPE, number of pregnancies at the start of trial/number of pregnancies at the end of trial; LT, length of treatment; G, patients
in the ginger group; C, patients in the control group; MOS, Medical Outcomes Study.
851VOL. 105, NO. 4, APRIL 2005 Borrelli et al Ginger and Pregnancy
were withdrawn. Outcomes included degree of nausea
and vomiting, change in body weight, adverse effects on
pregnancy, and pregnancy outcomes. The degree of nau-
sea and vomiting was evaluated by using 2 relief and
severity scoring systems. The relief score aimed to evaluate
the efficacy of ginger, whereas the severity score was used
to exclude a potential beneficial effect of ginger to the
second period of treatment (placebo). The results showed
that ginger was better than placebo in diminishing or elim-
inating the symptoms of hyperemesis gravidarum.
Vutyavanich et al
16
evaluated the effectiveness of
ginger on pregnancy-induced nausea and vomiting in a
double-masked, placebo-controlled RCT. Sixty-seven
(70 at the beginning of the trial) women before the 17th
week of gestation who manifested nausea (with or with-
out vomiting) and did not take any other medication in
the week before the study were evaluated. Subjects re-
ceived either 250 mg ginger or placebo 4 times daily for
4 days. Ginger preparations were obtained from fresh
ginger root, which was chopped into small pieces, baked
at 60°C for 24 hours, and then ground into powder.
Outcomes included change in nausea symptoms and
number of vomiting episodes. Occurrence of side effects
and adverse effects on pregnancy outcomes, such as
abortion, preterm birth, congenital anomaly, perinatal
death, and mode of delivery, were also taken into ac-
count. The degree of nausea and the number of vomiting
episodes were recorded 24 hours before treatment, as
well as twice daily (nausea) or one time daily (vomiting)
each subsequent day of treatment. To avoid the subjec-
tivity of nausea symptoms, 2 independent measurement
scales, a visual analogue scale (objective) and a 5-item
Likert scale (subjective), were used to quantify the changes
in severity. The results showed a significantly (time-depen-
dent) greater reduction in nausea score and in the number
of vomiting episodes in the ginger group than in the placebo
group. Reductions of nausea score and vomiting epi-
sodes were significant compared with placebo only on
day 3 and day 2 of treatment, respectively.
The third double-blind RCT included 23 pregnant
women (26 at the beginning of the trial), in the first
trimester of pregnancy, with nausea and with or without
vomiting.
17
Patients received either a tablespoon of
syrup containing 250 mg ginger or placebo syrup 4 times
daily for 2 weeks. Ginger rhizome juice was obtained via
a carbon dioxide supercritical extract of dried ginger
rhizome. The level of nausea and number of vomiting
episodes were recorded daily in a diary and quantified
on a numerical scale of 1 to 10. The effect of ginger on
pregnancy weight, but not on pregnancy outcomes, was
also analyzed. After 9 days, treatment, nausea levels
were reduced in 77% and 20% of patients in the ginger
and placebo groups, respectively. Moreover, 67% of
women in the ginger group and 20% of women in the
placebo group (who were vomiting daily at the begin-
ning of the treatment) stopped vomiting by day 6.
One hundred thirty-eight (128 completed the trial)
pregnant women before 17 weeks of gestation
18
were
enrolled in the fourth double-blind RCT. Patients re-
quested antiemetics for the nausea symptoms and did
not take any other medication in the week before the
study. Subjects received either a 500-mg capsule of gin-
ger or 10-mg capsule of vitamin B6 orally 3 times daily.
Ginger preparations were obtained from fresh middle-
aged ginger root, which was chopped into small pieces,
dried in sunlight, and ground into powder. Outcomes
included change in nausea symptoms and number of
vomiting episodes and occurrence of adverse effects
(drowsiness, palpitations, heartburn, and mouth dry-
ness). Effects of ginger on pregnancy outcomes were not
analyzed. The degree of nausea (using the visual ana-
logue scale) and the number of vomiting episodes were
measured 24 hours before treatment, as well as 3 times
daily on each subsequent day of treatment. Both ginger
and vitamin B6 significantly reduced the degree of nau-
sea and the number of vomiting episodes. The reduc-
tions of nausea score and nausea episodes were signifi-
cant after a 1-day treatment.
A double-blind, placebo-controlled RCT evaluated
the effectiveness of a ginger extract (EV.EXT35) on 120
women with morning sickness before 17th week of ges-
tation.
19
Subjects received either 125 mg of ginger extract
(equivalent to 1.5 g of dried ginger) or placebo (soy bean
oil) 4 times daily for 4 days. No data were reported on
the preparation of the ginger extract. Outcomes included
the frequency, duration, and distress caused by the
symptoms of nausea, vomiting, and retching. Secondary
outcomes included gestational age, birth weight, and
occurrence of side effects and adverse effects on preg-
nancy outcomes such as abortion, stillbirth, congenital
abnormalities, and neonatal death. Pregnancy-related
symptoms were recorded 24 hours before and during the
4 days of treatment (4 time a day) using the Rhodes
Index of Nausea, Vomiting, and Retching (an 8-item,
5-point Likert-type tool). The follow-up of the study
included 81 women (women from the placebo and gin-
ger groups who were given an 18-day ginger supply
following the end of the trial). Outcomes were compared
with the general infant population delivered at the Royal
Hospital for Women in Sydney. The results showed a
significant reduction in nausea experience, occurrence, and
distress in the ginger and in the placebo groups. However,
the reduction of nausea scores was significantly higher in
the ginger than in the placebo group. Similar results were
observed for retching symptoms. There was no significant
852 Borrelli et al Ginger and Pregnancy OBSTETRICS & GYNECOLOGY
difference between ginger extract and placebo groups for
any of the vomiting symptoms.
The most recent double-blind RCT involved 291
women (235 subjects completed the trial) between 8 and
16 weeks of gestation.
20
Subjects received either ginger
(350 mg) or vitamin B6 (25 mg) 3 times daily for 3 weeks.
Women were allowed to use other medications during
the trial (25% used an antiemetic, no data on the dosage
used). No information was reported on the preparation
of the ginger powder. Outcomes included both change in
nausea, dry retching, and vomiting episodes (from base-
line at days 7, 14, and 21, measured by the Rhodes Index
of Nausea and Vomiting, Form 2,
9
5-point Likert scale)
and improvement in health status (measured by the
Medical Outcomes Study 36-Item Short Form Health
Survey). The baseline pregnancy-related symptoms
were recorded for 3 days before treatment. Secondary
outcomes included the occurrence of side effects and
adverse pregnancy outcomes such as antepartum hem-
orrhage, pregnancy-induced hypertension, preeclamp-
sia, perinatal and neonatal death, preterm birth, and
congenital abnormalities. The results showed that ginger
was therapeutically equivalent to vitamin B6 in alleviat-
ing nausea, dry retching, and vomiting. However, 20%
of the pregnant women still continued to use antiemetics
at the end of the trial. A significant difference was found
in the percentage of women reporting belching while
using ginger compared with those using vitamin B6 (9%
and 0% for ginger and vitamin B6 groups, respectively).
Five of the 6 RCTs
15,16,18–20
described above and 1
prospective observational cohort study (described in
detail below)
21
specifically evaluated ginger safety in
pregnancy. Four RCTs, as well as the observational
study, investigated ginger-induced adverse effects on
pregnancies
16,18–21
and on the fetus (pregnancy out
-
comes).
15,16,19–21
Pregnancy outcomes, collected after
the delivery, included antepartum hemorrhage, pre-
eclampsia, preterm birth, perinatal and neonatal death,
congenital abnormalities, and birth weight. There were
no reports of adverse events during ginger treatment.
Adverse effects on pregnancies were observed in 4 of
6 clinical trials
16,18–20
. These included headache,
16
diar
-
rhea and abdominal discomfort,
16
drowsiness,
18
re
-
flux,
19
and heartburn.
16,18–20
The follow-up of
RCTs
15,16,19,20
showed no difference in the occurrence
of spontaneous abortions, stillbirth, term delivery and
cesarean deliveries, neonatal death, gestational age, and
congenital abnormalities between women who were ex-
posed to ginger and women exposed to vitamin B6
20
or
placebo.
15,16
Similar results were found when the effect
of ginger on pregnancy outcomes was compared with the
general population.
18
The observational cohort comparative study involved
the enrollment of 187 pregnant women exposed to gin-
ger and 187 women exposed to nonteratogen drugs
(which were not antiemetics) in the first trimester of
pregnancy.
21
Among the 187 women exposed to ginger,
39% used ginger concurrently with an antiemetic drug.
All subjects answered a structured questionnaire that
elicited information about medical indication for ginger
use, dosage, frequency of administration, and timing of
exposure, as well as maternal demographics and obstet-
ric history. After the delivery, women were questioned
regarding the course of the pregnancy, the health of the
child, the specific details of the exposure to ginger, and
any other exposures or use of drugs during the preg-
nancy. Outcomes included the incidence of major mal-
formations (congenital anomalies and social acceptabil-
ity of the individual), rates of spontaneous or therapeutic
abortions, live births and stillbirths, gestational age at
birth, and birth weight. Dosage and origin of ginger were
not documented. No statistically significant differences
between the 2 groups regarding live births, spontaneous
abortions, stillbirths, therapeutic abortions, birth weight,
or gestational age were found. A significant difference
was detected in the rates of low birth weight infants, ie,
those weighing less than 2,500 g (1.6% and 6.4% in the
ginger and comparison groups, respectively; P .05),
despite the presence of 8 sets of twins in the ginger group.
CONCLUSION
This systematic review suggests that ginger may be a safe
and effective option for the treatment of nausea and
vomiting in pregnancy. This finding corroborates the
results of previous inconclusive analyses based on less
extensive data.
3,48
These studies were from Australia (2
studies), Thailand (2 studies), Canada (1 study), and
Denmark (1 study). Whether or not demographic or
social/cultural similarities and differences among these
populations can be generalized to the universe of preg-
nant women worldwide cannot be extrapolated from the
present review. According to the Jadad score,
14
the quality
of the RCTs retrieved was good to excellent: adequate
blinding of participants and investigators, appropriate
method to generate the sequence of randomization, and
the presence of adequate control conditions. However,
several shortcomings have been noted.
Two clinical trials compared ginger with vitamin B6.
Both studies concluded that ginger was as effective as
vitamin B6 in reducing nausea and the number of vom-
iting episodes.
18,20
However, it should be noted that the
efficacy of vitamin B6 in the treatment of nausea and
vomiting in pregnancy is not compelling.
3
Moreover, a
number of studies demonstrated that placebo treatment
853VOL. 105, NO. 4, APRIL 2005 Borrelli et al Ginger and Pregnancy
is useful in the relief of nausea.
19,49
For these reasons,
these comparative studies
18,20
should be viewed with
caution. Also, it should be noted that in one study
20
20%
of women used conventional antiemetics during the trial.
Four clinical studies compared the efficacy of ginger with
that of a placebo.
15–17,19
These studies were of good
methodological quality: women did not take other med-
ications during the trial,
15–17,19
the compliance of the
subjects was checked,
15–17,19
the severity of pregnancy-
related symptoms was recorded more than once per
day,
16,19
and an objective measurement of the nausea
severity was obtained using 2 independent measurement
scales.
15,16
One of the main problems in crossover trials
is the possibility of a carryover effect of the active sub-
stance in the second treatment. In the study performed
by Fischer-Rasmussen et al,
15
a severity score was used
both to avoid a carryover effect of ginger and to objectify
the symptoms of hyperemesis. In all clinical trials, ginger
was taken 3 or 4 times a day, independently of the
occurrence of nausea and/or vomiting. Moreover, al-
though the single acute dose of ginger varied in each
study, the daily dose was approximately1gin5ofthe6
studies reviewed (with periods ranging from 8 to 20
weeks).
A prospective observational cohort study and the
follow-up of 4 RCTs (reported above) consistently
showed that there are no significant side effects or ad-
verse effects on pregnancy outcomes.
15,16,19,21
This is
consistent with the results of the majority of animal
studies,
12
although a mutagenic activity has been docu
-
mented for an ethanolic ginger extract in vitro.
50
How
-
ever, the short duration of treatment periods and the
small number of patients taking ginger (n 303) in
RCTs may have been insufficient to properly test the
safety of the ginger with regard to pregnancy outcomes.
Moreover, the cohort study had a small sample size (n
187) and was based on a self-selected sample of women
who called a help line and may have differed in some
ways from the general population. An increase both in
the mean of the birth weight of the babies and in the
occurrence of multiple pregnancies (twins) has been
observed in the pregnancies exposed to ginger. The
increased birth weight is in line with clinical studies
reporting a lower birth weight in infants of women
experiencing nausea and vomiting during pregnancy.
51
However, the correlation between nausea and birth
weight has been recently questioned.
52,53
The mecha
-
nism of the action of ginger on pregnancy symptoms has
not been fully identified although several hypotheses
have been proposed. It has been reported that symptoms
of nausea and vomiting during pregnancy improved in
direct correlation to the improvement in pregnancy-
induced gastric dysrhythmias.
54
Therefore, ginger-in
-
duced reduction of pregnancy symptoms may be due to
a direct effect of the drug on the gastrointestinal tract.
The activity of ginger has been attributed to nonvolatile
pungent components, namely shogaols and gingerols.
55
In conclusion, considering the largely positive results
of RCTs and the absence of adverse effects on preg-
nancy outcomes, ginger may be an effective treatment in
managing nausea and vomiting symptoms during preg-
nancy. However, more observational studies and also
larger randomized clinical trials to make a definite state-
ment on the safety of ginger in pregnancy are needed.
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Address reprint requests to: Francesca Borrelli or Angelo A.
Izzo, Department of Experimental Pharmacology, University
of Naples Federico II, Via D. Montesano 49, 80131 Naples,
Italy; e-mail: franborr@unina.it.
Received July 6, 2004. Received in revised form October 12, 2004.
Accepted December 2, 2004.
856 Borrelli et al Ginger and Pregnancy OBSTETRICS & GYNECOLOGY
    • "The findings of this updated SR compare well with the findings of previously conducted reviews [10,14,16,17,343536 on the same topic. Limited meta-analysis could be performed , often due to the heterogeneity in participants, interventions, outcome measures and comparison groups encountered. "
    [Show abstract] [Hide abstract] 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. 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. 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. 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.
    Full-text · Article · Mar 2014
    • "Although this symptom gets spontaneously recovered with the time passing, it can place a great stress on the pregnant woman and those around her and disturb her work so that, in 25% of cases, the employed pregnant women often require a leave. This symptom can even lead to depression [4]. Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective. Comparing the effectiveness of vitamin B6 (40 mg twice daily) and ginger (250 mg four times daily) in treatment of pregnancy nausea. Methods. In a clinical trial in health centers of Qazvin University of Medical Sciences from November 2010 to February 2011 on pregnant mothers, the effects of vitamin B6 (40 mg twice daily) and ginger (250 mg four times daily) were evaluated in treatment of pregnancy nausea. Results. In both groups, treatments with vitamin B6 or ginger led to significant reduction in MPUQE score. Scores of symptoms at the day before treatment in vitamin B6 and ginger groups were 9.35 ± 1.97 and 9.80 ± 2.03, respectively, and reduced to 5.98 ± 1.45 and 6.28 ± 1.63, respectively, in the fourth day of treatment; however, mean changes in the two groups were not significantly different. Mean changes of MPUQE score in ginger and vitamin B6 groups were 8.32 ± 2.19 and 7.77 ± 1.80, respectively, showing no significant difference (P = 0.172). Conclusion. Vomiting was more reduced in vitamin B6 group; however, this reduction was not statistically significant. There was no significant difference between the two groups in nausea occurrences and their duration. No side effect was observed in either group.
    Full-text · Article · Oct 2013
    • "If ginger is to be used in medicinal purposes, then the determination of its major components should be characterized and standardized. None of the ginger powders or extracts used during the previous clinical trial were analyzed prior to use (Vutyavanich et al. 2001; Keating and Chez 2002; Willetts et al. 2003; Borrelli et al. 2005; Chrubasik et al. 2005), and this lead to a major limitation of these studies. Moreover, major components of ginger such as 6-gingerol have been shown to exhibit antioxidant and anti-inflammatory properties (Kiuchi et al. 1992; Phan et al. 2005) to suppress cytokine formation (Kjuchi et al. 1992; Phan et al. ) and to promote angiogenesis (Kim et al. 2005 ). "
    [Show abstract] [Hide abstract] ABSTRACT: Randomly amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers were used to analyze the genetic stability of ten local cultivars collected fromManipur, India with the released ginger variety Nadia. A total of 15 RAPD and 8 ISSR primers resulted in 107 and 53 distinct and reproducible bands, respectively. A lack of polymorphism revealed the genetic stability among the local cultivars. Unlike molecular markers, analysis of essential oil composition by gas chromatography–mass spectrometry (GC-MS) revealed variation among 11 clones. Among the eight major constituents determined by GC-MS, cinnamyl acetate was found only in one cultivar, whereasa different cultivar did not contain any trans-geraniol. These variations indicated the presence of polymorphism among local cultivars.
    Full-text · Article · Jun 2013
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