Efficacy of Ginger for Alleviating the Symptoms of Primary Dysmenorrhea

13 Pages·2015·0.46 MB·English

PainMedicine2015;16:2243–2255
WileyPeriodicals,Inc.
Efficacy of Ginger for Alleviating the Symptoms
of Primary Dysmenorrhea: A Systematic
Review and Meta-analysis of Randomized
Clinical Trials
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James W. Daily,Ph.D.,* XinZhang,BS,† Cochrane Library, Korean databases, Chinese medi- ca
DaSol Kim, MS,† andSunminPark, Ph.D.† caldatabases,andIndianscientificdatabase.Search de
m
terms used were: “ginger” or “Zingiber officinale” ic
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*Dept.ofR&D, DailyManufacturing Inc.,Rockwell, and “dysmenorrhea” and “pain.” Studies using gin- u
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North Carolina,USA; †DepartmentofFoodand ger as a treatment of primary dysmenorrhea were .co
considered for inclusion. The major outcome of pri- m
Nutrition, Obesity/DiabetesResearchCenter, Hoseo /p
marydysmenorrheawasassessedusingapainvisual a
University,Asan, South Korea in
analoguescore(PVAS). m
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Reprintrequeststo:SunminPark,DepartmentofFood Results. Initialsearchesyielded29articles.Ofthese icin
andNutrition,HoseoUniversity,165 Sechul-Ri, e
originalresults,sevenmetspecificselectioncriteria. /a
BaeBang-YupAsan-Si,ChungNam-Do,336-795, FouroftheRCTscomparedthetherapeuticefficacy rtic
SouthKorea,Tel:[phone];Fax:[phone]- ofgingerwithaplaceboduringthefirst3–4daysof le-a
0670;E-mail: [email protected]. the menstrual cycle and were included in the meta bs
analysis. The meta-analysis of these data showed a tra
c
Conflicts ofInterest:JamesW.Daily IIIis Presidentof significanteffectofgingerinreducingPVASinsub- t/1
6
DailyManufacturing,Inc.,amanufacturerofdietary jects having primary dysmenorrhea (risk ratio, /1
2
supplements,nootherauthorshaveanyconflictsof 21.85;95%CIof22.87,20.84,P50.0003).SixRCTs /2
2
interest. outof7exhibitedlowtomoderateofriskofbias. 43
/2
4
Conclusion. CollectivelytheseRCTsprovidesugges- 6
AuthorContribution:S.P.designedthe studyand tive evidence for the effectiveness of 750–2000 mg 029
S.P., J.W.D.,S.J.,and D.S.K. searchedRCTpapers 4
gingerpowderduringthefirst3–4daysofmenstrual b
and reviewedthe papers. S.P.andJ.W.D. organized cycleforprimarydysmenorrhea. y g
the dataandthe statisticalanalysisandcontributed to ue
s
writing ofthemanuscript.S.P.had primary KeyWords.Ginger;Dysmenorrhea;PainVisualAna- t o
n
responsibility forfinalcontent.The finalmanuscript log Scale; Randomized Clinical Trials; Systematic 2
8
hasbeenread andapprovedby all authors. Review M
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Introduction 2
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1
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Abstract
Primary dysmenorrhea is one of the most prevalent
gynaecologic disorders, affecting more than half of all
Objective. Therehasbeennoattempttodatetosyn- women of reproductive age. Primary dysmenorrhea is
thesizetheavailableevidencefortheefficacyofginger defined as pain associated with menstruation in the
for treating primary dysmenorrhea. This systematic absence of underlying organic disease [1]. It usually
reviewevaluatesthecurrentevidencefortheeffective- begins 6–12 months after menarche and it accompa-
nessofgingerfortreatingprimarydysmenorrhea. nies spasmodic cramping pain in the lower abdomen
that can disseminate into the lower back and thighs [1].
Methods. Literature searcheswere conducted using Symptoms of dysmenorrhea can be incapacitating and
12electronicdatabasesincludingPubMed,EMBASE, womenexperiencingseveresymptomsofdysmenorrhea
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Dailyet al.
are unable to engage in normal activity and experience osteoarthritis trials, 1 dysmenorrhea trial and 3 acute
increased absence from school or work. It is estimated muscle pain trials. The authors concluded that ginger
that severe dysmenorrhea results in the loss of 600 mil- may reduce subjective experience of pain in some con-
lion working hours and $2 billion in lost productivity ditions.Inaddition,inarecentmeta-analysisofrandom-
annually [2]. The prevalence of primary dysmenorrhea ized placebo-controlled trials ginger was reported to
varies from 30% to 90% among different ethnicities with have efficacy for pain relief in osteoarthritis [15]. There-
various severities[3]. fore, ginger has scientific support to justify its history of
use for pain treatment as antiquity [16], especially in
Although the cause of primary dysmenorrhea is not fully Chinese and Asian-Indian traditional medicine [17]. Sev-
understood, it seems clear that increased production of eral studies have also demonstrated that ginger may D
prostaglandins derived from cyclooxygenase-2 (COX)-2 have beneficial effects for cancer prevention [18], ow
n
and other inflammatory mediators cause excessive con- pregnancy-related nausea and vomiting [19], chemo- lo
tractions of the uterus with consequential pain and therapy nausea [20], nausea, and vomiting after surgery ad
e
cinrhaimbiptioinng o[4f,5C].OPXr-e2viobuys sntoundsiepsechifaicvenroenpsotreterodidtahlatanthtie- [d2e1n]caensdupopsoterotinagrthtrhiteisu[s2e2].ofHgoinwgeevrerf,ordmesapnityedtihseeaesveis- d from
inflammatory drugs (NSAIDs) decreases prostaglandin involving inflammation, nausea and pain, the efficacy of h
synthesis, contributing to their analgesic, antipyretic and ginger for treating or managing primary dysmenorrhea ttp
s
analgesic properties and making them effective for hasnotrecently been systemically reviewed.Asthepre- ://a
ameliorating the severity of menstrual pain in women c
vious review on ginger for pain, several randomized a
[5–7]. However, frequent use of these medications have d
clinical trials of ginger supplementation have been con- e
been reported to have a failure rate of 20–25% [8], and m
ducted in young women. The purpose of the current ic
have adverse effects ranging from minor symptoms .o
review was to systemically evaluate all randomized clini- u
such as diarrhea, stomachache, and nausea to serious p
cal trials of ginger for treating primary dysmenorrhea .c
illness such as chronic kidney disease [9,10]. Although o
and to elucidate the efficacy of ginger for alleviating the m
the majority of patients experience no ill effects from symptoms of primary dysmenorrhea. To the best of our /pa
NSAIDS, many would benefit by having an alternative knowledge this is the first systematic review and meta- inm
treatment for reducing pain treatment for primary dys-
mheernbosrrhhaevaewaitnhti-minifnlaimmaml aatdovryersaendeffaenctaslg[e1s1ic]. Aacstivsiotimese, amnaarlyysdisysomfeRnCorTrsheoan. the effectiveness of ginger for pri- edicin
e
they might be useful as alternatives to NSAIDS or for /a
decreasing the effective dose of NSAIDS for treating pri- Methods rtic
le
mary dysmenorrhea[12]. -a
Data SourcesandSelection Criteria b
s
Ginger root (Zingiber officinal Roscoe.) is used world- tra
wide as a spice and seasoning as well as a traditional The following electronic databases were searched: ct/1
PubMed, EMBASE, Cochrane Library, Korean databases 6
medicine. Ginger contains abundant nonvolatile pungent /1
such as DBpia, the Research Information Service System 2
constituents such as various types of gingerols, sho- /2
(RISS), and the Korean Studies Information Service Sys- 2
gaols, zingerone, and paradol [8]. Ginger and ginger’s 4
tem (KISS), Chinese medical databases such as China 3
components have pleiotropic pharmacological activities, /2
National Knowledge Infrastructure (CNKI) and the Chinese 4
such as gastrointestinal, antioxidant, cardiovascular, 6
analgesic, and anti-inflammatory activities [9]. Several Scientific Journals Database, the Indian Medical Journals 02
9
studies have reported ginger to exert anti-inflammatory and the Indian Journals. Dissertations were also included. 4 b
effects by the inhibition of inducible cyclooxygenase The keywords and Medical Sub Headings (MeSH) were: y g
(COX)-2, NF-jB, and 5-lipoxygenase (5-LOX) [8,9]. “ginger,” (Primary) “Zingiber officinale,” “dysmenorrhea,” ue
Additionally, ginger and its constituents, especially sho- “pain,” “randomized,” “placebo,” “controlled trial,” and st o
gaols, work as agonists of transient receptor potential “clinical trial.” All randomized clinical trials that studied the n
2
cation channel subfamily V member 1 (TRPV1) that is effects of ginger on primary dysmenorrhea in young 8
associated with the transmission of physical and chemi- women were included. Studies that investigated the Ma
cal stimuli [8]. TRPV1 has been a prime target for the effects of complex herbal remedies that included ginger rch
development of novel pain relievers (analgesics). Both asaningredientwereexcluded. 2
0
antagonists and agonists of the receptor are used for 19
pain treatment. Under the prolonged exposure of its Data Extraction,Quality andValidityAssessment
agonists such as capsaicins and shogaols TRPV1 is
desensitized,whichleadstothealleviation ofpain [13]. The search was conducted in the databases with
proper languages of English, Korean and Chinese with
There is growing evidence that ginger has anti- the following key words of mesh terminology: ginger,
inflammatory and analgesic efficacy in humans with pain, and dysmenorrhea. Three independent reviewers
osteoarthritis, primary dysmenorrhea and other acute (SJ, SP, DSK) screened the papers. In the first screen-
pains. Terry et al. [14] conducted a systemic review of ing the related papers were identified by the titles and
research on ginger for the treatment of pains originating abstracts of the papers and the relevant articles were
from different conditions, using 6 RCTs including 2 retrieved in full text and validated for inclusion in the
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Ginger andPrimary Dysmenorrhea
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Figure 1 Flowchartof the selectionprocess ofthe randomizedclinical trials forsystematic review. m
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systemic review. The fourth reviewer (JWD) independ- among the studies, but in all of the studies, the subjects ine
ently validatedtheselected thepapers. hnaodrrhperaim. aPrryimdayrsymdeynsomrrheenaorrbhuetaniost dseecfinoenddaraysdhyasvmineg- /article
Eligibility Criteria for Studiesfor ThisReview pain during at least 50% of menstrual cycles or first 3 -a
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All prospective randomized clinical studies using ginger dscaaylsesa.nFdurptahienrmscoorere, eoafc3h-4stbudasyecdoonsnis1te0dviosfua2l cayncalleosg. strac
for the treatment of dysmenorrhea in women having pri- Subjects in the experimental group were provided 750– t/1
6
mary dysmenorrhea were included for this systematic 2,000 mg ginger powder capsules per day for the first 3 /1
2
review. Exclusion criteria included in vitro studies of gin- days of the menstrual cycle, whereas those in the con- /2
2
ger for primary dysmenorrhea, studies with only an trol group received placebo capsules such as lactose 43
abstract available, nonclinical trial studies, studies in [23–26]. In three studies analgesic mediations such as /24
6
which primary dysmenorrhea was not the primary out- mefenamic acid [27,28] or exercise [29] were used as 0
2
come measured, and then we eliminated the duplicates. positive controls. Five RCTs had a two-arm parallel 94
A flow diagram of the article selection process is shown design: 4 RCTs contained ginger powder and placebo b
y
in Figure 1. Although no language barriers were groups [24–27], but 1 RCT included ginger powder1 g
u
imposed, all studies included in this review were written exercise and exercise group [29]. Two RCTs adopted a es
in English. Dissertations about randomized clinical stud- three-arm parallel design including ginger powder group t o
n
ieswereincluded. and two control groups: 1 RCT contained two analgesic 2
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groups using mefenamic acid and iburopen [28] whereas M
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SubjectsandIntervention 1 RCT included one placebo and one analgesic group rc
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(zincsulfate)[23]. 2
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This systematic review included all RCTs that investi- 1
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gated the effect of ginger powder on the symptoms of Outcome Measures
primary dysmenorrhea in young women. The age of
subjects varied among the studies but within the range Outcome measures to be included in the meta analysis
of 13–30 years of age. Most subjects were teenagers. were severity and duration of pain during menstruation.
Although the exclusion criteria also varied among the The severity of pain was assessed before and after
studies, most studies excluded subjects with irregular intervention by a visual analogue scale. The pain visual
menstrual cycles, those using hormonal medication, analog scale (PVAS) is a tool widely used to measure
birth control pills or intrauterine contraceptive devices pain. The PVAS is a valid measure that has been used
and having a history of pregnancy and strenuous exer- inmanystudiestoevaluatetheseverity ofpainincluding
cise. The eligibility of subjects was somewhat different menstruation [30,31]. Its reliability varies from 0.76 to
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Dailyet al.
0.97 in different studies [32,33]. Subjects answered a differences and standard deviations were used for the
perception of pain intensity on a 10 cm horizontal scale: meta-analysis. Two studies gave the percentage of sub-
the score 0 and 10 represents no pain and worst possi- jects who improved due to the treatments [27,28], and
ble pain. Duration of pain was answered by each sub- one study did not provide standard deviations of PVIS
ject to indicate the number of hours she had scores [25]. Thus, four studies [23,24,26,29] were
experienced pain during the first three days of the men- includedinthe metaanalysis.
strual period.
Heterogeneity of the included studies was tested using
Quality Assessmentof the Articles the Higgins I2 test and meaningful heterogeneity was
determined by 50% of I2 value. When I2 value was D
The Cochrane tool was used to assess quality of the greater than 50, a random-effect model was used for ow
n
RCT articles included in this systematic review by deter- the meta-analysis. Funnel plots were used to detect lo
mining the risk of bias [34]. This validated tool consisted reporting biases for this systematic review as the num- ad
e
ofthefollowing7categories:“Randomsequencegener- berofstudiesinducedwaslessthan10. d
ation,” “Allocation concealment,” “Blinding of partic- fro
m
ipants,” “Incomplete outcome data,” “Selective outcome SubgroupAnalysis h
reporting,” and “Other bias.” Each category was scored ttp
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as H, high risk of bias (ROB), U, uncertain ROB, or L, Each study had two cycles and each cycle was consid- ://a
low ROB. Three independent reviewers (DSK, SP, SJ) ered as an individual study. In addition, the studies con- c
a
performed the quality assessment and disagreement on tained different control treatments: four studies had a d
e
scoreswereresolvedthroughdiscussion. placebo control [23–26], two studies had mefenamic m
ic
acid[27,28];andonestudyhadexercise[29]aspositive .o
u
Data Analysis controls. According to control treatments, studies were p
.c
divided into two subgroups: placebo studies and anal- o
m
The response rates in the ginger and placebo arms gesicstudies. Thestudy containing exercise asthe con- /p
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were used for calculating the risk ratio, or relative risk trol groupwasconsidered morelikean analgesicgroup, in
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(RR) (weighted according to sample size). RR and 95% butbecausethetwostudieshavingananalgesiccontrol
e
confidence interval (CI) were calculated using the groups did not provide means and standard deviations, dic
response rates for ginger (success of pain relief) as a the exercise group in the Gupta study [29] was consid- in
e
basis. Standard mean differences (SMD) and 95% CI eredaplacebocontrol. /a
were also calculated for a pain visual analogue scale rtic
le
(AVS)usingthe CochraneCollaboration’s software(Rev- Results -a
b
Man Version 5.0 for Windows. Copenhagen: The Nordic s
Cochrane Centre). The variance of the change was cal- Summary of IncludedStudies tra
c
culated using a correlation factor of 0.4 as suggested t/1
6
by the Cochrane Collaboration. If appropriate, we then In the initial electronic searches a total of 29 studies /1
2
pooled data across studies using random effects mod- were found and 7 duplicates were removed. After 12 /2
2
els, if excessive statistical heterogeneity did not exist, studies (7 in vitro studies, 2 that were not clinical trials, 4
3
the tau2 was pooled using a random effects model 2 that did not have primary dysmenorrhea as an out- /2
4
because of clinical heterogeneity between each study come—mixed cases of primary and secondary dysme- 6
0
such as age, dose of ginger and treatment duration. norrhea) were excluded, 10 studies remained. Finally, 7 2
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The meta-analysis included data from parallel-group RCTs met the inclusion criteria after removing 3 non- 4 b
design studies. The duration of treatment, the first 3 RCT studies (Figure 1). The 7 RCTs were used for the y g
daysofthemenstrualcycle,wasequivalentinallgroups systematic review [23–29]. The main data from included ue
s
and the dosage was also quite similar at 750–2000 mg/ RCTs were summarized in Table 1.Surprisingly, 6 RCTs t o
day. However, the control group was different among were conducted in Iran [23,24,26–29] and 1 RCT was n 2
groups and the control group was divided into placebo, from India, although ginger is commonly consumed 8
M
analgesic (mefenamic acid, ibuprofen or zinc sulfate) worldwide[25].FiveRCTshadatwo-armparalleldesign a
andexercise. (ginger powder and placebo groups) [23–26,29] and 2 rch
RCT adopted a three-arm parallel design including gin- 2
0
Six studies contained two cycles and one study [24] ger powder [27,28]. In three-arm parallel studies, Ozgoli 19
consisted of 1 cycle. Five studies contained the same et al. included two analgesicgroups suchas mefenamic
methods for each cycle. However, the Kashefi et al. acid and iburopen as the control groups without a pla-
study [23] used different methods: the first cycle was cebo group [28] and Kashefi et al. contained one pla-
the same as the rest of the protocol but the second ceboandoneanalgesicgroups(zincsulfate)[27].
cycle began providing ginger or placebo from 2 days
prior to the menstruation and lasting for 5 days. Both Riskof Bias
cycles of all studies except the Jenabi study [24] were
used for the meta analysis. As the data used for the The risk of bias assessment for the included RCTs is
meta-analysis were a continuous variable of the severity presented in Table 2. Among 7 RCTs, 2 RCTs were
of the pain, as PVIS, and the duration of the pain, mean classified as high quality [24,26], 4 RCTs had a
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Adverseeffect None Headache,heartburninbothgroups
Author’sConclusions Gingerisaseffectiveasmefenamicacidforpainreliefinprimarydysmenorrhea.GingerisanalternativetreatmentforprimarydysmenorrheaGingerandzincsulfatehadsimilarpositiveeffectsontheimprovementofprimarydysmenorrheapaininyoungwomen.
e e e
cl cl cl
EffectSize Firstcycle>P0.05>P0.05secondcy>P0.05>P0.05 PlaceboFirstcycle<P0.001secondcy<P0.001ZincFirstcycle<P0.001secondcy<P0.001
D
ea ControlResults Firstcycle61.600.8019(46.3)secondcycle61.490.7827(45.0) PlaceboFirstcycle67.131.3esecondcycle66.951.67ZincsulfateFirstcycle66.181.7secondcycle63.121.2 ownloaded from
smenorrh ExperimentResults Firstcycle61.390.6322(53.9)secondcycle61.620.7133(55.0) Firstcycle66.21.40secondcycl63.081.52 https://acad
y e
ofprimaryd MainOutcome Dysmenor-rheapain;SeverityofdysmenorrheaN(%) Dysmenor-rheapainscore(1–10-ScoreVAS) mic.oup.com/p
dertreatment ControlIntervention(Dose,Duration,Source) Mefenamicacid250mg/capsuleEvery8huntilpainrelief,for2cycles PlaceboCapsule;Unknowndose;3times/day/4dayfor2cycles;LactoseZincsulfate:220mgCapsule;3times/day/4dayfor2cycles ainmedicine/artic
w le
ofgingerpo ExperimentalIntervention(Dose,Duration,Source) Gingerpowder:250mg/capsule;Every6huntilpainrelief,for2cycles;Zintoma(gingerpowder) Gingerpowder:250mg/capsule;3times/day/4dayfor2cycles;Gingerpowder -abstract/16/12/2
edclinicaltrials Excluded Irregularmen-strualcycles,Historyofregularexercise,Secondarydys-menorrhea,UseofIUDorOCP SecondarydysmenorrheaUsinghormonalmedications,birthcontrolpills,orpainreliefmedications. 243/2460294 by g
placebo-controll Included 5Ginger(n11),5Placebo(n11)Primarydysmenor-rheaforatleast50%ofmenstrualcycleslastingfor1day.Painintensity>40mmbasedona100mmvisualanalogscale(VAS)Ginger(Firstcycle5n47,second5cyclen45),Zincsulfate5(Firstcyclen54,secondcycle5n53),Placebo5(Firstcyclen45,secondcycle5n42),Regularmenstrualcycles,Experienc-ingdysmenorrheaduringthefirstthreedaysofmen-strualbleeding,Obtainingascore>4Basedon10scoreofVAS uest on 28 March 2
randomized No.ofSubjects;AgeofSubjects 22;18andover;(Gingermean:626.62.0Placebomean:626.62.1) 150;15–18;(Gingermean612.81.1;Zincsulfatemean6131.0;Placebomean612.41.2) 019
of
ry el el
umma StudyDesign RCT2Parallarms RCT3Parallarms
S
1
Table FirstauthoryearRef.no. Shirvanietal.;2015[27] Kashefietal.;2014[23]
e d
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Advereffect Notreport None None
e
Author’sConclusions Combinedeffectofgingerandexercisehavehigherefficacythanexercisealone. Gingeriseffectivinminimizingthepainseverityinprimarydysmenorrhea. Treatmentofprimarydysmenorrheainstudentswithgingerfor5dayshadastaticallysignificanteffectonrelievingintensityanddurationofpain.
e
cl
EffectSize Firstcycle5P0.3045P0.145secondcy5P0.0395P0.015 <P0.001 Protocol-15P0.0155P0.017Protocol-15P0.0295P0.210 D
ControlResults Firstcycle64.431.99641.8337.37secondcycle64.132.12644.2050.39 67.111.12 Protocol-166.582.02621.3625.59Protocol-266.012.65615.5714.72 ownloaded fro
ExperimentResults Firstcycle63.852.45630.2924.58secondcycle62.912.45621.2617.55 64.811.70 Protocol-165.122.69614.718.36Protocol-264.612.55610.8814.54 m https://acade
m
MainOutcome Painscore:10-scorenumericalrat-ingscale(NRS)150-scoremenstrualdis-tressques-tionnaire(MDQ)) Dysmenor-rheapainscore(1–10-scoreVAS) SeverityofpainDurationofpain(hout/basedon72hour)(1–10-scoreVAS) ic.oup.com/pa
ControlIntervention(Dose,Duration,Source) OnlyExerciseFewmusclestrengtheningandstretchingexercisesasperliterature2time/20minFirstthreedaysofmenstruation PlaceboCapsule;Notreporteddoseandsource Placebo1CapsuleTotalpowder3times/dayProtocol-12daysbeforethemenstrualperiodandcontinuedthroughthefirstthreedaysProtocol2Firstthreedays inmedicine/article
ExperimentalIntervention(Dose,Duration,Source) Gingerpowderwithexercise500mg2times/dayFirstthreedaysofmenstruation;Fewmusclestrengtheningandstretchingexercises2time/20minFirstthreedaysofmenstruationGingerpowder500mg/capsule;1time/day/3day1cycleGingerwaspur-chasedatpharmacyGingerpowder500mg/capsule3times/dayProtocol-12daysbeforethemenstrualperiodandcontinuedthroughthefirstthreedaysProtocol-2Firstthreedays -abstract/16/12/22
Excluded Physicallyhandi-capped,Anyconditioninwhichexerciseiscontraindicated,Secondarycauseongynecological,Marriedorpreg-nant,Irregularandabsentformorethan2months Notreported Diagnosesofadisease,Historyofpreg-nancy,Takingoralcontracep-tives,2<BMI19kg/m2>or25kg/m 43/2460294 by gu
Included Ginger(n=34),Control(n=30)Attainedmenarche.Haveprimarydysmenorrhea Ginger(n=35),Placebo(n=34)Underwentgeneralphysicalexamina->tions,painscore3basedonthe1–10scoreofVASGinger(n=59),Placebo(n=46)Single,menstrualcycle(21–35days)2–6daysofflowAveragebloodloss20–60ml,severeprimarydysmenorrhea est on 28 March 20
1
No.ofSubjects;AgeofSubjects 64;17–19;(Gingermean514.0,Controlmean513.3) 70;13–19; 120;18andover(Gingermean621.42.0Placebomean621.32.2) 9
d el el el
ntinue StudyDesign RCT2Parallarms RCT2Parallarms RCT2Parallarms
o
C
1 a
Table FirstauthoryearRef.no. Guptaetal.;2013[29] Jenabi;2013[24] Rahnametal.2012;[26]
e d d
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Advereffect Notreport Notreport
e
Author’sConclusions Combinationofexerciseandoralintakeofgingerpowderwereeffectiveforreducingseverityofsomofsheselectedsymptomsofdysmenorrhea. Gingerwasaseffectiveasmefenamicacidandibuprofeninrelievingpaininwomenwithprimarydysmenorrhea.
d d
e e
EffectSize Notreport Notreport D
o
w
n
ControlResults 1.72NotreportedSD-value 66%gotbetter loaded fro
m
h
ExperimentResults Ex11.36Ex21.04NotreportedSD-value 62%gotbetter ttps://acade
m
MainOutcome Dysmenor-rheapainscore(5-scoreLik-ertscale) Averbalmultidimen-sionalscoringsystem ic.oup.com/pa
ControlIntervention(Dose,Duration,Source) Placebocontrolgroup(sourcewasnotreported) Mefenamicacidcapsule250mg4times/dayFirstthreedaysofmenstruationPonstan;Ibuprofen400mg/capsule4times/dayFirstthreedaysofmenstruationGrufen; inmedicine/article
-a
ExperimentalIntervention(Dose,Duration,Source) Ex1Gingerpowder1g/capsule;1times/day;Firstthreedaysofmenstruation.Ex2Gingerpowder1g/capsule;2times/day;FirstthreedaysofmenstruationGingerrhizomepowder250mg/capsule4times/dayFirstthreedaysofmenstruationZintoma; bstract/16/12/22
Excluded Irregularorinfre-quentmenstrualcycle,Usinganintra-uterinecontra-ceptivedeviceortakingoralcon-traceptivepill. Pre-existingdiag-noseddisease,Historyofgesta-tionortakingoralcontraceptive,medicinalorherbalsensitiv-<ities,BMI19or>26,milddysmenorrhea 43/2460294 by gu
Included Ex1(n=25),Ex2(n=25),Control(n=25)Primarydysmenor-rheainmajority>(50%)ofmen-strualcycles,dys-menorrheaforatleastonedayofmenses,reproduc-tiveage Mefenamicacid5(n50),Ibuprofen5(n50),5Ginger(n50)second-thirdgradeofseverityofdys-menorrheabasedongrades1–4ofself-administeredquestionnaire est on 28 March 20
No.ofSubjects;AgeofSubjects 75;Notreportedagerangeandaverage; 150;18andover;(Mefenamicacidmean621.82.3Ibuprofenmean621.32.3Gingermean621.52.6) Controlgroup. 19
n,
o
C
ontinued StudyDesign RCT2Parallelarms RCT3Parallelarms entgroup;
C m
1 eri
Table FirstauthoryearRef.no. Halder;2011fig25] Ozgolietal.2009[28] Ex,Exp
Dailyet al.
Table 2 Risk of bias in included trials
Patient Reporting
Random and Drop-out Intention- Selective Other No.
Sequence Allocation Practitioner Assessor or toTreat Outcome Potential of
Generation Concealment Blinding Blinding Withdrawal Analysis Reporting Bias Reference
Shirvani U U U U L L L U [28]
etal.
(2014) D
o
Kashefi U U L L L L L U [24] w
n
etal. lo
a
(2014) de
d
Gupta U U H H L U U U [30] fro
etal. m
(2013) h
ttp
Jenabi L U U U L L L U [25] s
(2013) ://a
c
Rahnama L U L U L L L U [27] ad
e
etal. m
(2012) ic.o
Halder U U U U L L L U [26] up
(2011) .co
m
Ozgoli U U L L L U U U [29] /p
etal. ain
(2009) m
e
d
ic
in
e
/a
rtic
le
-a
b
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tra
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Figure 2 Forest plot of the meta-analysis for the scores of the pain visual analog scale. (A) Inclusion of both cycles of
the 4 randomized clinical studies. (B) Inclusion of the one cycle of the 4 randomized clinical studies. Each study is identi-
fiedbyfirstauthorandyear.[Colorfigurecanbeviewedintheonlineissue,whichisavailableatwileyonlinelibrary.com.]
2250
Ginger andPrimary Dysmenorrhea
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Figure 3 Forest plot of the meta-analysis for the scores of the pain visual analog scale of RCTs with a placebo m
group as the control. (A) Inclusion of both cycles. (B) Inclusion of the one cycle. [Color figure can be viewed in the ed
ic
onlineissue, whichis available at wileyonlinelibrary.com.] in
e
/a
moderate quality and 1 RCT had a low quality [29]. Two the control were used for meta-analysis (Figure 3A and rtic
studies used a proper method for randomization of the B): the PVISscores were significantly lower in the ginger le-a
subjects such as coin flipping and computer generated group (n5198) as compared to the placebo control b
s
random numbers [24,26] but the remaining studies did group (n5168) including both cycles if available tra
c
not describe how the subjects were randomized. In (P50.0001) (Figure 3A). In studies containing only one t/1
addition, 3 RCTs used blinding of patients and practi- cycle, the consumption of ginger (n5139) resulted in 6/1
tioners [23,26,28] but the remaining 4 RCTs did not lower PVAS scores than that of the placebo (n5122) 2/2
mention their method of blinding. The drop-out rates (P50.0003)(Figure3B). 24
were not high and all RCTs included in this review gave 3/2
thereasonsforwithdrawals. Among the RCTs, 2 RCTs [27,28] used an analgesic 46
0
treatment as the control group. Each study calculated 2
9
Outcomes the percentage of the PVAS improvement from the 4 b
baseline. Both studies showed similar percentages of y g
The severity of pain from primary dysmenorrhea was improvement in the ginger and analgesic groups (Table ue
scaledbyPVISandthe resultswere givenasthescores 1). In addition, in one study [29] the exercise group was st o
in 5 RCTs [23–26,29] but two RCTs reported scores as considered as the control group. The PVAS pain score n 2
a percent better thanthe baseline [27,28]. Asoneof the was similar between the exercise and ginger groups in 8 M
remaining five studies did not include standard devia- the first cycle but it was lower in the ginger group than a
tions, four studies [23,24,26,29] were included in the the exercise group in the second cycle (P50.039). rch
meta-analysis. The pooled results of PVAS scores from 2
Therefore, subjects treated with ginger powder experi- 0
the 4 RCT studies are provided in Figure 2A and B as a enced less pain from primary dysmenorrhea than the 19
forest plot. In the meta analysis with pooling of both
placebo supplemented subjects, furthermore the pain in
cycles of the 4 RCTs, the pain scores were significantly
the in the ginger group was less than in the exercise
lower in the ginger group (n5266) than the control
groupandsimilarto theanalgesicgroups.
group (n5228) (Figure 2A; P50.0003). In addition, the
results of the pain scores were the same when pooling
one cycle of 4 RCTs (Figure 2B; P<0.000001). How- PublicationBias
ever, as the RCT of Gupta et al. [29] used an exercise
grouprather than aplacebo groupas the control,it was An asymmetrical funnel plot was produced by this
deleted from the meta analysis. The pools of the meta-analysis (the hollow circles in Figure 4), which indi-
remaining three RCT groups with the placebo group as catedpublicationbias.
2251
Dailyet al.
burn injury [37], migraine headache when combined
with Ferverfew herb [38], acetic acid-induced pain [39],
and chronic low back pain [40]. However, even though
ginger has been shown to be effective for many types
ofpain, itis notnecessarily efficaciousforall pain.Stud-
ies of the use of ginger for exercise induced pain have
yielded inconsistent results with some showing modest
effects [41,42] and some no effects at all [43–45] for
treating exercise-induced muscle soreness. Although
the results are inconsistent, an observation by Black D
and O’Connor [45] may provide an explanation. They ow
n
observed that the lack of effect of ginger on cycling lo
exercise-induced pain in quadriceps muscle is consist- ad
e
ent with a lack of effect of aspirin in similar muscle pain. d
They noted that the ineffectiveness of aspirin suggests fro
Figure 4 Funnel plot of the meta-analysis for the m
that prostaglandins may not play a major role in h
scores of the pain visual analog scale. The hollow exercise-induced skeletal muscle pain. As mentioned in ttp
cfigiruclreescraenprbeesevnitewtheedsitnudthieesoinnltinhee imsseutae-,awnahliycshisi.s[Cavoaloil-r tghlaenIdnitnrsodbuyctCioOn,X-s2upinphreibsistiionngmthaeypbroedouncetioonfothfeprmosatjao-r s://ac
a
able at wileyonlinelibrary.com.] mechanisms of the analgesic and anti-inflammatory d
e
actions of ginger [6–9]. Therefore, although ginger has m
ic
Adverse Events been demonstrated to have a wide range of analgesic .ou
efficacies, studies such as this that evaluates its effec- p
.c
Six RCT did not report adverse effects whereas 1 RCT tivenessonspecifictypesofpainareimportant. om
reported heartburn, headache and diarrhea as adverse /p
a
effects [23]. However, the symptoms were not limited to Bioavailability of the active components of herbs and in
m
spices is a major limitation of most botanical medicines
the ginger group (750 mg ginger/day) and there was no e
significant differences in these symptoms between [46]; however ginger and its components appear to be dic
well absorbed. One hour after oral consumption of ginger in
groups (P>0.05). Thus, ginger administration resulted e
its major components: 6-shogaol, 10-gingerol, 6-gingerol, /a
in no increase in adverse effects over placebo in the 7 and 8-gingerol are detected in the plasma in rats and rtic
RCTsincluded inthisreview. le
humans[47,48]andat48–60h6-gingerol,and6-shogaol -a
b
areexcretedmainlyintobileandsomeintourine[49]. s
Discussion tra
c
It is important that the one RCT to report adverse t/1
Thismeta-analysisprovidedevidencethatgingercanameli- 6
orate pain associated dysmenorrhea in women. The relief effects of treatments reported only mild symptoms and /12
frompainwashighlysignificantandinthestudiesinwhich with no differences between the ginger treated group /22
and placebo group [23]. In a recent systematic review 4
analgesics wereused as a positive control,gingerpowder 3
and meta-analysis of ginger for nausea and vomiting /2
wasequallyaseffectiveastheanalgesicdrugtreatment.All 4
during pregnancy, the authors found 1,500 mg per day 6
ofthestudies,boththeRCT’sincludedinthemeta-analysis 0
to be most effective and without any adverse effects 2
9
afsomnrdatrltleh(a2ot2sine–g1t5hd0aystsmwueebnrjeeocrntrsho)et,aarnepdpaoninrot.enHdeotawhloaentveegrin,pgrthoeevridwsetaudsdcieeofsfnewvcitneivcree- [hu4ipg8h]t,oear2nddgo/tskhegesr.eboTwdheyerewoernaioglhicntoddnicosaeutsmionpnotsitoonefxaohdfibvgietirnasgneeyremfpfeoocrwttsadlieotyrf 4 by gue
ing evidence for efficacy. The doses used in the studies s
rangedfrom750mgto2,000mgofgingerpowderperday orartsab[5n0o]r.mTahlechcaunrrgeenstlyinavhaeilmabalteolosgtuicdaielspainrdamicaetteersthaint t on
andtherewasnocleardifferenceinefficacyamongthedos- gingerisverysafeatoptimallyeffectivedosages. 28
ages.Therefore,itwouldbeprudenttobegintreatmentwith M
a
750mgperday,andincreasethedosewhenneeded.The To the best of our knowledge, this is the first systematic rch
current majortreatmentfor primary dysmenorrheais using review and meta-analysis of RCTs on the effectiveness of 2
0
NSAIDs to reduce abdominal pain by attenuating uterine ginger for primary dysmenorrhea. Even though the results 19
hypercontractility. However, NSAIDs are not completely indicate that ginger is highly effective for treating dysme-
effectiveandhaveconsiderableadverseeffects,morbidity, norrhea, there are important limitations to the study that
andmortalityassociatedwiththeiruse[1].Therefore,ginger need to be considered. The number of trials and total
powdermightbeusefulasatherapeuticagentforprimary sample size of the primary studies are low. A standard
dysmenorrheainsteadoforcombinedwithNSAIDS. scoring system was used to quantify the likelihood of bias
inherent in the studies based on the description of ran-
Numerousstudieshaveinvestigatedgingerfortheamel- domization, blinding and withdrawals [34]. The seven
ioration of pain and inflammation in various diseases, RCTsincludedinthesystematicreviewhadlowtomoder-
and recent reviews and studies support its efficacy for ate risk of bias. Three RCTs [24,27,29] reported double-
pain relief in rheumatoid arthritis [35], osteoarthritis [36], blinding procedures but did not report details. No RCT
2252