Author/Date

Study type

Study size/No. of Patients at End

Exposure (ginger dose/day)

Study period

Length of Treatment (days)

Main outcome measures

 Main results

Chittumma et al., 2007

Randomized double-blind controlled trial.

126/123

Ginger powder
capsules (325 mg ×2,
3x/d, =
1950 mg/day).

4 days

4

Change in nausea and vomiting scores (3 symptoms on Rhodes index);
occurrence of side-effects.

Only minor side effects observed. No difence between the groups.

Ensiyeh et al., 2005

Double-blind randomised controlled trial.

70/69

Ginger powder
capsules (500 mg
2×/d =1000 mg/day)

3 months

4

Severity of nausea (VAS 0–10); number of vomiting episodes; general response to treatment (5-item Likert scale); occurrence of side-effects or adverse
pregnancy outcome.

Two spontaneous abortions in ginger group, 1 in B6 group; no congenital anomalies observed in babies brough to term.

Fischer-Rassmussen et al., 1991

Double-blind randomised crossover trial.

30/27

Ginger powder
capsules (250 mg
4 times per day =
1000 mg/day).

11 days

4

Preference of treatment period; relief scores (4-point scoring system); outcome of pregnancy.

One spontaneous abortion, One elected. No adverse effects were observed in remaining 25 subjects.

Portnoi, 2003

Not specified.

187 pregnant women.

Various, not specified.

up to 12 months post birth.

Minimum of 3 days.

Safety and effectiveness of ginger for nausea and vomiting of pregnancy (NVP).

Three major malformations were reported in the ginger group, ventricular septal defect (VSD), right lung abnormality, and kidney abnormality (pelviectasis).  One incidence of idiopathic central precocious puberty at age 2 years. No significant difference between the two groups in terms of live births, spontaneous abortions, stillbirths, therapeutic abortions, birth weight, or gestational age.

Smith, 2004

Randomized, controlled equivalence trial.

291 women, less than 16 weeks pregnant.

1.05 g ginger.

3 weeks.

3 weeks.

Ginger verses B6 for the treatment of nausea or vomiting in pregnancy.

Three spontaneous abortions in ginger group, 9 abortions in B6 group.

Vutyavanich, 2001

Double blind

32

Ginger powder
capsules (250 mg
4x/day =1000
mg/day).

5 months.

4

Severity of nausea (VAS 0–10); number of vomiting episodes; general response to treatment after 1 week (5-item Likert
scale); occurrence of side-effects and adverse pregnancy outcomes.

No significant adverse effects of ginger on pregnancy outcome.

Author/date

Study design

Population/study size

Study Duration

Exposure

Outcome

 Results

Comment

Bordia
et al., 1997

Placebo controlled
trial.

Patients with
confirmed
myocardial
infarction N = 60.

3 months. Outcomes
measured at: baseline, 1.5
months and 3 months.

Dose: 4g per day Unstandardised
capsules.

Platelet aggregation—
Agonist(s): ADP and Epi.

Ginger had no
significant effect on
both measures of
aggregation.

Ginger had no significant effect on blood lipids or blood sugar.

Bordia
et al., 1997

NA

NA

NA

NA

Fibrinogen;

NA

No mention of
randomisation.

Bordia
et al., 1997

NA

NA

NA

NA

Fibrinolytic activity.

P value not reported.

Lumb.
1994

Randomised,
double-blinded
placebo-controlled
crossover
trial.

Healthy male
volunteers N=8.

Total study period:
2 x 1 day, at least 14
days washout period. Outcomes measured
immediately before,
3 hrs, and 24 hrs post
consumption of ginger.

Dose: 2g (4 x 500 mg) dried ginger per day Unstandardized
capsules.

Platelet aggregation; - Agonist(s): AA, ADP, collagen, ristocetin, ADP; Bleeding time; Platelet count; Thromboelastography.

No significant
changes in any
outcome at any time
point.

NA

Srivastava
1989

Open-label
single-arm trial.

Healthy female
volunteers, N = 7.

Total study period: 7
days. Outcomes
measured at
baseline and 7days post-consumption.

Dose: 5g raw ginger
per day.

Platelet thromboxane B2 production.

Ginger consumption
resulted in a 37%
inhibition of
thromboxane B2
production (p<0.01).

NA

Young et al., 2006

Not specified.

20

72 days.

1 g ginger (+ 10 mg nifedipine).

Synergistic effect of ginger and nifedipine on anti-platelet aggregation in normal human volunteers and hypertensive patients.

Ginger and nifedipine had synergistic
effect on anti-platelet aggregation; Ginger increased anti-platelet aggregation effect of nifedipine in all patients.

 NA

Author

Test System

Study size

Exposure

Characterisation of test substance

Duration

Main outcome measure

Outcome

Wilkinson 2000

Sprague-Dawley rats, F.

43

Oral, drinking water on days 6-15.

20 g/L or 50 g/L ginger tea.

20 days.

Reproductive and developmental toxicity.

Embryonic loss in the treated groups 2 times that of the controls. Exposed fetuses found to be significantly heavier than control. No gross structural malformations observed.

Author

Test System

Study size

Exposure

Characterisation of test substance

Main outcome measure

Outcome

Srivastava
1989

Open-label
single-arm trial.

Healthy female
volunteers, N = 7.

Total study period: 7
days. Outcomes
measured at
baseline and 7 days
post-consumption.

Dose: 5g raw ginger
per day.

Platelet thromboxane B2 production.

Ginger consumption
resulted in a 37%
inhibition of
thromboxane B2
production (p<0.01).

Author/Date

Study type

Study size/No. of Patients at End

Exposure (ginger dose/day)  

Study period

Length of Treatment (days)

Main outcome measures

 Main results

Laekeman et al., 2021

Observational study, clinical feasability trial.

51/44

maximum of 2 tablets of 50 mg EXT.GR10 a day [limited data on actual amount administered]

During pregnancy.

NA

Patient satisfaction pregnancy complications (including hypertension and diabetes) and birth complications (including stillbirth, premature delivery, low birth weight).

Incidence of premature birth, low birth weight and hypertension in treatment group higher than in general population. Pilot study but not considered to indicate a safety concern.

Willetts et al., 2003

Double-blind randomised placebo-controlled trial.

120/99

Ginger extract
 capsules (125 mg
 4x/d =1000 mg/day).

8 months.

4

Used RINVR to measure frequency, duration, distress caused by nausea, vomiting and retching; long term follow-up for birth outcome.

Three spontaneous abortions observed in ginger group.

Author/date

Study design

Population/study size

Study Duration  

Exposure

Outcome

 Results

Comment

Bordia
 et al., 1997

 NA

20

1 day. Outcomes
 measured at:
 baseline, 4 hours
 post-consumption.

10 g single dose. Unstandardised capsules.

Platelet aggregation. - Agonist(s): ADP and Epi.

Reduction of both
 measures of platelet
 aggregation when
 compared to placebo
 (p <0.05).

 NA

Jiang et al.,
 2004

Randomized,
 open label,
 three-way crossover
 trial.

Healthy male
 volunteers Age: 20–36 N =12.

Total study period:
 3x13 days, 14 days
 washout period
 between each study
 period.

Dose: 3.6g (3x 0.4g, 3x per day) ginger extract Unstandardized capsules consumed with 25 mg dose of rac-warfarin,
 consumed once per study period.

Platelet aggregation, Agonist: AA; INR; Plasma warfarin
 enantiomer protein
 binding & warfarin
 enantiomer
 concentrations
 Urinary S-
 7-hydroxywarfarin.

No significant
 changes in any
 outcome.

P value not reported.

Rubin et al., 2019

Case report

Female, 70 yrs

NA

48 mg daily Chewable ginger supplement for approx. 1 month.

INR - 8.0 approx. 1 month after taking ginger supplement.

INR reduced to 2.6 following cessation of ginger supplementation and pause in  warfarin administration. Remained within normal range on resumption of warfarin.

Patient also taking clonazepam 1 mg,
 metoprolol succinate 25 mg, paroxetine 10 mg, phenytoin
 30 mg, rosuvastatin 20 mg, warfarin 7.5 mg, and warfarin 10 mg
 10 mg.

 Verma
 et al., 1993

Randomised
placebo controlled trial.

Healthy male
 volunteers; N = 20.

Total study period:
 14 days, high calorie
 diet for first 7 days, high-calorie diet and ginger/placebo consumed
 for next 7 days. Outcomes
 measured at baseline, 7, and 14 days.

Dose: 5g (4 x 625 mg, twice per day); dry ginger powder - Unstandardized
 capsules Consumed with
 100g (2x50g) butter, 2 cups of milk, 8 slices of bread.

Platelet aggregation.  Agonist(s): ADP and Epi.

Ginger significantly
 reduced platelet
 aggregation using both agonists when compared to placebo
 group (p<0.001).

Platelet aggregation reduced close to
 baseline but did not
 decrease further.

Author

Test System

Exposure

Characterisation of test substance

Main outcome measure

Outcome

Abudayyak et al., 2015

Ames: Salmonella typhimurium TA98 and TA100 strains; Cytotoxicity assay: Rat kidney NRK-52E cell line.

Cytotoxicity assay: (0.75, 1.50, 3.00, 6.00, 12.00,
 25.00, 50.00, and 75.00 mg/ml, genotoxicity: 0.78, 1.56, 3.13, 6.25, 12.50, and 25.00 mg/ml.

Aq, chloroform and MeOH ginger extracts.

Cytotoxicity and genotoxicity.

Chloroform extract cytotoxic: IC50 = 9.08 mg/ml; aqueous extract mutagenic at all concentrations against T98 strain, in presence of S9 mix.

Mohammed et al., 2016

chick embryonic heart micromass; mouse D3 embryonic stem cell systems (ESD3).

0.75–100 uM Micromass assay: 6 days, ESD3: 12 days.

6-gingerol

Embryotoxicity

no significant changes in contractile and cellular activity or changes in total protein content in 6-gingerol-treated primary embryonic chick cardiomyocytes. 

 NA

NA

NA

NA

NA

Inhibition in contractile activity at 12.5–50 μg/mL.

 NA

NA

NA

NA

NA

Change in both cellular activity and protein content in a dose-dependent manner at high concs (12.5–100 μg/mL).

 NA

NA

NA

NA

NA

Significant decrease in cardiomyocyte differentiation for all tested concentrations except 0.75 μg/mL in ESD3.

 NA

NA

NA

NA

NA

Significant decrease in cellular activity and protein content of stem cell-derived cardiomyocytes with increased 6-gingerol concentration exposure.

Nakamura & Yamamoto (1982)

 Escherichia coli Hs30.

Not specified.

Juice of ginger rhizome, 6-gingerol.

Mutagenicity

ginger juice supressed spontaneous mutation; 6-gingerol mutagenic in isolation.

Nakamura & Yamamoto 1983

 Escherichia coli Hs30.

Not specified.

6-shogaol, 6-gingerol.

Mutagenicity.

[6]-Shogaol was 10⁴ times less
 mutagenic, at a concentration of 700uM, than [6]-gingerol.

Nirmala et al., 2007

Wistar rats, male

Salmonella typhimurium strains TA 98 and TA 100.

Ginger paste and powder, unboiled, boiled, unfried, fried. 

Ames test: Ginger paste: 1, 2 and 3 mg; powder: 0.5, 1 and 1.5 g.

 Anti-mutagenicity.

Anti-mutagenic potential unaltered by treatment of ginger. 

Plengsuriyakarn et al., 2012

Cholangiocarcinoma (CCA) cell line 6 (CL-6), hepatocarcinoma (HepG2) and normal human renal epithelium (HRE). 

1.95, 3.90, 7.81, 15.62, 31.25, 62.5, 125, and 250 µg/ml.

Crude ethanolic ginger extract.

Cytotoxicity

IC50 and cytotoxicity 10.95 and 53.15 μg/ml.

Soudamini et al., 1995 

Salmonella typhimurium strains TA 100, 98
 and TA 1535.

25 and 50 mg/plate.

ethanolic mixture of powdered ginger.

Mutagenicity

mutagenicity in both TA 1535 and TA 100 at both concentrations.

Zaeoung et al., 2005

breast (MCF7) and colon (LS174T) cell lines.

Not specified.

aqueous extract and volatile oils.

Cytotoxicity

IC50 > 39.2 μg/ml.

Author

Test System

Study size

Exposure

Characterisation of test substance

Duration

Main outcome measure

Outcome

Alnaqeeb et al., 2003 (abstract)

Rats, female

Unknown

Oral and intraperitoneal. 50 mg/kg and 500 mg/kg

Aqueous ginger extract

28 days

 NA

Increased levels of serum aspartate aminotransferase (AST) and decreased levels of alanine aminotransferase (ALT) in orally dosed rats.

Dissabandara & Chandrasekara, 2007

Sprague-Dawley rats.

15 in 3 groups, otherwise not specified.

Oral: 500 mg/kg/day and 1000 mg/kg/day during days 5 to 15 of gestation.

Powdered ginger extract.

Animals treated with ginger for 10 days.

Effect of powdered ginger extract administered prenatally on postnatal development.

Lower intake of food and water and lower weight gain in ginger treated group.

ElMazoudy and Attia, 2018 (abstract only)

ICR mice

Unknown

250, 500, 1000, or 2000 mg/kg bw/d aqueous ginger extract.

Powdered dried ginger root

35-day treatment study; 20 day study  (antifertility and abortifacient loss).

Effect on oestrus cycle and implantation in female mice.

Female copulation index was significantly reduced at 2000 and 1000 mg/kg bw/d groups; female pregnancy index significantly decreased at the highest dose.  No. of implantation sites and live fetuses in the 2000 mg/kg bw/d group lower than the other treated and control groups.

Hosseini et al., 2015 (abstract only)

Rats, female and male offspring

72 (groups of 9)

Oral: 50, 100 and 200 mg/kg bw during neonatal and perinatal periods.

Alcoholic ginger extract

Unknown

Serum testosterone, LH and FSH.  Effect on spermatogenic cell lines in male mature offspring rats.

Significant increase in testosterone levels and number of spermatogenic cells. Significant reduction in FSH and LH at doses of 100 and 200 mg/kg bw compared to control.

Jeena et al., 2011

Wistar rat

30

Oral: 100, 250, and 500 mg/kg per day once daily.

Ginger essential oil.

13 weeks.

Oral Toxicity.

No mortaility or abnormal changes observed in relative organ weights w.r.t. body weight. Increase in serum Na levels in male rats treated with 500 mg/kg/d. slight increase in total bilirubin in female rats, along with a decrease in AST and ALT levels. No significant changes in hepatic function parameters (alkaline phosphatase, total protein, albumin and globulin content).

Malik and Sharma, 2011

Wistar rat, male.

Not specified.

gastric gavage: 250, 500 and 1000 mg/kg, (corresponding to 5, 10 and 20% of the NOAEL of the lyophilised ginger powder (5000 mg/kg).

Lyophilsed ginger juice powder.

Experiment 2: 8 weeks. Exp 1&2 not specified.

Acute Toxicity.

no signs of toxicity or mortality.

Peneme et al., 2023

Swiss mice.

6

5000 mg/kg aqueous ginger extract.

Ginger powder extracted into water.

OECD guideline no. 423.

Acute toxicity.

no signs of toxicity or mortality.

NA

NA

20

17 β-oestradiol, (1 mg/kg) or ginger extract (300 or 600 mg/kg) per day.

Ginger powder extracted into water.

2 weeks.

Effect on oestrus cycle and plasma oestradiol levels.

Changes in body weight and eosinophil indices for 600 mg/kg bw indicated disruption of oestrus cycle.

Plengsuriyakarn et al., 2012

OV and nitrosamine (OV/
 DMN)-induced CCA hamsters.

90

1000, 3000, and 5000 mg/kg bw/d.

 NA

30 days

Acute Toxicity.

 NA

Rong et al., 2009.

Sprague–Dawley rats, male and Female.

40.

Gavage: 500, 1000 and 2000 mg/kg bw/day.

Powdered Japanese ginger.

37

35 day repeat dose.

No increase in mortality. Slightly reduced absolute and relative weights of testes (by 14.4% and 11.5%, respectively) at highest dose.

Shalaby and Hamowieh, 2010

Sprague Dawley rats.

120

Oral, 5 to 17.5 g/kg bw.

Water or methanolic ginger extract.

65 days.

Fertility, serum testosterone and acute toxicity.

oral Lethal Doses (LD50) of the methanolic and water extracts - 10.25 and 11.75 g/kg bw respectively. No symptoms of toxicity observed at doses up to 5 g/kg bw. Both extracts increased fertility index, sexual organ weight, and sperm motility and count after 65 days.

 NA

NA

NA

NA

NA

 NA

NA

Methanolic extract: Testosterone levels increased to 4.08 ± 0.10 and 7.13 ± 0.14 ng/dL (both significant at P < 0.001); Water extract (150 and 300 mg/kg bw): Serum testosterone levels increased   4.06 ± 0.03 and 5.04 ± 0.08 ng/dL (both significant at P < 0.001). 

 NA

NA

NA

100 and 200 mg/kg bw for 65 days and water extracts at doses of 150 and 300 mg/kg bw.

 NA

 NA

Fertility Index

Mild to moderate degenerative changes of spermatogenic cells, diffuse oedema and incomplete arrest of spermatogenesis. Mild degeneration of spermatogenic cells and slight oedema of interstitial cells in testes of rats orally administered 300 mg/kg bw water extract. LOAEL of 200 mg/kg bw/day for the methanolic extract suggested.

Weidner & Sigwart, 2001

Wistar rats, pregnant female.

176 (88 Females).

Gastric intubation: 100, 333 and 1000 mg/kg from days 6-15.

EV.EXT 33, a patented Zingiber officinale extract (comprising 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, and 8-shogaol (1.9 w/w of the extract).

21 days.

Teratogenicity.

No maternal or developmental toxicity observed.

Author

Test System

Exposure

Characterisation of test substance

Main outcome measure

Outcome

Dugasani et al., 2010

Mouse leukaemic monocyte (RAW 264.7)
 macrophages and human polymorphonuclear neutrophils (PMN).

1, 3 and 6 uM.

[6]-gingerol, [8]-gingerol, [10]-gingerol
 and [6]-shogaol.

compare the antioxidant and antiinflammatory
 activities of gingerols and their natural analogues to determine their structure–activity
 relationship and molecular mechanisms.

Dose dependant inhibition of activated PGE2 release. Inhibition reached 58, 66, 73 and 87%, respectively, at 6uM.

Jolad et al., 2004

HL-60 cells.

Not specified.

ginger constituents: gingerols, shogaols, 3-dihydroshogaols, gingerdiols.

Effects of ginger components on LPS-induced PGE2 production.

No cytotoxicity demonstrated.

Jolad et al., 2005

HL-60 cells.

Not specified.

Ginger constituents containing gingerols, shogaols, 3-dihydroshogaols, gingerdiols.

Effects of ginger components on LPS-induced PGE2 production.

Inhibition of LPS-stimulated
 PGE2 production (IC50 = 0.05 0.08 ug/ml) with Gingerol fractions. 

Kim et al., 2012

Human liver microsomes.

0.05–5 ug/ml.

Aqueous ethanolic ginger extract (30% EtOH).

Inhibitory effect on CYP450-mediated drug metabolism. 

Concentration-dependent
 inhibitory effects on CYP2C19; IC50 value of 3.8 g/ml.

Kimura et al., 2010;

Human CYP3A4 and CYP2C9 microsomes.

Not specified.

 NA

Inhibitory effect on CYP3A4 and CYP2C9 activity.

significant inhibition of CYP3A4 IC50 5.1u g/ml or CYP2C9 IC50 (10ug/ml) activity.

Lantz et al., 2007

U937 cells

0.1 ug/ml for 6 hrs.

Ginger extract and mixtures of 6-, 8- 10-gingerols and 6-, 8-, 10-shogaols.

Effect on inflammatory
 mediator production.

No effect on COX-2 expression.

Mukkavilli et al., 2014

Human liver microsomes.

Ginger extract: 500 mg/ml (containing 15 mg/
 ml 6G, 3.4 mg/ml 8G, 3.9 mg/ml 10G, 3.0 mg/ml 6S); All
 individual components of gingerols assessed at 100 mg/mL
 (equivalent to 29 mg/ml 6G, 32 mg/ml 8G, 35 mg/ml 10G and
 28 mg/ml of 6S).

Ginger extract: (containing 6-Gingerol, 8-Gingerol, 10-Gingerol, 6-Shogaol). All
 individual components of gingerols were assessed at 100 mg/mL
 equivalent to 29 mg/mL 6G, 32 mg/mL 8G, 35 mg/mL 10G and
 28 mg/mL of 6S.

effect of ginger extract and major 
 constituents on CYP P450 enzyme activity. 

Inhibition of CYP1A2 (IC50 -
 221.5 mg/ml) by ginger extract. No effect on CYP2A6; maximum inhibition on CYP2B6: IC50
 - 22 mg/ml; IC50 - 122.5 mg/mL against CYP2C8
 in the presence of amodiaquine; IC50 - 93.5 mg/mL against CYP2C9,
 in the presence of diclofenac; Inhibition of CYP3A in the presence of testosterone: no effect in the presence of midazolam.

Author

Test System

Study size

Exposure

Characterisation of test substance

Main outcome measure

Outcome

Srivas, 1984

Human platelets and rat aorta.

NA

15-20 ul (concentrations not given).

Ginger extracts in water, n-hexane, chloroform, and ethyl acetate.

Effect of ginger extracts on in vitro platelet aggregation.

Inhibition of arachidonic acid (AA), epinephrine, adenosine diphosphate (ADP), and collagen-induced platelet aggregation.

Srivastava, 1986

Platelet rich plasma (no further information given).

NA

10-20 ul (concentrations not given).

 NA

Effect of ginger and components on platelet aggregation and eicosanoid biosynthesis.

Reduced thromboxane formation from exogenous AA; Inhibition of AA, epinephrine, ADP and collagen-induced platelet aggregation.

Suekawa et al., 1986 (abstract only)

Rat hind paw and aorta, rabbits.

Unknown.

Unknown.

6-shogaol.

Effect of 6-shogaol on arachidonic acid cascade.

Inhibition of carrageenin-induced swelling of hind paw in rats and arachidonic acid (AA)-induced platelet aggregation in rabbits. Inhibition of prostaglandin 12 (PGI2) release in rat aorta. Possibly caused by COX inhibition.

Thomson et al., 2002

Sprague-Dawley rats, Adult, F; ex vivo.

36

50 mg/kg or 500 mg/kg daily by gavage or intraperitoneally (IP) for 4 weeks.

Aqueous ginger extract, equivalent of 500 mg/ml.

ex vivo effect
 of aqueous extract of ginger on the synthesis of
 thromboxane-B2, prostaglandin-E2, and cholesterol, 
 triglyceride levels in the serum of normal rats.

Serum PGE2 reduced and both dose levels; high dose significantly reduced serum TXB2 both orally and IP; A non-significant reduction in the level of 
 TXB2 observed when ginger was injected IP but not significantly different from saline group.

 NA

NA

NA

NA

NA

  NA

significant reduction in levels of
 cholesterol in rats given high dose; No significant change in triglyceride levels with either dose either orally or IP.

Author

Test System

Study size

Exposure

Characterisation of test substance

Duration

Main outcome measure

Outcome

Al-Omari et al., 2012

Albino rat, M

30: 5 groups of 6; 72: 12 groups of 6. 

25, 50 and 100 mg/kg bw by gavage; single dose (50 mg/kg bw) and up to one week.

Ginger crude extract.

Multiple dose: 2 weeks; single dose: 1 week.

Effect on glibenclamide and insulin; hypoglycaemic and antihyperglycemic effects in normoglycemic- and streptozotocin-induced (STZ) diabetic rats.

Significant decrease in blood glucose level (BGL) in normoglycemic rats after 1 & 2 hrs (50 mg/kg). Significant decrease in non-fasting BGL (N-FBGL) in STZ- diabetic rats.

Egashira et al., 2012

Sprague-Dawley rat, M (7 weeks old)

Not specified.

10 mL/kg orally.

50% ginger juice.

1-3 days.

interaction between ginger juice and tacrolimus.

Significant increase in tacrolimus blood concentrations in rats treated with ginger juice, compared to those treated with water or orange juice.

Okonta et al., 2008

Rabbits (3F, 2M)

5

1 ml/kg, orally.

Ginger extract.

3 days.

Effect of ginger on the pharmacokinetics of metronidazole.

Significant increase in absorption and plasma half-life; significant decrease in the elimination rate constant and clearance of metronidazole.