Extracts and concentrates of ginger

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.