Annex B
On this page
Skip the menu of subheadings on this page.Annex B: Summary of Studies
Traditional/culinary uses of ginger
Human Studies
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 |
4 days |
4 |
Change in nausea and vomiting scores (3 symptoms on Rhodes index); |
Results showed that ginger is |
Ensiyeh et al., 2005 |
Double-blind randomised controlled trial. |
70/69 |
Ginger powder |
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 |
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 |
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 |
5 months. |
4 |
Severity of nausea (VAS 0–10); number of vomiting episodes; general response to treatment after 1 week (5-item Likert |
Ginger was significantly more effective than the placebo in relieving the severity of nausea in pregnancy (p = 0.014). |
Human studies – Platelet Aggregation
Author/date |
Study design |
Population/study size |
Study Duration |
Exposure |
Outcome |
Results |
Comment |
Bordia |
Placebo controlled |
Patients with |
3 months. Outcomes |
Dose: 4g per day Unstandardised capsules. |
Platelet aggregation— |
Ginger had no |
Ginger had no significant effect on blood lipids or blood sugar. |
Bordia |
NA |
NA |
NA |
NA |
Fibrinogen; |
NA |
No mention of |
Bordia |
NA |
NA |
NA |
NA |
Fibrinolytic activity. |
P value not reported. |
|
Lumb. |
Randomised, |
Healthy male |
Total study period: |
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 |
NA |
Srivastava |
Open-label |
Healthy female |
Total study period: 7 days. Outcomes |
Dose: 5g raw ginger per day. |
Platelet thromboxane B2 production. |
Ginger consumption |
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 |
NA |
In vitro studies
Author |
Test System |
Exposure |
Characterisation of test substance |
Main outcome measure |
Outcome |
In vivo studies
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 2x that of the controls. Exposed foetuses found to be significantly heavier than control. No gross structural malformations observed. |
Effect on CYPs and prostaglandin activity
Author |
Test System |
Exposure |
Characterisation of test substance |
Main outcome measure |
Outcome |
Effect on Platelet Aggregation
Author |
Test System |
Study size |
Exposure |
Characterisation of test substance |
Main outcome measure |
Outcome |
Srivastava |
Open-label |
Healthy female |
Total study period: 7 |
Dose: 5g raw ginger |
Platelet thromboxane B2 production. |
Ginger consumption |
Herb-drug interactions
Author |
Test System |
Study size |
Exposure |
Characterisation of test substance |
Duration |
Main outcome measure |
Outcome |
Extracts and concentrates of ginger
Human Studies
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 |
Laekman et al., 2021 |
Observational study, clinical trial. |
51/44. |
maximum of 2 tablets of 50 mg EXT.GR10 a day [limited data on actual amount administered]. |
During pregnancy. |
|
Patient satisfaction pregnancy complications (including hypertension and diabetes) and birth complications (including stillbirth, premature delivery, low birth weight). |
Increased incidence of premature birth, low birth weight and hypertension in treatment group when compared with general population. |
Willetts et al., 2003 |
Double-blind randomised placebo-controlled trial. |
120/99. |
Ginger extract |
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. |
Human studies – Platelet Aggregation
Author/date |
Study design |
Population/study size |
Study Duration |
Exposure |
Outcome |
Results |
Comment |
Bordia |
NA |
20 |
1 day. Outcomes |
10 g single dose. Unstandardised capsules. |
Platelet aggregation. - Agonist(s): ADP and Epi. |
Reduction of both |
NA |
Jiang et al., |
Randomized, |
Healthy male |
Total study period: |
Dose: 3.6g (3x 0.4g, 3x per day) ginger extract Unstandardized |
Platelet aggregation, Agonist: AA; INR; Plasma warfarin |
No significant |
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.
|
Patient also taking clonazepam 1 mg, |
Verma |
Randomised placebo controlled |
Healthy male |
Total study period: |
Dose: 5g (4 x 625 mg, twice per day); dry ginger powder - Unstandardized capsules Consumed with |
Platelet aggregation. Agonist(s): ADP and Epi |
Ginger significantly reduced platelet |
Platelet aggregation reduced close to baseline but did not |
In vitro studies
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, |
Aq, chloroform and MeOH ginger extracts. |
Cytotoxicity and genotoxicity. |
Chloroform extractcytotoxic: 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 μM. |
NA |
NA |
NA |
NA |
NA |
Change in both cellular activity and protein content in a dose-dependent manner at high concs (12.5–100 μM). |
NA |
NA |
NA |
NA |
NA |
Significant decrease in cardiomyocyte differentiation for all tested concentrations except 0.75 μM 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. |
Sivaswami et al., 1991 (Abstract) |
Salmonella typhimurium strains TA 98, TA 100 and TA 1535. |
Unknown. |
Essential oil from ginger. |
Mutagenicity. |
Non mutagenic. |
Soudamini et al., 1995 |
Salmonella typhimurium strains TA 100, 98 |
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. |
In vivo studies
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 developmen. |
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/ |
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 consecutive days. |
|
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 consecutive 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. |
Effect on CYPs and prostaglandin activity
Author |
Test System |
Exposure |
Characterisation of test substance |
Main outcome measure |
Outcome |
Dugasani et al., 2010 |
Mouse leukaemic monocyte (RAW 264.7) |
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 |
Dose dependant inhibition of activated PGE2 release. Inhibition reached 58, 66, 73 |
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 |
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 |
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 |
No effect on COX-2 expression. |
Mukkavilli et al., 2014 |
Human liver microsomes. |
Ginger extract: 500 mg/ml (containing 15 mg/ |
Ginger extract: (containing 6-Gingerol, 8-Gingerol, 10-Gingerol, 6-Shogaol). All |
effect of ginger extract and major constituents on CYP P450 enzyme activity. |
Inhibition of CYP1A2 (IC50 - |
Effect on Platelet Aggregation
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 |
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 |
Herb-drug interactions
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. |