Table 1 Summary of articles selected to evaluate the effectiveness of Ginger, ginger extract, or Alpenitin during pregnancy and lactation
Study | Model | Treated/Control | Intervention(s) | Supplementation Period | Maternal Outcomes | Neonatal Outcomes | Summary of Findings |
|---|---|---|---|---|---|---|---|
Studies with multiple outcomes | |||||||
Balubaid, 2010 | Rat (Rattus norvegicus) | 3 / 1 | 1. control 2. 0.07 mg tetracycline/kg/day 3. therapeutic dose of ginger 4. 0.07 mg tetracycline/kg/day + similar dose of ginger ale *Treated daily one week prior to pregnancy. Route of administration not clear. | One week before pregnancy | Body weight Liver weight | Embryo number Embryo weight Embryo liver weight Congenital anomaly | The authors concluded that tetracycline decreased dam and embryo weight (and liver weight of each) and that ginger ale rescued the effects of tetracycline on these outcomes. They also reported no congenital anomalies in offspring. The presentation of the data and lack of statistical rigor make interpreting these conclusions difficult. |
El Mazoudy, 2018 | Mouse (ICR-CD1) | 5 / 1 | Dose response of ginger (Zingiber officinale roscoe, aqueous extract) ranging from 250–2000 mg/kg | Not specified | Fertility Weight status Toxicity | Fetal death Developmental outcomes Toxicity | The highest two doses of ginger (1000 and 2000 mg/kg/day) caused decreased maternal weight gain (p ≤ 0.05) and decreased food consumption (not clear that this is gestational weight or not). Estrous cycle length increased (p ≤ 0.05) and total estrous cycles decreased with the highest dose of ginger (2000 mg/kg/day); diestrus index also decreased in this group (p ≤ 0.05).The highest ginger dose resulted in decreased implantation and pre- and post-implantation fetus loss (p ≤ 0.05).Crown-rump length also decreased in the highest ginger exposure group (p ≤ 0.05). |
Haijin, 2013 | Mouse (Balb/c) | 3 / 1 | Lipopolysaccharide (LPS)-induced mastitis model + dose response (10, 25, 50 mg/kg IP alpinetin; with alpinetin given 1 h before LPS stimulation) | 1 h before LPS stimulation | Lactation Immune function |  | Alpinetin decreased LPS-induced myeloperoxidase (MPO) activity in a dose-response fashion and reduced inflammatory cytokine levels (TNFa, IL-1B, IL-6) after LPS treatment in mammary tissue homogenate. Statistical representations are shown but did not address dose-response specifically. |
Weidner, 2001 | Rat (Wister SPR) | 4 / 1 | 1. Control 2. 100 mg/kg/d Zingiber officinale ethanol extract EV.EXT 33 (eurovita extract) 3. 300 mg/kg/d EV.EXT 33 4. 1000 mg/kg/d EV.EXT 33 *Delivered via gastric intubation on days 6–15 of gestation | Gestation (days 6–15) | Fertility Gestational weight gain Mortality Toxicity | Developmental outcomes | Maternal body weight was lower in the 1000 mg/kg/d dose at 22 days gestation (p < 0.05). No effect of EV.EXT 33 on implantations, fertility index, number of corpora lutea, implantation loss, resorptions, number of fetuses born, uterine weight, or placental weight. No effect of EV.EXT 33 on skeletal malformations. |
Wilkinson, 2000 | Rat (Sprague Dawley) | 2 / 1 | 1. control 2. 20 g/L ginger tea in drinking water 3. 50 g/L ginger tea in drinking water *Administered days 6–15 of gestation | Gestation (days 6–15) | Fertility Gestational weight gain Toxicity | Birth weight Fetal death Developmental outcomes | Ginger tea decreased fluid consumption at highest (50 g/L) dose (p < 0.01), not clear how this may affect results. Ginger tea did not affect gestational weight gain; did not affect maternal liver, kidney, placenta, or uterus weight. Ginger tea did not affect implantations/dam but did increase resorptions (p < 0.05). Fetal weight was increased by ginger tea (p < 0.01); crown-rump length was increased in males only in the 50 g/L exposure group (p < 0.01). |
Studies with primarily toxicity prevention outcomes | |||||||
EL-Aziz, 2018 | Rat (Sprague-Dawley) | 4 / 1 | 1. Control 2. Zingiber officinale 3. CdCl2 4. Zingiber officinale + CdCl2 *Given through oral intragastric tube during either gestation or gestation and lactation (depending on study group). | During gestation or gestation + lactation | Weight gain Toxicity prevention | Toxicity prevention | Zingiber officinale rescued gestational weight gain, which was severely reduced by CdCl2 exposure (p < 0.001); partially rescued effects of ClCl2 on gravid uterine weight and placental weight (p < 0.001). Histology images are shown for maternal and fetal liver and kidney, but findings from images are not quantified. However, authors state that CdCl2-induced damage to these tissues was improved/prevented by zingiber officinale. |
El-Borm, 2021a | Rat (Wistar) | 3 / 1 | 1. control 2. ginger (water extract of ginger, 200 mg/kg) 3. labetalol (medication used to treat hypertension during pregnancy, 300 mg/kg) 4. ginger + labetalol *Given through oral injection during organogenesis (6th -15th day of gestation) | Organogenesis (days 6–15 of gestation) |  | Toxicity prevention | Labetalol caused changes in offspring cardiac muscle physiology, as evidenced by histology, and authors state that this was rescued by ginger (findings not quantified); these findings were confirmed by electron microscopy (also not quantified). Flow cytometry revealed more apoptotic (p < 0.001), and fewer viable, fetal cardiac cells as a result of labetalol, and these outcomes were partially rescued by ginger. |
El-Borm, 2021b | Rat (Wistar) | 3 / 1 | 1. control 2. ginger (water extract of ginger, 200 mg/kg) 3. labetalol (medication used to treat hypertension during pregnancy, 300 mg/kg) 4. ginger + labetalol *Given through oral injection (6th -20th day of gestation) | Gestation (days 6–20) | Toxicity prevention |  | In maternal cardiac tissue labetalol induced histological changes including disorganization of cardiac fibers and blood vessel dilation and congestion; these outcomes were rescued by ginger (findings not quantified); similar observations were seen using electron microscopy (findings not quantified). Labetalol increased apoptosis in maternal cardiac muscle as measured by caspase-3 immunohistochemistry (p < 0.001), and the caspase-3 staining was partially rescued in the labetalol + ginger group (p < 0.001). Labetalol decreased placental weight, and this was rescued in the labetalol + ginger group. Similar histological, electron microscopy, and immunohistochemical (caspase-3) findings were observed in the placenta as in maternal cardiac muscle. Only caspase-3 staining was quantified, though again it was elevated by labetalol and rescued in the labetalol + ginger group. |
Farag, 2010 | Rats (albino) | 8 / 1 | 1. control 2. 1% (w/2) ginger 3. lead acetate (120 ug/animal/d) 4. fenitrothion (pesticide; 10 mg/kg/d) 5. lead + fenitrothion 6. fenitrothion + ginger 7. lead + ginger 8. lead + fenitrothion + ginger | During pregnancy | Gestational weight gain Toxicity prevention | Birth weight Fetal death Developmental outcomes Toxicity prevention | All combination treatment groups (including those with ginger) increased gestational weight gain (p < 0.05). Ginger alone affected some plasma/blood biomarkers of liver function, but not to the extent that the combination treatments affected these parameters. Uterine morphology largely unchanged: number of corpora lutea per dam was increased in combination groups (p < 0.05) but not by ginger alone. Mean fetal weight and placental weight (p < 0.05) were also increased in combination groups, but not by ginger alone. Skeletal malformations are noted in the combination groups but are not characterized statistically; it does not look like ginger is causing malformations or that it is rescuing malformations caused by the other two agents. |
Othman, 2022 | Mouse | 3 / 1 | 1. control 2. 350 mg/kg/day body weight methyl ethyl ketone (MEK) 3. 350 mg/kg/day MEK + 25 mg/kg/day gingerol | During gestation | Gestational weight gain Toxicity prevention | Birth weight Developmental outcomes Toxicity prevention | Gestational weight gain was reduced by MEK exposure (p < 0.01), and this was rescued by gingerol exposure. Offspring weight also reduced by MEK exposure (p < 0.01) and rescued by gingerol. Similar outcomes were seen with markers of kidney function and liver function in both dams and offspring. Apoptotic index and fibrosis score (in liver and kidney) were increased by MEK (p < 0.01) and rescued by gingerol albeit to a lesser extent than other outcomes. Lipid peroxidation thiobarbituric acid reactive substances (TBARS) increased in pups in kidney, liver, and brain (p < 0.01) by MEK and rescued by gingerol at gestational days 7, 14, and 21. Oxidative stress parameters in pups are also shown, but difficult to interpret as presented. |
Studies investigating toxicity of compounds extracted from Zingiberaceae family | |||||||
Inegbenebor, 2009a | Rat (Sprague-Dawley) | 4 / 1 | 1.Control 2. 0.5 mg alligator pepper 3. 1.0 mg alligator pepper 4. 1.5 mg alligator pepper 5. 2.0 mg alligator pepper *Administered as a bolus dose. | Not specified | Gestational weight gain | Birth weight | At even the lowest dose of alligator pepper, gestational weight gain was reduced by 50% (p < 0.01). Mean litter weight was reduced only in the 2.0 mg dose group (p < 0.001). |
Inegbenebor, 2009b | Rat (Sprague-Dawley) | 1 / 1 | 1. control 2. 50 mg alligator pepper / 20 g chow *Administered once on fourth day after mating | Once on fourth day after mating | Gestational weight gain Toxicity |  | Gestational weight gain was reduced by > 50% in experimental group (p < 0.001). Significant toxicity noted. No litters born to dams from experimental group. |