Systematic review of the impact of ginger extract and alpinetin on pregnancy outcomes in animal models.

Background: The objective of this systematic review was to evaluate existing scientific evidence regarding the effectiveness and safety of preparations of bioactive compounds of the Zingiberaceae family in animal models during gestation and lactation.

Methods: A systematic protocol was registered with the Open Science Framework (OSF) ( https://doi.org/10.17605/OSF.IO/ADU68 ). The literature search was conducted on selected databases such as MEDLINE, Embase, Center for Agricultural and Biosciences International, and the International Pharmaceutical Abstracts databases. The full search strategy is included in the Supplementary Materials. Main keywords related to population included terms related to pregnancy and lactation; keywords related to intervention included key terms for alpinetin, ginger, and Zingiberaceae plants. We included maternal (i.e., dam) and neonatal (i.e., pup) outcome(s) reported in studies with ginger preparations in various forms given during pregnancy or lactation compared to placebo. Risk of bias was assessed using the Systematic Review Center for Laboratory animal experimentation (SYRCLE) risk of bias tool.

Results: Twelve studies published between 2000 and 2022 were included in the review. Ginger and its bioactive compounds, [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol, were found to have protective effects against gestational and developmental toxicities. This included mitigating and preventing organ toxicity (e.g., liver and kidney), improved gestational weight gain, and improved placental function; fetal benefits included prevention of organ damage (e.g., liver, kidney, cardiac), improved fetal growth, reduced oxidative stress, and reduced death. In studies involving toxic exposures such as heavy metals and pesticides, ginger mitigated adverse effects on maternal and fetal health, improving outcomes such as placental function birth weight, and organ development (e.g., liver, kidney, cardiac). Alpinetin, a flavonoid rich in ginger plants, showed anti-inflammatory effects in lactation by reducing cytokine levels and improving mammary tissue health. Studies on fetal development reported improvements in birth weight, growth metrics, and reductions in death rates when ginger was administered at moderate doses, specifically ginger tea 20 g/L-50 g/L or gingerol 25 mg/kg/body weight. However, higher doses (specifically, 50 mg alligator pepper, 2,000 mg/kg body weight Zingiber officinale) caused adverse reproductive outcomes such as reduced weight gain (< 50%), maternal toxicity, disrupted estrous cycle, and increased fetal death. Sensitivity analysis confirmed that lower dosages of rhizome-derived ginger preparations (Zingiber officinale) (< 200 mg/kg/day) were safer.

Conclusion: The majority of the included studies reported protective effects of lower dose Zingiberaceae preparations (< 200 mg/kg/day) on gestational and developmental toxicities in animal models. Standardization of ginger interventions and more robust study designs are needed to optimize ginger form, amounts, preparation, doses, and timing of exposures to understand how maximize benefits while minimizing potential adverse effects in animal models before such data can be translated meaningfully to humans.

Clinical trial number: Not applicable.