Agent Detail

GINGER

Agent Number 2195
CAS Number NONE
Last Updated 12/29/2021

Agent Summary

Quick take: Studies in rats and human reports suggested that ginger use during pregnancy does not interfere with embryo development.


Ginger (Zingiber officinale) is a tropical plant the rhizomes of which are used for culinary and medicinal purposes. Ginger contains monoterpenes, sesquiterpenes, and phenolic ketones, mainly gingerols and their derivative shogaols (25). Ginger, an ingredient in traditional Chinese herbal formulas, has been used to treat gastrointestinal disorders and arthritis among other conditions (26). There is variation in the composition of ginger root preparations (10).

Ginger is a thromboxane synthase inhibitor in vitro (3). Thromboxane synthesis inhibition would be expected to affect platelet aggregation, but clinical studies designed to assess the effect of ginger on bleeding risk (4-6) have found no effect on platelet aggregation of up to 15 g raw ginger, 40 g cooked ginger, or 4 g dried ginger daily; however, dried ginger 10 g/day decreased platelet aggregation (4). Some reports suggest that ginger might have anticoagulant effects (19,20). One commentator expressed concern about this potential pharmacological action during pregnancy (21).

Experimental animal development

Female rats given a commercial ginger extract 100, 333, or 1000 mg/kg/day by gavage on days 6-15 of gestation showed no effect on food consumption or maternal weight gain and no effect on fertility, pregnancy with viable fetuses, weight of the gravid uterus, placental weight, number of fetuses per litter, early or late resorptions, number of implantations, corpora lutea, preimplantation loss, or post-implantation loss (7). No differences in fetal body weight or sex ratio were noted. The study authors stated that there were differences in skeletal development but did not show statistically significant differences in skeletal end points.

Pregnant rats given ginger in drinking water at 20 or 50 g/L did not show maternal toxicity or gross malformations in fetuses, but embryonic loss was increased (8). Fetuses exposed to ginger weighed more than controls independent of litter size. Skeletal variations were similar between exposed and control fetuses, but exposed fetuses had more advanced skeletal development than controls, consistent with their heavier weights. The ginger dose levels in this study were 446 and 1050 mg/kg/day.

The thromboxane synthase inhibitor action of ginger led one researcher to speculate that ginger might affect testosterone receptor binding and alter sex steroid differentiation of the fetal brain (3). Two studies of ginger in rats showed no difference in sex ratio or genital development (7,8).

Human pregnancy

In a clinical trial, pregnancy outcomes were assessed in 27 women (1). One patient in the ginger group experienced a spontaneous abortion and one patient in the placebo group underwent induced abortion. Twenty-five patients went to term and all infants were normal in appearance, birthweight, and Apgar scores (1). In a prospective study based on women contacting a teratology information service, no increase in adverse outcomes was detected in 187 women who reported using ginger in early pregnancy (11). Among 1020 women who retrospectively reported using ginger during gestation there was no increase in adverse outcome compared to unexposed controls (18). A case control study from the National Birth Defects Prevention Study did not identify an association between ginger therapy during pregnancy and facial clefts, neural tube defects, or hypospadias (16).

A 2003 review found that neither ginger nor other alternate treatments were effective for hyperemesis gravidarum (12). A report on the effectiveness of ginger for treatment of nausea and vomiting in pregnancy did not seem to be placebo-controlled (13). Two other double-blind, randomized, placebo-controlled trials suggested that dried ginger root in doses up to 1 g/day may be an effective treatment for mild hyperemesis during pregnancy (1,2). Ginger 1.05 g/day was similar to vitamin B6 #1190 75 mg/day for the treatment of nausea in pregnancy; neither agent was effective at reducing nausea, retching, or vomiting (14). There were no differences in pregnancy outcomes except that the ginger group had more live births. A 2013 review of 4 studies that included randomized controls to evaluate the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy concluded that ginger was effective for this indication (17). Use of ginger in early pregnancy did not increase adverse outcomes There was no increased risk of major malformations among 159 pregnant women who used dried ginger as a medication when compared to a control group of 306 pregnant women (22).

An increase in stillbirth among treated women was more prominent when treated women were compared to the general population, odds ratio 7.9, 95% CI 2.9-21.4 (22). Comparison to a population control rather than a contemporaneous control detracts from the reliability of this finding. There was variability in dose of ginger, and there were exposures to other herbal medicines. A questionnaire study identified a lower mean gestational age in women who reported ginger use; however, mean gestational age in exposed women was normal and there was no comment on the prevalence of preterm birth (28).

Lactation

A daily dose of dried ginger 1000 mg given to lactating mothers for seven days postpartum increased milk volume on day 3 of treatment but not on day 7 (23). There was no effect of ginger on serum prolactin concentration.

Reproduction

Ginger aromatherapy had an aphrodisiacal effect on fruit flies. Male fruit flies exposed to ginger root essential oil outcompeted unexposed males in matings (9). Ginger contains alpha-copaene, a male attractant. Ginger root increased fertility, serum testosterone, and weights of testis, seminal vesicles, and prostate in diabetic male mice (15). Mice dosed orally with ginger at 2000 mg/kg/day showed prolongation of the estrous cycle, reduced number of live fetuses, and increased fetal resorption in the face of maternal toxicity (24). Maternal and reproductive toxicity were not observed at 500 mg/kg/day. A 2018 review discussed experimental studies showing increased testosterone production in response to ginger (27).

Selected References

  1. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U: Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 38:19-24, 1991.

  2. Vutyavanich T, Kraisarin T, Ruangsri R-A. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 2001;97:577-582.

  3. Backon J: Ginger in preventing nausea and vomiting of pregnancy: a caveat due to its thromboxane synthetase activity and effect on testosterone binding. Eur J Obstet Gynecol Rep Bio 1991;42:163.

  4. Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins, Leukotrienes and Essential Fatty Acids 1997;56(5):379-384.

  5. Janssen PLTMK, Meyboom S, van Staveren WA, de Vegt F, Katan MB. Consumption of ginger (Zingiber officinale Roscoe) does not affect ex vivo platelet thromboxane production in humans. Eur J Clin Nutr 1996;50:772-774.

  6. Lumb AB. Effect of dried ginger on human platelet function. Thromb Haemostas 1994; 71:110-111.

  7. Weidner MS, Sigwart K. Investigation of the teratogenic potential of a zingiber officinale extract in the rat. Reprod Toxicol. 2001;15:75-80.

  8. Wilkinson JM. Effect of ginger tea on the fetal development of Sprague-Dawley rats. Reprod Toxicol. 2000;14:507-512.

  9. Shelly TE, McInnis DO. Exposure to ginger root oil enhances mating success of irradiated, mass-reared males of Mediterranean fruit fly (Diptera: Tephritidae). J Econ Entomol. 2001;94(6):1413-1418.

  10. Schwertner HA, Rios DC, Pascoe JE: Variation in concentration and labeling of ginger root dietary supplements. Obstet Gynecol 2006;107:1337-1343.

  11. Portnoi G, Chng LA, Karimi-Tabesh L et al: Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol 2003;189:1374-1277.

  12. Jewell D, Young G: Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2003(4):CD000145.

  13. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B: Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.

  14. Smith C, Crowther C, Willson K, Hotham N, McMillian V. A randomized controlled trial of ginger to treat nausea and vomiting of pregnancy. Obstet Gynecol 2004;103:639-645.

  15. Shalaby MA, Hamowieh AR: Safety and efficacy of Zingiber officinale roots on fertility of male diabetic rats. Food Chem Toxicol. 2010; 48(10):2920-2924.

  16. Anderka M, Mitchell AA, Louik C, Werler MM, Hernandez-Diaz S, Rasmussen SA; National Birth Defects Prevention Study. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth Defects Res A Clin Mol Teratol. 2012 Jan;94(1):22-30. doi: 10.1002/bdra.22865. Epub 2011 Nov 19. PubMed PMID: 22102545; PubMed Central PMCID: PMC3299087.

  17. Ding M, Leach M, Bradley H. The effectiveness and safety of ginger for pregnancy-induced nausea and vomiting: a systematic review. Women Birth. 2013 Mar;26(1):e26-30. Doi: 10.1016/j.wombi.2012.08.001. Epub 2012 Aug 28. PubMed PMID: 22951628.

  18. Heitmann K, Nordeng H, Holst L. Safety of ginger use in pregnancy: results from a large population-based cohort study. Eur J Clin Pharmacol. 2013 Feb;69(2):269-277. doi: 10.1007/s00228-012-1331-5. Epub 2012 Jun 17. PubMed PMID: 22706624.

  19. Kruth P, Brosi E, Fux R, Morike K, Gleiter CH. Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother. 2004 Feb;38(2):257-260. Epub 2003 Dec 19. Review. PubMed PMID: 14742762.

  20. Nurtjahja-Tjendraputra E, Ammit AJ, Roufogalis BD, Tran VH, Duke CC. Effective anti-platelet and COX-1 enzyme inhibitors from pungent constituents of ginger. Thromb Res. 2003;111(4-5):259-265.

  21. Tiran D. Ginger to reduce nausea and vomiting during pregnancy: evidence of effectiveness is not the same as proof of safety. Complement Ther Clin Pract. 2012 Feb;18(1):22-25. doi: 10.1016/j.ctcp.2011.08.007. Epub 2011 Sep 15. Review. PubMed PMID: 22196569.

  22. Choi JS, Han JY, Ahn HK, Lee SW, Koong MK, Velazquez-Armenta EY, Nava-Ocampo AA. 2015. Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizome siccus) for a variety of illnesses during pregnancy. J Obstet Gynaecol 35(2): 125-130.

  23. Paritakul P, Ruangrongmorakot K, Laosooksathit W, Suksamarnwong M, Puapornpong P. 2016. The effect of ginger on breast milk volume in the early postpartum period: A randomized, double-blind controlled trial. Breastfeed Med 11: 361-365.

  24. ElMazoudy RH, Attia AA. 2018. Ginger causes subfertility and abortifacient in mice by targeting both estrous cycle and blastocyst implantation without teratogenesis. Phytomedicine 50: 300-308.

  25. Gupta S, Pandotra P, Ram G, Anand R, Gupta AP, Husain K, Bedi YS, Mallavarapu GR. Composition of a monoterpenoid-rich essential oil from the rhizome of Zingiber officinale from north western Himalayas. Nat Prod Commun. 2011 Jan;6(1):93-96. PMID: 21366054.

  26. Acualt.com. Uses of ginger in traditional Chinese medicine. 2019. https://acualt.com/herbs/uses-of-ginger-in-traditional-chinese-medicine/

  27. Banihani SA. Ginger and testosterone. Biomolecules 2018;8:119 doi:10.3390/biom8040119

  28. Trabace L, Tucci P, Ciuffreda L, Matteo M, Fortunato F, Campolongo P, Trezza V, Cuomo V. "Natural" relief of pregnancy-related symptoms and neonatal outcomes: above all do no harm. J Ethnopharmacol. 2015 Nov 4;174:396-402. doi: 10.1016/j.jep.2015.08.046. PMID: 26325431.

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