Is Ginger Safe For Use During Pregnancy?

Background

Pregnancy-associated nausea and vomiting may affect over half of pregnancies. With the increasing interest in natural medicine in recent years, ginger has received attention as a remedy for this common problem.1 Several studies have shown ginger to be beneficial in treating nausea and vomiting in pregnancy with no fetal harm noted. However, use during pregnancy is controversial due to limited safety data. In fact, Finnish authorities recently determined that ginger tea, supplements, and drink powders must carry the statement, "Not recommended for pregnant women."2,3 This article reviews the evidence for the efficacy and safety of ginger during pregnancy.

Efficacy of Ginger for Nausea and Vomiting of Pregnancy

Ginger seems to be more effective than placebo and comparable to vitamin B6 (pyridoxine) or dimenhydrinate for treatment of nausea and vomiting during pregnancy.1,4-12 However, the onset of action of ginger appears to be slower than dimenhydrinate; ginger takes about three days to work compared to one day with dimenhydrinate.11 Most studies have used 1000 mg given in divided doses.1,4,6,10,11

Safety of Ginger During Pregnancy

The risk for major malformations in infants of women taking ginger does not appear to be higher than the baseline rate of 1% to 3%.4-8,10 However, there is some concern that ginger might affect fetal sex hormones, and an anecdotal report of spontaneous abortion during week 12 of pregnancy in a patient who used ginger for morning sickness.4,13

New labeling requirements in Finland were not based on new human evidence of harm. Rather, the concerns were based on a lack of sufficient safety evidence and in vitro data showing that certain ginger constituents cause cell death.3 The ginger constituent 6-gingerol exhibits cytotoxicity in vitro through generation of reactive oxygen radicals.14 [6]-Shogaol is another cytotoxic ginger constituent.15 An alcoholic ginger extract exhibited cytotoxicity in cell culture and inhibited thymidine incorporation into DNA.16

Another concern is mutagenicity. [6]-Gingerol and 9-shogaol are mutagenic in E.coli and Salmonella typhimurium.17,18 [6]-Gingerol was the more mutagenic compound in E.coli.17 It has been hypothesized that specific side chains present on gingerol and shogaol are responsible for their mutagenicity. The ginger constituent zingerone suppressed their mutagenicity in a dose-dependent manner in Salmonella typhimurium.18

Ginger tea fed to pregnant rats during organogenesis was associated with embryo loss, and heavier offspring with more mature skeletal development. But in another study, ginger extract up to 1000 mg/kg/day fed to rats during organogenesis was neither embryotoxic nor teratogenic.19

Commentary

Both the American College of Obstetrics and Gynecology and the Society of Obstetricians and Gynaecologists of Canada include ginger in their guidelines as a nonpharmacologic option for the treatment of nausea and vomiting in pregnancy.20,21 But it is not first-line, and safety concerns exist. In addition to the Finnish labeling requirements, Denmark has taken action against high-dose (i.e., 6 grams daily) ginger supplements sold in their country due to inadequate safety data. However, they state it is not dangerous to consume ginger-containing foods during pregnancy.22 The German Commission E contraindicates ginger root in pregnancy based on the in vitro data described above.17,18,23 However, the American Botanical Council disagrees, because problems have not been associated with a daily dose of 1 gram in human pregnancies.23

For pregnant patients interested in a natural approach to nausea and vomiting, pyridoxine may be a safer option, as it is considered nonteratogenic.21 Pyridoxine 25 mg three times daily was compared to ginger 650 mg three times daily. Both treatments decreased nausea and vomiting score (Rhode's score) compared to baseline, but ginger decreased the score more than pyridoxine (p<0.05).9 Doses of pyridoxine as low as 10 mg three times daily have shown efficacy compared to placebo [Evidence level B; lower quality RCT].24 In the interest of using the lowest effective dose, recommend 10 mg (if available) three or four times daily to start, increasing to 25 mg three or four times daily if needed.5,20,21 A dose of doxylamine 12.5 mg can be given with each pyridoxine dose for additional benefit.20 In Canada, Diclectin (pyridoxine 10 mg and doxylamine 10 mg) four times daily (morning, noon, and two at bedtime) is an option.21

Levels of Evidence

In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish.

Level

Definition

A

High-quality randomized controlled trial (RCT)

High-quality meta-analysis (quantitative systematic review)

B

Nonrandomized clinical trial

Nonquantitative systematic review

Lower quality RCT

Clinical cohort study

Case-control study

Historical control

Epidemiologic study

C

Consensus

Expert opinion

D

Anecdotal evidence

In vitro or animal study

Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.

Project Leader in preparation of this Detail-Document: Melanie Cupp, Pharm.D., BCPS

References

  1. Ozgoli G, Goli M, Simbar M. Effects of ginger capsules on pregnancy, nausaea, and vomiting. J Altern Complement Med 2009;15:243-6.
  2. Evira. Evira requires a warning label on food supplements containing ginger as well as on ginger tea and corresponding drink powders. July 23, 2009. http://www.evira.fi/portal/en/food/current_issues/?bid=1678 (Accessed October 5, 2009).
  3. Evira. Warning label to be added on food supplements containing ginger as well as on ginger tea, and corresponding drink powders. http://www.evira.fi/portal/en/food/control_and_entrepreneurs/labelling_of_foodstuffs/
    warning_labelling_and_instructions_for_use/warning_label_to_be_added_on_food_supplements_
    containing_ginger_as_well_as_on_ginger_tea__and_corresponding_drink_powders/     (Accessed October 5, 2009).
  4. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991;38:19-24.
  5. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2000;(2):CD000145.
  6. Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 2001;97:577-82.
  7. 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;189:1374-7.
  8. Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol 2005;105:849-56.
  9. 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.
  10. Smith C, Crowther C, Wilson K, et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45.
  11. Pongrojpaw D, Somprasit C, Chanthasenanont A. A randomized comparison of ginger and dimenhydrinate in the treatment of nausea and vomiting in pregnancy. J Med Assoc Thai 2007;90:1703-9.
  12. Ensiyeh J, Sakineh MA. Comparing ginger and vitamin B6 for the treatment of nausea and vomiting in pregnancy: a randomized controlled trial. Midwifery 2008 Feb 11 [Epub ahead of print].
  13. 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 Reprod Biol 1991;42:163-4.
  14. Nigam N, Bhui K, Prasad S, et al. [6]-Gingerol induces reactive oxygen species regulated mitochondrial cell death pathway in human epidermoid carcinoma A431 cells. Chem Biol Interact 2009;181:77-84.
  15. Kim JS, Lee SI, Park HW, et al. Cytotoxic components from the dried rhizomes of Zingiber officinale Roscoe. Arch Pharm Res 2008;31:415-8.
  16. Unnikrishnan MC, Kuttan R. Cytotoxicity of extracts of spices to cultured cells. Nutr Cancer 1988;11:251-7.
  17. Nakamura H, Yamamoto T. The active part of the [6]-gingerol molecule in mutagenesis. Mutat Res 1983;122:87-94.
  18. Nagabhushan M, Amonkar AJ, Bhide SV. Mutagenicity of gingerol and shogaol and antimutagenicity of zingerone in Salmonella/microsome assay. Cancer Lett 1987;36:221-33.
  19. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2008.
  20. American College of Obstetrics and Gynecology. ACOG Practice Bulletin: Nausea and vomiting of pregnancy. Obestet Gynecol 2004;103:803-14.
  21. Arsenault MY, Lane CA, MacKinnon CJ, et al. The management of nausea and vomiting of pregnancy (SOGC clinical practice guidelines). J Obstet Gynaecol Can 2002;24:817-31.
  22. Holst L, Wright D, Haavik S, Nordeng H. The use and user of herbal remedies during pregnancy. J Altern Complement Med 2009;15:787-92.
  23. Blumenthal M. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin, TX: American Botanical Council; 1998.
  24. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol 1995;173:881-4.

Cite this Detail-Document as follows: Is ginger safe for use during pregnancy? Pharmacist's Letter/Prescriber's Letter 2009;25(11):251108.

November 2009

Related Articles