By Mary Hardy, MD, and Jay Udani, MD
Nausea in early pregnancy affects up to 80% of gravid women and can be a significant cause of morbidity during pregnancy.1 A severe form of nausea and vomiting of pregnancy (NVP), hyperemesis gravidarum, can cause 1-3% of women to become malnourished or dehydrated and may require hospitalization.2 Many women are reluctant to use conventional medication for the control of NVP due to the uncertainty of risk to the fetus. Thus, pregnant women, who often perceive CAM therapies to be safer than conventional medication, are very interested in the use of these modalities to control nausea.
Ginger has been shown to decrease nausea from many different etiologies3 and has been recommended as an intervention for nausea and vomiting in early pregnancy as well.4 In fact, almost 52% of obstetrician/gynecologists included in a recent survey recommend ginger for NVP5 and their patients are taking both the advice and the ginger. In one qualitative study, pregnant women were 4.4 times more likely to use an herbal remedy than an OTC or prescription medication.5 A survey performed by the Motherisk Program in Toronto, a group that specializes in assessing risk of drug use during pregnancy, demonstrated that 61% of their sample used CAM therapies to decrease NVP with ginger tea (50.7%), acupressure (46%), and vitamin B6 (29%) being the most commonly used therapies.6
Perceived safety of ginger appears to be an important component of a women’s decision to use ginger during pregnancy. Women who called the Motherisk Program agreed strongly with statements that reflected their reluctance to use drugs and concerns that drug use might harm their babies. Their use of CAM therapies, including ginger, did not appear to be directed by their medical providers as these women were five times more likely to cite friends and family as their source of information about CAM than their doctor or pharmacist (40% vs. 8%).6
As medical providers interested in the health of women, it behooves us to become educated about the common therapies our patients use so that we may more effectively advise them. The most common herbal therapy used by pregnant women is ginger. This fact, coupled with the publication of some new clinical trials, warrants a review of the use of ginger for NVP.
History/Tradition
Ginger is a perennial plant with thick underground stems called rhizomes, which are used for medical and culinary purposes. The aboveground stem can grow to heights of 24 feet. Ginger is native to southern Asia, but now is cultivated extensively throughout the tropics. The very best quality ginger is grown in Jamaica, but more than 80% of the ginger imported to the United States is reported to come from China and India.7
Medicinal use of ginger has been broadly documented in cultures as diverse as Indian, Chinese, Arabic, Greek, and Roman. It is cited in ancient Ayurvedic, Sanskrit, and Chinese texts as early as the fourth century B.C. for conditions such as stomachache, diarrhea, nausea, cholera, hemorrhage, and toothache.8,9 In traditional Chinese medicine, a distinction is made between fresh ginger (sheng jiang) and dried ginger (gan jiang).10 Both are considered warming herbs, although dried ginger is thought to be "hotter" than fresh.
In addition to its medicinal applications, ginger also is widely used as a spice in foods, beverages, candies, and liqueurs, and also is used commonly in many cosmetic products. The Chinese use fresh ginger in many dishes, not only for its spicy flavor and perfume, but also as a yang ingredient—to balance cooling (or yin) dishes. Five-spice powder and many curries contain dried ginger and thus large amounts are eaten with food in Asian and Indian countries.
Pharmacology
The pharmacologically active components of ginger include an oleoresin and pungent "principles." The oleoresin (5-8% of total matter) contains an essential aromatic oil (1-2%) consisting mainly of sesqueterpene lactones, such as zingiberene.11 The pungent or hot "principles" are phenolic compounds, primarily gingerols, which are a mixture of closely related compounds differentiated by the number of carbon atoms in their side chain ([6], [8], [10]-gingerol).12 Shogaols, more pungent and more bitter, seem to form from gingerols mainly as a result of drying.7 The constituents that likely account for ginger’s antiemetic effect are the shogaols and gingerols12,13
Ginger has many other pharmacologic effects, including anti-inflammatory, antipyretic, analgesic, and anti- oxidant actions.11 Ginger also has been reported in vitro to affect platelet aggregation via its inhibition of platelet thromboxane.14 No adverse effects on human platelet function or episodes of bleeding have been confirmed clinically.11
Mechanism of Action
Ginger’s mechanism of action for the prevention and treatment of nausea is not clear. Studies have shown increased gastric motility,8 but not increased gastric emptying.15 Ginger enhances salivary and gastric secretion, and has documented antispasmodic effects associated with its fat-soluble components, such as galanolactone, and its ability to antagonize serotonin receptor sites.7 Unlike other anti-emetics, ginger’s mechanism of action is not CNS-mediated.16
Clinical Studies
Ginger has been tested as an anti-emetic in a number of clinical scenarios including for the control of nausea associated with sea/motion sickness, surgery, and chemotherapy as well as pregnancy.3 A search of the medical literature revealed seven trials of ginger specifically for the treatment of NVP. One qualitative trial5 and one observational trial17 were found. The other five trials are controlled clinical trials. Four tested ginger against a placebo18-21 and one tested ginger against vitamin B6.22
In a qualitative study on self-directed use of anti-emetic herbs in NVP, 26 of 27 women interviewed used herbs during their pregnancies.5 Six women reported using ginger (three alone and three in combination with peppermint) with moderate success. Some women reported heartburn or aversion to the smell or taste of ginger. This study provides interesting insight into a group of pre-identified users of herbs for NVP, but this study design does not permit us to draw any conclusions about the efficacy of ginger for this indication.
In a much larger observational prospective cohort trial conducted by the Motherisk Program, 187 women who called Motherisk for counseling regarding safety of ginger use in pregnancy were matched with similar controls who did not use ginger.17 All women were followed throughout their pregnancies and for up to 12 months after delivery. Although women were not advised to take any particular form or dose of ginger, the patients used a wide variety of ginger preparations, including fresh herb, tea, cookies, and other foods, e.g., candied ginger. However, dried ginger capsules were the most popular preparation used (49% women). Most women used ginger alone and one-third combined it with other anti-emetic drugs. Almost half rated ginger as totally ineffective in controlling their symptoms. However, capsules were significantly more likely to be rated as effective than all other forms of ginger therapy combined (P < 0.001). Observational data again cannot draw conclusive inferences about causality and/or efficacy of a given therapy. Despite that limitation, this design provides useful data about safety and fetal outcome as well some indications about patterns of use and response to ginger during early pregnancy.
The oldest controlled clinical trial found in the literature enrolled 30 hospitalized women with hyperemesis gravidarum in a randomized, double-blind, crossover trial. Dried ginger capsules (250 mg) or placebo were given to patients four times per day for four days.18 After a two-day washout period, patients were then given four days of the other substance. Subjective measures of relief were significantly greater with ginger (70.4%, P = 0.003). Objective measures backed these findings significantly as well (P = 0.035). Although, this trial showed a decrease in nausea and vomiting after 10 days of treatment with ginger, several issues exist that may limit the broad application of these data. The number of women studied was small (n = 30), they were hospitalized with relatively severe symptoms and they were receiving a great deal of additional therapy. This group is not typical of the large majority of women who suffer from NVP, but it is encouraging that even in this group of more severely affected women ginger was able to show a benefit.
Following this trial, a group in Thailand, where ginger is used extensively as a folk treatment and dietary spice, conducted a trial to address these issues in less severely ill women.19 Seventy women complaining of first trimester nausea at an outpatient obstetrical visit were enrolled in this study. They were given a dried ginger powder (250 mg four times a day for four days) that had been prepared by the investigators from fresh ginger root. Nausea as assessed by a visual analog scale (VAS) was significantly lower in the treatment group by day 2 and continued to decrease for the next two days (P = 0.014). Episodes of vomiting also decreased for the treatment group (1.4 vs. 0.3; P < 0.001). Subjectively, 28 of 32 treated women also reported an improvement in symptoms compared with only 10 of 35 placebo patients. Ginger apparently was effective after a short treatment time, but it is a weakness of this trial that women were not followed for a longer time. Thus, this trial does not tell us anything about the durability of a response to ginger. However, it was a well-designed and executed trial.
Keating and Chez, who suspected that ginger could be given in a more easily absorbed form, tested a commercially available ginger syrup, rather than a dried ginger capsule, for effectiveness in controlling first trimester nausea.20 A syrup that contained the equivalent of 250 mg of ginger root was consumed by 26 women four times a day for two weeks. By the tenth day, the treatment group reported a better clinical response than the placebo group. This was a small pilot study and no statistical analysis was performed. However, the trend was consistent with the other published studies that favored treatment with ginger. This more unusual formulation was well accepted by the patients.
One hundred twenty women with NVP unresponsive to dietary intervention were enrolled in a double-blind, placebo-controlled trial that tested the effect of 125 mg standardized ginger extract (equivalent to 1.5 g dried ginger) given four times a day for four days.21 No other characterization of extract, such as content of shogaols or gingerols, was reported. Although a placebo effect was noted for the main outcome measures, statistically significant decreases in the experience of nausea were recorded on all four days of the trial except day 3 (P values not reported). There also was a decrease in retching without a change in the number of episodes of vomiting between the two groups. Twenty-one subjects did not complete the trial and were not included in the analysis. Four patients, all in the active treatment group, withdrew due to intolerance of study medication, presumably due to heartburn and/or reflux. One participant taking ginger reported an allergic reaction. Sixteen additional patients withdrew or were lost to follow up before the end of the trial. No increase in fetal malformation, gestational age, or apgar scores were noted. No increased rate of post-partum hemorrhage was reported.
This study included a large number of women, was well-designed, tested a number of outcomes, and was well-executed. The only flaws in this study were the 17.5% dropout rate, the fact that these patients were not included in an intention-to-treat analysis, and the incomplete reporting of key statistics. The short duration of this trial does not contribute to our knowledge of the long-term utility of ginger for NVP. A higher rate of adverse events was reported in this trial, which may reflect the relatively high dose (equivalent to 5 g/d fresh ginger) delivered by the extract. This suggests that the increase in adverse events reported may have been related to the preparation or increased dose of ginger.
Another group from Thailand performed a randomized, double-blind trial in which ginger was tested against B6, a presumed active therapy, instead of placebo.22 In this trial, 138 women enrolled before 16 weeks of gestation were randomized to receive either 500 mg dried ginger or 10 mg vitamin B6 three times per day for one week. Nausea was measured using VAS and the number of episodes of vomiting was noted over the four days of the trial. Both treatments decreased nausea significantly from baseline (P < 0.001). The decreases were greater with ginger than B6, but this difference was not statistically significant. Similar results were seen with number of episodes of vomiting as well. Heartburn and sedation were reported equally in both groups and occurred less than 10% of the time. This study compared the effect of ginger to a presumed active control (B6) and found them to be equivalent. Thus, ginger is only as good as B6 is felt to be. The large number of women included in this trial is a strength, while the short duration does not tell us anything about a long-term effect of ginger. The dose here was somewhat lower than in other trials (750 mg/d vs. 1,000 mg/d), but still seemed to be effective.
Limitations of Clinical Studies
Generally, trials favor treatment, which would encourage use for NVP. Most have used dried ginger and this seems to be the preferred preparation. However, at least two other forms have shown efficacy, an extract and a syrup. Two short-term intervention trials showed rapid onset of the effect of ginger, but did not provide information about long-term use or risk. Not all studies addressed fetal outcome, but in those studies that did, no increased rate of harm to fetus was shown. Preparations appeared to be well tolerated with a small number of women complaining of gastrointestinal upset.
Safety
Fresh ginger in amounts used in foods is generally considered to be safe.
Although some authorities raise a concern about dried ginger and the adverse risk to fetus10,11,23 others do not categorically restrict use.13,24 No data in vitro,25-27 in animal studies,28 or in the human clinical trials discussed here support this ban for doses equivalent to 1 g/d of dried ginger root. No increases in major fetal malformations or fetal loss in excess of baseline rates were noted.
Further, it has been postulated that ginger could, as a thromboxane synthetase inhibitor, interfere with testosterone binding and sexual differentiation in the fetus.29 This thesis has never been supported with data and it is rejected outright by some experts.5
Summary
Ginger does seem to be helpful in treating NVP in early pregnancy. Preferred treatment seems to be capsules and recommended dose for efficacy and safety is 1 g/d of dried ginger in 3-4 divided doses. Ginger foods, syrups, or teas also should be encouraged if a patient prefers these dosage forms as they are well tolerated. Ginger works quickly and appears, at the recommended doses, to be safe for use in routine pregnancies. For more severe forms of NVP, ginger could be included as one intervention in a comprehensive treatment plan and could provide additional benefit.
Dr. Udani is Medical Director, Northridge Hospital Integrative Medicine Program, and Assistant Clinical Professor, UCLA School of Medicine.
References
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Hardy M, Udani J. Does ginger help with symptoms of nausea in early pregnancy? Altern Ther Women's Health 2004;6(4):25-29.
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