Treating Pregnancy-Related Nausea and Vomiting with Ginger

Background

Nausea with or without emesis is one of the most common complaints in early pregnancy. It is estimated that up to 80% of women experience some degree of nausea in the first trimester (usually between 8 and 12 wk gestation). Approximately 20% of women will continue to experience symptoms past the 20th week.^1,2 Hyperemesis gravidarum is generally defined as severe nausea and vomiting characterized by dehydration and electrolyte disturbances that require hospitalization. This condition occurs in <1% of pregnancies and is often confused with severe nausea and vomiting of pregnancy. Women with the former condition cannot tolerate oral therapy, while those with the latter condition can.^1–3

Treatment options for nausea and vomiting of pregnancy are limited because of concerns about safety. Initially, treatment consists of identifying and avoiding nausea triggers, avoidance of spicy and fatty foods, and cessation of iron supplements. If these nonpharmacologic approaches do not alleviate symptoms, other options, including multivitamins, vitamin B₆, doxylamine, ginger, antihistamines, anticholinergics, and corticosteroids, may be tried. ⁴ Many patients prefer to avoid “drugs” during pregnancy, choosing instead “natural” alternatives. One of these popular options is ginger. The efficacy and safety of this product is still in question, and it is classified as pregnancy category C. ⁵ Ginger root is commonly used as a flavoring agent in food and beverages and as a fragrance additive in cosmetic products. The antiemetic constituents of ginger exert their effects in the gastrointestinal tract, but the specific mechanism is unknown. In vitro, it has been shown to have some ability to antagonize serotonin 5-HT3 receptors. ⁶

While ginger is commonly recommended for pregnant women by health food store employees ⁷ and does appear to be well tolerated in doses up to 5 g, there are some concerns. Adverse effects are uncommon, but may include gastrointestinal upset, heartburn, diarrhea, and mouth/throat irritation. Drug interactions appear rare with this product. There are many theoretical interactions with ginger, but only one case report of increased anticoagulation with phenprocoumon has been published. Follow-up studies have not shown ginger to have a clinically significant impact on warfarin concentrations. Excessive doses of ginger may affect the action of antidiabetic drugs in some patients.^6,8

Dietary supplements and herbal products are not regulated as drugs by the Food and Drug Administration (FDA). They are legislated under the Dietary Supplement Health and Education Act, and this legislation does not currently have enforced principles of good manufacturing practices. Contamination with prescription medications, heavy metals, and pesticides is a concern with many supplements, and the concern is amplified in the population of pregnant women.

The relatively good safety profile of ginger and possible efficacy have led researchers to evaluate the role of ginger in the management of pregnancy-induced nausea and vomiting. A literature search was performed using Iowa Drug Information Service (1966–September 2004), International Pharmaceutical Abstracts (1971–September 2004), EMBASE (1966–September 2004), and MEDLINE (1966–September 2004). Text search terms included ginger, nausea, vomiting, emesis, and pregnancy, and results were restricted to articles published in English. Seven articles were located for review, and all were utilized for this article.

Literature Review

A prospective cohort study was performed to evaluate pregnancy outcomes in women who used ginger during the first trimester of their pregnancy. ¹ There were 187 women enrolled in both the ginger and no-exposure groups (N = 374). Women reporting any amount of ginger exposure were questioned as to type of ginger, dosage, timing of exposure, and duration of use. All participants were asked about demographics and obstetric history. Follow-up was performed no later than 12 months after birth or termination of pregnancy.

There were no statistical differences between the ginger and control groups when comparing number of stillbirths (2 vs 1), spontaneous abortions (3 vs 8), major malformations (3 vs 2), and mean gestational age ± SD at delivery (39 ± 2 wk in both groups). There were 12 infants in the control group with low birth weight (<2500 g) compared with 3 in the ginger group (p = 0.033). The investigators determined that using ginger during the first trimester of pregnancy does not appear to increase the risk of serious adverse effects on the fetus. ¹

As with all prospective studies, there was no control over many of the variables (eg, product used, duration, counseling), so the evidence is not conclusive. There was a higher rate of twins born in the ginger group (8/187 compared with the population average of 1/80), which may be due to the more severe nausea generally associated with multiple-fetus pregnancy. ¹

A double-blind, placebo-controlled, randomized trial was performed to evaluate the efficacy of ginger syrup as an antiemetic in the first trimester of pregnancy. ⁹ Twenty-six (14 treatment, 12 placebo) women received 1 tablespoon of syrup containing 250 mg of ginger or placebo 4 times a day for 2 weeks. Subjects recorded doses taken, number of vomiting episodes, degree of nausea, and perspective of daily functioning. A 10-point scale (1 = best, 10 = worst) was used to evaluate the degree of nausea and impairment of daily functioning. Ten subjects in the ginger group and 2 in the placebo group experienced at least a 4-point improvement in the nausea scale following treatment. By day 6 of the study, 8 women in the ginger group and 2 in the placebo group had stopped vomiting.

The researchers did not perform statistical analysis of the data because of small study size. All study participants delivered with no complications. Taste was a confounder in this trial since the placebo was flavored with lemon oil, making blinding difficult. The sample size was small due to the difficulty in enrolling participants. Although all of the women were <12 weeks' pregnant, no follow-up was performed to assess possible teratogenicity. ⁹

The effectiveness of ginger for nausea and vomiting in pregnancy was evaluated in another double-blind, placebo-controlled, randomized trial. ¹⁰ Seventy (32 ginger, 38 control) women in varying stages of pregnancy who experienced nausea with or without vomiting were instructed to take 1 capsule (250 mg of ginger or placebo) 4 times a day for 4 days. Subjects rated their nausea both on a 10-centimeter visual analog scale (0 = no nausea, 10 = worst nausea) and a 5-item Likert scale (much worse to much better) twice a day. Women were also asked to record vomiting episodes before and during treatment.

Visual analog scores for the ginger group experienced significantly more improvement 2.1 ± 1.9 from baseline versus 0.9 ± 2.2 (mean ± SD) for the placebo group (p = 0.014). Twenty women in the ginger group and one in the placebo group rated nausea “much better” on the Likert scale. In addition, 9 subjects in the placebo group and none in the ginger group reported nausea as worse on the scale (p < 0.001). Significantly fewer women in the ginger group reported vomiting than in the placebo group (12 vs 23, respectively; p = 0.021) after 4 days. Three spontaneous abortions occurred in the placebo treatment arm and one in the ginger group, with no congenital anomalies reported for either group. While the study was generally well conducted, the ginger capsules were not tested to determine exact composition of the preparation used. The study period (4 days) may have been too short to show full effect, but due to the short treatment period, there was good adherence (>77% for both groups). ¹⁰

A double-blind, placebo-controlled, randomized trial including 120 women evaluated the effectiveness of ginger in treating nausea in pregnancy ¹¹ Women were required to be <20 weeks' pregnant. Sixty women received capsules containing 125 mg of ginger or placebo 4 times a day for 4 days. The Rhodes Index of Nausea, Vomiting, and Retching (a 5-point scale ranging from 0 to 12, with a higher score indicating more symptoms) was completed one hour after each dose. There was an almost equal reduction in nausea and vomiting in both groups. The ginger group had significantly lower scores than the placebo group for retching on the first 2 days only (values not given; p = 0.05).

Follow-up indicated there were 3 spontaneous abortions in the ginger treatment arm and 1 in the placebo group, with no congenital anomalies reported for either group. The rates of birth defects from the combined study participants were no greater than in the average population, although since organogenesis occurs before 12 weeks of gestation, the inclusion of women with more advanced pregnancies could have impacted the accuracy of the results. The authors reported significant reductions in nausea scores in both groups. ¹¹

The efficacy of ginger was compared with that of vitamin B₆ in treating pregnancy-related nausea and vomiting. ¹² This double-blind, randomized, non-inferiority trial enrolled 291 (146 ginger, 145 vitamin B₆) women. The participants received one capsule of either ginger 350 mg or vitamin B₆ 25 mg 3 times a day for 3 weeks. The Rhodes Index of Nausea, Vomiting, and Retching and the Medical Outcomes Study 36 short-form health survey (an 8-multi-item scale, with higher scores indicating a better outcome) were used to assess efficacy. Ginger and vitamin B₆ showed equivalent reduction in symptoms of nausea (3.6 vs 3.9), vomiting (0.9 vs 1.4), and retching (0.5 vs 0.7). For both groups, there was overall improvement in health status, but vitamin B₆ was superior to ginger in 6 of 8 items on the Medical Outcomes Study 36.

There were 9 spontaneous abortions and 3 stillbirths in the vitamin B₆ group and 3 spontaneous abortions and no stillbirths in the ginger group. There were no significant differences in the number of congenital abnormalities between groups. During this trial, the women were allowed to continue any medications other than vitamin B₆ and ginger, which could have affected the results.

Another double-blind, randomized trial comparing ginger and vitamin B₆ enrolled 128 (64 in each group) women at or before 16 weeks of pregnancy. ¹³ The subjects received either 500-mg ginger capsules or 10-mg vitamin B₆ capsules 3 times a day for 3 days. A 10-centimeter visual analog scale (0 = no nausea, 10 = worst nausea possible) was used to grade nausea before the first capsule was taken and 3 times a day during the study period, and the number of daily vomiting episodes was recorded. The mean improvement in nausea scores ± SD, compared with baseline, was 1.4 ± 2.22 in the ginger group (p < 0.001) and 2.0 ± 2.19 in the vitamin B₆ group (p < 0.001). Mean reduction in number of vomiting episodes, compared with baseline, was 0.7 ± 2.18 in the ginger group (p = 0.003) and 0.5 ± 1.44 in the vitamin B₆ group (p = 0.008). The total number of women vomiting was less in the ginger group than in the vitamin B₆ group (28 and 38 respectively; p = 0.146).

Since the authors did not follow the women after delivery, it is not possible to assess the safety of ginger based on these trial results; however, there did not appear to be differences between groups in tolerability and adverse effect profile. The lack of comparison between the ginger and vitamin B₆ groups does not account for the possibility of the placebo effect. Additionally, ginger was not standardized and chemical composition was not tested. ¹³

Women presenting with hyperemesis gravidarum before their twentieth week of pregnancy were enrolled in a double-blind, randomized, crossover trial comparing ginger with lactose placebo. ³ Thirty women were hospitalized and received either 250 mg of ginger or placebo 4 times a day for 4 days, then switched after a 2-day washout period. A scoring system was created that assigned numerical values to changes in nausea and vomiting and the patient's opinion about the treatment. Negative numbers were given for worsening symptoms, zero was utilized for no change, and positive numbers were given for improvement of symptoms. The mean relief from symptom values was significant with 3.9 for the ginger period and 0.4 for the placebo period (p = 0.035). When women were asked which treatment they preferred, 19 (70.4%) chose the ginger treatment, 4 (14.8%) preferred the placebo treatment, and 4 (14.8%) indicated no preference (p = 0.003). One miscarriage and no deformities or other birth complications were reported.

While the authors of this study intended to investigate women with hyperemesis gravidarum, their use of oral therapy indicates that the patients were experiencing severe nausea and vomiting, not hyperemesis. Limitations of this study include the lack of standardized ginger therapy, an inappropriately defined population, and a small sample size. ³

Summary

There is evidence suggesting that ginger is effective in reducing nausea and vomiting experienced during pregnancy. The studies used divided doses ranging between 500 and 1500 mg/day, with no higher incidence of birth defects, miscarriages, or deformities than in the general population. While most of the studies concluded that there was no increased risk of birth defects in women taking ginger, the inclusion of those >12 weeks' gestation means that their data are, in reality, inconclusive.

Without more stringent product quality regulations and large-scale trials confirming safety and efficacy, ginger should not be universally recommended. Patients should be counseled regarding the limits of the currently available literature. However, current data do indicate that ginger is low risk and probably effective in the management of nausea and vomiting in the first trimester of pregnancy and may be a good option for patients not responding to nonpharmacologic interventions.