The Use of Ginger to Alleviate Nausea

By Gerald T. Keegan, MD, FACS, and Lynn Keegan, RN, PhD, AHN-BC, FAAN, Dr. Gerald Keegan is Emeritus Staff, Scott & White Clinic and Hospital, and former Professor of Surgery (Urology), Texas A&M University School of Medicine. Dr. Lynn Keegan is Director, Holistic Nursing Consultants, Port Angeles, WA. Drs. Keegan are stockholders in Astra Zeneca, Glaxo Wellcome, and Pfizer.

Nausea is defined as a sensation of unease or discomfort perceived in the stomach and in the consciousness with an urge to vomit. As anyone who has been nauseated can recall, the unpleasant distress often is accompanied by cholinergic reactions such as increased salivation. Although nausea in itself is not an illness, it is the manifestation of other underlying physical or psychological conditions or maladies. This article addresses the effects of ginger on three common sources of nausea: pregnancy, chemotherapy, and drug reactions including postoperative nausea as well as motion sickness (kinetosis). The other causes of nausea are multiple and are not within the scope of this article.

Ginger (Zingiber officinale) is a plant belonging to the Zingiberacea family. The part of the plant that is used medicinally is the root or rhizome. Although it is a native of southern Asia, the plant is cultivated in many wet tropical areas such as Jamaica, China, Nigeria, India, and Haiti.1

History

The cultivation of ginger began in southern China and rapidly spread to the surrounding areas. The medicinal uses of the plant are recorded in the Vedic literature from the period around 500 BC. Ginger was called "maha aushadhi," which meant great medicine. In traditional Indian medicine it was used as a carminative or antiflatulent. Subsequently, the Greek physician Galen used ginger to treat conditions of bodily imbalance.1,2 Chinese women traditionally eat ginger root during pregnancy to combat nausea, and ginger ale and ginger beer commonly have been used as "stomach settlers."2-4

Chemistry and Mechanisms of Action

In both the fresh and the dried ginger powder, the gingerols have been identified as the major active component. The most abundant of the gingerols is 5-hydroxy-1-(4-hydroxy-3-methoxy phenyl)decan-3-one. Other similar constituents include shogoal, zingerone, and paradol.1 A proposed mechanism of action for ginger in the treatment of nausea may be related to its prevention of gastric dysrhythmias and the elevation of plasma vasopressin.5

A study in China investigated 13 volunteers with a history of motion sickness. The patients underwent circular vection, during which nausea (scored 0-3, i.e., none to severe), electrogastrographic recordings, and plasma vasopressin levels were assessed with or without ginger pretreatment in a crossover double-blind, randomized controlled trial (DBRCT). Circular vection induced a maximal nausea score of 2.5 ± 0.2 and increased both tachygastric activity and plasma vasopressin. Pretreatment with ginger (1,000 mg and 2,000 mg) reduced both the subjective sensation of nausea as well as the objectively measured parameters of tachygastria and plasma vasopressin. The use of ginger also prolonged the latency before the onset of nausea and shortened the recovery time after vection cessation. In a parallel study, the intravenous infusion of vasopressin (0.1 U/min and 0.2 U/min) induced the development of nausea and increased bradygastric activity. The authors concluded that ginger effectively reduced nausea, tachygastric activity, and vasopressin release induced by circular vection.5 It also is possible that part of the antinauseant effect may be anti-inflammatory in nature and mediated through inhibition of prostaglandin and leukotriene biosynthesis.6,7

Animal Studies

Because of the subjective nature of the perception of nausea and because of its multiple causes via different mechanisms, few animal studies are available. One study from Italy evaluated the effect of ginger on the contractions of the bowel induced by electrical stimulation (EFS) or acetylcholine in the isolated rat ileum. Ginger (0.01-1000 mcg/mL) was found to inhibit both EFS- and acetylcholine-evoked contractions of the bowel. The effect of the ginger was greater in the EFS group than in the acetylcholine group. The depressant effect of ginger on EFS-induced contractions was reduced by the vanilloid receptor antagonist capsazepine (10-5 M), but unaffected by the alpha(2)-adrenergic antagonist yohimbine (10-7 M), the CB(1) receptor antagonist SR141716A (10-6 M), the opioid antagonist naloxone (10-6 M), or by the NO synthase inhibitor L-NAME (3 x 10-4 M). The authors also noted that zingerone, one of the active ingredients of ginger, did not possess inhibitory effects, but they were unable to isolate the active agent. The authors concluded that ginger produced its effect by neurologically modulating both prejunctional and postjunctional inhibitory effects on ileal contractility. They further theorized that the prejunctional inhibitory effect of ginger on enteric excitatory transmission could involve a capsazepine-sensible site (possibly vanilloid receptors).8

Human Studies

Pregnancy. There have been numerous clinical trials on the effects of ginger on the nausea and vomiting of pregnancy. Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70-85% of women. About half of pregnant women experience vomiting.9 Conventional antiemetics are burdened with the potential of teratogenic effects during the critical embryogenic period of pregnancy. Thus, a safe and effective natural remedy would be a welcome addition.

A systematic review in Germany was aimed at assessing the evidence for or against the efficacy and safety of ginger therapy for nausea and vomiting during pregnancy. Only DBRCTs were included. Six DBRCTs (n = 675) and a prospective observational cohort study (n = 187) met all inclusion criteria. Four of the six DBRCTs (n = 246) showed superiority of ginger over placebo; the other two DBRCTs (n = 429) indicated that ginger was as effective as the reference drug (vitamin B6) in relieving the severity of nausea and vomiting episodes. The observational study retrieved and DBRCTs (including follow-up periods) showed the absence of significant side effects or adverse effects on pregnancy outcomes. There were no spontaneous or case reports of adverse events during ginger treatment in pregnancy.10

Similarly, another review of four recent well-controlled DBRCTs provided convincing evidence for the effectiveness of ginger in treating nausea and vomiting of pregnancy. It also provides a dosage update for the various forms of ginger.11

Scientists in Germany conducted a comprehensive review of the literature to summarize the pharmacological and clinical effects of this popular and widespread agent. They concluded that clinical and experimental studies suggest that ginger has some antiemetic properties, clinical evidence beyond doubt is only available for pregnancy-related nausea and vomiting. Meta-analyses could not demonstrate the postoperative antiemetic effectiveness, and effect in motion sickness or nausea/vomiting of other etiology.12

A study was undertaken at Ohio Northern University to review the literature assessing the safety and efficacy of the use of ginger to treat nausea and vomiting in pregnancy. The authors noted that various doses and forms of ginger were used to treat women during their first and second trimesters of pregnancy. In this review, ginger was shown to improve the symptoms of nausea and vomiting compared with placebo in pregnant women. The authors concluded that although data were insufficient to recommend ginger universally and that there were some concerns with product quality due to limited regulation of dietary supplements, ginger appears to be a fairly low-risk and effective treatment for nausea and vomiting associated with pregnancy.13

An Australian study was designed to estimate whether the use of ginger to treat nausea or vomiting in pregnancy is equivalent to pyridoxine hydrochloride (vitamin B6). A randomized, controlled equivalence trial involving 291 women less than 16 weeks pregnant was undertaken. Women took 1.05 g/d of ginger or 75 mg/d of vitamin B6 for three weeks. Differences from baseline in nausea and vomiting scores were estimated for both groups at days 7, 14, and 21. Ginger was found to be equivalent to vitamin B6 in reducing nausea, retching, and vomiting, averaged over time, with no evidence of different effects at the three time points.14

Another DBRCT evaluating the effects of ginger and pyridoxine was performed in Bangkok women with nausea and vomiting of pregnancy at or before 16 weeks of gestation. Subjects were randomly allocated into two groups to take either 500 mg of ginger orally or an identical 10 mg capsule of vitamin B6 three times daily for three days. Subjects graded the severity of their nausea using visual analogue scales before treatment and recorded the number of vomiting episodes in the previous 24 hours and again during three consecutive days of treatment. The 64 subjects in each group remained in the study. The demographic data were comparable in both groups. The ginger and vitamin B6 significantly reduced the nausea scores from 5.0 and 5.3 to 3.3 respectively (P < 0.001). The mean score change after treatment with ginger was 1.4, less than with vitamin B6, which was 2.0 but with no statistically significant difference. Ginger and vitamin B6 also significantly reduced the number of vomiting episodes from 1.9 to 1.2 and 1.7 to 1.2 respectively (P < 0.01). The mean number change after treatment with ginger was 0.7, more than with vitamin B6, which was 0.5 but with no statistically significant difference (P = 0.498). Minor side effects in both groups included sedation and heartburn, with a non-significant difference. The authors concluded that the nausea score and the number of vomiting episodes were significantly reduced following ginger and vitamin B6 therapy. Comparing the efficacy, there was no significant difference between ginger and vitamin B6 for the treatment of nausea and vomiting during pregnancy.15

The effectiveness of ginger in relieving the nausea and vomiting of pregnancy is well-established and the safety of using this agent is documented by previous studies as well as a Canadian study in which the primary objective of the study was to examine ginger's safety and efficacy. Pregnant women (n = 187) who were taking ginger during the first trimester of pregnancy were enrolled in the study. The women were compared with a group of women who were exposed to nonteratogenic drugs that were not antiemetic medications. The women were followed to ascertain the outcome of the pregnancy and the health of their infants. They also were asked to rate on a scale of 0 to 10 ginger's effectiveness for their symptoms. There were 181 live births, two stillbirths, three spontaneous abortions, and one therapeutic abortion. The mean birth weight was 3,542 g ± 543 g, the mean gestational age was 39 ± 2 weeks, and there were three major malformations. There were no statistical differences in the outcomes between the ginger group and the comparison group with the exception of more infants weighing less than 2,500 g in the comparison group (12 vs. 3, P ≤ 0.001). The results suggest that ginger does not appear to increase the rates of major malformations above the baseline rate of 1-3% and that it has a mild effect in the treatment of nausea and vomiting in pregnancy.16

Hyperemesis gravidarum, pernicious vomiting associated with pregnancy, in some cases is so severe that the patient requires hospitalization and intravenous fluid replacement. Investigators in England searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Central Register of Controlled Trials and studied 28 randomized trials of treatment for nausea and/or vomiting in early pregnancy.17 For hyperemesis gravidarum, seven trials were identified testing treatments with oral ginger root extract, oral or injected corticosteroids, or injected adrenocorticotropic hormone, intravenous diazepam, and acupuncture. Although the mild nausea was reduced by all the studied agents, no treatments for hyperemesis gravidarum were shown to be of any benefit. Evidence from observational studies suggests no evidence of teratogenecity from any of these treatments.9

Chemotherapy. The treatment of cancer with various forms of chemotherapy has been a great advance in medical practice. Chemotherapy, however, frequently is accompanied by troublesome nausea and vomiting. The current standard of practice for the treatment of this condition is the use of the serotonin 5-HT3 receptor antagonists. The treatment regimen of ondansetron, a serotonin 5-HT3 receptor antagonist, in combination with dexamethasone is effective against acute nausea and vomiting, but fails to control delayed nausea and vomiting and is quite expensive. Metoclopramide along with other antiemetics are used to treat delayed nausea and vomiting. The high doses of metoclopramide needed may produce extra pyramidal side effects. Therefore, alternative cost-effective agents with a minimum of side effects are being sought to supplement the use of the standard medications. Ginger also showed good activity against chemotherapy-induced nausea and vomiting in animal models and is being studied in this context.18 Studies at the Hospital for Sick Children in Toronto have suggested that ginger is one complementary intervention that may be beneficial in treating children receiving chemotherapy.19

Postoperative nausea and kinetosis. Studies of the use of ginger for the treatment of postoperative nausea, other drug-induced nausea, and motion sickness have been mixed. A systematic literature search using MEDLINE, EMBASE, and the Cochrane-Library identified 100 published reports covering 1,073 patients who had received ginger. Of these reports, 16 contained information regarding the antiemetic activity of the phytotherapeutic agent against motion sickness, postoperative nausea and vomiting, and morning sickness and hyperemesis gravidarum. The authors concluded that there was no clear evidence for the efficacy of ginger for postoperative nausea and vomiting or kinetosis. However, they concluded that taking up to 6 g/d of ginger for the treatment of nausea and vomiting in pregnancy was helpful and seemed to be associated with few side effects.20

A study in Thailand was designed to specifically determine the impact of a fixed dose of ginger compared with placebo on 24-hour postoperative nausea and vomiting. Five randomized trials including a total of 363 patients were pooled for analysis of preventing postoperative nausea and vomiting and postoperative vomiting. The summary relative risks of ginger for postoperative nausea and vomiting and postoperative vomiting were 0.69 (95% confidence interval 0.54 to 0.89) and 0.61 (95% confidence interval 0.45 to 0.84), respectively. Abdominal discomfort was the only side effect reported. These authors concluded that the result of their meta-analysis demonstrated that a fixed dose at least 1 g of ginger is more effective than placebo for the prevention of postoperative nausea and vomiting and postoperative vomiting.21

The use of ginger in the treatment of motion sickness, although traditionally and anecdotally strongly supported2 is not clearly verified in the most recent clinical trials using meta-analytic techniques.4,20

Adverse Effects and Precautions

Ginger is a very well-tolerated agent. The main side effect reported in most studies was abdominal discomfort.21 An extensive analysis of side effects in pregnant patients treated with up to 6 g/d found that 3.3% suffered from slight side effects, mainly mild gastrointestinal symptoms and sleepiness, both not requiring specific treatments. Although one severe adverse event was reported in a single study (an abortion occurred in the 12th week of gestation) a total of 136 patients were treated with ginger within the first trimester of pregnancy without complications.20 Although the clinical experience suggests safety, pharmacokinetic data are only available for [6]-gingerol and zingiberene and available safety data do not rule out potential toxicity especially if ginger consumption is prolonged over longer periods.12

Most authors believe that there is a strong possibility that ginger inhibits platelet activity, specifically platelet aggregation, but confirmatory studies are still lacking.12,22 Caution should be used when combining ginger compounds (either fresh or dried) with anticoagulant therapy especially warfarin.23 Patients undergoing surgery should consult with their physicians because of the possible anticoagulant effects.24

Dosage Recommendations

For nausea and indigestion, the usual recommended dosage is 2-4 g/d of the fresh root. This is the equivalent of 0.25-1 g of the powdered root or 1.5-3 mL of the ginger tincture. Chewing small amounts of fresh ginger also may be helpful.

Summary

The use of ginger in the treatment of nausea and vomiting of pregnancy is well established. This alternative therapy also may play an ancillary role in alleviating the nausea experienced by patents undergoing chemotherapy. Although anecdotally widely used and theoretically possible, the evidence of significant relief of kinetosis is not well-established clinically. The results of using ginger in the relief of postoperative nausea are mixed. Ginger does appear to have a good safety profile.

References

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