Ginger for Motion Sickness, Hyperemesis Gravidarum,
Ginger for Motion Sickness, Hyperemesis Gravidarum, Chemotherapy, and Anesthesia
December 1998; Volume 1: 133-137
By Jay Udani, MD, and Mary Hardy, MD
The discomfort and disturbance nausea causes can strike all too predictably. Pleasure trips in cars or boats may be ruined by motion sickness. Hyperemesis gravidarum may characterize early pregnancy. Peri- and post-chemotherapy waves are unsettling. Anesthesia-induced nausea may complicate postoperative respiration and recovery.
Many classes of drugs are currently used to counter or prevent nausea. Zingiber officinale, or ginger, is a rhizome that has been used to prevent and treat nausea for centuries, and it might work as preventive or therapeutic adjunct or single agent in any of the settings noted above.
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 is now 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.1
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.2 Pythagoras is reputed to have used ginger as a digestive aid, and the first century Roman herbalist Discorides included ginger in his herbal text, which became the basis for much of the practice of medicine throughout the middle ages.3
In addition to its medicinal applications, ginger is also widely used as a spice in foods, beverages, candies, and liqueurs, and is also commonly used 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.
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 sequeterpene lactones, such as zingiberene. The pungent or hot "principles" are phenolic compounds, such as gingerols or shogaols. Shogaols, more pungent and more bitter, seem to form from gingerols mainly as a result of drying.1 Ginger’s pungency is due to gingerol, and the aroma is due to ginger oil which contains 50 different constituents. Pungency and aroma are a good, quick way to gauge freshness. Most studies have used dried whole herb rather than fresh herb for practical reasons.
Ginger has many other pharmacologic effects, including antioxidant properties; inhibition of platelet aggregation; and modulation of prostaglandin, thromboxane, and leukotriene synthesis.
Mechanism of Action
Ginger’s mechanism of action for the prevention and treatment of nausea is not clear. Studies have shown increased gastric motility,2 but not increased gastric emptying.4 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.2 Unlike other antiemetics, ginger’s mechanism of
action is not CNS-mediated.5
Clinical Studies
We conducted a systematic review of the literature using MEDLINE, PubMed, the Internet, and alternative medicine literature CD-ROMs using the keywords "ginger," "nausea," and "emesis." There have been a series of studies examining ginger as an antiemetic. The clinical scenarios in these studies have been diverse and include post-anesthetic nausea, hyperemesis gravidarum, chemo-therapy-induced nausea, motion sickness and seasickness.
At least four studies of ginger to reduce postoperative nausea and vomiting have been conducted, with conflict-ing results. All four are of women who had undergone laparoscopic gynecological procedures. The earliest study involved 60 women randomized to receive 1 g of ginger, 10 mg metoclopramide, or placebo.6 Women receiving both ginger and metoclopramide had significantly fewer episodes of nausea (P < 0.05) and less use of antiemetic after surgery (P < 0.05). There was no significant difference between the metoclopramide and ginger groups, and all three groups had identical side effect profiles. In 1993, an almost identical study was performed involving 120 women, with similar outcomes.7
In 1995, yet another study was performed with 108 women randomized to receive placebo, ginger 0.5 g, or ginger 1.0 g.8 All patients were premedicated with oral diazepam one hour prior to surgery. This study found an increase in incidence of moderate or severe nausea and vomiting in both groups taking ginger compared with placebo. In fact, the risk of nausea or vomiting increased with the higher ginger dose. The odds ratio for 0.5 g ginger for nausea was 1.39 and for vomiting was 1.55. This was the first negative study seen in this population.
The most recent study was done in 1998 and randomized 120 patients to placebo, droperidol, 1 g ginger po, or ginger plus droperidol.9 There were no significant differences in nausea or vomiting between the four treatment groups; in essence, droperidol and ginger showed no improvement over placebo. The side effect profiles for all four groups were also identical.
Investigators in the only randomized, double-blind, crossover trial of ginger for hyperemesis gravidarum gave patients 250 mg of ginger or placebo qid for four days, with a two-day washout period, and then four days of the other substance.10 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).
Only one study evaluating ginger for nausea associated with chemotherapy was found: a case series of 11 patients undergoing 8-MOP photopheresis for cutaneous T cell lymphoma who had a history of chemotherapy-induced nausea.11 In this non-randomized, non-blinded protocol, patients were given 1590 mg of ginger 30 minutes prior to chemotherapy administration. A nonsignificant reduction in nausea was seen on the nausea scale (a non-validated scale) compared with historical controls.
Multiple studies have been performed using ginger to prevent motion sickness. Three randomized, controlled trials of experimentally induced motion sickness have been performed, two of which showed no effect of ginger on prevention or treatment of motion sickness.5,12 The third study compared 1 g of ginger to 100 mg dimenhydramine or placebo, each given one-half hour prior to experimentation using a revolving chair.13 The ginger group tolerated the revolving chair significantly better than the dimenhydramine or placebo groups.
The one trial of ginger for the treatment of seasickness was a double-blind, randomized, placebo-controlled study of 80 naval cadets on rough high seas voyages.14 Cadets who complained of seasickness were given 1 g of ginger or placebo every hour for four hours. Ginger significantly reduced seasickness measured by vomiting and cold sweats (P < 0.05). Ginger tended to reduce nausea and vertigo, but not significantly.
Formulation
Standardized preparations are not necessarily recommended because the clinical studies to date have not used them. There is currently no consensus regarding to which constituents to standardize. Given the nature and severity of the illness being treated, i.e., a self-limited condition, clinical response is an adequate endpoint and the need for highly standardized product is not critical.
All food forms of ginger can be used, but dried capsules are preferable. Candied ginger is usually not dried well enough to be therapeutic, and the pickled and candied forms have not been tested formally. The liquid sources of ginger (ginger ale or ginger tea) generally have such low concentrations of ginger that large quantities of liquid are required to consume adequate amounts of ginger.
When buying ginger tablets or capsules, look for the amount of ginger in each capsule, and look for a lot number and expiration date. Although some products are standardized, the smell and taste of ginger are better guides to freshness and therefore, by extension, efficacy.
A botanical monograph on ginger has recently been approved by the United States Pharmacopeia for inclusion in the national formulary.15
Dose
The usual dosage for preventing motion sickness is 1 g (tablets or capsules) of dried powdered gingerroot given orally one-half hour prior to voyage.16 Ginger is less effective when given to a patient who is already nauseated.
Adverse Effects
The use of ginger in pregnancy for hyperemesis gravidarum is controversial among botanical experts. Ginger’s effect on testosterone binding and on thromboxane synthetase activity warrant pause in recommending ginger for pregnant women.17
The risk of bleeding is slight, but real. Concerns about ginger increasing bleeding were not supported by a study of patients undergoing a laparoscopic gynecological procedure who showed no difference in intra-operative or postoperative bleeding complications.7
In the only study of hyperemesis gravidarum, fetal loss rate was not reported, but it is not clear whether investigators kept track of this variable at all.10 Two leading authoritative sources categorize ginger as "not to be used during pregnancy."18,19 An editor’s note in the German Commission E monographs opines that there are no data to support this admonition,19 but the caution is based upon two Japanese studies20,21 in the 1980s showing in vitro mutagenic properties of isolated ginger compounds.19 An earlier study showed ginger to possess anti-mutagenic activity.22
There are no conclusive data about ginger in pregnancy, and so caution and prudence must prevail.
Ginger is also not recommended for patients with gallstones as ginger is a cholagogue and increases the flow of bile.18 In addition, large doses of ginger have been known to cause heartburn.16
Recommendation
Ginger is an ancient spice that has documented antiemetic effects in post-anesthesia, hyperemesis gravidarum, chemotherapy, and seasickness. The data are not conclusive in any setting, but it is reasonable to use a trial of ginger for the prevention of postoperative nausea, motion sickness, and seasickness. Despite common food and folk use, physicians should not recommend ginger for nausea during pregnancy. The caution becomes a warning if the pregnant patient has a history of bleeding disorders or miscarriage. The data on ginger for the prevention and treatment of chemotherapy-induced nausea are too poor to draw conclusions.
For patients who wish to try it, we recommend 1 g of ginger 30 minutes prior to an activity that may induce motion sickness or seasickness, as well as prior to surgery, assuming the patient is allowed to take medications po.
References
1. Wichtl M. Herbal Drugs and Phytopharmaceuticals. 2nd ed. Boca Raton, Fla.: Scientific Publishers; 1994:537.
2. Anonymous. Ginger (Zingiber Officinale). Am J Natural Medicine 1996;7:12-16.
3. Castleman M. The Healing Herbs. Emmaus, Pa.: Rodale Press; 1991:67.
4. Phillips S, et al. Zingiber officinale does not affect gastric emptying rate. A randomised, placebo-controlled, crossover trial. Anaesthesia 1993;48:393-395.
5. Holtmann S, et al. The anti-motion sickness mechanism of ginger. A comparative study with placebo and dimenhydrinate. Acta Otolaryngol 1989;108:168-174.
6. Bone ME, et al. Ginger root—a new antiemetic. The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery. Anaesthesia 1990;45:669-671.
7. Phillips S, et al. Zingiber officinale (ginger)—an antiemetic for day case surgery. Anaesthesia 1993;48:715-717.
8. Arfeen Z, et al. A double-blind randomized controlled trial of ginger for the prevention of postoperative nausea and vomiting. Anaesth Intensive Care 1995;23: 449-452.
9. Visalyaputra S, et al. The efficacy of ginger root in the prevention of postoperative nausea and vomiting after outpatient gynaecological laparoscopy. Anaesthesia 1998;53:506-510.
10. Fischer-Rasmussen W, et al. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991;38:19-24.
11. Meyer K. Zingiber Officinale (ginger) used to prevent 8-MOP associated nausea. Dermatol Nurs 1995;7: 242-244.
12. Stewart JJ, et al. Effects of ginger on motion sickness susceptibility and gastric function. Pharmacology 1991;42:111-120.
13. Mowrey DB, Clayson DE. Motion sickness, ginger, and psychophysics. Lancet 1982;1:655-657.
14. Grontved A, et al. Ginger root against seasickness. A controlled trial on the open sea. Acta Otolaryngol 1988;105:45-49.
15. Srinivasan V. USP Adopts Ginger Monograph. Herbalgram 1997;12.
16. Anonymous. Zingiberis Rhizoma (Ginger). In: European Scientific Cooperative on Phytotherapy. Monographs on the Medicinal Uses of Plant Drugs. UK: University of Exeter Press; 1997:1-7.
17. 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;42:163-164.
18. Anonymous. Botanical Safety Handbook. Boca Raton, Fla.: CRC Press; 1997:125.
19. Anonymous. Ginger Root. In: Blumenthal M, ed. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council; 1988:135-136.
20. Namakura H. Mutagen and antimutagen in ginger, Zingiber Officinale. Mutat Res 1982;119-126.
21. Nagabhushan M, et al. Mutagenicity of gingerol and shogaol and antimutagenicity of zingerone in Salmonella/ microsome assay. Cancer Lett 1987;36:221-223.
22. Kada T, et al. Anti-mutagenic action of vegetable factors on the mutagenic principle of tryptophan pyrolysate. Mutat Res 1978;53:351-353.
Dr. Udani is a Fellow in Integrative Medicine and Health Services Research and Dr. Hardy is the Director of Integrative Services at Cedars Sinai Medical Center in Los Angeles. Dr. Hardy is an Associate Clinical Professor of Medicine at the University of Southern California.
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