Ginger (Zingiber officinale) for Motion Sickness
By C.W. Fetrow, PharmD
The irregularly shaped roots (rhizomes) of ginger (zingiber officinale) are used extensively in Chinese, Indian, and Japanese cultures where they are believed to have anti-inflammatory, analgesic, cholesterol-lowering, and antithrombotic properties. Al-though ginger has been evaluated for the treatment of nausea and vomiting associated with hyperemesis gravidarum, anesthesia, and chemotherapy, this review will focus on ginger for motion sickness.
Pharmacologic Effects/Mechanism of Action
Compounds known as gingerols may contribute to ginger’s pungent taste, as well as its pharmacologic effects.1 Components possess potential anti-inflammatory2,3 and antiplatelet effects.4-6
Few in vitro and animal experiments investigate ginger’s antiemetic potential. Animal studies have shown efficacy in preventing cisplatin-induced emesis and effects on GI motility equivalent to metoclopramide and domperidone,7 although human trials failed to confirm the latter.8,9 There is speculation that the mechanism of action may be both central and peripheral (anticholinergic and antihistaminic),10 and that ginger has effects similar to, but less than,11 the serotonin-receptor (5-HT3) antagonists ondansetron and granisetron.12 Human studies seem to support the notion that the mechanism of pharmacologic action is probably not central, but local to the gastrointestinal tract.13,14
Clinical Trials
Eight adult trials have focused on ginger’s effect on motion sickness; three of these took place in "real-life" settings and the others under various inducement situations such as spinning chairs or vestibular stimulation. Four have been selected for detailing below.
The first controlled study of ginger for motion sickness used a revolving, motor-driven chair to mimic seasickness.15 (For a review of clinical studies, see Table 1.) Doses of 100 mg dimenhydrinate, 940 mg powdered whole ginger root, or chickweed herb (Stellaria media, used as placebo) were given to 36 blindfolded, seasickness-prone subjects 2-25 minutes prior to the test. Ginger subjects averaged 5.5 minutes in the chair (half made it the full 6 minutes), while dimenhydrinate and chickweed subjects remained in the chair an average of 3.5 and 1.5 minutes, respectively (no subjects lasted 6 minutes; three in the chickweed group vomited). Differences in means for gastrointestinal distress were statistically significant for the three groups. Although the results are intriguing, the design of this trial has been questioned and decreases confidence in the results. Level II, major limitations (See enclosed insert, "Applying Evidence-Based Medicine to Dietary Supplements," for a complete explanation of the evaluation standards and scales used in rating clinical studies.)
| Table 1-Human clinical trials evaluating efficacy of ginger's antiemetic/antivertigo effects | ||||||
| Trial | N | Trial Type | Control | Results | LOE | Limitations |
| Riebenfeld20 | 60 | Seasickness | Dimenhydrinate | No difference | II | Major |
| Schmid17 | 1,489 | Seasickness | Six common anti-nausea agents | Few differences | II | Major |
| Stewart9 | 8 | MSPT§ | Scopolamine, placebo | Negative | II | Major |
| Grontved16 | 80 | Seasickness | Placebo | Pos/Neg | II | Major |
| Wood21 | 8 | MSPT§ | Six common anti-nausea agents | Negative | II | Major |
| Grontved14 | 28 | MSPT | Placebo | Pos/Neg | II | Major |
| Stott22 | 16 | MSPT§ | Hyoscine, placebo, cinnarizine | Negative | II | Major |
| Mowrey15 | 36 | MSPT | Chickweed, dimenhydrinate | Positive | II | Major |
| MSPT = Motion Sickness Provocation Testing | ||||||
| § Crossover or multiple test design | ||||||
| Significant decrease in vomiting and cold sweats, decrease in nausea and vertigo not significant | ||||||
| Significant decrease in vertigo, but no nystagmus | ||||||
In a randomized, double-blind crossover, placebo-controlled trial, Grontved and colleagues studied the effects of powdered ginger root on vertigo and nystagmus in eight healthy volunteers upon caloric stimulation of the vestibular system.14 Approximately one hour after consuming 1,000 mg of powdered ginger root or placebo (lactose), subjects were placed supine in a dark room with head tilted 30º forward. The vestibular system was challenged with 44º C water for 40 seconds. Subjects ranked intensity of vertigo on a scale of 0 to 5. Provoked nystagmus was measured. The process was carried out three times at 20-minute intervals, for both ginger and placebo, resulting in 48 scores for each measurement. Analysis showed ginger reduced vertigo significantly better than placebo (P < 0.05). There was essentially no effect on nystagmus duration or maximum slow phase velocity of nystagmus. Nausea occurred on three occasions in the placebo group; vomiting did not occur in either group. Level II, major limitations
Another trial examined powdered ginger root vs. placebo and seasickness in 80 "unseasoned" Danish Naval cadets.16 During the first encounter of "heavy seas," 40 cadets received 1,000 mg powdered ginger root and 40 received placebo in a randomized, double-blind fashion. All but one cadet recorded scores for nausea, vertigo, vomiting, and cold sweats on a score card each hour for the first four hours after the dose. Forty-eight cadets (61%) reported motion sickness symptoms; 16 (40%) in the ginger group and 15 (38.4%) in the placebo group reported no symptoms. Interestingly, the ship’s physician felt symptoms were somewhat underreported. Analysis revealed no significant differences for total symptom scores in the first three hours. At hour 4, a significant difference was found for ginger over placebo for total symptom score (P < 0.05). Ginger was significantly better than placebo in reducing frequency of vomiting and cold sweats (P < 0.05 for both). Level II, major limitations
In two randomized, partial double-dummy controlled studies, efficacy of 500 mg ginger root was compared to six common seasickness prophylactics (cinnarizine, cinnarizine with domperidone, cyclizine, dimenhydrinate with caffeine, meclozine with caffeine, and scopolamine) in 1,741 subjects taking a whale safari.17 Study one subjects took medications two hours before departure and could request a second dose during the trip. Study two subjects (scopolamine TTS and cinnarizine) received the first dose the evening prior and a second dose two hours before departure. Outcomes were measured by means of a questionnaire utilizing the standard Graybiel assessment scale. Efficacy results showed differences between groups that did not reach significance, with a trend of more illness for scopolamine. Although power had been calculated, no group reached the 240 subjects needed. Other design considerations leave much doubt for interpretation of results. Level II, major limitations
Adverse Events
Heartburn-like symptoms have been reported with oral administration.9
Interactions
Potential interactions with anticoagulants or anti-platelet agents are hypothetical and based on reported antiplatelet effects,4,5 although one study found no antithrombotic activity after one week of use.6 The concern about interaction with drugs influenced by changes in gastrointestinal transit time is unwarranted, as ginger does not affect gastric emptying.8,9
Contraindications
Until the question of antiplatelet effects is resolved, caution is warranted for patients on anticoagulant or antiplatelet therapy or at high risk for bleeding complications. Certain components of ginger have been reported to be mutagenic in in vitro investigations, while other constituent are antimutagenic.18,19 Effects of these components together are not known. These concerns must be addressed in future investigations prior to recommending therapeutic use in pregnancy.
Formulation and Dosage
No consensus exists for formal standardization of ginger products or dosing. Most clinical trials have utilized powdered whole ginger root in single doses of 500-1,000 mg, usually administered 15-90 minutes prior to noxious stimulus or tid.
Conclusion
Results of eight trials evaluating efficacy of ginger for motion sickness have shown varied results. Study designs have varied considerably and all have serious limitations including outcome measures, patient populations, randomization, statistical power, and dosing. Side effect reporting has been scarce in these trials; however, investigations primarily did not focus on this aspect or failed to mention it at all. Ginger’s purported antithrombotic effect on platelets remains controversial.
Recommendation
Despite centuries of historical use and some evidence that ginger does affect the gastrointestinal system, the current body of clinical evidence does not support a recommendation for prevention or treatment of motion sickness. Adverse effects appear to be negligible, but are not well studied. Pregnant women should be careful to avoid excess consumption of supplemental ginger. Grade B
References
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16. Grontved A, et al. Ginger root against seasickness. A controlled trial on the open sea. Acta Otolaryngol 1988;105:45-49.
17. Schmid R, et al. Comparison of seven commonly used agents for prophylaxis of seasickness. J Travel Med 1994;1:203-206.
18. Nagabhushan M, Amonkar A. Mutagenicity of gingerol and shogaol and antimutagenicity of zingerone in Salmonella/microsomal assay. Cancer Lett 1987;36:221-223.
19. Unnikrishnan M, Kuttan R. Cytotoxicity of extracts of spices to cultured cells. Nutr Cancer 1988;11:251-257.
20. Riebenfeld D, Borzone L. Randomized double-blind study comparing ginger (Zintona) and dimenhydrinate in motion sickness. In: Health Notes Complement Med 1999;6:98-101.
21. Wood CD, et al. Comparison of efficacy of ginger with various antimotion sickness drugs. Clin Res Pract Drug Reg Affairs 1988;6:129-136.
22. Stott JRR, et al. A double blind comparative trial of powdered ginger root, hyosine HBr, and cinnarizine in the prophylaxis of motion sickness induced by cross coupled stimulation. NATO Advisory Group for Aerospace Research and Development; conference proceedings #372;1984:39-139-5.
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