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Complement Ther Med. Author manuscript; available in PMC 2015 Feb 1.
Published in final edited form as:
Complement Ther Med. 2014 Feb; 22(1): 17–20.
Published online 2014 Jan 8. doi:10.1016/j.ctim.2013.12.015
PMCID: PMC3958926
NIHMSID: NIHMS554318
PMID: 24559811
Miranda A.L. VAN TILBURG, PhD, Olafur S. PALSSON, PsyD, Yehuda RINGEL, MD, and William E WHITEHEAD, PhD
Author information Copyright and License information PMC Disclaimer
The publisher's final edited version of this article is available at Complement Ther Med
Abstract
Objectives
Ginger is one of the most commonly used herbal medicine for IrritableBowel Syndrome (IBS) but no data exists about its effectiveness.
Design
Double blind randomized controlled trial
Setting
University of North Carolina, Chapel Hill North Carolina, USA
Intervention
Forty-five IBS patients were randomly assigned to three groups:placebo, one gram of ginger, and two grams of ginger daily for 28 days.
Main outcome measures
The IBS severity scale (IBS-SS) was administered, as well as adequaterelief of symptoms scale. A responder was defined as having at least25% reduction in IBS-SS post-treatment.
Results
There were 57.1% responders to placebo, 46.7% to onegram and 33.3% to two grams of ginger. Adequate relief was reportedby 53.3% on placebo and 53.3% in both ginger groupscombined. Side effects were mild and reported by 35.7% in theplacebo and 16.7% in the ginger groups.
Conclusions
This double blind randomized controlled pilot study suggests gingeris well tolerated but did not perform better than placebo. Larger trials areneeded before any definitive conclusions can be drawn.
Keywords: Irritable Bowel Syndrome, ginger, Randomized Controlled Trial, placebo
Introduction
Irritable Bowel Syndrome (IBS) is a common chronic condition consisting ofabdominal pain with changes in bowel habits. The effectiveness of treatments for IBSare limited and about 40% of patients use alternative medicine to treattheir symptoms1. The most popularalternative medicine in a large study of 600 IBS patients was ginger1.
Ginger root is the rhizome of the perennial plant ZingiberOfficinalis Roscoe. Ginger contains 1–3% of oils.Ginger dosing is often standardized according to gingerol content which is assumedto have antiemetic, analgesic, sedative, antibacterial and other physiologicaleffects though other non-volatiles may have some of the same effects2–4. Ginger is on the American Food and Drug AdministrationGenerally Recognized as Safe list meaning that it is considered safe and is exemptedfrom premarket review, approval, and clinical testing before marketing (http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/ucm2006850.htm).
There is some evidence to suggest that ginger can affect IBS symptoms. InMicromedex (an evidence based clinical reference tool for hospitals and physicians;www.micromedex.com) ginger is classified as a broad spectrumantiemetic, and is effective in treating nausea and vomiting associated withpregnancy5 andsurgery6. Ginger has alsobeen found to influence pain and gut motility2, 4. Thus, ginger maybe useful in reducing both pain and stool changes in IBS.
Given the known gastrointestinal effects of ginger, its common use among IBSpatients and its wide availability and low cost, ginger should be tested as apotential treatment for IBS. The goal of this pilot study was to test the effects ofginger on IBS symptoms through a randomized placebo and dose dependent controlledtrial. We chose to run a pilot study to look for signal and magnitude of clinicaleffect to support the rational and direct the design of a larger study
Methods
Subjects
Subjects were 45 patients age 18 and older with a physician diagnosis ofIrritable Bowel Syndrome (IBS) verified by Rome III criteria. Patients wereidentified by sending a mass e-mail to all students, staff, and faculty at theUniversity of North Carolina. All participants needed to have symptoms at leastonce a week severe enough to interfere with daily activities and report being ona stable dose of current medications for IBS for at least 4 weeks. Subjects wereexcluded if they reported: (a) regular use of ginger (b) gingerallergy/intolerance, (c) history of surgical resection of part of thegastrointestinal tract, (d) being pregnant or planning to become pregnant, or(e) use of cardiotonic or diabetic medications contra-indicated for use withginger.
The study employed a randomized, controlled, parallel group design inwhich 15 subjects were randomly assigned to each of three arms: placebo, onegram ginger daily, or two grams ginger daily. Treatment duration was 28 days.Most previous trials of gastrointestinal related symptoms, such asnausea/vomiting associated with cancer or pregnancy, have used similar1–2 grams daily doses5, 7. Given that no previous studieshave tested the use of ginger in IBS patients, we have no information to guidepower analyses for a trial. Therefore, we chose to run an initial trial with 15subjects in each arm to look for signal and magnitude of clinical effect tosupport the rational and direct the design of a larger study.
Study design
All patients completed consent, screening and baseline questionnairesonline. More patients expressed interest in participation than the required 45– only the first 45 were invited to participate. Upon randomization (bya perl-based computer program), a one month supply of ginger or placebo capsuleswas sent by mail. Packages included instructions on starting and stopping dates.Patients were contacted within 24 hours of ingesting first capsule, and biweeklythereafter to check for compliance and side effects. The study was approved bythe Institutional Review Board of the University of North Carolina(approval# 07-1035).
Ginger and placebo capsules
The ginger and placebo capsules were blister packed to ensureblinding8, by acompounding pharmacy. The pharmaceutical grade ginger contained 2.29 mg/g ofgingerols and 6-shogaols. The placebo contained brown sugar. The pharmacy codedthe capsules for blinding and sent a coding key via mail at studycompletion.
Measures
Irritable Bowel Syndrome Severity Scale (IBS-SS)
The IBS-SS 9measures IBS severity with five items (severity and frequency of pain,abdominal distension, bowel dissatisfaction, and interference with life)rated on a 0–100 scale. A responder was defined as at least a25% reduction in IBS-SS scores post-treatment.
Adequate Relief Rating Scale (ARRS)
At the end of treatment, patients were asked to respond to thequestion, “In the last week, have you had adequate relief of yourabdominal pain and other symptoms of IBS (yes or no)?”10.
Data analyses
Paired t-test were run to compare IBS severity scores before and aftertreatment. Percentage of responders and ARRS was compared across the threetreatment arms with Chi2 tests.
Results
One-hundred-eighty-one interested patients responded to study notices andcompleted screening. Of this group the first 45 eligible patients were invited toparticipate (see Figure 1 for a CONSORTdiagram). No differences between the 3 treatment arms were found in gender, age andIBS-SS scores at baseline. Treatment compliance was acceptable: 97.3% in theplacebo group, 98.5% in the 1 gram ginger group, and 85.2% in the 2gram ginger group. Side effects were mild and reported by 35.7% in theplacebo and 16.7% in the ginger groups. Except for two subjects who reportedheadaches and tiredness, all side effects were gastrointestinal symptoms includingheart-burn, nausea, difficulty passing stool, more frequent stools, loose stools,bloating and hunger suppression.
Figure 1
Consort flow diagram.
IBS severity scores before and after treatment are given in Table 1. Placeboand 1 gram ginger groups saw a significant reduction in symptoms by 34.8%and 26.4% respectively. Number of treatment responders across groups was notdifferent (57.1% placebo, 46.7% 1 gr ginger, 33.3% 2 gramsginger; p>.05). Adequate relief was reported by 53.3% in the placebogroup and 53.3% in both the ginger groups (p>.05).
Discussion
Ginger is one of the most commonly used herbal medicines by IBSpatients1. This is thefirst study to date that examines the effectiveness of ginger in IBS. Since this isa pilot study, it may not be powered to find significant results. Therefore, weexamined trends in the effects of ginger that would suggest ginger might be aneffective treatment in a larger trial. Instead, we found a trend for IBS symptoms toimprove more with placebo than ginger.
This study had several strengths including the randomized controlled design,the use of pharmaceutical grade ginger with known gingerol content, and assuringblinding of study participants by using blister packs. However, the study also hadseveral limitations, including the small sample size, the short treatment duration,recruitment among university employees and students as well as the absence ofblinding of investigators during the analysis phase of the study. These limit ourability to generalize and draw any definitive conclusions about the effects ofginger on IBS. Larger trials of longer duration are needed.
The placebo effect is known to be strong in studies on treatment response inIBS patients. On average a 40% placebo response has been found in IBStrials11. Our placeboresponse was considerably higher at 57%. The placebo group also reportedtwice as many side effects as the ginger group, corroborating the placebo effect.The placebo effect includes a regression to the mean, natural history of the diseaseas well as treatment expectancies. Treatment expectancies can be raised by verbaland non-verbal cues12 of whichmany will be delivered within the clinic setting and direct patient-physicianinteractions. We minimized most of these factors by having no participants visit aclinic, no face-to-face contact with the researchers, and taking efforts to assureblinding (by using blister packs to conceal smell and providing color and texture ofplacebo comparable to ginger). Most other IBS treatment trials have not minimized ormanipulated the placebo response11.
However, the placebo effect is influenced by many factors some of which arenot always obvious. For example, patients do not have to be blinded to display astrong placebo effect if the right cues are provided. Kaptchuk and colleagues showedthat an open label inactive placebo pill produced better outcomes in IBS patientscompared to no treatment13. InKaptchuk’s study the placebo was introduced as powerful, having aconditioned effect on the body, and becoming stronger with a positive attitude.These instructions may have increased the likelihood of a positive response toplacebo. Although we took measures to blind our participants and minimizenonspecific placebo effects within patient-clinician interactions, we may haveraised treatment expectancies by informing potential subjects in the consent formthat many IBS patients use ginger to treat symptoms, ginger can have effects on painand motility, and ginger may be a potential new treatment for IBS. Thus, we may havegenerated a placebo response with the information we provided to the subjects.Future studies are needed to examine context and cues in treatment trials ofginger.
Previous studies have shown that ginger effectively treats gastrointestinalsymptoms, has antiemetic as well as pain relieving effects, and is one of the mostwidely used herbal medicines by IBS patients1, 2, 4–7. These observations suggest a role of ginger in the treatment ofIBS. The current study does not support this, but is in need of replication.Ginger’s placebo response needs to be accounted for when designing futureclinical trials. Investigators should pay attention to cues and suggestions of theefficacy of ginger in IBS.
Kaptchuk and colleagues13suggests that recommending a placebo may be reasonable for certain disorders such asIBS, if carefully monitored by the physician. Whether or not ginger may prove to beeffective for IBS in future trials, in the light of Kaptchuk and collegues’comments, clinicians may choose to be supportive of the use of ginger in patientswho report adequate relief with this treatment while informing the patient aboutpossible interactions with other medications and side effects.
There are additional issues, which will need to be addressed in futurestudies. Given ginger’s prokinetic effect2 and efficacy in treating nausea5–7, ginger may be more effective for certain subtypes of IBS or forthose IBS patients who also complain of nausea or functional dyspepsia. Thisemphasizes the need to explore the mechanisms by which ginger may affect IBSsymptoms – whether it is through anti-inflammatory, prokinetic, or othereffects. Mechanistic studies may give insight into the group of patients most likelyto benefit from treatment. Furthermore, although we used doses of ginger known to beeffective for the treatment of nausea and vomiting, larger doses may be needed toreach efficacy in IBS. Ginger is generally safe up to 6 grams daily, which may havea much larger effect. Similarly, a different extract preparation with moreconcentrated gingerol content may also provide higher response rates. One caveat isthat in our small study the efficacy of ginger decreased with larger doses. Weobserved a 26% decrease in symptoms with 1 gram versus 12% decreasein symptoms with 2 grams of ginger. Optimal ginger dosing will need to be examinedfor future trials.
In summary, the current study does not find evidence for the use of gingerin treating IBS but future larger trials are needed before any definitiveconclusions can be drawn. The considerable placebo response to ginger in this smallgroup is in need of further exploration and will have to be addressed in futuretrials of ginger.
Table 1
IBS severity scores before and after treatment
| Pre-treatment Mean(SD) | Post-treatment Mean(SD) | p | |
|---|---|---|---|
| Placebo | 253.2 (65.9) | 165.0 (49.3) | .001 |
| 1 gram ginger | 260.0 (65.5) | 191.3 (95.8) | .007 |
| 2 grams ginger | 222.7 (53.3) | 198.9 (88.9) | .233 |
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Acknowledgments
This study was supported by R24 DK067674. The sponsor had no role in the study.
Drs van Tilburg, Palsson and Whitehead were involved in conception, design of thestudy, acquisition, analysis and interpretation of the data, and drafting of themanuscript Dr Ringel was involved in data acquisition and drafting of themanuscript.
Footnotes
Conflict of interest statement
No competing financial interests exist.
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