Effects of a ginger extract on knee pain in patients with osteoarthritis

ARTHRITIS & RHEUMATISM Vol. 44, No. 11, November 2001, pp 2531–2538 2001, American College of Rheumatology Published by Wiley-Liss, Inc.
Effects of a Ginger Extract on Knee Pain in Patients With Osteoarthritis R. D. Altman1 and K. C. Marcussen2 Objective. To evaluate the efficacy and safety of a
the 2 groups. Patients receiving ginger extract experi-
standardized and highly concentrated extract of 2 gin-
enced more gastrointestinal (GI) adverse events than
ger species, Zingiber officinale and Alpinia galanga
did the placebo group (59 patients versus 21 patients).
(EV.EXT 77), in patients with osteoarthritis (OA) of the
GI adverse events were mostly mild.
Conclusion. A highly purified and standardized
Methods. Two hundred sixty-one patients with
ginger extract had a statistically significant effect on
OA of the knee and moderate-to-severe pain were en-
reducing symptoms of OA of the knee. This effect was
rolled in a randomized, double-blind, placebo-
moderate. There was a good safety profile, with mostly
controlled, multicenter, parallel-group, 6-week study.
mild GI adverse events in the ginger extract group.
After washout, patients received ginger extract or pla-
cebo twice daily, with acetaminophen allowed as rescue
Present-day therapy for osteoarthritis (OA) of medication. The primary efficacy variable was the pro-
the knee is directed at symptoms, since there is no portion of responders experiencing a reduction in "knee
established disease-modifying therapy. Treatment pro- pain on standing," using an intent-to-treat analysis. A
grams involve a combination of nonpharmacologic and responder was defined by a reduction in pain of >15
pharmacologic measures, utilizing a combination of an- mm on a visual analog scale.
algesia, antiinflammatory, and intraarticular programs Results. In the 247 evaluable patients, the per-
(1–3). If these are unsuccessful, a variety of surgical centage of responders experiencing a reduction in knee
interventions are appropriate. Since none of the medic- pain on standing was superior in the ginger extract
inal programs consistently provides adequate relief of group compared with the control group (63% versus
pain, yet has attendant risk, the search continues for 50%; P ⴝ 0.048). Analysis of the secondary efficacy
agents that might provide improvement in symptoms variables revealed a consistently greater response in the
with minimal risk. While scientists have turned to the ginger extract group compared with the control group,
investigation of newly discovered pharmaceuticals, many when analyzing mean values: reduction in knee pain on
patients have turned to herbal and other remedies that standing (24.5 mm versus 16.4 mm; P ⴝ 0.005), reduc-
have not been adequately studied.
tion in knee pain after walking 50 feet (15.1 mm versus
The purpose of the present study was to test an 8.7 mm; P ⴝ 0.016), and reduction in the Western
extract of Zingiber officinale Roscoe and Alpinia galanga Ontario and McMaster Universities osteoarthritis com-
posite index (12.9 mm versus 9.0 mm; P ⴝ 0.087).
Linnaeus Willdenow (both are of the Zingiberaceae Change in global status and reduction in intake of
family, commonly called "gingers"). The Zingiberaceae rescue medication were numerically greater in the gin-
family consists of 49 genera and 1,300 species, of which ger extract group. Change in quality of life was equal in
there are 80–90 species of Zingiber and 250 species of Alpinia (4). The subspecies used in the tested extract Supported by Gra¨ngeMatic Ltd, Dublin, Ireland.
were selected after analysis and testing of ⬎100 varieties 1R. D. Altman, MD: Miami Veterans Affairs Medical Center (species and subspecies) of Zingiberaceae for antiin- and University of Miami, Miami, Florida; 2K. C. Marcussen, MD: flammatory effects, by in vivo assays and using animal Narayana Research, Winter, Wisconsin.
Address correspondence and reprint requests to K. C. Mar- models. The species selected by this process were grown cussen, MD, Narayana Research, W 7041 Olmstead Road, Winter, WI and harvested under controlled conditions.
Ginger is a very popular spice and the world Submitted for publication August 23, 2000; accepted in revised form April 11, 2001.
production is estimated at 100,000 tons annually, of ALTMAN AND MARCUSSEN which 80% is grown in China (5). Ginger also has a long search based on the traditional use of the gingers has led tradition of medicinal use and has been used as an to the development of a patented ginger extract antiinflammatory agent for musculoskeletal diseases, (EV.EXT 77). In vitro experiments have shown that the including rheumatism, in Ayurvedic and Chinese medi- combined extract also inhibits the production of tumor cine for more than 2,500 years (6,7). The German necrosis factor ␣ (TNF␣) through inhibition of gene Commission E Monographs contains reviews of drugs, expression in human OA synoviocytes and chondrocytes including herbal drugs, for quality, safety, and effective- ness. As a result of this review of more than 300 herbs by In this study, we have evaluated the safety and an expert committee under the German Federal Insti- efficacy of the extract in a double-blind, placebo- tute for Drugs and Medical Devices, many herbs have controlled study with intent-to-treat (ITT) analysis.
been excluded from sales in Germany. The Monographs lists ginger for use in dyspepsia and prevention of motion sickness (8). In the standard German text, PATIENTS AND METHODS
Hager's Handbuch der Pharmazeutischen Praxis, ginger is Study design. The study was a 6-week, double-blind,
listed as being used against nervousness, chronic inflam- placebo-controlled, parallel-group trial performed at 10 clini- mation of the intestine, coughing, conditions of the cal centers in the US. It was designed according to guidelines urinary tract and lower abdomen, rheumatism, and a on conduct of clinical trials as reported by the Osteoarthritis sore throat (9).
Research Society International (22) and as outlined in the International Conference on Harmonisation clinical practice Pharmacologically, ginger, similar to other plants, guidelines (23). The protocol followed the 1975 Declaration of is a very complex mixture of compounds. Zingiber offi- Helsinki as revised in 1983, with institutional review board cinale contains several hundred known constituents (10), approval, and all patients provided their oral and written among them gingeroles, beta-carotene, capsaicin, caffeic informed consent. Patients were centrally randomized to re- acid, and curcumin. In addition, salicylate has been ceive treatment by a computer-generated allocation schedule, balanced by center, and both the investigators and the patients found in ginger in amounts of 4.5 mg/100 gm fresh root were blinded to treatment assignment.
(11). This would correspond to ⬍1 mg salicylate in 1 Patients. Patients had OA of the knee by the American
capsule of the presently tested ginger extract. The College of Rheumatology classification criteria using the deci- actions and especially the interactions of these ingredi- sion tree format that includes radiographs (24). The radio- ents have not been (and probably can not be easily) graphic changes had to include at least osteophytes and evaluated. Various powders, formulations, and extracts correspond to OA grades 2, 3, or 4 by the Kellgren and Lawrence criteria (25).
have, however, been commercially used and tested, both Admission criteria included the presence of knee pain in vitro and in vivo, in animal models. In these models, on standing that had to be between 40 mm and 90 mm on a ginger has been shown to act as a dual inhibitor of both 100-mm visual analog scale (VAS) during the preceding 24 cyclooxygenase (COX) and lipooxygenase (12), to in- hours. This was assessed after a 1-week washout period. Both hibit leukotriene synthesis (13), and to reduce men and women ⱖ18 years old were included. Pain had to be of a degree so that it could be tolerated with alleviation using caregeenan-induced rat-paw edema (14,15), an animal acetaminophen as an escape medication for 6 weeks. Prior model of inflammation.
treatment for OA was not a requirement. Patients with any of Another related plant, galanga, commonly called the following were excluded: rheumatoid arthritis, fibromyal- greater galanga, is also widely used as a spice in the East gia, gout, recurrent or active pseudogout, cancer or other and as a remedy for various ailments. It has an antiin- serious disease, signs or history of liver or kidney failure, asthma requiring treatment with steroids, treatment with oral flammatory action through inhibition of prostaglandin corticosteroids within the prior 4 weeks, intraarticular knee synthesis (16), and has traditionally been used for rheu- depo-corticosteroids within the previous 3 months, intraartic- matic conditions in South East Asian medicine (17). The ular hyaluronate within the previous 6 months, prior treatment volatile oil of Alpinia galanga L., which can be obtained with immunosuppressive drugs such as gold or penicillamine, by steam distillation of the rhizome, is a complex mixture arthroscopy of the target joint within the previous year, significant injury to the target joint within the previous 6 containing 1,8-cineol and 1⬘-acetoxychavicol acetate months, other investigational drugs within the previous 1 which has antifungal (18) and antitumor (19) activity.
month, fever ⬎38°C at screening, and allergy to acetamino- The German Commission E Monographs lists the use of phen or ginger.
Alpinia officinarum, which is closely related to Alpinia After screening, patients entered a 1-week "washout" galanga, for dyspepsia and loss of appetite. The US Food for antiinflammatory and analgesic medications, during which they were allowed to take acetaminophen as needed up to 4 and Drug Administration lists ginger and Alpinia offici- gm/day. Aspirin for anticoagulation up to 325 mg daily was narum as "generally regarded as safe" (20). New re- allowed throughout the study.
GINGER EXTRACT IN OA OF THE KNEE If patients were determined to be eligible for the study, coded according to World Health Organization adverse reac- a baseline assessment of pain was performed after washout of tion terminology (28). The adverse events were analyzed by medications that would affect the arthritis and prior to ran- preferred terms and by system organ classes.
domization. Each center was block-randomized with 130 pa- Statistical analysis. Blinding was maintained until the
tients receiving ginger extract and 131 patients receiving final database was cleaned and locked. However, there was an interim analysis of 116 patients that was performed at a Treatment. During the 6-week treatment period, pa-
significance level of 0.01% by an independent statistician. The tients ingested 1 capsule twice daily, morning and evening.
results were disclosed to the sponsor only. Neither the inves- Each capsule contained 255 mg of EV.EXT 77, extracted from tigators nor the clinical research organization monitoring the 2,500–4,000 mg of dried ginger rhizomes and 500–1,500 mg of study were aware of the results.
dried galanga rhizomes and produced according to good Sample-size calculation was based on results of an manufacturing practice (Eurovita Holding, Karlslunde, Den- unpublished clinical trial using a ginger extract. Statistical mark). Matching placebo capsules contained coconut oil. To evaluation was performed using SAS (SAS Institute, Cary, minimize a possible pungent sensation, patients were in- NC). The statistical analysis was performed using analysis of structed to swallow the whole (intact) capsule with a glassful of covariance for analysis of means, with baseline scores, center, water at the time of a meal.
sex, treatment-by-center interaction, and age as the covariates.
Acetaminophen was permitted as a rescue medication.
Chi-square tests were used for analysis of responders, Stu- Patients were instructed to take the rescue medication only dent's t-test to analyze intake of rescue medication, and when needed, to a maximum dosage of 2 tablets 4 times daily, Fisher's exact test for comparing incidence of adverse events i.e., 4 gm/day.
between groups. Except for the analysis of intake of rescue Drug accountability was calculated by pill count for medication, the ITT last observation carried forward method both the study treatment and the rescue medication.
was used. All analyses were performed 2-sided, with a mini- Assessments. The OA knee deemed to be more symp-
tomatic was defined as the target joint by the investigator, and mum significance level of 5%.
the knee-specific pain was assessed for this joint. The primary efficacy parameter was the proportion of responders experi- encing at least a 15-mm reduction in pain between baseline and the final visit for knee pain on standing during the preceding 12 Patients. There was no clinically relevant differ-
hours, as measured by a 100-mm VAS. Pain on standing is a ence in the demographics between the 2 treatment validated measure of pain and coincides with question 5 of the Western Ontario and McMaster Universities (WOMAC) OA groups (Table 1). The patients were predominantly composite index (26). At the time of the design of this study, women and predominantly white. Patients in both study the full WOMAC index was not generally accepted as a groups were generally overweight, since the average primary efficacy variable in clinical trials of OA of the knee.
body mass index was ⬎30 kg/m2 (range 18–65 kg/m2).
Secondary efficacy measures that were used to com- All patients with at least 1 visit after the baseline pare the 2 study groups were as follows: 1) average improve- ment in pain on standing, as measured by a 100-mm VAS; 2) evaluation were included in the ITT analysis. Fourteen consumption of rescue medication; 3) WOMAC index as patients, 8 receiving placebo and 6 receiving ginger measured by VAS, with one end of the scale being "no extract, discontinued the trial before completing any pain/stiffness/difficulty" and the other end, "extreme pain/ evaluation of efficacy. Among the patients in the pla- stiffness/difficulty" (the total score was calculated as the mean response); 4) patient assessment of global status, in which the cebo group who discontinued, 3 dropped out due to question, "Given all the ways your osteoarthritis affects you, adverse events, 4 were lost to followup, and 1 withdrew how have you been doing the last 24 hours?" was evaluated on consent. Among the patients receiving ginger extract a 5-point Likert scale (1 ⫽ very poor, 2 ⫽ poor, 3 ⫽ average, who discontinued, 3 dropped out due to adverse events 4 ⫽ good, 5 ⫽ very good); 5) quality of life assessment using and 3 were lost to followup. Thus, the modified ITT the Short Form 12 (SF-12), which asks questions regarding the patient's condition during the preceding 4 weeks (27); and 6) analysis included the 247 patients (95% of the total pain in the knee after walking 50 feet, recorded immediately enrolled) who completed any postbaseline efficacy eval- after walking and measured by a 100-mm VAS.
uation. A total of 194 patients (74%) completed the Efficacy and safety assessments were performed at study without protocol violations. Fifty-seven patients baseline and after 2 and 6 weeks of treatment. The SF-12 was administered at screening and after 6 weeks of treatment only.
discontinued prematurely (22% of the randomized pop- Safety was assessed via open-ended questions concerning ulation) (Table 2). The overall withdrawal rate was 28% changes in the patients' health at each visit, supported by in the ginger extract group and 16% among those patients' responses on diary cards. For all adverse events, the receiving placebo. The withdrawal rate due to adverse onset, duration, and intensity (mild, moderate, or severe) of events was 13% in the ginger extract group and 5% in the event, as well as the action taken and outcome, were recorded. The relationship between an adverse event and the the placebo group. There were no followup data avail- study medication was assessed, by the investigator, as none, able for the patients who withdrew from the study remote, possible, probable, or definite. Adverse events were

ALTMAN AND MARCUSSEN Table 1. Demographic characteristics of study population*
Age, mean ⫾ SD years Body mass index, mean ⫾ SD kg/m2 Diagnosed OA, mean ⫾ SD years Radiographic classification of * OA ⫽ osteoarthritis.
† By the Kellgren and Lawrence criteria (25).
Compliance. Compliance was calculated from the
extract group (78 of 130, or 60%) than in the placebo amount of study medication (number of capsules) re- group (62 of 131, or 47%) (P ⫽ 0.040). The analysis of turned and the number of empty slots in the blister means for pain on standing showed that the ginger cards. Compliance was 98 ⫾ 12% (mean ⫾ SD) for the extract group improved an average 8.1 mm more than ginger extract group and 98 ⫾ 18% for the placebo did the placebo group (P ⫽ 0.005) (Figure 1).
A subset analysis was performed for increased Primary efficacy variable: pain on standing. Pain
responder levels. For ⱖ20-mm improvement in pain on on standing after 6 weeks of treatment showed improve- standing, the ginger extract group showed a response ment in both treatment groups. However, as the primary superior to that of the placebo group (n ⫽ 73 [59%] efficacy parameter, there was a higher percentage of versus n ⫽ 56 [46%]; P ⫽ 0.036). For a ⱖ25-mm responders (improvement ⱖ15 mm on the VAS pain improvement, the ginger extract group again displayed a scale) in the ginger extract group (n ⫽ 78 [63%]) than in the placebo group (n ⫽ 62 [50%]; P ⫽ 0.048). An ITT analysis of all patients enrolled, regardless of whether they underwent any postbaseline efficacy evaluation, also showed a higher rate of responders in the ginger Table 2. Discontinuations among the randomized population*
Primary reason for early termination Perceived lack of efficacy Intercurrent illness Figure 1. Knee pain on standing as measured by 100-mm visual
analog scale after 2 and 6 weeks in patients with osteoarthritis
receiving placebo (n ⫽ 123) or ginger extract (n ⫽ 124), in the * Values are the number of patients.
intent-to-treat analysis. Bars show the mean pain rating (in mm) and † P ⫽ 0.025 versus placebo.
95% confidence intervals.
GINGER EXTRACT IN OA OF THE KNEE Table 3. Results of secondary parameters in the intent-to-treat analysis
Placebo (n ⫽ 123)* Ginger extract (n ⫽ 124)* Pain after walking 50 feet * Numbers of patients vary between 121 and 124 at the single visits, and for quality of life (QOL), between 111 and 114.
† Western Ontario and McMaster Universities osteoarthritis index (WOMAC) consists of 24 questions, assessed on 100-mm visual analog scale, analyzed in 3 subscales as the average score for 5 questions on pain, 2 questions on stiffness, and 17 questions on function. The total score is calculated as the mean score for all 24 questions.
‡ The Short Form 12 (SF-12) consists of 12 questions that are combined into 8 scales, which are summarized in the physical and mental component summaries shown here.
superior response compared with that of the placebo Figure 2 shows the response on the individual questions group (n ⫽ 65 [52%] versus n ⫽ 48 [39%]; P ⫽ 0.035).
of the WOMAC questionnaire, with responses to ques- In an analysis of the patients who completed the tions 6, 7, 11, 14, and 15 showing a significant improve- study per protocol and experienced ⱖ15-mm improve- ment among patients receiving the ginger extract. Im- ment in pain on standing, results were similar to those of provement in patient global status was numerically the ITT analysis, although the difference between the 2 better in the ginger extract group and was statistically treatment groups was smaller. The ginger extract group superior in a per protocol analysis (P ⫽ 0.042). There showed a response that was numerically superior (60 of was no difference in the SF-12 score, since there was 92, or 65%) to that of the placebo group (54 of 102, or little change from baseline in either group. Acetamino- 53%) (P ⫽ 0.083). In other parameters, significant phen use was equal in the 2 study groups (mean ⫾ SD improvements comparable with those in the ITT analysis number of tablets daily 2.0 ⫾ 1.9 in the ginger extract group and 2.2 ⫾ 2.0 in the placebo group).
Secondary efficacy variables. The results of the
Analysis of individual variables showed no effect secondary parameters were consistent with the findings of age (⬎65 years versus ⬍65 years), sex, center, or with the primary parameter (Table 3). Pain after walking treatment-per-center interaction on the efficacy para- also demonstrated a significant improvement in the meters. This analysis did show a difference in the ginger extract group compared with the placebo group.
baseline scores, especially in global status, with the The change in total WOMAC score was numerically placebo group having the worse scores. This difference superior in the ginger extract group versus the placebo cannot be explained, but it was adjusted for through the group, with the greatest improvement seen in stiffness.
analysis of covariance.
ALTMAN AND MARCUSSEN There was concern that the adverse events might affect the blinding of treatment status. Therefore, we examined the percentage of responders for pain on standing in the ginger extract group in the presence or absence of GI adverse events. There were 65% respond- ers in the presence of dyspepsia, eructation, or nausea, and 62% responders in the absence of these adverse GI events (P ⫽ 0.85). Through this analysis, the adverse events were not found to significantly affect the outcome of the study.
Patients were informed about the possible pun- gency upon entering the study. Experience of the pun- gent taste was captured as adverse events to an extent, Figure 2. Mean change from baseline to the fourth visit in each
which may explain the incidence of these events. Still, functional measure of the Western Ontario and McMaster Universi-ties osteoarthritis index for the 2 treatment groups, in the intent-to- the possibility exists that some subjects were not truly treat analysis. Bars show the mean and standard error.
blinded due to the pungency of the ginger extract.
Adverse events. There were 314 adverse events
reported on diary cards and by questioning. Seventy-six In a 1999 Gallup questionnaire among Ameri- patients (59%) receiving ginger extract experienced 202 cans with arthritis, 28% thought that herbals have a role adverse events. Forty-nine patients (37%) receiving pla- in the treatment of arthritis, and 17% believed that cebo experienced 112 adverse events. Only 1 group of herbals have a preventative role (29). In a 1997 US adverse events showed a significant difference between survey among 2,055 people, 27% of those with arthritis the treatment groups: gastrointestinal (GI) adverse had used an alternative treatment for the disease within events were more common in the ginger extract group the last year (30). Herbal remedies and other nutraceu- (116 events in 59 patients [45%]) compared with the ticals or botanicals are thus increasingly used by both the placebo group (28 events in 21 patients [16%]).
healthy and the sick. Unfortunately, few of the remedies None of the GI adverse events were considered have been tested for efficacy and safety in well-designed serious by the investigators; 70% were reported as mild, clinical trials.
24% moderate, and 6% severe. When analyzing the In order to address this issue, in a 6-week, events by preferred terms, the only events seen signifi- randomized clinical trial using ITT analysis in patients cantly more often in the ginger extract group were with OA of the knee, treatment with a ginger and eructation, dyspepsia, and nausea. Words used by the galanga extract (EV.EXT 77) demonstrated a reduction patients included burping, belching, bad taste in the in knee pain on standing when compared with patients mouth, stomach upset, heartburn, and a burning sensa- receiving placebo. Additional analyses of the primary tion in the stomach. To examine whether preexisting efficacy variable as well as changes in the WOMAC conditions had any influence on this response, the index and global status were consistent with the results patients' medical history was related to the adverse of the primary efficacy variable. In this short-term study, events. Thirty-six patients in each treatment group had a there was no essential difference in the ginger and previous diagnosis of reflux disease, dyspepsia, ulcer, placebo groups for quality of life (measured by the heartburn, gastritis, or hiatus hernia. Of these, 4 patients SF-12) or consumption of rescue analgesia (acetamino- (11%) in the placebo group and 10 (28%) receiving phen). The treatment group also had an increase in GI ginger extract had at least 1 of the adverse events, including adverse events.
dyspepsia, eructation, or nausea; it was concluded that The benefits found in this trial are consistent with there was no connection to previous conditions.
the results described in the few existing reports in the There was no statistically significant difference literature. Three published studies on the use of ginger between the number of severe adverse events in the 2 in arthritis have been identified. Two were collections of treatment groups. One serious adverse event occurred in anecdotal reports (31,32). In the larger cohort, involving the study, a myocardial infarction in a patient receiving 56 patients with rheumatic disorders, more than 75% experienced relief of pain and swelling after an average GINGER EXTRACT IN OA OF THE KNEE dosage of 3 gm raw ginger per day for periods varying or bleeding after intake of ginger despite widespread use between 3 months and 2 years (32). A randomized of ginger throughout the world. Surprisingly, both ginger clinical trial included 67 patients, of whom 56 were able (38) and galanga (39) have been shown to protect to be evaluated (33). This was a 3-way, crossover study against ulcers in animal studies. The lack of severe GI comparing ibuprofen, ginger extract, and placebo. The adverse events seen in this study is consistent with the ranking of efficacy was ibuprofen ⬎ ginger extract ⬎ observations in the above-mentioned studies as well as in placebo for VAS scores on pain and the Lequesne index, studies on other uses of ginger: seasickness (40), post- but no significant difference was seen when comparing operative antiemetic (41,42), and vertigo (43).
ginger extract and placebo directly. Exploratory testing A warning has been reported on the possible of the first period of treatment (before crossover) was effect of ginger on bleeding time (44). In vitro studies performed and this showed a better effect of both have shown that ginger inhibits thromboxane synthesis ibuprofen and ginger extract compared with that of and thereby platelet aggregation (45). In humans, an ex placebo (P ⬍ 0.05 by chi-square test).
In the WOMAC subgroups in the present study, vivo study tested a single dose of 2 gm dried ginger (46).
the greatest improvement was seen in stiffness. The Another 3-way crossover study compared the oral intake WOMAC index is described as being more sensitive to of 15 gm raw ginger/day, 40 gm cooked stem ginger/day, change in pain, followed by stiffness and function (34).
and placebo for 2 weeks in 18 healthy volunteers (47).
Further investigation into the effects of ginger on stiff- None of the tested ginger preparations produced any ness appears warranted, since this may indicate a differ- significant change in thromboxane synthesis. We could ent mechanism of action than most other OA remedies.
find no published data on adverse events connected with This was a short-term study. At 6 weeks, the coagulation with ginger.
placebo effect appeared to fade, whereas the group The average body mass index for this study treated with ginger extract continued to improve.
population was high. Patients were enrolled without Longer-term studies are needed.
weight restrictions and may constitute a typical OA Although the COX-2–specific inhibitors have less population in the US. The dosing of the ginger extract GI adverse effects than do nonselective nonsteroidal given was empirically based on the 1–2 capsules per day antiinflammatory drugs (NSAIDs), their overall safety that is typically consumed in Europe. In retrospect, versus placebo is not entirely known, and there are no there may be concern that the US patients may have studies comparing COX-2–specific inhibitors with the been underdosed. Without a dose-finding study, it is ginger extract. Both nonselective NSAIDs and COX-2– uncertain if a higher dose would have a better effect.
specific inhibitors have potential renal adverse effects In conclusion, this study showed that a highly (35) not described with the ginger extracts.
purified ginger extract has demonstrated a statistical Some of the patients reported mild GI side effect of reducing pain in patients with OA of the knee.
effects in the form of dyspepsia, eructation, and nausea.
There was a good safety profile with mostly mild GI side These may be caused by the pungent taste of the ginger effects. Long-term effects bear further investigation.
extract. Adverse events for NSAIDs can be classified into 3 categories (36): 1) "nuisance" symptoms, such as heartburn, nausea, dyspepsia, and abdominal pain; 2) mucosal lesions; and 3) serious GI complications, such We thank Dr. Fong Wang Clow for preparing the as bleeding and perforation. On average, 10–12% of statistical plan and Rebecca Hoagland for performing the patients will experience dyspepsia while taking a nonse- statistical analysis. In addition to Dr. Altman, contributing lective NSAID, sometimes leading to death (36,37).
investigators were as follows: Neal Birnbaum, MD, Pacific Rheumatology Associates, San Francisco, California; Lon Bla- Because ginger inhibits prostaglandin synthesis, there is ser, MD, Marshfield Clinic, Marshfield, Wisconsin; Jacque the potential for GI ulceration. However, the effect of Caldwell, MD, Halifax Clinical Research Institute, Daytona NSAIDs on the inflammatory process is mainly caused Beach, Florida; Guy Fiocco, MD, Gundersen Lutheran Clinic, by inhibition of prostaglandin synthesis. Contrary to this, La Crosse, Wisconsin; Elie Gertner, MD, Regions Hospital, St.
the ginger extract is a complex mixture that reduces Paul, Minnesota; Larry Gilderman, MD, University Clinical inflammation through inhibition of prostaglandin syn- Research, Pembroke Pines, Florida; Robert Leff, MD, Duluth Clinic, Duluth, Minnesota; Howard Offenberg, MD, Halifax thesis, inhibition of lipooxygenase (13), and reduced Clinical Research Institute, New Smyrna Beach, Florida; and production of TNF␣ (21).
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