Osteoarthritis of the knee and hip are common disorders that produce chronic pain and disability. Pharmacologic management of pain with analgesics and nonsteroidal antiinflammatory agents (NSAIDs) is not adequate for some people, and NSAIDs may have serious adverse effects (1). Alternative treatments, such as acupuncture and herbs, are promoted as gentle, effective, and safe, and many people are exploring their use for osteoarthritis and other chronic disorders. Ginger is a popular herbal medication whose principal uses include treatment of motion sickness, disorders of the gastrointestinal tract, and arthritis (2). The mechanisms of action of ginger are not clear, but there is limited evidence of inhibition of inflammation in experimental animals, and of inhibition of the synthesis of prostaglandins and leukotrienes (3).
The efficacy and safety of most alternative treatments have not been established by controlled trials. Since the use of herbal medications has increased substantially in the last decade, it is imperative that good scientific evidence be presented to health care professionals and consumers to provide a basis for making informed decisions. As reported in this issue of Arthritis & Rheumatism, Altman and Marcussen (4) have performed a randomized, double-blind, placebo-controlled trial of the use of a ginger extract for treatment of osteoarthritis of the knee. The study was well designed and conducted, but examination of the data reveals that the beneficial effects of ginger over placebo were small and inconsistent. The authors state that pain on standing was their primary outcome measure because at the time that the study was planned, the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was not considered a standard measure for osteoarthritis of the knee. The WOMAC is now considered an excellent disease-specific instrument for knee osteoarthritis (5), and it is used as a primary outcome measure in most trials for this condition. Since the WOMAC was used in this study, it should be considered as the benchmark efficacy instrument. Unfortunately, the WOMAC results were not impressive, since no statistical or clinical significance favoring ginger over placebo was observed. Furthermore, the beneficial effect observed for pain on standing, a mean difference of 8.1 mm compared with placebo, was quite modest. No beneficial effects were observed in other measures, such as quality of life, and there was no difference between the groups in consumption of acetaminophen as a rescue medication.
An additional concern about this study relates to possible bias caused by lack of effective blinding. Patients were informed when entering the study of a possible pungent taste associated with ginger. The authors comment that “evidence of the pungent taste was captured as adverse events to an extent,” but it is unclear how many patients experienced this sensation and if it could have contributed to the difference between the ginger and placebo groups.
A recent study, which is not cited by the authors, appears to have used the same ginger extract to treat osteoarthritis of the hip and knee (6). That study compared ginger, ibuprofen, and placebo, and used 3-week treatment periods in a crossover design that included a 1-week washout between treatments. In the study as a whole, there was a significant difference between ibuprofen and placebo in the relief of pain and in the Lequesne functional index, but not between ginger and placebo. Using “explorative statistical methods,” a significant difference between ginger and placebo could be detected only in the first period of treatment before crossover.
With regard to safety, there was a significant increase in discontinuation of treatment because of adverse events in the group treated with ginger (see Table 2 in Altman and Marcussen ). Most of the adverse events involved the gastrointestinal tract and were not considered to be a serious problem by the authors. However, the safety of ginger cannot be established on the basis of this trial alone, because of the brief duration of the trial, the limited number of patients, the absence of any laboratory monitoring of renal or hepatic function, and the selection of patients. The withdrawal of a significant number of patients in the treatment group because of gastrointestinal complaints is noteworthy, because this group included only 130 patients who were treated for 6 weeks. Osteoarthritis is a chronic condition, and a realistic evaluation of adverse effects would require a longer treatment period, larger numbers of patients, and monitoring of hematologic, renal, and hepatic function.
It is common for adverse effects of prescription drugs, which may be studied in thousands of patients prior to US Food and Drug Administration approval, to be identified only after the drug is licensed and used by millions of people. Patients were excluded from this trial if they had a history of liver or kidney failure or other serious diseases. The majority of patients with osteoarthritis are in their sixth decade of age or older, they frequently have comorbid conditions, including impaired renal function, and are taking multiple medications. Most people take herbal medications without consultation with health care practitioners, and herbal products are usually sold without any information about potential adverse effects, including possible herb–drug interactions.
In their report (4), the authors cite the absence of published reports about adverse effects of ginger as evidence of its safety, but people may be unaware of the adverse effects of herbs or fail to report them. A recent report from the Office of the Inspector General of the Department of Health and Human Services (7) emphasized the inadequacy of current mechanisms for detecting adverse effects of dietary supplements. A number of herbal medications inhibit platelet function and may be associated with bleeding during surgery or in patients who are receiving anticoagulants (8–10). St. John's wort accelerates the hepatic metabolism of many drugs (11) and it may decrease their concentration below the therapeutic range.
Altman and Marcussen are to be commended for conducting a scientifically designed study to assess the efficacy of a popular herbal preparation. However, because we are concerned that publication of their article in an influential journal may lead to misrepresentation of the results in lay media or in advertisements, our opinion should be clear. We believe that ginger should not be recommended at present for treatment of arthritis because of the limited efficacy shown in this study, its lack of clear efficacy in a previous trial, and the lack of meaningful information about its safety. Alternative therapies should meet the same standards for efficacy and safety as conventional therapies, and ginger has not yet met those standards.