The study by Barrett and colleagues in this issue (2) is a valuable contribution to the literature on echinacea because it addresses many of the shortcomings of earlier studies. Barrett and colleagues assessed the effect of echinacea on the severity and duration of common cold symptoms in a sample of young adults with naturally acquired colds. No effect of echinacea was demonstrated on the overall course and severity of colds or on the severity of individual symptoms. The study had sufficient power to detect a 22% reduction in severity of symptoms, similar to the treatment effect of antihistamines on rhinorrhea or oral adrenergic agents on nasal obstruction. Although this study was carefully done and the results are clear, Barrett and colleagues correctly state that their work will not end the discussion about the efficacy of echinacea for the common cold.

One obstacle to the performance of definitive studies on this issue is the fact that different medicinal preparations of echinacea have different compositions. Three different species of echinacea, each with a different phytochemical composition, are used for medicinal purposes. In addition to the selection of plant species, the composition of the final product may be altered by the part of the plant used, the method of extraction, and even the season in which the plant is harvested. As a result of these effects, variability in phytochemical composition has been described not only among different echinacea preparations but also between lots of the same product (3). It has been suggested that different preparations of echinacea be standardized by measuring specific components, as Barrett and colleagues did. However, given the many variables that influence the composition of the preparations, it may be difficult to reproduce the material used in a particular study even when this information is provided.

Another obstacle to a systematic approach to the study of echinacea is that neither its "active" component nor its mechanism of action for treatment of cold have been defined. Several constituents of echinacea have been evaluated and shown to have various biological effects. The relevance of the reported effects to common cold pathogenesis, however, is not obvious. Extracts of echinacea have been reported to have antiviral activity, but there are no reports of antiviral effects on viral respiratory pathogens (4-8). As noted by Barrett and colleagues, the putative benefit of echinacea for treatment of respiratory infections is frequently attributed to the immunostimulatory properties of the various constituents (9). A growing body of literature, however, suggests that the symptoms of viral respiratory infection are mediated, at least in part, by the host inflammatory responses (10). It is not clear that enhancement of the host response would be expected to have a beneficial effect on symptom severity. Reports of immunosuppressive activity associated with some constituents of echinacea may be more promising with regard to providing a potential mechanism of action (11-13). Unless an active constituent or combination of constituents can be identified or a desired biological activity defined, we cannot address such fundamental issues as dosing, bioavailability, or pharmacokinetics. In the absence of this information, it is difficult to generalize the results of any individual study beyond the specific conditions under which the study was conducted.

Despite these difficulties, the evaluation of echinacea as a treatment for the common cold remains a valid subject for clinical investigation. The common cold is a mild and self-limited illness, but its complications—otitis media, sinusitis, and exacerbations of reactive airway disease—are important medical problems. Treatments that might prevent these complications are of obvious importance. Efforts to identify effective treatments for the common cold have met with limited success, and no treatments have been shown to prevent medically important complications. Given the need for effective therapies, it is difficult to ignore the widespread use of echinacea and the persistence of the anecdotal reports of benefit. As efforts to evaluate this remedy proceed, future studies must incorporate a careful characterization of the phytochemical profile of the study material and an assessment of the effects of treatment on the pathophysiologic processes associated with viral respiratory illness. Although echinacea is characterized as an "alternative" medicine, the usual standards of scientific evidence should be met before its efficacy is accepted by the medical community.