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Antimicrobial Agents and Chemotherapy, January 2001, p. 369-370, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.369-370.2001

LETTERS TO THE EDITOR

Need for Additional, Specific Information in Studies with Echinacea

	LETTER

It was with great interest that I read the June 2000 publication titled "Ineffectiveness of Echinacea for Prevention of Experimental Rhinovirus Colds" (7). Unlike other recently published trials examining the efficacy of echinacea for cold treatment (4, 6), this trial found no significant effect of a 300-mg dose of an echinacea product containing 0.16% cichoric (chicoric) acid and negligible amounts of alkamides and echinacoside, compared to a placebo. This study was unique in that it involved patients inoculated with rhinovirus. Unfortunately, this trial failed to report the echinacea species used, the plant parts used, the formulation, and the method of extraction. We are told a dose of 300 mg was administered, but the reader is left to question whether this is a liquid formulation or a dried extract. If an extract, is it an aqueous or alcoholic extract? The German Commission E has approved the aerial parts of the Echinacea purpurea plant, manufactured as a fresh-pressed juice in 22% ethanol by volume, as a preservative (e.g., Echinacin and Echinaguard) and the roots of the E. pallida plant, manufactured as a water-alcohol extract, for clinical use (2). The root of E. purpurea and the root of E. angustifolia were not approved, due to a lack of clinical trials (2). It is true that recent trials have used a variety of different species and formulations; this information is generally provided in Materials and Methods and helps to discern which types of preparations are most likely to be clinically effective. In the study of Brinkeborn et al., a dried ethanolic extract of E. purpurea (95% herb, 5% root) was shown to significantly reduce cold symptoms compared to placebo, while a root preparation of E. purpurea did not (4). These findings seem to coincide with the German Commission E's recommendation.

Chemical constituents among echinacea species include the lipophilic fractions (e.g., alkamides and polyacetylenes), water-soluble polysaccharides, caffeoyl conjugates (e.g., echinacoside, cichoric acid, and caffeic acid), and flavonoids (3). The alkamides, polysaccharides, and chicoric acid are most often recognized for their immune-modulating effects (8). The concentration of these constituents depends on the species, the plant parts used, and the method of extraction. In the trial reported in June, the percent of cichoric acid is stated and the relative lack of alkamides is addressed, but the presence of polysaccharides is unknown. If the preparation was prepared by alcohol extraction, it is likely that the concentration of polysaccharides would have been lower. Merely knowing the concentration of cichoric acid does not provide sufficient information. Cichoric acid is present in both the above- and the below-ground parts of E. purpurea as well as other species (3). If this was a root preparation of E. purpurea, similar to the one studied by Brinkeborn et al., the observed lack of effectiveness might not be surprising. To date, the evidence for the effectiveness of echinacea for cold treatment appears promising (1, 5). Future studies should provide a detailed description of the herb being used and the method of preparation. This, in turn, will allow future research to focus on those preparations that appear most promising.

	REFERENCES

	AUTHORS' REPLY

We appreciate C. Dennehy's interest in our paper. Our study addressed the efficacy of echinacea when given as a prophylaxis, as opposed to as a treatment, for rhinovirus infection. The results of our study are consistent with recent reports that found no prophylactic effect of echinacea in natural cold models (3, 5). While the results of our study, in which echinacea was continued after onset of illness, also suggest that there was no treatment effect, this question will need to be more directly addressed in a future study.

The echinacea used in our study was labeled as a 4% phenolic extract of a mixture of E. purpurea and E. angustifolia, formulated as a powder and given in a 300-mg dose three times each day. However, we believe that this information is of limited usefulness and may be misleading when designing and reporting the results of a medicinal plant study. As noted by C. Dennehy, the chemical constituents of a given echinacea preparation may be affected by a variety of factors, such as plant species, component part (flower, stem, and/or root), extraction procedure, and final delivery form (tincture, juice, or powder). Thus, assumptions about the chemical composition and ratio of the phytochemical constituents of an echinacea preparation based on current labeling standards are of limited value. To emphasize this point, errors in the identification of echinacea species have been reported (1, 2) and it has recently been suggested that such unanticipated variables as the geographic location where the herb is grown and the time of year it is harvested may impact the final chemical composition (6). Given these multiple (and potentially unknown) influences, it seems preferable that scientific reports provide information about the phytochemical profile of the preparation used.

It should be noted, however, that describing the phytochemical profile is not an attempt to define the active components of echinacea. While various chemical constituents of echinacea have been found to have immunologic and virologic effects, there are no studies that have shown a correlation between any specific chemical constituent or biologic effect and efficacy for prevention or treatment of the common cold. Nonetheless, we believe that it should be possible to identify marker constituents (and ratios of constituents) that correlate with biological activity and allow the generalization of study results to products with similar phytochemical profiles.

Finally, the role of echinacea in either the prevention or the treatment of the common cold remains to be determined. Studies of echinacea for prophylaxis have been generally disappointing; however, it is possible that different preparations with different phytochemical profiles may have a beneficial effect. Although a number of reports have suggested that echinacea may be effective for treatment of the common cold, the design and/or execution of these studies has been criticized and definitive studies remain to be done. Effective clinical trial designs are available for the evaluation of common cold therapies (e.g., see references 4 and 7), and we believe that studies of echinacea preparations using these well-established designs will allow an objective assessment of the effects of different echinacea preparations on the common cold.

	REFERENCES

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