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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 |
| 1.
|
Barrett, B.,
M. Vohmann, and C. Calabrese.
1999.
Echinacea for upper respiratory tract infection.
J. Fam. Pract.
48:628-635[Medline].
|
| 2.
|
Blumenthal, M.,
A. Goldberg, and J. Brinckmann (ed.).
2000.
Herbal medicine: the expanded German Commission E monographs.
American Botanical Council, Integrative Medicine Communications, Newton, Mass.
|
| 3.
|
Bone, K.
1997.
Echinacea: what makes it work?
Alt. Med. Rev.
2:87-93.
|
| 4.
|
Brinkeborn, R. M.,
D. V. Shah, and F. H. Degenring.
1999.
Echinaforce and other echinacea fresh plant preparations in the treatment of the common cold.
Phytomedicine
6:1-5[Medline].
|
| 5.
|
Melchart, D.,
K. Linde,
P. Fischer, et al.
1999.
Echinacea for preventing and treating the common cold (protocol for a Cochrane review).
The Cochrane Library, Oxford, United Kingdom.
|
| 6.
|
O'Hoheisel, M. D.,
S. Sandberg,
M. Bulitta, et al.
1997.
Echinaguard treatment shortens the course of the common cold: a double-blind, placebo-controlled trial.
Eur. J. Clin. Res.
9:261-268.
|
| 7.
|
Turner, R. B.,
D. K. Riker, and J. D. Gangemi.
2000.
Ineffectiveness of echinacea for prevention of experimental rhinovirus colds.
Antimicrob. Agents Chemother.
44:1708-1709[Abstract/Free Full Text].
|
| 8.
|
Wagner, H.
1997.
Herbal immunostimulants for the prophylaxis and therapy of colds and influenza.
Eur. J. Herb. Med.
3:22-30.
|
| | | | |
Cathi Dennehy
UCSF, Division of Clinical Pharmacy
San Francisco, California 94143-0622
Phone: (415) 476-2862
Fax: (415) 476-6632
E-mail:
cathi{at}itsa.ucsf.edu
|
| |
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 |
| 1.
|
Bauer, R.,
I. A. Khan,
H. Lotter,
H. Wagner, and V. Wray.
1985.
Structure and stereochemistry of new sesquiterpene esters from Echinacea purpurea (L.) MOENCH.
Helv. Chim. Acta
68:2355-2358[CrossRef].
|
| 2.
|
Bauer, R.,
I. A. Khan, and H. Wagner.
1988.
TLC and HPLC analysis of Echinacea pallida and E. angustifolia roots.
Planta Med.
54:426-430[Medline].
|
| 3.
|
Grimm, W., and H. H. Muller.
1999.
A randomized controlled trial of the effect of fluid extract of Echinacea purpurea on the incidence and severity of colds and respiratory infections.
Am. J. Med.
106:138-143[CrossRef][Medline].
|
| 4.
|
Gwaltney, J. M., Jr.,
J. Park,
R. A. Paul,
D. A. Edelman,
R. R. O'Connor, and R. B. Turner.
1996.
Randomized controlled trial of clemastine fumarate for treatment of experimental rhinovirus colds.
Clin. Infect. Dis.
22:656-662[Medline].
|
| 5.
|
Melchart, D.,
E. Walther,
K. Linde,
R. Brandmaier, and C. Lersch.
1998.
Echinacea root extracts for the prevention of upper respiratory tract infections: a double-blind, placebo-controlled randomized trial.
Arch. Fam. Med.
7:541-545[Abstract/Free Full Text].
|
| 6.
|
Shalaby, A.,
E. A. Angina, and A. S. El-Gengaihi.
1997.
Response of Echinaceae to some agricultural practices.
J. Herbs Spices Med. Plants
6:34-35.
|
| 7.
|
Turner, R. B.,
S. J. Sperber,
J. V. Sorrentino,
R. R. O'Connor,
J. Rogers,
A. R. Batouli, and J. M. Gwaltney, Jr.
1997.
Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold.
Clin. Infect. Dis.
25:824-830[Medline].
|
| | | | |
Ronald B. Turner
Department of Pediatrics
Medical University of South Carolina
Charleston, South Carolina
|
| | | | |
J. David Gangemi
Department of Medicine
Medical University of South Carolina
Charleston, South Carolina
|
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
