Echinacea angustifolia in Rhinovirus Infections
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《新英格兰医药杂志》
To the Editor: The trial by Turner et al. (July 28 issue)1 could have benefited from the inclusion of additional treatment groups with higher daily doses of echinacea. The dose equivalent of 900 mg of dried root derives from the German Commission E monograph for Echinacea pallida root, a different species from E. angustifolia.2 E. angustifolia root is not officially approved and thus has no recommended dosage in Germany, owing to a lack of sufficient supporting data. The 1999 World Health Organization monograph on E. angustifolia root cites a 3-g daily dose, which is 330 percent of the dose used in this trial.3 The 3-g daily dose is also recommended by the Canadian Natural Health Products Directorate.4
Outcomes of rigorously designed clinical trials usually pertain only to the specific variables of such trials. A higher dosage, approximating the levels used by many consumers and recommended by many alternative health care providers, might have made this trial more relevant to the real-world use and potential benefits of echinacea.
Mark Blumenthal
American Botanical Council
Austin, TX 78714
mark@herbalgram.org
Norman R. Farnsworth, Ph.D.
University of Illinois at Chicago
Chicago, IL 60612
References
Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med 2005;353:341-348.
Blumenthal M, Busse WR, Goldberg A, Hall T, Riggins CW, Rister RS, eds. The complete German Commission E monographs: therapeutic guide to herbal medicines. Klein S, Rister RS, trans. Austin, Tex.: American Botanical Council, 1998.
Echinacea radix. In: WHO monographs on selected medicinal plants. Geneva: World Health Organization, 1999.
Health Canada. Echinacea: natural health products directorate. Draft January 2004. (Accessed October 13, 2005, at http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodnatur/mono_echinacea_pallida_e.pdf.)
To the Editor: Turner et al. recently reported the results of a trial that evaluated the efficacy of E. angustifolia in the prevention and treatment of experimental rhinovirus type 39 infection. Although the trial was well designed and adequately powered, there are several caveats that need to be highlighted. First, there was no evidence that the herb used was E. angustifolia, given that product identification and validation tests, such as chromatography, were not performed. Second, there was some confusion as to whether the product was an extract or a tincture and, therefore, some uncertainty about the strength of the formulation. Hence, it is difficult to ascertain whether the administered dose of echinacea was adequate. Finally, the authors inappropriately conclude that echinacea is ineffective in the treatment of rhinovirus infection, with only 1 of more than 100 subtypes of rhinovirus having been tested. Thus, any claim that echinacea is ineffective in the prophylaxis and treatment of the common cold cannot be validated without further tests to determine the efficacy of the extract on other viral agents.
Matthew Leach, R.N.
University of South Australia
Adelaide SA 5001, Australia
matthew.leach@unisa.edu.au
The authors reply: The details regarding the identification and phytochemical characterization of E. angustifolia requested by Mr. Leach were provided as online supplementary material to our publication. This appendix is available on the Journal's Web site (www.nejm.org) and provides detailed information about the "strength" of the three formulations as defined according to the concentrations of various polysaccharides and alkamides.
The use of a single rhinovirus serotype in the challenge model is one of many variables that were controlled in the study, as compared with studies performed in the natural setting. The controlled conditions of our model have generally resulted in larger effect sizes and increased sensitivity in the detection of treatment effects than have studies involving the use of natural-infection models.1,2,3,4 We are not aware of examples of treatments that were effective in natural models but had negative results in adequately designed studies involving the experimental model. It is possible, however, that different treatment effects might have been detected under different experimental conditions.
The suggestion that a higher dose of echinacea might have produced different results raises important issues about the study and the use of herbal products. The dosage recommendations cited by Mr. Blumenthal and Dr. Farnsworth do not appear to be based on experimental or pharmacokinetic data. Furthermore, it is not clear how the dose of echinacea should be measured and interpreted. As demonstrated in our study, the same root-equivalent dose of echinacea can be extracted in different ways to produce dramatically different "doses" of the different phytochemical constituents. The lack of standardization of products, the absence of definitive information about the mechanism of action or the active constituents, and the limited pharmacokinetic data regarding the various constituents preclude a meaningful discussion of an appropriate dosing regimen.
Implicit in the comments of these correspondents is an assumption that, had the study been designed or executed differently, a beneficial effect of echinacea would have been demonstrated. Given the available data, we believe it is most reasonable to conclude that echinacea is not useful as a treatment for the common cold. This conclusion should stand until those who promote, manufacture, and sell these products produce convincing evidence of a clinically meaningful benefit.
Ronald B. Turner, M.D.
University of Virginia School of Medicine
Charlottesville, VA 22908
rbt2n@virginia.edu
J. David Gangemi, Ph.D.
Clemson University
Clemson, SC 29634
References
Gwaltney JM Jr, Buier RM, Rogers JL. The influence of signal variation, bias, noise and effect size on statistical significance in treatment studies of the common cold. Antiviral Res 1996;29:287-295.
Gwaltney JM Jr, Park J, Paul RA, Edelman DA, O'Connor RR, Turner RB. Randomized controlled trial of clemastine fumarate for treatment of experimental rhinovirus colds. Clin Infect Dis 1996;22:656-662.
Turner RB, Cetnarowski WE. Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 2000;31:1202-1208.
Turner RB, Sperber SJ, Sorrentino JV, et al. Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold. Clin Infect Dis 1997;25:824-830.
Outcomes of rigorously designed clinical trials usually pertain only to the specific variables of such trials. A higher dosage, approximating the levels used by many consumers and recommended by many alternative health care providers, might have made this trial more relevant to the real-world use and potential benefits of echinacea.
Mark Blumenthal
American Botanical Council
Austin, TX 78714
mark@herbalgram.org
Norman R. Farnsworth, Ph.D.
University of Illinois at Chicago
Chicago, IL 60612
References
Turner RB, Bauer R, Woelkart K, Hulsey TC, Gangemi JD. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med 2005;353:341-348.
Blumenthal M, Busse WR, Goldberg A, Hall T, Riggins CW, Rister RS, eds. The complete German Commission E monographs: therapeutic guide to herbal medicines. Klein S, Rister RS, trans. Austin, Tex.: American Botanical Council, 1998.
Echinacea radix. In: WHO monographs on selected medicinal plants. Geneva: World Health Organization, 1999.
Health Canada. Echinacea: natural health products directorate. Draft January 2004. (Accessed October 13, 2005, at http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodnatur/mono_echinacea_pallida_e.pdf.)
To the Editor: Turner et al. recently reported the results of a trial that evaluated the efficacy of E. angustifolia in the prevention and treatment of experimental rhinovirus type 39 infection. Although the trial was well designed and adequately powered, there are several caveats that need to be highlighted. First, there was no evidence that the herb used was E. angustifolia, given that product identification and validation tests, such as chromatography, were not performed. Second, there was some confusion as to whether the product was an extract or a tincture and, therefore, some uncertainty about the strength of the formulation. Hence, it is difficult to ascertain whether the administered dose of echinacea was adequate. Finally, the authors inappropriately conclude that echinacea is ineffective in the treatment of rhinovirus infection, with only 1 of more than 100 subtypes of rhinovirus having been tested. Thus, any claim that echinacea is ineffective in the prophylaxis and treatment of the common cold cannot be validated without further tests to determine the efficacy of the extract on other viral agents.
Matthew Leach, R.N.
University of South Australia
Adelaide SA 5001, Australia
matthew.leach@unisa.edu.au
The authors reply: The details regarding the identification and phytochemical characterization of E. angustifolia requested by Mr. Leach were provided as online supplementary material to our publication. This appendix is available on the Journal's Web site (www.nejm.org) and provides detailed information about the "strength" of the three formulations as defined according to the concentrations of various polysaccharides and alkamides.
The use of a single rhinovirus serotype in the challenge model is one of many variables that were controlled in the study, as compared with studies performed in the natural setting. The controlled conditions of our model have generally resulted in larger effect sizes and increased sensitivity in the detection of treatment effects than have studies involving the use of natural-infection models.1,2,3,4 We are not aware of examples of treatments that were effective in natural models but had negative results in adequately designed studies involving the experimental model. It is possible, however, that different treatment effects might have been detected under different experimental conditions.
The suggestion that a higher dose of echinacea might have produced different results raises important issues about the study and the use of herbal products. The dosage recommendations cited by Mr. Blumenthal and Dr. Farnsworth do not appear to be based on experimental or pharmacokinetic data. Furthermore, it is not clear how the dose of echinacea should be measured and interpreted. As demonstrated in our study, the same root-equivalent dose of echinacea can be extracted in different ways to produce dramatically different "doses" of the different phytochemical constituents. The lack of standardization of products, the absence of definitive information about the mechanism of action or the active constituents, and the limited pharmacokinetic data regarding the various constituents preclude a meaningful discussion of an appropriate dosing regimen.
Implicit in the comments of these correspondents is an assumption that, had the study been designed or executed differently, a beneficial effect of echinacea would have been demonstrated. Given the available data, we believe it is most reasonable to conclude that echinacea is not useful as a treatment for the common cold. This conclusion should stand until those who promote, manufacture, and sell these products produce convincing evidence of a clinically meaningful benefit.
Ronald B. Turner, M.D.
University of Virginia School of Medicine
Charlottesville, VA 22908
rbt2n@virginia.edu
J. David Gangemi, Ph.D.
Clemson University
Clemson, SC 29634
References
Gwaltney JM Jr, Buier RM, Rogers JL. The influence of signal variation, bias, noise and effect size on statistical significance in treatment studies of the common cold. Antiviral Res 1996;29:287-295.
Gwaltney JM Jr, Park J, Paul RA, Edelman DA, O'Connor RR, Turner RB. Randomized controlled trial of clemastine fumarate for treatment of experimental rhinovirus colds. Clin Infect Dis 1996;22:656-662.
Turner RB, Cetnarowski WE. Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds. Clin Infect Dis 2000;31:1202-1208.
Turner RB, Sperber SJ, Sorrentino JV, et al. Effectiveness of clemastine fumarate for treatment of rhinorrhea and sneezing associated with the common cold. Clin Infect Dis 1997;25:824-830.