Clinical Briefs: Echinacea: Another Negative Trial

With Comments from Russell H. Greenfield, MD

Dr. Greenfield is Medical Director, Carolinas Integrative Health, Carolinas HealthCare System, Charlotte, NC, and Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC.

Source: Turner RB, et al. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med 2005; 353:341-348.

Goal: To evaluate the effects of different chemical constituents from E. angustifolia on rhinovirus infection and symptoms of the common cold in healthy young adults.

Design: Randomized, placebo-controlled, double-blind prospective cohort trial.

Subjects: Volunteers (n = 437) who upon testing were susceptible to rhinovirus type 39 (data available for analysis from 399 subjects).

Methods: Prospective subjects were tested for sensitivity to rhinovirus 39 (serum neutralizing antibody titer £ 1:4) and then randomized to prophylaxis (beginning seven days before virus exposure) or treatment (virus exposure to day 5) groups with one of three chemically distinct preparations of E. angustifolia root or placebo. There were seven treatment groups: one of three preparations offered during both prophylaxis and treatment phases, or placebo offered during the prophylaxis phase and one of three extracts employed during treatment phase, or the control group that received placebo during both phases. After direct nasal challenge with the rhinovirus, subjects were isolated in individual hotel rooms for five days. Treatment was offered three times daily as 1.5 cc of tincture containing the equivalent of 300 mg echinacea root (900 mg /d). Symptom scores were evaluated every morning and evening, and nasal lavage was performed every morning (to detect unsuspected viral infections, rhinovirus type 39, and to measure interleukin-8 and leukocyte concentrations).

Results: No statistically significant treatment effects were identified for any one of the three E. angustifolia extracts.

Conclusions: Specified extracts of E. angustifolia root provide no clinically significant benefit with regard to infection with a rhinovirus and the symptoms associated with the common cold.

Study strengths: Methodologically sound trial (save for dosage employed), including antibody testing before virus challenge and isolation after exposure; repeated analyses of study treatments to ensure consistency; compliance.

Study weaknesses: Employed subtherapeutic dosage of echinacea material (critical flaw).

Of note: Conventional medical practice offers no effective antiviral treatment against rhinoviruses; while rhinoviruses cause an estimated 40% of all colds, there are numerous subtypes of rhinovirus (> 100), and other viruses known to cause the common cold include coronaviruses, respiratory syncytial virus, and adenovirus (that stated, the model used in this study has accurately predicted response to treatment in other studies); the various preparations (extracted with supercritical CO2, 60% or 20% ethanol) came from a single lot of E. angustifolia root; the more typical dose of E. angustifolia root is close to 3 g daily.

We knew that: Multiple studies on the efficacy of echinacea have been published and have produced conflicting results; at least three different species of echinacea, with different phytochemical characteristics, are used clinically (E. pallida var angustifolia, E. purpurea, and E. pallida var pallida), with E. purpurea being used most commonly in the United States; variability in phytochemical composition has led to efforts to isolate and standardize active participles; polysaccharides, derivatives of caffeic acid, and alkamides present have all been shown to possess biologic activity in vitro and in vivo and are presumed to represent the active participles in echinacea; extraction procedures, manufacturing techniques, plant parts used, geography, and time of plant harvesting impact the chemical constituents found within an echinacea product; there is a known correlation between cold symptom severity and level of interleukin-8 and polymorphonuclear-leukocyte response.

Clinical import: This study is very well done save for the major complicating factor of the low dosage of material used (again, the typical recommended dosage of echinacea is three times higher than that employed in the trial). The results show that a subtherapeutic dosage of the specified extracts of E. angustifolia offer no benefit over placebo in preventing or treating the common cold, adding little to our understanding of echinacea’s benefits or lack thereof. The authors rightly state that it will be difficult to conclusively prove that echinacea has no benefit in the treatment of the common cold in light of the wide variety of echinacea preparations available. It is possible that higher doses may be effective, that some people respond to echinacea while others do not, and that other constituents, or the natural milieu of the constituents, play a significant role in the effectiveness of echinacea against the common cold, if there be any. Even against the background of the lack of conventional treatment against the common cold, however, the authors are likewise correct in stating the burden of proof should lie with those advocating the use of echinacea.

Unfortunately, as evidenced in the accompanying editorial by a longtime unapologetic critic of integrative medicine, there are those who would use evidence of ineffectiveness specific to a given therapy as evidence of the lack of efficacy for all of complementary and alternative medicine (CAM). To extrapolate the findings of a single echinacea study to protest against the use of any CAM therapy is as misguided as equating COX-2 inhibitors with all prescription aids. Those promoting themselves as possessors of singular wisdom enabling clear discernment of what is implausible do a disservice to science. A scientist observes an association between intervention and effect, and develops a hypothesis that can then be tested, with results serving to support or refute that hypothesis. Fixed perceptions are often fixed misperceptions, and a knee-jerk dismissal of data (either for or against an intervention) rarely serves the common good let alone the balanced appraisal of evidence, the goal to which this publication aspires. Those putting limits on what is “plausible” would have curtailed previous work that has proven revolutionary in health care, including the discovery of the association between peptic ulcer disease and the microbe Helicobacter pylori. Fundamentalism in any form can prove dangerous and has no place in modern health care, nor in the pages of The New England Journal of Medicine.

What to do with this article: Remember that you read the abstract.