Bruce Barrett, MD, PhD Monica Vohmann, MD Carlo Calabrese, ND, MPH Madison, Wisconsin, and Seattle, Washington Submitted, revised, February 25, 1999. From the Department of Family Medicine, University of Wisconsin-Madison (B.B., M.V.) and Bastyr University, Seattle (C.C.). Requests for reprints should be addressed to Bruce Barrett, MD, PhD, Department of Family Medicine, University of Wisconsin-Madison, 777 S Mills, Madison, WI 53715. E-mail: bbarrett@fammed.wisc.edu.
References
Forth and colleagues58 reported a study of 95 patients with URIs randomized to either Esberitox liquid, Esberitox tablet, or identical placebo. Participants took treatments 3 times daily from November until late February, filling out incidence and severity questionnaires every 14 days. A relative risk reduction of 38% (P <.005) was reported for nasal symptoms in the Echinacea tablet group compared with placebo. Other outcomes were reported as similar in all groups.
Data collection for a trial designed to study the efficacy of Echinacea for URI prevention was recently completed at Bastyr University in Seattle, Washington. Subjects who had experienced at least 3 respiratory infections in the 6 months before enrollment were treated with 8 mL E purpurea juice on an intermittent basis over 6 months and were followed in terms of incidence of URI and severity and duration of symptoms. Granolocyte and monocyte phagocytosis differences were assessed using an ex vivo laboratory model. Data analysis is currently under way, with results forthcoming.
Another prevention trial is under way at Oregon Health Sciences University. Explicit methods are not available.
Discussion
In the treatment of acute URI, 8 of 9 randomized trials report some evidence of benefit of Echinacea. Although we attempted to review all trials, including those that were not yet published, we only located 1 unpublished trial, which reported a negative result; therefore, the influence of publication bias remains unknown. Although there is a moderate degree of methodologic deficiency in all of the reviewed studies, and statistical significance is not reached for all outcomes, the published evidence supports the ability of Echinacea to decrease the severity and duration of acute URI. This evidence is not conclusive, however, and higher quality trials are needed. Future trials should include: (1) larger, more representative populations; (2) more precisely defined inclusion and exclusion criteria; (3) more precisely defined objective and validated outcomes measurement; (4) data to verify the inability of participants to distinguish placebo from drug; and (5) better characterization of the active constituents and mechanism of action.
Nevertheless, the current evidence suggests that Echinacea may work as an early treatment for uncomplicated acute URI. Hoheisel and coworkers65 reported a 50% reduction in the proportion of people with first sign of a cold who went on to have a “real cold” (from 60% to 40%). Of those subjects who had a “real cold,” those taking Echinacea had markedly shorter lengths of illness (from a median duration of 8 days to a median duration of 4 days). Brinkeborn and colleagues66 reported a modest but statistically significant reduction in severity in what appears to be a moderately well-designed trial. The study by Dorn57 and the 2 studies by Bräunig and coworkers55,56 reported comparable clinical benefits, with 20% to 50% reductions in severity claimed. We interpret evidence from the highest quality trials to suggest that early dosing is important,67 as is sufficient dosing.55 The clinical significance of expected benefits cannot be precisely estimated.
The evidence for Echinacea’s ability to prevent rather than treat URI is not as promising. Published studies are few, of moderate quality, and report trends rather than statistically significant differences.58,60,61 The most recent and best designed of these prevention trials reported nonsignificant trends toward benefits consistent with a 10% to 20% reduction in incidence.68 We feel that the safety of long-term prophylactic dosing has not been sufficiently demonstrated, at least when valued against uncertain trends toward minor benefit. Neither expected benefits nor risks have been characterized properly, so no recommendations on preventive treatment can be made.
Despite equivocal clinical effects, the safety data on Echinacea are relatively strong, at least when compared with many other herbal medicines. In oral doses greater than 15 g per kg and intravenous doses greater than 5 g per kg, it has proved impossible to kill either a rat or a mouse, hence median lethal dose is so far incalculable.67 Extended (4-week) dosing of rats and mice up to 8 g per kg per day has similarly failed to show adverse effects, with red blood cells, white blood cells, platelets, liver enzymes, creatinine, urea, cholesterol, triglycerides, blood glucose, and body weight as measured end points.69 In a number of mutagenicity studies, no adverse effects were noted. An open-label trial with more than 1000 patients found the following side effects: unpleasant taste (1.7%), nausea or vomiting (0.5%), abdominal pain (0.3%), and diarrhea (0.3%).29 During the years 1989 to 1995, 4 of 13 adverse events reported in association with Echinacea were thought to be causally related by the German authority. When compared with a denominator of several million patient courses, the reported adverse effect rate, and hence the estimated risk, is quite small. Serious allergic or anaphylactic events have been reported, however, so some caution is needed.70
