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
Reitz59 described the results of a trial of Esberitox-N among 150 participants with respiratory infections. Esberitox-N is a commercial preparation containing extracts from E angustifolia and E pallida roots, along with small amounts of Baptisia and Thuja occidentalis extracts. Participants were randomized to treatment or placebo (containing Vitamin C) for 8 weeks and were followed in a double-blinded manner for approximately 1 year. Outcomes measured at 7 and 14 days and monthly thereafter included 8 symptoms, 3 signs, and blood work, including a complete blood cell count and an immunoglobulin measurement. Reitz reported that the majority of symptoms and signs at 7 and 14 days were significantly better in the Esberitox group than with placebo, but provided little statistical analysis to support this claim. Relative improvements in nasal symptoms were noted most prominently. No differences in laboratory measurements were reported.
The 1984 trial by Vorberg62 included 100 participants treated with either vitamin C as placebo or Esberitox. In addition to the ingredients in Esberitox-N, Esberitox contains homeopathic dilutions of Apis, Crotal, Silicea, and Lachesis. Outcomes were self-reported symptoms and physician-reported signs, all assessed on a 0 to 3 scale of severity at days 3 and 10. Headache (P <.001), cough (P <.05), and subfebrile temperature (P <.01) differed significantly, favoring the Esberitox over the vitamin C group. Fatigue, sore throat, difficulty swallowing, nasal drainage, and physician-reported pharyngeal erythema and edema all trended toward benefit in the Esberitox group.
Of the 13 studies we reviewed, the one by Galea and Thacker64 was singular because it reported no measurable benefit, was conducted in North America, and so far remains unpublished. This study treated a total of 190 undergraduate Canadian students with either placebo or a 250-mg capsule preparation of dried E angustifolia 3 times per day. Participants were recruited at first sign of URI and followed up by presence or absence of 8 symptoms for 10 days. No clear trends or statistically significant differences were found between the Echinacea and placebo groups. The relatively low dose and the lack of measures of severity may account for these negative findings.
A treatment trial of a capsulized mixture of dried powder made from the herb (25%) and root (25%) of E purpurea and the root of E angustifolia (50%) is currently under way at the Department of Family Medicine at the University of Wisconsin-Madison. Participants are recruited within 36 hours of first symptoms of URI. Capsulized dried plant material is taken in 1 g doses, 6 times on the first day and 3 times on each subsequent day. Symptom-based outcomes are measured daily using Likert-scale severity measures.
Prevention Trials
Melchart and colleagues68 conducted a 3-arm prevention trial in which 302 volunteers took 50 drops of either placebo or 1 of 2 alcohol extracts from the root of either E angustifolia or E purpurea twice daily for 12 weeks. This was the first head-to-head trial of Echinacea preparations. Median time to onset of first URI was similar among the 3 groups. Compared with placebo, the relative risk of an infection was 0.80 in the E purpurea group and 0.87 in the E angustifolia group. These differences were not statistically significant, hence the null hypothesis that Echinacea is no better than placebo at preventing URI could not be rejected. The authors speculated that a larger study might be able to show an effect, as their study did not have the power to demonstrate a hypothetical 10% to 20% relative risk benefit.
Schöneberger and coworkers61 conducted a trial in which 108 patients “with increased susceptibility to colds” were divided into treatment and placebo groups and followed for 8 weeks. Doses of 4 mL juice from the above-ground parts of E purpurea (Echinacin or Echinagard) were given twice daily for the entire 8-week period. The treatment group had 19 people (35%) without infections compared with 14 (26%) in the placebo group. Average duration of infection was 5.3 days in the treatment group compared with 7.5 days in the placebo group. When infections were grouped into 3 classes according to severity, the treatment group had fewer individuals in all 3 classes (33 vs 34 in mild; 8 vs 13 in moderate; 0 vs 3 in severe). Although these results were not statistically significant, all trends reported were in favor of Echinacea treatment. Grimm and Muller’s 1999 analysis and interpretation of this trial65 was less optimistic than Schöneberger’s original report.
Schmidt and colleagues60 reported a trial of Resistan as prevention of URI among 646 college students at the University of Cologne. Resistan was taken daily for 8 weeks, and students were monitored every 2 weeks and during each URI or flu-like infection. The symptoms assessed on a 0 to 3 scale were cough, sore throat, difficulty swallowing, nasal drainage, congestion, headache, muscle aches, and fatigue. Overall frequency of infection was 15% lower in the Echinacea group than in the placebo group, trending toward statistical significance (P = .08). A subgroup analysis of those patients judged to be especially prone to infection (3 or more colds per year for each of the previous 3 years) showed a statistically significant (P <.05) relative risk reduction in verum (27%) compared with placebo (15%).
