Reviewed: Karsch-Völk M, Barrett B, Kiefer D, Bauer R, Ardjomand-Woelkart K, Linde K. Echinacea for preventing and treating the common cold [published online February 20, 2014]. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD000530.pub3.

Preparations of the echinacea plant of the daisy family (Asteraceae) are used widely to treat or prevent the common cold. Three different species of the genus Echinacea — E. purpurea, E. pallida, and E. angustifolia — are used medicinally. Echinacea preparations vary greatly, utilizing different parts of the plant (fresh or dried root, aerial parts [leaf and/or flower], fresh-pressed juice from aerial parts, and combinations thereof), various manufacturing methods, and other herbs or homeopathic components are sometimes added. The authors of this paper conducted a systematic review to assess whether or not evidence from randomized controlled clinical trials exists to support the efficacy and safety of echinacea preparations compared with placebo in preventing and/or treating the common cold. (Multiple authors have written about the challenge of conducting a meaningful meta-analysis of trials involving echinacea preparations, insofar as the clinical literature is based on so many different types of preparations.1,2)

This review is the third in a series of systematic reviews of clinical trials on echinacea preparations by these authors, the last one of which was published in 2006.3 Since then, “several new trials have been published and evidence may have changed. Therefore, a major update of this review was necessary,” wrote the authors.

Included Trials, Participants, and Preparations

The authors searched numerous databases — including CENTRAL, MEDLINE, Embase, CINAHL, AMED, LILACS, Web of Science, CAMBASE, the Centre for Complementary Medicine Research, WHO ICTRP, and clinicaltrials.gov — screened references, and questioned experts in the field about published and unpublished studies.

The review included placebo-controlled trials of oral echinacea monopreparations with clinical outcome measures related to occurrence, severity and duration of infections, and safety. Both prevention and treatment studies were included. The authors identified 82 papers describing clinical trials that tested echinacea preparations alone or in combination with other plant extracts. Of those, 24 double-blind trials (in 29 publications) with 4,631 participants in total met the inclusion criteria. Those trials comprised 33 comparisons of various echinacea preparations and placebo. (Some clinical trials may use more than one variation of an experimental treatment, which results in multiple “comparisons” in a single study.) Of the 24 trials, 10 (with 13 comparisons) were prevention studies, and 15 (with 20 comparisons) were treatment studies (one trial evaluated both prevention and treatment).

All studies enrolled adults, except for one conducted with child participants. The trials were conducted in the following countries: 12 in the United States, five in Germany, three in Canada, two in Sweden, one in the United Kingdom, and one in Australia. Two trials from the United States and one from Canada were available only as unpublished manuscripts. Rated using the Cochrane “risk of bias” tool, 10 trials were considered to have a low risk of bias, six to have an unclear risk, and eight to have a high risk.

Most of the echinacea preparations used in the trials were of the following compositions: pressed juices stabilized with alcohol (12 trials; made from fresh aerial parts of the plant), alcohol (ethanol) tinctures made from root and/or aerial parts (five trials), or tablets/capsules made from dried extracts of root and/or aerial parts (12 trials).

Analyses and Results

Occurrence of the common cold was investigated in all 10 prevention trials; other outcomes such as the number of participants with more than one cold episode and duration/severity of cold episodes were measured in some of those trials as well.

Subjects with at least one cold episode

Nine prevention trials with 12 comparisons reported the number of participants with at least one cold episode, and three trials with four comparisons reported the number of participants with more than one cold episode. Differences were observed between echinacea and placebo groups in individual trials, while pooling all trials (1,167 total participants) yielded a significant risk reduction (RR=0.83; 95% CI: 0.75-0.92; P<0.001). Results were highly consistent across the studies despite certain asymmetry in the funnel plot (Eggers test; P=0.03). The largest clinical study by Jawad et al4 (n=755; 673 completed) reported total experienced cold episodes under echinacea and placebo prevention rather than patient-related data and came to a similar effect size of 26% with regard to cumulated episodes and total episode days (P<0.05).

Severity and duration

Four prevention trials with five comparisons reported duration of cold episodes. One small four-week trial5 with 32 participants found a significant effect of standardized E. purpurea (plant parts not reported) supplementation over placebo (cold duration of was an average of 5.2 days longer in the placebo group). Effect sizes between all included studies, however, varied considerably.

Data in five prevention trials with seven comparisons were used to calculate the effect of the treatments on severity of cold episodes. A pooled analysis indicated a small beneficial effect of echinacea over placebo.

Of the nine treatment trials with nine comparisons assessing both severity and duration, two trials using E. purpurea preparations of juice from above-ground plant parts (487 total participants) and two trials (184 total participants) using a standardized extract of E. purpurea flower, stem, and root (Echinilin®; Inovobiologic, Inc.; Calgary, Alberta; same as Echinamide®; Natural Factors; Coquitlam, British Columbia) reported conflicting results; only one of these trials found a significantly shorter cold duration in the echinacea group. No significant differences were reported among the other trials (using E. purpurea and/or E. angustifolia).

Adverse side effects

Eight prevention trials (with nine comparisons) included information on subjects’ reported adverse side effects. There were no significant differences recorded except in one study6 (with 111 total participants in the final analysis) that found significantly fewer reported adverse effects in the placebo group. A trend toward fewer adverse effects in the placebo groups compared with the echinacea groups was seen in most of the other prevention trials. In the treatment studies, the number of participants reporting adverse effects did not differ significantly between echinacea and control groups.

Dropout rates

The authors also examined the number of participants who dropped out of studies. Of the prevention trials, seven studies with eight comparisons reported the number of participants who dropped out because of adverse effects (the main outcome measure for safety and acceptability). Two prevention studies4,7 (1,072 total participants) reported a significantly higher dropout rate in the echinacea groups than in the placebo groups. The other trials reported no significant differences in the dropout rates. In a pooled analysis, the authors report that 12.7% of participants in the echinacea groups and 9.0% in the placebo groups dropped out of the prevention studies, which was an insignificant difference (P=0.06).

For the treatment trials, the dropout rates tended to be similar in the echinacea and placebo groups. In 11 trials with 14 comparisons, only three of 1,088 participants who received an echinacea product and none of the 930 participants who received placebo dropped out because of adverse effects.

Conclusions and Recommendations

This review included more treatment trials — investigating whether taking echinacea preparations after the onset of cold symptoms shortened the duration compared with placebo — than prevention trials. While “the overall evidence for clinically relevant treatment effects over placebo is weak,” wrote the authors, some echinacea products may be more effective than placebo for treating colds. The prevention trials showed a trend toward preventive effects of the echinacea interventions, with a “relative risk reduction of 10% to 20%.” The number of participants who dropped out or reported adverse effects did not differ significantly between treatment and control groups in all trials combined.

The current Cochrane analysis by Karsch-VÖlk et al reviewed a total of 24 prevention and acute treatment studies on a large variety of echinacea monopreparations (i.e., no other botanicals or active ingredients were present). Various products prepared from different echinacea species, with different plant parts, and in different forms have been compared with placebo in randomized trials, as reported in this review. “The great heterogeneity of preparations tested makes conclusions difficult,” stated the authors of this review. “The most important recommendation for consumers and clinicians is to be aware that the available Echinacea products differ greatly.”

Acknowledging that further research is needed, the authors cautioned that with the many diverse products on the market, applying the knowledge gained from research is challenging. The use of chemically well-defined preparations is important and will improve researchers’ ability to compare results of future studies. “Echinacea products have not here been shown to provide benefits for treating colds, although, it is possible there is a weak benefit from some Echinacea products,” the authors concluded. “[T]he results of individual prophylaxis trials consistently show positive (if nonsignificant) trends, although potential effects are of questionable clinical relevance.”

Principally, the new Cochrane analysis acknowledges echinacea as having a possible “weak benefit” for cold and flu management. At the same time, it highlights the necessity for chemically characterized, properly manufactured, and clinically researched extracts, since commercially available echinacea products vary considerably.

—Heather S. Oliff, PhD

References

1. Barrett B. New review on echinacea reinvigorates debate on evidence of popular herb’s benefits. HerbalGram. 2006;70:36-39.
2. Brinker F. Echinacea differences matter: traditional uses of Echinacea angustifolia root extracts vs. modern clinical trials with Echinacea purpurea fresh plant extracts. HerbalGram. 2013;97:46-57.
3. Linde K, Barrett B, Wolkart K, Bauer R, Melchart D. Echinacea for preventing and treating the common cold (review). The Cochrane Library. 2006;1:1-39.
4. Jawad M, Schoop R, Suter A, Klein P, Eccles R. Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double-blind, placebo-controlled trial. Evid Based Compl Alternat Med. 2012;2012:841315.
5. Hall H, Fahlmann MM, Engels JH. Echinacea purpurea and mucosal immunity. Int J Sports Med. 2007;28(9):792-797.
6. Zhang X, Lowe D, Badesha G, et al. A double-blinded trial evaluating the effectiveness of Echinacea in countering upper respiratory tract infections. 2003. [Unpublished report.]
7. Turner RB, Bauer R, Woelkart K, Hurley TC, Gangemi D. An evaluation of Echinacea angustifolia in experimental rhinovirus infections. N Engl J Med. 2005;353(4):341-348.