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Echinacea is one of the most commonly used herbal products, but controversy exists about its benefit in the Lancet Infect Dis 2007; 7:
prevention and treatment of the common cold. Thus, we did a meta-analysis evaluating the effect of echinacea on 473–80
the incidence and duration of the common cold. 14 unique studies were included in the meta-analysis. Incidence of University of Connecticut
School of Pharmacy, Storrs, CT,
the common cold was reported as an odds ratio (OR) with 95% CI, and duration of the common cold was reported
USA (S A Shah PharmD,
as the weighted mean difference (WMD) with 95% CI. Weighted averages and mean differences were calculated by S Sander PharmD,
a random-effects model (DerSimonian-Laird methodology). Heterogeneity was assessed by the Q statistic and C M White PharmD,
review of L’Abbé plots, and publication bias was assessed through the Egger weighted regression statistic and visual M Rinaldi PharmD,
C I Coleman PharmD);
inspection of funnel plots. Echinacea decreased the odds of developing the common cold by 58% (OR 0·42; 95% CI University of Connecticut
0·25–0·71; Q statistic p<0·001) and the duration of a cold by 1·4 days (WMD –1·44, –2·24 to –0·64; p=0·01). Health Center Division of
Similarly, significant reductions were maintained in subgroup analyses limited to Echinaguard/Echinacin use, Infectious Diseases,
concomitant supplement use, method of cold exposure, Jadad scores less than 3, or use of a fixed-effects model. Farmington, CT, USA
(M Rinaldi); and Division of
Published evidence supports echinacea’s benefit in decreasing the incidence and duration of the common cold. Drug Information, Hartford
Hospital, Hartford, CT, USA
Introduction Melchart and colleagues13 concluded that echinacea (S A Shah, S Sander, C M White,
According to the National Institute of Allergy and preparations from the aerial part of the plant were C I Coleman)
Infectious Diseases, the US population has 1 billion colds effective for the treatment of colds but the evidence for Correspondence to:
Dr Craig I Coleman,
annually. Adults have between two and four colds per the prevention of a cold was lacking.13 It is important to
University of Connecticut School
year, whereas children have between six and ten colds.1 note, however, that this review excluded studies using an of Pharmacy, Hartford Hospital,
Although rhinovirus and coronavirus are the most experimental rhinovirus infection and echinacea 80 Seymour Street,
common viruses precipitating cold symptoms, preparations with supplements, and it did not include a CB 309 Hartford, CT 06102, USA.
Tel +1 860 545 2096;
approximately 200 other viruses are also known to cause more recent study by Turner and colleagues.14 We fax +1 860 545 2277;
the common cold. In the USA, about 40% of lost work therefore did a meta-analysis evaluating the effect of ccolema@harthosp.org
time and 30% of time lost from school are attributed to echinacea on the incidence and duration of the common
symptoms caused by the common cold.2 The common cold in randomised placebo-controlled studies.
cold is also associated with a large financial burden on
society, with about US$1·5 billion spent annually for Methods
physicians’ visits and another $2 billion spent on non- Search strategy and selection criteria
prescription cough and cold treatments.3 A literature search using the terms “Echinacea” and
In 2002, approximately 20% of the adult US population “Purple coneflower” (limited to human beings and
used nutraceuticals (herbal products, functional foods, clinical trials) was done by three independent reviewers
animal based supplements). Echinacea, a collection of (SAS, CMW, and CIC) using Medline (1966 to April,
nine related plant species indigenous to North America,
was the most common nutraceutical used and was
consumed by over 40·3% of these people.4,5 Echinacea
angustifolia, Echinacea pallida, and Echinacea purpurea
(figure 1) are the most common species recognised for
their medicinal value.6 The mechanism of action
underlying the proposed immunostimulatory effects of
echinacea remains unclear. Some evidence suggests that
upregulation of tumour necrosis factor-α mRNA, which is
stimulated by agonistic activity of the cannabinoid receptor
(CB2) by alkamides present in echinacea, has a role.7
The German Commission E, WHO, and the Canadian
Natural Health Products Directorate have advocated
Maxine Adcock/Science Photo Library
Patient Echinacea species Use of Concomitant Dose Virus exposure Duration Jadad
population Echinaguard or supplement score
Echinacin
Turner et al (2005)14 Healthy E angustifolia No No Three times a day equivalent to Inoculation with 7 days pre and 5 days 4
volunteers 900 mg/day rhinovirus 39 post-inoculation
Cohen et al (2004)28 Healthy E purpurea/ No Vitamin C, 5 mL twice a day for ages 1–3 years, Natural 12 weeks 5
volunteers, E angustifolia propolis 7·5 mL twice a day for ages 4–5
children years. Increase to four times a day
during episode flare only
Sperber et al (2004)22 Healthy E purpurea Echinaguard No 2.5 mL three times a day Inoculation with 7 days pre and 5 days 4
volunteers rhinovirus 39 post-inoculation
Taylor et al (2003)32 Active cold, E purpurea No No 3·75 mL twice a day for ages Natural 10 days 5
children 2–5 years and 5 mL twice a day
for ages 6–11 years
Barrett et al (2002)20 Active cold E purpurea/ No Thyme, 6 g on day 1 and 3 g on Natural 10 days 5
E angustifolia peppermint, citric subsequent days
acid
Schulten et al (2001)23 Healthy E purpurea Echinacin No 5 mL twice a day Natural At first sign of cold for 5
volunteers 10 days
Turner et al (2000)31 Healthy Not specified No No 300 mg three times a day Inoculation with 14 days pre and 5 days 1
volunteers rhinovirus 23 post-inoculation
Lindenmuth and Active cold E purpurea/ No Lemongrass leaf, Five to six bags per day titrated Natural 12 weeks 3
Lindenmuth (2000)29 E angustifolia spearmint down to one bag on day 5
Grimm and Muller Healthy E purpurea Echinacin No 4 mL twice a day Natural 8 weeks 5
(1999)24 volunteers
Berg (1998)25 Healthy E purpurea Echinacin No 8 mL/day Natural 28 days 1
volunteers
Melchart et al Healthy E purpurea/ No No 50 drops twice a day for 12 weeks Natural 12 weeks 5
(1998)15 volunteers E angustifolia
Hoheisel et al (1997)27 Healthy E purpurea Echinaguard No 20 drops every 2 h in water on Natural At first sign of cold for 5
volunteers day 1 followed by three times a 10 days
day for 9 days
Scaglione and Lund Active cold E purpurea No Vitamin C, Four tablets daily equivalent to Natural For duration of the cold 2
(1995)30 rosemary leaf, 100 mg/day
eucalyptus,
fennel seed
Braunig and Knick Active cold E pallida No No 90 drops equivalent to 900 mg/ Natural 8–10 days 3
(1993)16 day
NA=not applicable. *Data shown as number of events/total population. †Reported data is number of cold episodes, not number of patients with cold. ‡Reported data as difference
of –0·52 days, 95% CI –1·09 to –0·22.
active ingredients contained in various products. A study internal validity but could reduce external validity of the
that evaluated echinacea preparations available in a retail analysis. Additionally, the selection of a random versus
setting showed that six (10%) of 59 preparations contained fixed-effect model in meta-analyses is controversial. The
no measurable echinacea.21 Furthermore, only nine (43%) use of a random-effect model in the calculation of
of 21 standardised preparations met the quality standards confidence intervals results in wider intervals and thus a
as described on the label.21 Five studies in this meta-analysis more conservative estimate of treatment effect compared
included an E purpurea product extracted in 22% alcohol with a fixed-effect model. To reconcile these issues,
(Echinaguard and Echinacin, Madaus AG, Cologne, sensitivity analysis was done, in which the meta-analysis
Germany).22–27 As such, an analysis of benefit using these was reanalysed excluding studies of weaker methodology
two products was done in a subgroup. Finally, studies (Jadad score less than 3) and using a fixed-effects model
included in this meta-analysis examined patients who were (Mantel-Haenszel methodology).
exposed to (or contracted) a cold either naturally13,15,16,23–30 or Egger weighted regression statistics and a visual
through investigator inoculation.14,22,31 Since the effect this inspection of funnel plots were used to assess for the
might have had on the efficacy of echinacea was not presence of publication bias.
known, separate analyses were done to evaluate studies
using natural and investigator-inoculated virus. Results
Studies of poorer methodological quality, such as Trials included
unblinded or open-labelled trials might exhibit exaggerated Study identification, inclusion, and exclusion are shown
treatment effects. Excluding them might result in increased in figure 2. Our initial search strategy yielded 738 citations.
Of these, 665 were excluded manually and electronically own right (p<0·0001), the subgroup receiving echinacea
by limiting our search to human beings and clinical trials. without a supplement showed only a trend towards
The remaining 73 abstracts were reviewed of which benefit (p=0·27).
50 were excluded for evaluating echinacea for outcomes In the analysis limited to five studies evaluating
other than cold incidence or duration. Therefore, Echinaguard or Echinacin products,22–25,27 similar significant
23 abstracts remained and underwent full-text article reductions in patients’ odds compared with the overall
review. Eight of the 23 studies did not report data on either analysis were observed (p=0·0009). A reduction in the odds
primary endpoint of the analysis (incidence or duration), of contracting a cold was observed when virus exposure
and one of the 23 used an active control. Therefore, occurred naturally or was investigator inoculated. A
14 unique studies14–16,20,22–25,27–32 were therefore included in decrease in duration of cold was also maintained when only
this meta-analysis, encompassing 1356 study participants natural virus exposure studies were evaluated.13,15,16,20,28–30,32
for incidence and 1630 participants for duration. For the endpoint of cold duration, no studies used
Table 1 shows characteristics of the included studies. Echinaguard/Echinacin or evaluated investigational
Seven studies evaluated monotherapy with rhinovirus inoculation; thus these analyses could not be
E purpurea,22–25,27,30,32 one study evaluated E angustifolia,14 undertaken. Finally, neither the use of a fixed-effects
one evaluated E pallida,13,16 one study did not specify model instead of a random-effects model nor the
which specific species of echinacea was studied,31 and exclusion of studies with a Jadad score less than 3 had
four studies evaluated a combination of different any effect on overall study conclusions.
Echinacea species.15,20,28,29 Two studies evaluated echinacea’s
effect in children.28,32 Five studies used either Echinaguard Discussion
or Echinacin products made by one company, More than 800 products containing echinacea are available,
Madaus AG.22–25,27 Virus exposure using rhinovirus which come in tablet, extract, fresh juice, tincture, and tea
inoculation was done in three studies,14,22,31 and four formulations.33 There are three commonly used species of
studies evaluated the effect of echinacea along with a echinacea, differing parts of the plant can be used in
supplement.20,28–30 different products (flower, stem, root), and the same plant
species may contain differing levels of constituent
Meta-analyses outcomes molecules in different parts of the year or geographical
A summary of individual study data on the incidence and location. Although concentration variances exist, all three
duration of colds is provided in table 2. Meta-analysis species of echinacea contain water-soluble polysaccharides,
showed that echinacea decreased the odds of a patient a lipophilic fraction (alkamides, polyacetylenes), caffeoyl
contracting a cold by 58% (odds ratio [OR] 0·42, 95% CI conjugates (echinacoside, chicoric acid, caffeic acid) and
0·25–0·71; Q statistic p<0·001), corresponding with a risk flavonoids.34,35 It is yet to be determined if it is one, a few, or
difference of –0·17 (–0·25 to –0·08; number needed to the combined effect of many constituents (mainly
treat 6). Echinacea was also found to decrease the duration alkamides, chicoric acid, and polysaccharides) that induce
of cold by 1·4 days (WMD –1·44, –2·24 to –0·64; p=0·01), immunostimulation. Despite all of these factors that can
as shown in figure 3 and figure 4. The Q statistic showed influence the efficacy of echinacea and the different doses
significant heterogeneity in both the incidence and
duration analyses. However, review of the L’Abbé plot for 100
incidence showed that included studies generally agreed
on echinacea’s positive effect, but not the magnitude of the
benefit (figure 5). Some degree of asymmetry was noted 80
upon review of the funnel plots for both the incidence and
Cold incidence in echinacea group
inoculation, the incidence was only reduced by 35%. One potential confounder in our analyses, it should be noted
postulation for the possible reduced benefits with direct that if these agents do in fact have beneficial properties Search strategy
inoculation is that echinacea works better on preventing that reduce the incidence and/or duration of the common and selection
the common cold caused by viruses other than rhinovirus. cold, then this would result in an underestimation of criteria
With over 200 viruses capable of causing the common cold, echinacea’s benefit. Second, although the Egger statistic These are described
echinacea could have modest effect against rhinovirus but shows absence of publication bias, our funnel plot shows in detail in the
marked effects against other viruses. Of the direct asymmetry, suggesting that the potential for publication Methods section on
rhinovirus inoculation trials, the most touted is the study bias cannot be eliminated. Publication bias arises when page 473.
by Turner and colleagues14 published in 2005. The authors trials with negative outcomes have a lower propensity to
compared patients given E angustifolia equivalent to be published. Third, heterogeneity was present in our
900 mg/day with placebo and showed that echinacea did meta-analysis; however, the L’Abbé plot shows that the
not have “clinically significant effects on infection with a heterogeneity is a result of studies’ disagreement in the
rhinovirus or on the clinical illness that results from it”. magnitude, but not the direction, of echinacea’s benefit.
The German Commission E has approved E purpurea at a Furthermore, after doing various subgroup analyses to
recommended dose of 900 mg but has not approved assess the effect of clinical heterogeneity, echinacea
E angustifolia.8 The 1999 WHO monograph recommends maintained significant effects on the reduction of cold
E angustifolia at a dose of 3 g, a dose more than three times incidence and duration. Finally, this analysis focuses on
the dose used by Turner and colleagues.38 As such, the dose the efficacy but not the safety of echinacea. Although
used in this trial may have been too low to be fully adverse events with echinacea are not commonly
effective. reported, gastrointestinal upset and rash have been
The previous meta-analysis done by Melchart and reported.6 Much more work needs to be done to elucidate
colleagues13 and updated in November, 2005,39 included the safety of prolonged therapy since its effect on the
16 trials encompassing 22 analyses and showed a benefit rate-corrected QT interval, blood pressure, and other
of echinacea for the treatment but not prevention of a safety parameters is not well known. Of note, echinacea
common cold.13,39 By comparison, our meta-analysis is a human cytochrome P450 3A4 enzyme inhibitor so
included 14 trials encompassing 16 analyses. Although our the potential for drug interactions also needs to be
results are in agreement with the previous meta-analysis, assessed.41
our results suggest an additional benefit of echinacea for
use in the prevention, as well as the treatment, of a cold. Conclusion
The meta-analysis by Linde and colleagues39 assessed a An analysis of the current evidence in the literature
cold severity endpoint, included two unpublished suggests that echinacea has a benefit in decreasing the
evaluations, and excluded studies that used experimental incidence and duration of the common cold; however,
rhinovirus inoculation or that combined echinacea with large-scale randomised prospective studies controlling
other nutraceutical ingredients. In our analysis we chose for variables such as species, quality of preparation and
not to evaluate cold severity because of concerns about the dose of echinacea, method of cold induction, and
potential heterogeneity of the methods used for cold objectivity of study endpoints evaluated are needed
severity assessment in the studies. We included studies before echinacea for the prevention or treatment of the
evaluating echinacea with other nutraceuticals in our common cold can become standard practice.
analysis, as well as studies evaluating direct rhinovirus Conflicts of interest
inoculation, which have the highest internal validity since We declare that we have no conflicts of interest.
the virus, the degree of exposure, and the exact time of References
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