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Echinacea is widely used to treat the common cold. To assess the potential benefits of echinacea as a treatment of common cold. Randomized, controlled trial. ( registration number: NCT00065715) Dane County, Wisconsin. 719 patients, aged 12 to 80 years, with new-onset common cold. Patients were assigned to 1 of 4 parallel groups: no pills, placebo pills (blinded), echinacea pills (blinded), or echinacea pills (unblinded, open-label). Echinacea groups received the equivalent of 10.2 g of dried echinacea root during the first 24 hours and 5.1 g during each of the next 4 days. Indistinguishable placebo tablets contained only inert ingredients. The primary outcome was the area under the curve for global severity, with severity assessed twice daily by self-report using the Wisconsin Upper Respiratory Symptom Survey, short version. Secondary outcomes included interleukin-8 levels and neutrophil counts from nasal wash, assessed at intake and 2 days later. Of the 719 patients enrolled, 713 completed the protocol. Mean age was 33.7 years, 64% were female, and 88% were white. Mean global severity was 236 and 258 for the blinded and unblinded echinacea groups, respectively; 264 for the blinded placebo group; and 286 for the no-pill group. A comparison of the 2 blinded groups showed a 28-point trend (95% CI, -69 to 13 points) toward benefit for echinacea (P = 0.089). Mean illness duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared with 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day (CI, -1.25 to 0.19 days) benefit (P = 0.075). Median change in interleukin-8 levels and neutrophil counts were also not statistically significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill group, 39 ng/L and 1 cell/hpf in the blinded placebo group, 58 ng/L and 2 cells/hpf in the blinded echinacea group, and 70 ng/L and 1 cell/hpf in the open-label echinacea group). Higher-than-expected variability limited power to detect small benefits. Illness duration and severity were not statistically significant with echinacea compared with placebo. These results do not support the ability of this dose of the echinacea formulation to substantively change the course of the common cold. National Center for Complementary and Alternative Medicine, National Institutes of Health.
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Echinacea for Treating the Common Cold
A Randomized Trial
Bruce Barrett, MD, PhD; Roger Brown, PhD; Dave Rakel, MD; Marlon Mundt, PhD; Kerry Bone, Dip Phyto; Shari Barlow, BA; and
Tola Ewers, MS
Background: Echinacea is widely used to treat the common cold.
Objective: To assess the potential benefits of echinacea as a treat-
ment of common cold.
Design: Randomized, controlled trial. ( registration
number: NCT00065715)
Setting: Dane County, Wisconsin.
Patients: 719 patients, aged 12 to 80 years, with new-onset com-
mon cold.
Intervention: Patients were assigned to 1 of 4 parallel groups: no
pills, placebo pills (blinded), echinacea pills (blinded), or echinacea
pills (unblinded, open-label). Echinacea groups received the equiv-
alent of 10.2 g of dried echinacea root during the first 24 hours
and 5.1 g during each of the next 4 days. Indistinguishable placebo
tablets contained only inert ingredients.
Measurements: The primary outcome was the area under the
curve for global severity, with severity assessed twice daily by
self-report using the Wisconsin Upper Respiratory Symptom Survey,
short version. Secondary outcomes included interleukin-8 levels and
neutrophil counts from nasal wash, assessed at intake and 2 days
Results: Of the 719 patients enrolled, 713 completed the protocol.
Mean age was 33.7 years, 64% were female, and 88% were
white. Mean global severity was 236 and 258 for the blinded and
unblinded echinacea groups, respectively; 264 for the blinded pla-
cebo group; and 286 for the no-pill group. A comparison of the 2
blinded groups showed a 28-point trend (95% CI, 69 to 13
points) toward benefit for echinacea (P0.089). Mean illness
duration in the blinded and unblinded echinacea groups was 6.34
and 6.76 days, respectively, compared with 6.87 days in the
blinded placebo group and 7.03 days in the no-pill group. A com-
parison of the blinded groups showed a nonsignificant 0.53-day
(CI, 1.25 to 0.19 days) benefit (P0.075). Median change in
interleukin-8 levels and neutrophil counts were also not statistically
significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill
group, 39 ng/L and 1 cell/hpf in the blinded placebo group, 58
ng/L and 2 cells/hpf in the blinded echinacea group, and 70 ng/L
and 1 cell/hpf in the open-label echinacea group).
Limitation: Higher-than-expected variability limited power to de-
tect small benefits.
Conclusion: Illness duration and severity were not statistically sig-
nificant with echinacea compared with placebo. These results do
not support the ability of this dose of the echinacea formulation to
substantively change the course of the common cold.
Primary Funding Source: National Center for Complementary and
Alternative Medicine, National Institutes of Health.
Ann Intern Med. 2010;153:769-777.
For author affiliations, see end of text.
Acute viral respiratory infection (common cold) is the
most frequent human illness. Its etiologic agents in-
clude rhinovirus, coronavirus, influenza, parainfluenza, re-
spiratory syncytial virus, adenovirus, enterovirus, and
metapneumovirus (1–3). Although influenza-caused illness
is the most serious and is often categorized separately, the
symptoms are usually indistinguishable from those pro-
duced by other viruses (4–7). Excluding influenza, the eco-
nomic costs of acute respiratory infection are estimated to
be about $40 billion, which makes acute respiratory infec-
tion 1 of the 10 most expensive illnesses (8). Most of this
effect comes from the estimated 20 million physician visits
and 40 million school days and workdays lost each year.
Available treatments are at best modestly effective at reduc-
ing symptoms (9), and none has been proven to shorten
illness duration.
The botanical genus Echinacea is native to North
America, where indigenous peoples used various echinacea
preparations for many illnesses (10). However, much of the
foundational biomedical research on echinacea was done in
Germany, where the plant was introduced in the 1920s
and used for various illnesses, including respiratory infec-
tion (11, 12). Immunoactivity, including macrophage ac-
tivation and cytokine expression, has been widely reported
(13–22), but the specific pathways, pharmacokinetics, and
mechanism of action of the various phytochemical constit-
uents are incompletely understood (23–29). Most com-
mercially available echinacea products derive primarily
from 2 species, Echinacea purpurea and E. angustifolia (30,
31), and can be divided into 2 general categories: stabilized
fresh juice of aerial parts of E. purpurea, which is rich in
such hydrophilic derivatives as polysaccharides and glyco-
proteins, and an aqueous–ethanolic extract of root material
from E. angustifolia or E. purpurea that is richer in li-
See also:
Editors’ Notes .............................770
Summary for Patients.......................I-43
Appendix Table
Appendix Figure
Conversion of graphics into slides
Annals of Internal Medicine Original Research
© 2010 American College of Physicians 769
pophilic constituents, such as alkamides. Other potentially
active constituents, such as echinacoside; cynarin; and
caffeic, caftaric, cichoric, and chlorogenic acids, are
found in various concentrations among the different
formulations. When we designed this study in 2002, we
decided to use a root-based, alkamide-rich preparation.
Research published since that time (32–38) has tended
to support our decision.
Several hundred scientific studies on echinacea, in-
cluding a dozen randomized trials that tested echinacea for
preventing or treating the common cold (39), had already
been published by the mid-1990s, when echinacea had
become popular in the United States. Nearly all of these
early trials reported either statistically significant benefit
or trends toward benefit (40). However, all were
manufacturer-sponsored and of moderate to poor quality.
In this context, we found it necessary to conduct our own
trial from 1999 to 2000 (41), which yielded negative re-
sults. Several new trials have been published since then,
some with positive results (42–44) and some with negative
results (45–48). Systematic reviews and meta-analyses have
varied in their inclusion criteria, review methods, results,
and interpretation (49–53). We designed and conducted
this trial because the effectiveness of echinacea was still
We asked 3 independent research questions, a some-
what unconventional approach. First, are there placebo
effects associated with blinded versus open-label pills?
Second, do physician–patient interactions influence cold
outcomes? Finally, are there effects attributable specifically
to echinacea, as assessed by blinded comparison? This
study addresses the third question; studies that address the
first 2 questions will be published elsewhere.
Our trial used a 2-way factorial design, in which par-
ticipants were randomly assigned to receive no, standard,
or enhanced clinical interaction in one direction (33.3%
chance) and to receive no pills, placebo (blinded), echina-
cea (blinded), or open-label echinacea (unblinded) in the
other direction (25% chance). Details of our rationale and
methods have been published elsewhere (54).
Setting and Participants
Our study was conducted at 2 sites in Dane County,
Wisconsin. Study promotion included newspaper advertis-
ing, posters, community talks, targeted mailings, e-mails,
and word of mouth. Prospective participants called an ad-
vertised telephone number and were screened for eligibil-
ity. Those who were eligible were met in person for in-
formed consent, following procedures approved by the
University of Wisconsin (UW) institutional review board.
After giving consent, participants rated themselves on sev-
eral self-report questionnaires. An envelope was then
opened to reveal allocation to a no-pill, blinded pill, or
open-label echinacea group. Participants received their first
dose of pills at the consent visit. Participants self-rated
symptoms twice daily until their colds had resolved, up to
a maximum of 14 days. Nasal wash, collected at enrollment
and 2 days later, was analyzed for interleukin-8 (IL-8) levels
and neutrophil counts (55–58). Participants were met for an
exit interview after their illness had resolved.
Inclusion and Exclusion Criteria
Prospective participants were required to answer “yes”
to either, “Do you think that you have a cold?” or “Do you
think you are coming down with a cold?” Symptoms had
to start within 36 hours before enrollment. Using Jackson
and colleagues’ criteria (59), participants had to report at
least 1 of nasal discharge, nasal obstruction, sneezing, or
sore throat (the other 4 Jackson criteria symptoms are
headache, malaise, chilliness, and cough). Participants
needed a total Jackson score of 2 or higher, after summing
the scores for each symptom on a scale of 0 (absent), 1
(mild), 2 (moderate), or 3 (severe). Prospective participants
had to be 12 years or older; those aged 12 to 17 years
required parental permission. Participants receiving antibi-
otics, antivirals, nasal steroids, decongestants, antihista-
mines, combination cold formulas, echinacea, zinc, or vi-
tamin C were excluded, as were those with a history of
allergic rhinitis who reported sneezing or itching of the
nose or eyes and those with a history of asthma who re-
ported current cough, wheezing, or shortness of breath (to
avoid confounding from allergy or asthma symptoms). Par-
ticipants who self-reported having autoimmune or im-
mune deficiency disease or being pregnant were also
Random Assignment, Allocation, and Blinding
We used SAS (SAS Institute, Cary, North Carolina) to
generate a single block of 804 unique identification num-
Echinacea is a popular nonprescription treatment for the
common cold. The efficacy of echinacea in this regard
continues to be debated after hundreds of studies.
In this randomized, controlled trial, a minor, nonstatisti-
cally significant decrease in illness duration and severity
was found in participants who received either blinded or
open-label echinacea compared with those who received
blinded placebo or no pills.
Higher-than-expected variability in the natural history of
cold episodes may have limited the power of this study to
demonstrate treatment differences.
This study is unlikely to change the debate on the efficacy
of echinacea in treating the common cold.
—The Editors
Original Research Echinacea for Treating the Common Cold
770 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12
bers so that each of 12 cells (3 clinician groups by 4 pill
groups) was represented equally. Using these codes, the
UW Hospitals Pharmaceutical Research Center Investiga-
tional Drug Service prepared consecutively numbered,
sealed envelopes to direct allocation. An envelope-within-
envelope strategy was used, so that group assignment
would be revealed as soon as the participant gave consent
and the research assistant opened the larger outer envelope.
Allocation concealment for the 2 blinded pill groups was
accomplished by using identical coated tablets and plastic
pill bottles. For the two thirds of the sample who would see
a clinician, a second, smaller envelope that directed alloca-
tion to a standard or enhanced visit group was opened by
the study clinician before entering the examination room.
The randomized allocation key was not shared with inves-
tigators until after all data were collected, entered, and
cleaned and analysis strategies were determined. Blinding
was tested at the exit interview by asking participants
which group they thought they had been assigned to.
Echinacea and Placebo
The echinacea and identical placebo tablets were man-
ufactured by MediHerb (Warwick, Queensland, Australia).
Echinacea tablets contained the equivalent of 675 mg of E.
purpurea root and 600 mg of E. angustifolia root, each
standardized to 2.1 mg of alkamides. Tablet excipients in-
cluded calcium acid phosphate, cellulose, silica, sodium
starch glycolate, hypromellose, and magnesium stearate.
Placebo and echinacea tablets contained the same propor-
tions of inert ingredients and were covered with identical
digestible coatings.
Participants received 2 tablets at enrollment, followed
by 2-tablet doses 3 more times within 24 hours of enroll-
ment. They then received 1 tablet 4 times per day for the
next 4 days. Thus, each participant received the equivalent
of 10.2 g of dried echinacea root during the first 24 hours
and the equivalent of 5.1 g during each of the next 4 days.
Outcomes and Follow-up
We prospectively defined the primary outcome as the
area under the curve for global severity, with duration and
severity assessed twice daily by self-report. Duration began
at enrollment and continued through the last time the par-
ticipant answered “yes” to, “Do you think you still have a
cold?” The date and time when questionnaires were com-
pleted was recorded, which allowed duration to be quanti-
fied as a continuous measure. To confirm that the illness
had ended, the last “yes” answer to, “Do you think you still
have a cold?” had to be followed by a “no” answer for 2
days in a row. We chose to limit monitoring to a maxi-
mum of 14 days to reduce potential bias from extended
Illness severity was assessed twice daily by using the
Wisconsin Upper Respiratory Symptom Survey, short ver-
sion (WURSS-21), a validated illness-specific quality-of-
life outcome instrument (60, 61). Items assess symptom
severity and functional impairment, with a score of 1 con-
sidered to be very mild; 3, mild; 5, moderate; and 7, severe.
The first item assesses overall illness severity, and the last
item assesses change since the previous day. Summing
scores on the intervening 19 items provides a global mea-
sure of illness severity. Summing across time points yields
an area under the curve for global severity, which we cal-
culated by using trapezoidal approximation.
Secondary outcomes included self-report on psycho-
social questionnaires and biomarkers of immune response
and inflammation. Self-report measures included general
health-related quality of life, perceived stress, interpersonal
support, optimism, and mood states. General health was
assessed daily by using the Medical Outcomes Study Short
Form-8 scale (62), a 24-hour recall version of the highly
validated Medical Outcomes Study Short Form-36 scale.
The Short Form-8 scale yields separate physical and mental
health scores by using an item-weighted algorithm (62).
General health was also assessed daily by using the Euro-
Qol’s feeling thermometer (63). Perceived stress was as-
sessed at baseline, day 3, and exit by using the 4-item
Cohen Perceived Stress Scale (6466) and daily by using a
100-mm visual analogue scale developed for this study.
Interpersonal support and optimism were measured at
baseline, day 3, and exit by using the Ryff Personal Rela-
tionships scale (67) and the revised Life Orientation Test
Adverse Effects and Safety Monitoring
Although allergic reactions to echinacea have been re-
ported, no major or dose-dependent risks for adverse ef-
fects are known (50). We assessed possible adverse effects
by asking participants at the exit interview whether they
had experienced bad taste, diarrhea, headache, nausea,
rash, or stomach upset at any time during their illness.
Participants were also asked open-ended questions about
possible adverse effects at the day 3 follow-up visit and
during telephone contact. A data safety and monitoring
committee met once yearly to review enrollment and side
effect data.
Data Collection, Entry, and Cleaning
Questionnaire booklets completed by participants
were scanned into electronic files by the UW Educational
Testing Service. Data collected during telephone monitor-
ing were recorded on paper and hand-entered twice, with
discrepancies resolved by comparison with the paper.
Statistical Analysis
Our trial was designed to have 80% power to detect a
20% between-group difference in the area under the curve
for global severity. A priori power calculations were based
on data collected with a predecessor instrument of the
WURSS-21. Assuming an
of 0.05,
of 0.20, 1-sided
testing, and proportionally stable standard deviations, the
protocol required enrollment of 800 participants to achieve
720 protocol completers. Intervention groups were kept
blinded during data cleaning, assessment of missingness
and response, and initial descriptive analyses. To calculate
Original ResearchEchinacea for Treating the Common Cold 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12 771
the area under the curve for global severity, we first aver-
aged morning and evening scores for each item of the
WURSS-21. If either morning or evening data were miss-
ing, existing data were used. Possible patterns of missing-
ness for WURSS-21 items were assessed by using the Little
missing completely at random test (69). Where appropri-
ate, the expectancy maximization algorithm was used for a
multiple imputation strategy, as outlined by Schafer (70).
Box–Cox transformation was considered for data with
skewed distribution. Primary efficacy analysis was done by
comparing results in the blinded echinacea and blinded
placebo groups. Comparisons of group means and medians
were done by using the ttest and the Mann–Whitney U
test, respectively. Potential treatment effects were assessed
with a general linear model (71) by using NCSS (NCSS,
Kaysville, Utah). Covariates designated as potential con-
founders and controlled for in this model included dura-
tion of symptomatic illness before enrollment, illness sever-
ity at enrollment, age, sex, ethnicity, education, income,
smoking status, general mental and physical health, and
allocation to clinician-related visits. Blinding was tested by
using the Fisher exact test of proportional difference. To
avoid the hazards associated with multiple testing, statisti-
cal testing was limited to primary outcomes in primary
comparison groups, and secondary outcomes were com-
pared in terms of CIs rather than Pvalues.
Role of the Funding Source
This trial was sponsored by the National Center for
Complementary and Alternative Medicine at the National
Institutes of Health. MediHerb provided the echinacea
and placebo tablets and conducted the phytochemical con-
tent analysis but did not contribute financially.
Enrollment opened in January 2004 and ended in Au-
gust 2008. Of the 3321 participants screened, 719 were
enrolled and randomly assigned (Appendix Figure, avail-
able at Retention was high. Two partic-
ipants were lost to follow-up, and 4 withdrew before pri-
mary outcome data could be gathered; reasons given were
“too sick or too busy to fill out questionnaires” and “desire
to take nonprotocol medications.” Approximately 98% of
intended data were collected. The largest data gap was with
nasal wash, for which 33 participants either declined the
second nasal wash or did not return within 24 to 72 hours
after the first wash. The Little test showed no discernible
patterns of missingness in the 0.27% of missing
WURSS-21 items. Imputation of WURSS-21 items and
calculation of global severity and duration values were
done before unblinding, using the previously outlined
Of the 719 participants, 64% were female, 88% were
white, and 84% reported having at least some college ed-
ucation. Age ranged from 12 to 80 years (mean age, 33.7
years [SD, 14.4]). About 12.8% were current smokers.
Baseline measures were similar across the 4 groups (Table
1). Five hundred twenty-two were enrolled in Madison
and 197 in Verona, Wisconsin. No significant between-site
differences were found for mean age (33.3 vs. 34.9 years;
P0.20), sex (63.4% vs. 66.0% female; P0.52), or
education level (84.6% vs. 82.3% with some college edu-
cation; P0.47).
Primary Outcome
The average area under the curve for global severity
and illness duration were lower in the blinded and open-
label echinacea groups than in either the blinded placebo
or no-pill groups (Table 2). Mean global severity was 236
and 258 for the blinded and unblinded echinacea groups,
respectively; 264 for the blinded placebo group; and 286
for the no-pill group. A primary efficacy analysis that com-
pared global severity in the blinded echinacea and placebo
groups yielded a mean difference of 28 points (95% CI,
69 to 13 points). Statistical testing yielded a Tof 1.34
(P0.089). Because of skewness, the Mann–Whitney U
test comparing median severity in the blinded placebo
group with that in the blinded echinacea group may be
more appropriate (206 vs. 193; z0.97; P0.170).
Mean illness duration in the blinded and unblinded echi-
nacea groups was 6.34 and 6.76 days, respectively, com-
pared with 6.87 days in the blinded placebo group and
Table 1. Baseline Characteristics of Participants
Characteristic All
No-Pill Group
Unblinded Echinacea
Group (
Blinded Placebo
Group (
Blinded Echinacea
Group (
Mean age (SD), y33.7 (14.4) 32.3 (14.2) 33.9 (14.5) 33.2 (13.5) 35.4 (15.3)
Women, %64.1 60.9 65.9 63.7 65.8
Nonwhite, %12.1 13.8 8.2 12.3 14.1
Current smoker, %12.8 14.4 11.6 11.2 14.1
Annual household income $25 000, %35.9 40.4 32.6 35.7 35.1
At least some college education, %84.0 84.0 86.4 85.6 80.0
Mean duration of symptoms before enrollment (SD), h22.8 (8.6) 23.6 (8.0) 22.3 (9.2) 23.3 (8.5) 22.0 (8.5)
Mean WURSS-44 score at enrollment (SD) 85.4 (51.4) 84.3 (50.0) 82.9 (46.6) 89.8 (54.4) 84.7 (54.3)
Mean SF-8 physical health score (SD) 48.5 (6.1) 48.7 (6.2) 48.7 (5.5) 48.2 (6.1) 48.2 (6.6)
Mean SF-8 mental health score (SD) 43.5 (9.7) 42.7 (9.8) 43.7 (10.1) 43.4 (9.1) 44.3 (9.6)
SF-8 Medical Outcomes Study Short Form-8; WURSS-44 Wisconsin Upper Respiratory Symptom Survey, long version.
Original Research Echinacea for Treating the Common Cold
772 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12
7.03 days in the no-pill group. An efficacy analysis that
compared illness duration in the blinded echinacea group
with that of the blinded placebo group yielded a mean
difference of 0.53 day (CI, 1.25 to 0.19 days) and a Tof
1.97 (P0.075). No statistically significant differences
were found when the 2 blinded groups were compared by
using a general linear model to control for potential con-
founders (P0.42 for area under the curve for severity;
P0.74 for duration.) Box–Cox transformation was used
for that model because the distribution of global severity
was skewed. Reported Pvalues are based on 1-sided testing
and were not adjusted for multiple testing.
Because echinacea is thought to work through im-
mune stimulation, which would make early dosing impor-
tant, we did a subgroup analysis of the 351 people who
were enrolled within 24 hours of their first symptom (Ta-
ble 2). Compared with the no-pill or blinded placebo
groups, both echinacea groups had lower illness duration
and global severity; however, none of the between-group
comparisons in this secondary analysis was statistically sig-
nificant. Applying the general linear model did not signif-
icantly change the results and conclusions.
Secondary Outcomes
Analysis of secondary outcomes did not demonstrate
effects clearly attributable to echinacea (Table 3). Nasal
neutrophil counts and IL-8 levels in nasal wash tended to
increase faster in the 2 echinacea groups than in either
control group, but these differences were not statistically
significant. Self-reported health measures, including those
for physical and mental health (Medical Outcomes Study
Short Form-8), stress (Cohen Perceived Stress Scale), opti-
mism (revised Life Orientation Test), and social support
(Ryff Personal Relationships scale) did not seem to be in-
fluenced by random assignment to echinacea.
Adverse Effects
Frequency of potential adverse effects was similar (sta-
tistically indistinguishable) in the 4 groups (Table 4). The
only possible exception was headache, for which 62% of
patients in the no-pill group reported having had a head-
ache at some time during their illness, compared with
fewer than 50% in the 3 pill groups. Responses to open-
ended questions about possible adverse effects during mon-
itoring showed no patterns of adverse effects attributable to
Adherence to dosing regimen was assessed by asking
participants, “Did you take all your pills as directed?” and
by counting the pills in returned pill bottles. Of the 545
people who received pills, 518 (95%) reported taking the
pills as directed. Of the 524 bottles returned, 486 (93%)
were empty, 27 (5%) had 4 or fewer pills, and 11 (2%) had
5 or more pills left in the bottles. Nothing indicated that
the patients who received echinacea took their pills differ-
ently from the patients who received placebo (Table 5).
Test of Blinding
Blinding seemed to be intact. Of the 363 participants
who received pills and were blinded, 141 (39%) guessed
their assignment correctly, 110 (30%) guessed incorrectly,
and 107 (29%) declined to guess (Table 5). Of the 179
participants in the blinded placebo group, 72 (40%) cor-
rectly guessed their assignment, compared with 69 (38%)
in the blinded echinacea group. A Fisher exact test of pro-
portional difference that included only participants who
were willing to guess their pill assignment yielded a Pvalue
of 0.053 (CI, 0.002 to 0.246). Although this does not
allow us to reject the null and conclude blind-breaking, it
Table 2. Primary Outcomes: Global Severity and Duration of Illness
Sample No-Pill Group Unblinded
Echinacea Group
Blinded Placebo
Blinded Echinacea
Group Differences
Participants providing main outcome data
Participants, n173 181 176 183
Median global severity (95% CI) 220 (189 to 238) 195 (169 to 213) 206 (177 to 256) 193 (163 to 218) 13 (37.8 to 38.4)
Mean global severity (SD) 286 (246) 258 (214) 264 (212) 236 (182) 28 (69.0 to 13.0)
Adjusted global severity (95% CI)* 10.3 (9.9 to 10.7) 10.1 (9.7 to 10.5) 10.0 (9.7 to 10.4) 10.1 (9.7 to 10.4) 0.10 (0.60 to 0.40)
Median duration (95% CI), d6.42 (6.13 to 7.21) 6.16 (5.31 to 6.60) 6.47 (5.82 to 7.12) 6.04 (5.30 to 6.53) 0.43 (1.01 to 0.95)
Mean duration (SD), d7.03 (3.49) 6.76 (3.48) 6.87 (3.62) 6.34 (3.31) 0.53 (1.25 to 0.19)
Subset enrolled <24 h after first symptom
Participants, n80 97 79 95
Median global severity (95% CI) 221 (177 to 277) 177 (140 to 213) 199 (162 to 259) 196 (160 to 250) 3.0 (51.5 to 49.2)
Mean global severity (SD) 281 (225) 250 (218) 257 (207) 246 (186) 11.0 (69.8 to 47.8)
Adjusted global severity (95% CI)* 10.6 (9.7 to 11.6) 10.1 (9.3 to 10.8) 9.7 (8.6 to 10.7) 10.1 (9.1 to 11.1) 0.41 (1.83 to 1.03)
Median duration (95% CI), d6.66 (6.13 to 7.30) 6.15 (5.06 to 7.00) 6.38 (4.78 to 7.37) 6.07 (4.98 to 6.68) 0.31 (1.13 to 1.10)
Mean duration (SD), d6.83 (3.23) 6.62 (3.47) 6.67 (3.52) 6.47 (3.31) 0.20 (1.22 to 0.82)
*Results from a general linear model, controlled for duration of symptoms before enrollment, symptom severity at enrollment, age, sex, ethnicity, education, income,
smoking status, physical health, mental health, and factorial allocation to clinician-related visits. Global severity was defined as the area under the time severity curve, with
severity assessed by the Wisconsin Upper Respiratory Symptom Survey, short version. Because the distribution of global severity was skewed, Box–Cox transformation was
used to better satisfy statistical assumptions.
Original ResearchEchinacea for Treating the Common Cold 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12 773
does leave open the possibility that a few people correctly
ascertained the group to which they had been assigned.
Phytochemical Analysis
Laboratories of the manufacturer (MediHerb) and the
natural products analysis company Chromadex (Clearwa-
ter, Florida) conducted independent phytochemical assays
at successive time points from 2004 to 2007. Both compa-
nies used high-performance liquid chromatography with
reference standards of known purified ingredients. The Ap-
pendix Table (available at shows the low-
est and highest results from MediHerb’s 4 laboratory assays
and Chromadex’s 3 assays. Phytochemical concentrations
seemed stable over time, with no trends toward lower con-
centration in later years (data not shown).
This dose regimen of the echinacea formulation did
not have a large effect on the course of the common cold,
compared with either blinded placebo or no pills. How-
ever, the trends were in the direction of benefit, amounting
to an average half-day reduction in the duration of a week-
long cold, or an approximate 10% reduction in overall
severity. Our previous research (72–74) suggests that few
people—no more than 1 in 4—would judge this level of
benefit worthwhile, given the cost, inconvenience, and pos-
sible adverse effects. Although these results do not allow us
to reject the null hypothesis and confidently claim evidence
of benefit, data are also insufficient to exclude the possibil-
ity of a clinically significant effect. The CIs of between-
group differences allow for the possibility of a 24-hour
reduction in duration and a 20% reduction in overall se-
verity attributable to echinacea, both of which might be
accepted as clinically significant by many persons with the
common cold (72–74).
Our study has limitations. Participants were all from
Dane County, Wisconsin, and had community-acquired,
self-reported colds. The etiologic agents and psychosocial
factors that influence colds may be different in other pop-
ulations or geographic areas. We also made no attempt to
base inclusion on viral cause; some of the illnesses repre-
sented here may have been caused by influenza or other
viruses. Although the age range was wide and both sexes
Table 3. Secondary Outcomes (Day 3 Assessments)
Outcome No-Pill Group Unblinded
Echinacea Group
Blinded Placebo
Blinded Echinacea
Group Differences
Biomarker data
Participants, n164 171 168 170
Median change in IL-8 levels (95% CI),
30 (2 to 89) 70 (18 to 134) 39 (12 to 106) 58 (18 to 105) 19.0 (75.2 to 72.0)
Median change in neutrophil counts
(95% CI), cells/hpf*
1(1 to 4) 1 (0 to 4) 1 (1 to 4) 2 (0 to 5) 1.0 (4.0 to 3.0)
Self-reported data
Participants, n174 182 179 184
Mean SF-8 physical health score (95% CI) 48.0 (47.1 to 49.0) 47.7 (46.8 to 48.6) 46.9 (45.9 to 48.0) 47.3 (46.2 to 48.4) 0.40 (1.13 to 1.93)
Mean SF-8 mental health score (95% CI) 43.8 (42.3 to 45.3) 43.7 (42.2 to 45.2) 42.5 (41.0 to 43.9) 44.4 (43.1 to 45.7) 1.90 (0.06 to 3.86)
Mean feeling thermometer score (95% CI) 60.3 (57.9 to 62.9) 62.5 (59.7 to 65.3) 62.5 (59.5 to 65.5) 63.6 (60.8 to 66.4) 1.10 (2.88 to 5.08)
Mean PSS-4 stress score (95% CI) 4.3 (3.9 to 4.8) 4.5 (4.1 to 4.9) 4.6 (4.1 to 5.0) 4.5 (4.0 to 5.0) 0.10 (0.76 to 0.56)
Mean VAS stress score (95% CI) 38.3 (34.3 to 42.3) 40.0 (36.2 to 43.8) 38.0 (34.5 to 41.5) 36.6 (32.9 to 40.3) 1.40 (6.33 to 3.53)
Mean LOT-R optimism score (95% CI) 22.7 (22.1 to 23.4) 22.9 (22.4 to 23.6) 22.1 (21.5 to 22.7) 23.1 (22.5 to 23.7) 1.00 (0.16 to 1.84)
Mean Ryff PR social support score (95% CI) 45.1 (44.1 to 46.3) 45.6 (44.6 to 46.8) 44.5 (43.1 to 45.6) 45.4 (44.2 to 46.4) 0.90 (0.65 to 2.45)
hpf high-power field; IL-8 interleukin-8; LOT-R revised Life Orientation Test; PSS-4 4-item Cohen Perceived Stress Scale; Ryff PR Ryff Personal Relationships
scale; SF-8 Medical Outcomes Study Short Form-8; VAS visual analog scale.
*Median change from day 1 intake to day 3.
Table 4. Potential Adverse Effects*
Adverse Effect No-Pill Group
Unblinded Echinacea
Group (
Blinded Placebo
Group (
Blinded Echinacea
Group (
Group Differences
Bad taste 8.9 (4.7 to 13.1) 9.1 (7.2 to 16.8) 12.4 (7.6 to 17.3) 3.3 (3.34 to 10.1)
Diarrhea 5.4 (2.0 to 8.9) 9.4 (5.2 to 13.7) 12.0 (7.2 to 16.8) 9.6 (5.3 to 13.9) 2.4 (8.70 to 4.90)
Headache 62.1 (54.7 to 69.4) 47.8 (40.5 to 55.1) 49.1 (41.7 to 56.5) 46.3 (39.0 to 53.7) 2.8 (12.7 to 8.18)
Nausea 10.2 (5.6 to 14.9) 6.7 (3.0 to 10.3) 12.6 (7.7 to 17.5) 15.8 (10.4 to 21.2) 3.2 (4.17 to 10.8)
Rash 1.8 (0.0 to 3.8) 1.7 (0.0 to 3.5) 1.1 (0.0 to 2.7) 1.1 (0.0 to 2.7) 0.0 (3.08 to 3.01)
Stomach upset 16.3 (10.7 to 21.9) 13.3 (8.4 to 18.3) 12.0 (7.2 to 16.8) 14.7 (9.5 to 19.9) 2.7 (4.04 to 10.7)
*Values are the percentages of participants (95% CI) who indicated at their exit interview that they had this symptom at some time during their illness.
Original Research Echinacea for Treating the Common Cold
774 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12
were well represented, racial and ethnic diversity was lim-
ited. In addition, this trial may have been underpowered.
Our power estimates used existing data from that time,
which showed a 0.70 ratio of standard deviation to mean.
Equivalent data from this trial provide a ratio of 0.80.
Looking at data gathered from 1999 to 2008, we now
conclude that a conventional randomized, controlled trial
would need slightly more than 200 people in each of 2
groups to have 80% power to detect a 20% difference in
global severity, using the WURSS-21 (61). A trial that
used illness duration or prespecified day-to-day change as a
primary outcome could be smaller, but the results would
be less meaningful. We also note that our results were
obtained with only 1 of many possible types of echinacea
formulations. Although the dosing and array of phyto-
chemical constituents that we used (Appendix Table) are
reasonably representative of currently available echinacea
preparations, a substantively different formulation could give
substantially different results. Finally, because randomized tri-
als provide results in terms of group averages, they may ob-
scure benefits (or harms) for individuals or subgroups.
In conclusion, the pharmacologic activity of echinacea
probably has only a small beneficial effect in persons with
the common cold. Our interpretation comes not only from
the trends observed in this trial but also from a reasonably
substantial body of scientific evidence, including positive
results from several reported trials and some cautiously op-
timistic meta-analyses (50–53). Any underlying benefit of
echinacea is not large and was not demonstrated by our
results. Individual choices about whether to use echinacea
to treat the common cold should be guided by personal
health values and preferences, as well as by the limited
evidence available.
From the University of Wisconsin, Madison, Wisconsin, and MediHerb,
Warwick, Queensland, and University of New England, Armidale, New
South Wales, Australia.
Acknowledgment: The authors thank St. Marys Hospital for allowing
the use of the Employee Health clinic room for physician visits and nasal
wash collection; the UW Department of Family Medicine for providing
an institutional base and collegial support; Mary Beth Plane, PhD, and
Terry Little for assistance with editing and formatting; Rebecca Mar-
nocha and the UW Hospital and Clinic’s Pharmaceutical Research Cen-
ter for putting pills in bottles and randomization codes in envelopes; and
the many research participants who generously contributed with their
time and energy during a period of illness.
Grant Support: By the National Center for Complementary and
Alternative Medicine at the National Institutes of Health (grant
R01AT001428 and a Patient-Oriented Career Development Grant [K23
AT00051] to Dr. Barrett) and the Robert Wood Johnson Foundation
Generalist Physician Faculty Scholars Program (Dr. Barrett). MediHerb
(Queensland, Australia) provided the placebo and echinacea tablets used
in this trial and conducted the phytochemical assays, all free of charge.
When the National Institutes of Health funds ran out before data col-
lection had been completed, Deans Robert Golden and Paul DeLuca of
the UW School of Medicine and Public Health facilitated financial sup-
port to allow the project to reach enrollment goals.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline
Reproducible Research Statement: Study protocol and data set: Available
from Dr. Barrett (address below). Statistical code: Not available.
Requests for Single Reprints: Bruce Barrett, MD, PhD, Department of
Family Medicine, University of Wisconsin–Madison, 1100 Delaplaine
Court, Madison, WI 53715.
Current author addresses and author contributions are available at www
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Variable Blinded
Received pills in bottles 179 184 182
Reported taking all pills as directed 169 173 176
Reported not taking all pills as directed 8 8 4
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Original ResearchEchinacea for Treating the Common Cold 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12 777
Current Author Addresses: Drs. Barrett and Mundt, Ms. Barlow, and
Ms. Ewers: Department of Family Medicine, University of Wisconsin,
1100 Delaplaine Court, Madison, WI 53715.
Dr. Brown: Department of Nursing, University of Wisconsin, Clinical
Science Center-H6, Box 2455, 600 Highland Avenue, Madison, WI
Dr. Rakel: University of Wisconsin Integrative Medicine, 595 Science
Drive, Madison, WI 53711.
Ms. Bone: Research & Development, MediHerb, Box 713, Warwick,
Queensland 4370, Australia.
Author Contributions: Conception and design: B. Barrett, R. Brown,
D. Rakel, M. Mundt, K. Bone.
Analysis and interpretation of the data: B. Barrett, R. Brown, D. Rakel,
M. Mundt, T. Ewers.
Drafting of the article: B. Barrett, R. Brown, D. Rakel, M. Mundt.
Critical revision of the article for important intellectual content: B. Bar-
rett, D. Rakel, M. Mundt, K. Bone.
Final approval of the article: B. Barrett, R. Brown, D. Rakel, M. Mundt,
K. Bone, T. Ewers.
Provision of study materials or patients: K. Bone, S. Barlow.
Statistical expertise: R. Brown, M. Mundt, T. Ewers.
Administrative, technical, or logistic support: S. Barlow.
Collection and assembly of data: S. Barlow.
Appendix Table. Phytochemical Composition of Echinacea
Component Range in MediHerb
Range in Chromadex
Caftaric acid 1.85–2.43 1.32–2.14
Chlorogenic acid NA 0.07–0.38
Cynarin NA 0.35–0.83
Cichoric acid 7.63–10.04 5.13–6.84
Echinacoside 4.09–5.30 3.80–3.87
Total phenolics† 12.98–16.87 9.80–13.30
DDYIA‡ NA 0.52–2.05
DDIA‡ NA 0.15–0.16
DZTIA‡ NA 1.05–10.2
Total 2-enes 0.54–0.89 NA
Total 2,4 dienes 2.48–3.57 NA
Total alkamides 3.06–4.46 1.73–12.4
DDIA dodeca-2(E),4(E)-dienoic acid isobutylamide; DDYIA dodec-2-ene-
8,10-diynoic acid isobutylamide; DZTIA dodeca-2(E),4(E),8(Z),10(Z)-
tetraenoic acid isobutylamide; NA not analyzed.
*Phytochemical content was analyzed independently in 4 assays by MediHerb
(Warwick, Queensland, Australia) and 3 assays by Chromadex (Clearwater, Flor-
ida) between 2004 and 2007. No time trends were seen.
Cichoric acid derivatives.
Specific alkamides measured by Chromadex.
Annals of Internal Medicine
W-246 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12
Appendix Figure. Study flow diagram.
Received allocated intervention
(n = 174)
Withdrew from study (n = 1)
Analyzed (n = 173)
Allocated to no pill
(n = 174)
Excluded (n = 2602)
Enrolled in other studies: 914
Duration of symptoms 36 h: 885
Declined participation: 245
Insufficient or unclear cold symptoms: 143
Symptoms suggesting asthma or allergies: 53
Other or undocumented: 362
Received allocated intervention
(n = 179)
Withdrew from study (n = 2)
Lost to follow-up (n = 1)
Analyzed (n = 176)
Allocated to blinded placebo
(n = 179)
Randomly assigned
(n = 719)
Assessed for eligibility
(n = 3321)
Consented and
(n = 719)
Received allocated intervention
(n = 184)
Withdrew from study (n = 1)
Analyzed (n = 183)
Allocated to blinded echinacea
(n = 184)
Received allocated intervention
(n = 182)
Lost to follow-up (n = 1)
Analyzed (n = 181)
Allocated to unblinded echinacea
(n = 182) 21 December 2010 Annals of Internal Medicine Volume 153 • Number 12 W-247
... Twenty nine studies (in 31 publications) met our eligibility criteria. 17,18,[27][28][29][30][31][32][33][34][35][36]19,[37][38][39][40][41][42][43][44][45][20][21][22][23][24][25][26] Nine of these reported data for the prevention meta-analysis, [17][18][19]21,22,27,32,39,42 seven for the duration, [18][19][20][22][23][24]27 and 16 for safety. 17,19,[37][38][39]41,42,45,[20][21][22][23]25,27,32,36 Eleven studies did not provide quantitative data for a meta-analysis but met the eligibility criteria to be considered in a narrative summary. ...
... Twenty nine studies (in 31 publications) met our eligibility criteria. 17,18,[27][28][29][30][31][32][33][34][35][36]19,[37][38][39][40][41][42][43][44][45][20][21][22][23][24][25][26] Nine of these reported data for the prevention meta-analysis, [17][18][19]21,22,27,32,39,42 seven for the duration, [18][19][20][22][23][24]27 and 16 for safety. 17,19,[37][38][39]41,42,45,[20][21][22][23]25,27,32,36 Eleven studies did not provide quantitative data for a meta-analysis but met the eligibility criteria to be considered in a narrative summary. ...
... In terms of the intervention; 16 of the trials reported using echinacea monotherapy; 14 with E. purpurea 17,18,[38][39][40]44,19,25,26,[30][31][32]34,37 two with E. angustifolia 21,29 and two with E. pallidae 28,41 and one trial 22 had separate groups for E. angustifolia and E. purpurea. Three trials did not specify which species of echinacea was used 23,43,45 and the remaining seven trials reported a mixed preparation treatment; 5 with E. purpurea and E. angustifolia 20,24,27,35,42 and two with E. purpurea and E. pallidae. 33,36 There were a wide variety of techniques used to prepare echinacea treatments utilising different parts of the plant, extraction methods and standardisation procedures. ...
Background: Echinacea preparations are commonly used to prevent and treat upper respiratory tract infection. Objectives: To assess current evidence for the safety and efficacy of echinacea containing preparations in preventing and treating upper respiratory tract infection. Data sources: MEDLINE, EMBASE, CAB extracts, Web of Science, Cochrane DARE, and the WHO ICTRP - 1980 to present day. Eligibility criteria: Randomised double-blind placebo-controlled trials using an echinacea preparation to prevent or treat upper respiratory tract infections. Participants and interventions: Participants who are otherwise healthy of any age and sex. We considered any echinacea containing preparation. Study appraisal and synthesis methods: We used the Cochrane collaborations tool for quality assessment of included studies and performed three meta-analyses; on the prevention, duration and safety of echinacea. Results: For the prevention of upper respiratory tract infection using echinacea we found a risk ratio of 0.78 [95% CI 0.68-0.88], for the treatment of upper respiratory tract infection using echinacea we found a mean difference in average duration of -0.45 [95% 1.85-0.94] days, finally for the safety meta-analyses we found a risk ratio of 1.09 [95% CI 0.95-1.25]. Limitations: The limitations of our review include the clinical heterogeneity - for example many different preparations were tested, the risk of selective reporting, deviations from our protocol and lack of contact with study authors. Conclusions: Our review presents evidence that echinacea might have a preventative effect on the incidence of upper respiratory tract infections but whether this effect is clinically meaningful is debatable. We did not find any evidence for an effect on the duration of upper respiratory tract infections. Regarding the safety of echinacea no risk is apparent in the short term at least. The strength of these conclusions is limited by the risk of selective reporting and methodological heterogeneity. Implications of key findings: Based on the results of this review users of echinacea can be assured that echinacea preparations are safe to consume in the short term however they should not be confident that commercially available remedies are likely to shorten the duration or effectively prevent URTI. Researchers interested in the potential preventative effects of echinacea identified in this study should aim to increase the methodological strength of any further trials. Prospero id: CRD42018090783.
... To our knowledge, the relationship between perceived contingency and beliefs about real-world health associations has never been tested, meaning that it is currently unclear whether pseudoscientific health beliefs are even related to biased perceptions of contingency. As an example, many people believe that Echinacea is effective for treating the common cold, but rigorous scientific studies indicate it is no more effective than placebo [9]. If these types of real-world pseudoscientific health beliefs are based on perceived contingency, then people who endorse the effectiveness of Echinacea in treating the common cold should have-or at least report-more experience recovering quickly from the common cold when Echinacea is consumed than when it is not. ...
Full-text available
Beliefs about cause and effect, including health beliefs, are thought to be related to the frequency of the target outcome (e.g., health recovery) occurring when the putative cause is present and when it is absent (treatment administered vs. no treatment); this is known as contingency learning. However, it is unclear whether unvalidated health beliefs, where there is no evidence of cause–effect contingency, are also influenced by the subjective perception of a meaningful contingency between events. In a survey, respondents were asked to judge a range of health beliefs and estimate the probability of the target outcome occurring with and without the putative cause present. Overall, we found evidence that causal beliefs are related to perceived cause–effect contingency. Interestingly, beliefs that were not predicted by perceived contingency were meaningfully related to scores on the paranormal belief scale. These findings suggest heterogeneity in pseudoscientific health beliefs and the need to tailor intervention strategies according to underlying causes.
... In addition, this medicine has a fewer side effects [21]. Another study reported that Echinacea significantly lowered the symptoms of common cold [23]. A study on the effects of Echinacea on prevention of acute respiratory infection in children at age range 1-5 years showed that there was a fewer incidence cases of upper air ways infections and sinusitis in the intervention group [24]. ...
Full-text available
Objectives Herbal medicines, as a treatment method, have received a great deal of attention. The effects of two herbal medicines namely Zingiber officinale and Echinacea on alleviation of clinical symptoms and hospitalization rate of suspected COVID-19 outpatients were examined. Methods A clinical trial with 100 suspected COVID-19 outpatients as participants was conducted. The participants were allocated randomly to two groups of 50 members. The intervention group received concurrent Zingiber officinale (Tablet Vomigone 500 mg II tds) and Echinacea (Tablet Rucoldup I tds) for seven days in addition to the standard treatment. The control group only received the standard treatment (Hydroxychloroquine). After seven days, alleviation of clinical symptoms and hospitalization rate were examined. In addition, 14 days after treatment, the hospitalization was assessed again by telephone follow up. Results The two groups were identical in terms of basic characteristics. Improvement level as to coughing, dyspnea, and muscle pain was higher in the intervention group (p value <0.05). There was no significant difference between the two groups in terms of the other symptoms. In addition, the hospitalization rate in the intervention and control groups were 2 and 6% respectively, which are not significantly different (p value >0.05). Conclusions Taking into account the efficiency and trivial side-effects of Zingiber officinale and Echinacea, using them for alleviation and control of the clinical symptoms in COVID-19 outpatients is recommended.
... 22 It is available in different length versions, more than 20 languages, and has been used in dozens of clinical trials in several countries. [23][24][25][26] The aim of this study was to assess the validity and reliability of a pediatric version of the WURSS for Kids (WURSS-K). WURSS-K is a 15-item instrument that focuses on both illness-specific symptoms and impact on quality of life, and is designed for use in children 4-10 years of age. ...
Acute respiratory infections (ARIs) are the most common illness seen in the pediatric ambulatory setting. Research in this area is hampered by the lack of validated ARI measures. The aim of this study was to assess the reliability and validity of the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K), a 15-item instrument, which measures illness-specific symptoms and impact on quality of life during an ARI. WURSS-K was administered to two populations: (1) children aged 4–10 years recruited from the local community and (2) 9- and 10-year-old children from an ongoing study, the Urban Environment and Childhood Asthma. Overall, 163 children with 249 ARI episodes completed WURSS-K. WURSS-K was analyzed using multiple models to evaluate reliability and validity for a two-factor structure (symptom and functionality) and a single global structure. These models provided evidence of reliability and validity with omega of 0.72 and 0.91 for symptoms and functionality along with the single structure with omega of 0.90. WURSS-K shows strong psychometric properties for validity and reliability as either a single global factor or a two-factor structure. This instrument will be useful in both therapeutic trials and observational studies among children with ARI in ambulatory settings. WURSS-K is a valid and reliable illness-specific quality of life instrument that evaluates the impacts of ARIs on children. WURSS-K is designed for children 4–10 years of age, for whom there is a lack of validated assessment tools. This now validated instrument will be useful for future observational studies and therapeutic trials among children with ARIs in ambulatory settings.
... Nowadays, if symptoms persist, the main pharmacological treatments include nonsteroidal anti-inflammatory drugs showing antipyretic, analgesic, and anti-inflammatory properties, topical and systemic steroids used to reduce mucose swelling, dextromethorphan and codeine used as centrally acting cough suppressant in adults, and antibiotics in the case of detected bacterial infections (Smith et al., 2012). As these drugs are associated with notable adverse effects (AEs), the utilization of complementary and alternative remedies is widely used in both treatment and prevention of URTIs (Barrett et al., 2010;Brinckmann et al., 2003;Lucas et al., 2018). ...
Background The most common symptoms of mild upper respiratory tract infections (URTIs) are sore throat, muffled dysphonia, and swelling and redness of the throat, which result from the inflammation process following acute bacterial or viral infection. Hypothesis/purpose As propolis is a natural resinous substance traditionally used to maintain oral cavity and upper respiratory tract health due to its antimicrobial and anti-inflammatory properties, the aim of this study is to evaluate the efficacy of an oral spray based on poplar-type propolis extract with a known and standardized polyphenol content, on the remission of the symptoms associated with mild uncomplicated URTIs. Study design A monocentric, randomized, double-blind, placebo-controlled clinical trial was performed. Methods This study was conducted in 122 healthy adults who had perceived mild upper respiratory tract infections. Participants, randomly assigned to receive either propolis oral spray (N = 58) or placebo (N = 64), underwent four visits (baseline = t0, after 3 days = t1 and after 5 days = t2 and after a follow-up of 15 days = t3) in an outpatient setting. Propolis oral spray total polyphenol content was 15 mg/ml. The dosage was 2-4 sprays three times/day (corresponding to 12-24 mg of polyphenols/day), for five days. The duration of the study was 8 weeks. Results After 3 days of treatment, 83% of subjects treated with propolis oral spray had remission of symptoms, while 72% of subjects in the placebo group had at least one remaining symptom. After five days, all subjects had recovered from all symptoms. This means that resolution from mild uncomplicated URTIs took place two days earlier, instead of taking place in five days as recorded in the control group. There was no relationship between the ingestion of propolis oral spray or placebo and adverse reactions. Conclusion Propolis oral spray can be used to improve both bacterial and viral uncomplicated URTI symptoms in a smaller number of days without the use of pharmacological treatment, leading to a prompt symptom resolution.
... Results of the first were flatly negative, 113 but results of the second trended in positive directions. 114 A trial using Echinacea angustifolia extracts in an induced cold rhinovirus inoculation study found little or no effect. 115 However, when all three rhinovirus inoculation studies are considered together, the results look more favorable. ...
... Echinacea has been used to treat upper respiratory tract infection during pregnancy, and was found to reduce the levels of preterm labor induced by proinflammatory cytokines such as TNF-α [83,84]. For many reasons, it has been speculated that Echinacea could potentially be used to modulate infectioninduced PTB [85,86]. Other plant-derived extracts, such as some essential oils, are an option for women looking for natural benefits, including skin care and aromatherapy during pregnancy [87]. ...
Background Worldwide, the progress in reducing neonatal mortality has been very slow. The rate of preterm birth has increased over the last 20 years in low-income and middle-income countries. Its association with increased mortality and morbidity is based on experimental studies and neonatal outcomes from countries with socioeconomic differences, which have considered implementing alternative healthcare strategies to prevent and reduce preterm births. Methods Currently, there is no widely effective strategy to prevent preterm birth. Pharmacological therapies are directed at inhibiting myometrial contractions to prolong parturition. Some drugs, medicinal plants and microorganisms possess myorelaxant, anti-inflammatory and immunomodulatory properties that have proved useful in preventing preterm birth associated with inflammation and infection. Results This review focuses on the existing literature regarding the use of different drugs, medicinal plants, and microorganisms that show promising benefits for the prevention of preterm birth associated with inflammation and infection. New alternative strategies involving the use of PDE-4 inhibitors, medicinal plants and probiotics could have a great impact on improving prenatal and neonatal outcomes and give babies the best start in life, ensuring lifelong health benefits. Conclusion Despite promising results from well-documented cases, only a small number of these alternative strategies have been studied in clinical trials. The development of new drugs and the use of medicinal plants and probiotics for the treatment and/or prevention of preterm birth is an area of growing interest due to their potential therapeutic benefits in the field of gynecology and obstetrics.
... For example, despite the lack of support within the scientific community for the efficacy of certain forms of complementary and alternative medicine (CAM), many people still believe in their effectiveness and may even prefer such treatments over those that are scientifically validated (Lilienfeld, Ritschel, Lynn, Cautin, & Latzman, 2014). Indeed, there is now a strong evidence base suggesting that some CAM treatments are completely ineffective (e.g., Barrett et al., 2010). In such cases, the putative cause has no impact on the targeted health outcome and statistical contingency between treatment and outcome is presumably zero or close to it. ...
Full-text available
Illusory causation refers to a consistent error in human learning in which the learner develops a false belief that two unrelated events are causally associated. Laboratory studies usually demonstrate illusory causation by presenting two events—a cue (e.g., drug treatment) and a discrete outcome (e.g., patient has recovered from illness)—probabilistically across many trials such that the presence of the cue does not alter the probability of the outcome. Illusory causation in these studies is further augmented when the base rate of the outcome is high, a characteristic known as the outcome density effect. Illusory causation and the outcome density effect provide laboratory models of false beliefs that emerge in everyday life. However, unlike laboratory research, the real-world beliefs to which illusory causation is most applicable (e.g., ineffective health therapies) often involve consequences that are not readily classified in a discrete or binary manner. This study used a causal learning task framed as a medical trial to investigate whether similar outcome density effects emerged when using continuous outcomes. Across two experiments, participants observed outcomes that were either likely to be relatively low (low outcome density) or likely to be relatively high (high outcome density) along a numerical scale from 0 (no health improvement) to 100 (full recovery). In Experiment 1, a bimodal distribution of outcome magnitudes, incorporating variance around a high and low modal value, produced illusory causation and outcome density effects equivalent to a condition with two fixed outcome values. In Experiment 2, the outcome density effect was evident when using unimodal skewed distributions of outcomes that contained more ambiguous values around the midpoint of the scale. Together, these findings provide empirical support for the relevance of the outcome density bias to real-world situations in which outcomes are not binary but occur to differing degrees. This has implications for the way in which we apply our understanding of causal illusions in the laboratory to the development of false beliefs in everyday life. Electronic supplementary material The online version of this article (10.1186/s41235-018-0149-9) contains supplementary material, which is available to authorized users.
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COVID-19 is the respiratory illness caused by the novel coronavirus, SARS-CoV-2. Cytokine storm appears to be a factor in COVID-19 mortality. Echinacea species have been used historically for immune modulation. A previous rapid review suggested that Echinacea supplementation may decrease the levels of pro-inflammatory cytokines involved in cytokine storm. The objective of the present systematic review was to identify all research that has assessed changes in levels of cytokines relevant to cytokine storm in response to administration of Echinacea supplementation. The following databases were searched: Medline (Ovid), AMED (Ovid), CINAHL (EBSCO), EMBASE (Ovid). Title and abstract screening, full text screening, and data extraction were completed in duplicate using a piloted extraction template. Risk of bias assessment was completed. Qualitative analysis was used to assess for trends in cytokine level changes. The search identified 279 unique publications. After full text screening, 105 studies met criteria for inclusion including 13 human studies, 24 animal studies, and 71 in vitro or ex vivo studies. The data suggest that Echinacea supplementation may be associated with a decrease in the pro-inflammatory cytokines IL-6, IL-8, and TNF, as well as an increase in the anti-inflammatory cytokine IL-10. The risk of bias in the included studies was generally high. While there is currently no substantive research on the therapeutic effects of Echinacea in the management of either cytokine storm or COVID-19, the present evidence related to the herb's impact on cytokine levels suggests that further research may be warranted in the form of a clinical trial involving patients with COVID-19.
Preparations of the plant Echinacea (familiy Compositae) are widely used in some European countries and in North America for common colds. Most consumers and physicians are not aware that products available under the term Echinacea differ appreciably in their composition, mainly due to the use of variable plant material, extraction methods and addition of other components. Now we assessed whether there is evidence that Echinacea preparations are 1) more effective than no treatment; 2) more effective than placebo; 3) similarly effective to other treatments in A) the prevention and B) the treatment of the common cold. Outcomes of interest in prevention trials were: number of individuals with one or more colds, and severity and duration of colds; and in treatment trials: total symptom scores, nasal symptoms and duration of colds. Sixteen trials including a total of 22 comparisons of an Echinacea preparation and a control group met the inclusion criteria. The majority had reasonable to good methodological quality. A variety of different Echinacea preparations were used. None of the three comparisons in the prevention trials showed an effect over placebo. Comparing an Echinacea preparation with placebo as treatment, a significant effect was reported in nine comparisons, a trend in one, and no difference in six. More than one trial was available only for preparations based on the aerial parts from Echinacea purpurea. Therefore we concluded that preparations based on aerial parts of E. purpurea might be effective for the early treatment of colds in adults but results are not fully consistent. Beneficial effects of other Echinacea preparations and for preventative purposes might exist but have not been shown in independently replicated, rigorous randomized trials. [1,2] Again a recent meta-analysis reported that standardized extracts of Echinacea were effective in the prevention of symptoms of the common cold after clinical inoculation, compared with placebo. [3] References: [1] Linde K., Barrett B. et al. (2006) The Cochrane Database of Systematic Reviews Issue 1. [2] Gillespie E.L., Coleman C.I. (2006) Conn. Med. 70: 93–97. [3] Schoop R., Klein P. et al. (2006) Clin. Ther. 28: 174–183.
Background Echinacea purpurea stimulates the immune response and is promoted to reduce symptom severity and the duration of upper respiratory tract infections. We sought to determine the efficacy of a standardized preparation of E purpurea in reducing symptom severity and duration of the common cold.Methods A randomized, double-blind, placebo-controlled design was used. Patients received either 100 mg of E purpurea (freeze-dried pressed juice from the aerial portion of the plant) or a lactose placebo 3 times daily until cold symptoms were relieved or until the end of 14 days, whichever came first. Symptoms (sneezing, nasal discharge, nasal congestion, headache, sore or scratchy throat, hoarseness, muscle aches, and cough) were scored subjectively by the patient and recorded daily in a diary. Kaplan-Meier curves were used to estimate the survival function of time to resolution in each group. The Wilcoxon rank sum test was used to compare time to resolution between the 2 groups.Results One hundred twenty-eight patients were enrolled within 24 hours of cold symptom onset. Group demographic distribution was comparable for sex, age, time from symptom onset to enrollment in the study, average number of colds per year, and smoking history. No statistically significant difference was observed between treatment groups for either total symptom scores (P range, .29-.90) or mean individual symptom scores (P range, .09-.93). The time to resolution of symptoms was not statistically different (P = .73).Conclusions Some studies have concluded that Echinacea effectively reduces the symptoms and duration of the common cold. We were unable to replicate such findings. Further studies using different preparations and dosages of E purpurea are necessary to validate previous claims.
Echinacea phytopharmaceuticals represent the most popular group of herbal immunostimulants in Europe and in the USA [1, 2]. According to a recent report, Echinacea products have been the best selling herbal products in natural food stores in the USA in 1997 with 11.93% (1996: 9.6%) of herbal supplement sales [3]. Including homeopathic preparations, more than 800 Echinacea-containing drugs are currently on the market in Germany. Most of the preparations contain the expressed sap of Echinacea purpurea aerial parts, or hydroalcoholic tinctures of E. pallida or E. purpurea roots. They are mainly used for the treatment of colds and infections [4]. Clinical effects have been demonstrated for the expressed sap of the aerial parts of Echinacea purpurea in the adjuvant therapy of relapsing infections of the respiratory and urinary tracts, as well as for alcoholic tinctures of E. pallida and E. purpurea roots as adjuvants in the therapy of the common cold and flu [5, 6]. In the USA, it is mostly encapsulated powders from roots and aerial parts, but also tinctures from the roots and aerial parts that are used. Many investigations of the constituents of Echinacea have been undertaken. So far, compounds from the classes of caffeic acid derivatives, flavonoids, polyacetylenes, alkamides, pyrrolizidine alkaloids, polysaccharides and glycoproteins have been isolated [7]. For the main interest of finding the active component, but also for standardization purposes, the question on the chemical composition of Echinacea herbs and preparations is essential. Therefore, the present knowledge on the chemical constituents, analysis, and immunomodulatory effects of Echinacea preparations shall be reviewed.
Previous research has shown that visual images of political candidates can influence voter perceptions. This study examines newspaper photographs of candidates to determine whether the favorableness of these pictures is related to the “political atmosphere” of individual newspapers. In particular, we examine 435 candidate photographs from several races covered by seven newspapers during the 1998 and 2002 general election seasons. Based on our analysis, we conclude that candidates endorsed by a particular newspaper—or whose political leanings match the political atmosphere of a given paper—generally have more favorable photographs of them published than their opponents.
A common concern when faced with multivariate data with missing values is whether the missing data are missing completely at random (MCAR); that is, whether missingness depends on the variables in the data set. One way of assessing this is to compare the means of recorded values of each variable between groups defined by whether other variables in the data set are missing or not. Although informative, this procedure yields potentially many correlated statistics for testing MCAR, resulting in multiple-comparison problems. This article proposes a single global test statistic for MCAR that uses all of the available data. The asymptotic null distribution is given, and the small-sample null distribution is derived for multivariate normal data with a monotone pattern of missing data. The test reduces to a standard t test when the data are bivariate with missing data confined to a single variable. A limited simulation study of empirical sizes for the test applied to normal and nonnormal data suggests that the test is conservative for small samples.
We performed a systematic review of controlled clinical trials to check the evidence for the immunomodulatory efficacy of preparations containing extracts of Echinacea. Trials were searched by on-line searches in Medline and Embase, a search in the private database Phytodok, contacts with researchers and drug companies, and by checking references in available articles. All available historically and prospectively controlled trials investigating the prophylactic or therapeutic immunomodulatory activity of preparations of Echinacea alone or in combination with other plant extracts or homeopathic dilutions in humans were included. Study characteristics, results, and conclusions of primary authors were analyzed using standardized evaluation forms and methodological quality assessment using a predefined score system. A total of 26 controlled clinical trials (18 randomized, 11 double-blind) were identified; 6 of these involved testing three different mono-extracts, and 20 involved testing three different preparations also containing other ingredients. Nineteen trials studied the efficacy of the prophylactic or curative treatment of infections; 4 trials the reduction of side-effects of antineoplastic therapies and 3 trials the modulation of various laboratory immune parameters. The primary authors claimed that 30 of the 34 treatment strategies showed a superior efficacy to those of the control groups. The methodological quality of most studies was low and only 8 trials scored more than half of the maximum possible score points. Existing controlled clinical trials indicate that preparations containing extracts of Echinacea can be efficacious immunomodulators. However, the evidence is still insufficient for clear therapeutic recommendations as to which preparation to use and which dose to employ for a specific indication. Further methodologically sound, randomized clinical trials should be conducted.