ABC quoted by AP, Bloomberg
News, and other major media
December 21, 2010. Today the Annals of Internal Medicine published a clinical trial on a proprietary
echinacea formulation and its potential effects on people with common cold
symptoms. The trial results do not show a statistically significant benefit for
the echinacea product, even though there was a “trend” toward a benefit in
reduction of symptoms and duration of symptoms.1
ABC Founder and Executive Director Mark Blumenthal was interviewed
about this trial last week by both the Associated Press and Bloomberg Business
Associated Press coverage
Predictably, the AP article was widely distributed and has been posted
on the websites of many leading newspapers and news outlets, including The
New York Times, The Washington Post, The
Los Angeles Times, USA
Today, The Seattle Times, The
Wall Street Journal, National Public Radio, mainstream television
news sites (ABC, MSNBC, Fox News), and many others.2
The AP article says, “Barrett and other experts said the findings
would probably be viewed as positive by echinacea supporters but as the ‘nail
in the coffin’ by critics
"‘It's not a compelling result in either direction,’ said
Mark Blumenthal, executive director of the American Botanical Council, which
follows research on herbal products. He said Barrett is on the group's advisory
“Blumenthal said the study was well designed, used a good quality
product at a reasonable dosage and tested echinacea in a real-world setting,
rather than giving colds to research volunteers.”2
Bloomberg News coverage
News reporter Nicole Ostrow quoted
Blumenthal’s comments about the diversity of echinacea products and problems
interpreting the clinical research:
“‘Echinacea products are not all alike,’ said Mark Blumenthal, founder and executive director of the
American Botanical Council, a nonprofit organization based in Austin, Texas, in
a telephone interview on Dec. 15. The challenge is determining which ones have
the most benefit or any benefit.’
“The studies showing the most efficacy for echinacea in fighting
colds looked at formulations made from the root and leaves of Echinacea
purpurea, one of three different species, he said. The tablets used
in the new study contained roots of the purpurea species and another, according
to the report.”3
Perspectives on the New Echinacea Trial
Blumenthal’s quotes in the AP and Bloomberg articles were based on
the following points he made about this trial during the interviews:
This is a large trial, possibly the largest randomized, controlled
trial on echinacea published to date, including 719 subjects. These subjects
were taken from the general population in 2 Wisconsin communities and the trial
is based on the susceptibility to infection by a cold virus. This is in
contrast to some echinacea trials in which a rhinovirus is actually inhaled in
a controlled situation.
The trial tested short-term use of the echinacea preparation,
mostly within 24 hours of the appearance of initial symptoms. Primary endpoints
measured in the trial were cold symptom severity and duration of symptoms,
while the secondary endpoints were levels of interleukin-8 and neutrophil,
markers for immune response, which did not increase overall in the
echinacea-treated subjects to statistical significance.
The trial used a good quality echinacea preparation, made by
MediHerb (Australia) and distributed in the United States by Standard Process
(Palmyra, WI). This echinacea preparation is sold to health practitioners only
and is not generally available in retail outlets or on the Internet.
The MediHerb echinacea preparation is in tablet form and contains
dried, concentrated extracts of two types of echinacea, the equivalent of 675
mg of E. purpurea
root and 600 mg of E. angustifolia root, each standardized to 2.1 mg of
alkamides, one of the key biologically active chemical compounds found in
echinacea roots. In this trial, based on the dosage regimen, the MediHerb
echinacea tablet contained a daily dose equivalent of 10.2 grams of (both
types) dried echinacea root during the first 24 hours after the subject noticed
the first symptoms of cold, and 5.1 grams per day of dried echinacea root
consumed during the next 4 days.
The trial contained 4 arms:
- 1 arm had
no placebo pill as a control;
- 1 arm had
a placebo pill;
- 1 arm
used the specific echinacea product in a double-blinded manner;
- 1 arm
received the echinacea tablet in an open label manner, unblended.
This trial was designed and conducted by people who are experts in
echinacea research and have published extensively on echinacea clinical trials,
particularly the lead researcher, Bruce Barrett, MD, PhD, a professor of family
medicine at the University of Wisconsin in Madison. Mr. Kerry Bone, founder of
MediHerb and an internationally respected author of herb books for health
professionals, was also a co-author of the trial.
There was a slight trend toward benefit in symptom reduction in
both echinacea groups, with a reduction in duration by about 12 hours, which,
although not statistically significant, the authors note may be considered
clinically significant by some patients.
The authors provided an interesting, cautiously worded, and
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. However, the trends were in the direction of benefit,
amounting to an average half-day reduction in the duration of a weeklong cold,
or an approximate 10% reduction in overall severity.1
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.1
Unlike some previous echinacea clinical trials which turned out
negative,4 these authors do not represent themselves as having produced the
definitive study on echinacea, and they carefully craft their language to show
that the conclusions, although not showing a statistically significant
beneficial effect, did show trends toward benefit, which are of therapeutic
value to some consumers.
There are many clinical trials on numerous types of echinacea
preparations in the clinical literature and recent systematic reviews of some
of these trials have concluded that there is benefit or trend towards benefit
for the echinacea preparations used in the selected trials.5,6 Blumenthal also
noted that conducting a meta-analysis of clinical trials on echinacea
preparations is difficult, if not impossible, since so many different types of
echinacea preparations are on the market and have been used in the many
clinical trials. The heterogeneity of these preparations is based on the fact
that there are three species of echinacea found in commerce: i.e., Echinacea
angustifolia, E. pallida and
E. purpurea, with
the latter being the most popular.
In addition, the echinacea preparations found in the US market
generally contain either dried herb material or alcoholic extracts from either
the root or the above-ground part of the plant (aerial part), or even fresh-pressed
juice from the fresh aerial parts. And, to further complicate matters for
researchers who are attempting conducted systematic review or meta-analysis of
clinical trials on these preparations, there are mixtures of these echinacea
materials from two or three species. Since echinacea species and their plant
parts contain different chemical profiles, these various products can have
different activities and benefits—as reflected in some of the clinical trials.
Blumenthal also told the AP that the most compelling clinical
literature published to date supports the clinical efficacy of two different
brands of extracts of Echinacea purpurea root and aerial parts. For the first, there
have been 3 clinical trials on the Echinaforce® extract produced by A. Vogel in
Switzerland, imported into the US and distributed in health food stores by
Bioforce USA.6 The second brand, called Echinamide®, on which 2 published
clinical trials7 have shown some benefit for cold symptoms is produced in
Canada by Natural Factors and sold in the US in health food stores.
Additional coverage of this trial not based on the AP story was
done by CNN (online), NBC Nightly News, and other outlets, although the AP
story is dominant.
Australian herbalist and co-author Kerry Bone, one of the trials
co-authors wrote in an email to Standard Process, the importer of the MediHerb
product used in the trial:
This is a well designed and conducted study delivering a robust
result. It demonstrated that initiating treatment with a traditional Echinacea
root product has only limited value in altering the course of the common cold
once it has taken hold. Perhaps a study with higher doses might have delivered
a better result. Nonetheless, it should not be a surprise to many herbal clinicians
like myself who have been mainly using Echinacea root as a preventative in
their practices. It might be contrary to popular thinking, but animal
experiments have shown that Echinacea root takes time to induce its immune
effects. This is why any benefit once an infection takes hold is probably
marginal and it is best suited as a preventative. I have been involved in
several clinical trials (either as co-author or advisor) that have demonstrated
the long-term use of Echinacea root boosts immunity and prevents infections.
One such positive trial of Echinacea root in reducing infections in long-haul
airline travellers is currently in press (K. Bone, e-mail, December 21, 2010).
Francis Brinker, ND, a respected herbal expert and author of Herb Contraindications and Drug Interactions
4th Edition (2011), and a member of the ABC Advisory Board*, wrote:
Once again, a good opportunity was lost. If the open label portion
of the study had been done with an equivalent liquid echinacea extract, or even
solid extract in lozenge form, I expect the beneficial results would have
reached statistical significance.
For years I have noticed that clinical studies done on echinacea
that include extracts of fresh Echinacea
purpurea whole plant or
aerial plant, especially in liquid form, are consistently positive compared to
those using dried echinacea species extracts (or powdered herbs), especially in
solid forms (tablets or capsules) to treat viral URTIs [upper respiratory tract
infections]. It makes eminently good sense to treat locally when possible, and
contact of echinacea extracts with the oropharangeal lymphatic tissue is
extremely important in acute URTI conditions. Use of solid extracts requires
systemic distribution that is useful as an adjunct, but not as the sole therapeutic
intervention when echinacea is concerned. Use of whole powdered echinacea parts
and species should be reserved for such or as a preventive measure. I
understand the preference when doing research to use a solid form, since
it makes a placebo-control much easier to make and administer, but it deprives
the study of utilizing a factor of known empirical efficacy (local tissue
exposure) (F. Brinker, e-mail, December 21, 2010).
In a follow-up email on December 23, Dr. Brinker added these
comments about the trial:
now read the article in toto, I would like to share some further thoughts and
address points made by the authors.
do applaud the care and consideration with which the study by Barret et al.
2010 was developed and executed. I personally know one of the clinicians
involved, Dr. Dave Rakel, a former residential fellow in the University of
Arizona's Program in Integrative Medicine. Dave is an excellent example of what
is right in medicine's pursuit of viable alternative practices to integrate as
adjuncts with conventional practice. All medical research is good to the degree
that it can teach us something about how patients can be treated effectively or
not. The important thing is to accurately interpret and apply the results.
this study failed in helping to demonstrate the efficacy of a particular
echinacea preparation for treating acute colds (though this does not imply that
the product may not be useful for other purposes), but it did provide further
evidence on the type of product that is not optimally effective in this
condition. This also serves an important purpose.
deconstructing the article I would like to begin by excerpting the last
sentence: "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.” What is the nature of the limited
evidence? On the first page of the article the authors describe 2 main types of
echinacea preparations in general:
stabilized fresh juice of aerial parts of E.
purpurea rich in hydrophilic derivatives such as
aqueous-ethanolic extracts or the roots of E.
purpurea or E. angustifolia
richer in hydrophobic constituents such as alkamides.
they did not distinguish liquid versus solid versions of each of these, e.g.,
whether the aerial juice is stabilized by 22% ethanol or by drying. This
distinction is demonstrably important as shown by the studies they cited of
positive and negative studies, and by their choice of the dried root extract
for this study.
the introduction they note 3 positive studies and 5 negative studies. The
positive studies and preparations used all include liquid extracts of E. purpurea aerial plant as follows:
Cohen et al 2004 used liquid extracts of E.
purpurea aerial plant and E.
angustifolia root along with vitamin C and propolis; Goel et al 2004 used a
liquid extract of E. purpurea whole
fresh plant; Sperber et al 2004 used liquid E.
purpurea aerial plant juice. These studies support the use of the first type
of preparation noted by the authors, if liquid extracts of the aerial parts are
included along with its liquid expressed juice. (Another positive study they
did not mention, Lindemuth & Lindemuth 2000, used tea made from E. purpurea herb and dry root extract
plus E. angustifolia herb. Use of E. angustifolia preparations as adjuncts
seems entirely appropriate.)
the 5 negative studies noted, none used liquid E. purpurea aerial plant extracts, but the preparations used are
the following: Barrett et al 2002 dried powders of E. angustifolia root and E.
purpurea root and herb in capsules; Taylor et al 2003 dried E. purpurea juice in a syrup vehicle;
Turner et al 2000 solid extract of uncharacterized echinacea (identified by the
authors in a follow-up letter as being labeled as containing "E. purpurea and E. angustifolia"); Turner et al 2005 liquid extracts of E. angustifolia root; Yale & Liu
2004 freeze-dried juice of E. purpurea
aerial plant in capsules.
future authors will add another "negative" study of echinacea
preparations to their lists: dried extracts of E. purpurea and E. angustifolia
roots. The authors of this article defend their choice of preparations by stating:
"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."
the studies to which they refer are in vitro research, except for 2 human
pharmacokinetic studies that demonstrate absorption of alkamides from the
MediHerb product. They do not point to any human clinical studies indicative of
the efficacy of such preparations, though they did cite several negative
studies that used echinacea root
preparations. (A positive study using a solid extract that should be
noted is Brinkeborn et al. 1999 using Echinaforce, a fresh E. purpurea whole plant extract, while a solid extract of E. purpurea root in this same study was
interesting corollary to this is that all of the published studies to date
using echinacea for the prevention of URTIs have utilized liquid extracts. It
should be recognized from an empirical rationale and the evidence that acute
infections can best be treated by concentrating the appropriate therapy
locally, i.e., with frequent use of liquid E.
purpurea aerial/whole plant extracts (as a gargle to maximize exposure to
oropharyngeal tissue and then swallowed), while prevention may be accomplished
with less frequent dosing of powdered echinacea roots, herb, or solid extracts
used for enhancing systemic resistance over a prolonged period. If dosage
(species, part, form, size, and frequency) is not optimized, then neither are
both approaches by the internal use of good quality echinacea powdered root,
herb, and/or solid extracts as an adjunct to the local and internal use of a
liquid fresh E. purpurea plant
preparation for treating acute URTIs therefore seems entirely appropriate and
In addition to Dr. Brinker’s comments, A. Vogel Bioforce AG, the
manufacturers of the Bioforce echinacea product noted above, released a
statement on December 23 in which it offered an analysis of the new trial by
Barrett et al.:
Statement from Med. Dept.
A.Vogel Bioforce AG on the Article by Barrett et al., Annals of Internal
Medicine (2010): “Echinacea for Treating the Common Cold
Barrett and colleagues have published a clinical
study, which questions the efficacy of echinacea in the treatment of the common
cold. The study was published in a scientific journal of high impact and can be
found at Barrett B, et al. Echinacea for treating the common cold. Annals of
Internal Medicine. 2010;153:769-777.
719 subjects (age > 12 years) with very mild signs and the personal impression of an upcoming
common cold were assigned to four groups of interventions, unless their
complaints existed for longer than 36 hours:
|Interventions||Number of Participants|
Subjects received 8 tablets on the first day and on
subsequent 4 days 4 tablets per day each containing the equivalent of:
- 675 mg of Echinacea purpurea root (alcoholic extract
of dried roots);
- 600 mg of Echinacea angustifolia root (alcoholic
extract of dried roots**);
- or the same number of Placebo tablets;
- or no treatment.
The primary endpoint was defined as the “area
under the curve” (AUC) for global severity with duration and severity.
Severity was assessed by WURSS-21 questionnaire and the duration by the
participants impression of having a cold.
The results showed only a statistically
insignificant trend in:
- reduction of the cold duration by
half a day and a;
- reduction of severity of
The study was designed assuming a relative benefit
of 20%, deduced from clinical trials with other echinacea preparations.
Comments to the
From a technical point of view the study by Barrett
is of high quality (placebo-control, randomization, blinding).
However, from the medicinal and therapeutical point
of view there are too many severe shortcomings, which completely dismantle the
relevance and validity of this study.
For the assessment of the primary endpoint the
authors used a WURSS-21 questionnaire to measure the severity of the common
cold. This questionnaire queries cold-unrelated symptoms like the ability to
think clearly or walk/climb stairs aside of the classical cold-related
symptoms. The WURSS-21 is a highly uncommon and rather unspecific tool (global)
to assess the course of cold infections accurately. It has been established by
the author himself and so far could not demonstrate significant efficacy for
any well-established cold remedy at all. Or in other words: “You cannot
measure the acceleration of a Porsche via using a thermometer on the wheel”.
Only volunteers with a minimal Jackson score of 2 were included in the study. The Jackson score is the mostly used score to
assess cold symptoms during a common cold and focuses only on common cold
symptoms. To our knowledge there is no data available to substantiate this
criteria for inclusion. A Jackson score of 2 represents a day with moderate
headache or a day with mild malaise and chilliness. Jackson who actually tried
to differentiate virally induced colds from any other unspecific complaints
(transitionally causing isolate complaints of the whole picture the cold
syndrome) defined a score of more than 14 over 5 days as the minimal
requirement for a cold infection.
Therefore it cannot be excluded that the study in
fact included participants without cold infection and the study sample must be
considered unsuitable. As demonstrated by Schoop et al. (2006) Echinacea helps
in common cold infections, when applying the Jackson’s criteria appropriately.
Although it has been claimed that this study
represents a very large study population, we notice that 4 groups and different
interventions were studies. Thereby the actual particular groups were much
smaller (N=164 – 171). Moreover, the sample size calculation was again based on
the assumption of a 20% effect while using the WURSS-21. Again we notice that
WURSS-21 has never demonstrated any kind of effect for echinacea in any study
and therefore the statistical fundament of the whole trial is null.
Interestingly the authors themselves challenged the
power of the study, admitting that their calculation basis was performed before
2004 would be outdated today. A minimal number of 200 subjects would have been
required to see significance.
Barrett used the dried roots of two echinacea
species, Echinacea purpurea and angustifolia. A very recent
well-designed clinical trial investigated various extracts of Echinacea
angustifolia dried roots in a fairly large population (N=437) and could
only demonstrate an insignificant trend in prevention and treatment of
clinically induced common colds. We do not understand why Barrett used a very
similar and highly specific extract, which before was never rigorously tested
in a clinical setting. Much evidence exists for the efficacy of Echinacea purpurea above-ground parts
which, supplemented with 5% of Echinacea
purpurea roots yield statistically significant effects (Goel V et al, 2005;
Goel et al, 2004; Brinkeborn et al, 1999).
Enrollment started in January 2004 and ended in
August 2008 and 3321 subject were screened to find 719 suitable subjects. With
the very broad inclusion criteria (age, definition of a cold) it is more than
astonishing why only every fifth subject fulfilled the requirements of
inclusion. Also we wondered how the last patient was enrolled in August – in
the mid of summer – and whether the stability of the Echinacea product was
monitored over the 4-years study period.
The study – although under
the surveillance of the government – raises more questions than it answers and
due to many serious flaws provides us with uncertain conclusions about the
general efficacy of echinacea. However, a statement about the generalization of
the new study results were given by the founder and executive director of the
American Botanical Counsil (ABC) Mark Blumenthal:
“the most compelling
clinical literature published to date supports the clinical efficacy of two
different brands of extracts of Echinacea purpurea root. For the first, there
have been 3 clinical trials on the Echinaforce® extract produced by A. Vogel in
Switzerland, imported into the US and distributed in health food stores by
Bioforce USA. The second brand, called Echinamide®, on which 2 published
clinical trials have shown some benefit for cold symptoms is produced in Canada
by Natural Factors and sold in the US in health food stores.”
The clinical study by
Barrett deserves attention because it primarily highlights the importance to:
echinacea products of documented clinical efficacy;
appropriate measures to detect clinical effects;
define cases of common colds;
- Plan the
size of the trial not on the grounds of misconceptions.
More information on echinacea from the extensive ABC online archives are available at an
webpage on the ABC website.
The trial was funded by the National Center for Complementary and Alternative
*Disclosure statement: Dr. Brinker is also a consultant to Eclectic Institute, a manufacturer of echinacea-based dietary supplements.
**The echinacea product was manufactured by MediHerb Company (Warwick, Queensland, Australia).
***A theoretical interpretation of confidence intervals allowed for estimation of maximal benefit of 20%.
1. Barrett B, Brown R, Rakel D, Mundt M, Bone K, Barlow S, Ewers T. Echinacea
for Treating the Common Cold: A Randomized Trial. Ann Intern Med.
2. Nano S. Got a cold? Study says Echinacea won’t help much. Associated
Press, Dec. 20, 2010. http://hosted.ap.org/dynamic/stories/U/US_MED_COLD_REMEDIES_ECHINACEA?SITE=NYONI&SECTION=HOME&TEMPLATE=DEFAULT.
Accessed Dec. 20, 2010.
3. Ostrow N. Echinacea Shows Little Benefit as
Remedy for Treating Colds, Study Finds. http://www.bloomberg.com/news/2010-12-20/echinacea-shows-little-benefit-as-remedy-for-treating-colds-study-finds.html.
Accessed Dec. 21, 2010.
4. Turner RB, Bauer R, Woelkart K, Hulsey TC,
Gangemi DJ. An evaluation of Echinacea angustifolia preparations in experimental
rhinovirus infections. N Engl J Med. 2005;353:341-348.
5. Shah SA, Sander S, White CM, Rinaldi M, Coleman CI. Evaluation of
echinacea for the prevention and treatment of the common cold: a meta-analysis.
Lancet Infect Dis. July 2007;7(7):473-480.
6. Schoop R, Klein P, Suter A, Johnston S. Echinacea in the prevention of
induced rhinovirus colds: a meta-analysis. Clin Ther.
7. Goel V, Lovlin R, Barton R, Lyon MR, Bauer R, Lee TD, et al. Efficacy of a
standardized echinacea preparation (Echinilin) for the treatment of the common
cold: a randomized, double-blind, placebo-controlled trial. J Clin Pharm
8. A. Vogel Bioforce AG. Statement from Med. Dept. A.Vogel Bioforce AG on the Article by Barrett
et al., Annals of Internal Medicine (2010): “Echinacea for Treating the
Common Cold”. Roggiwil, Switzerland. Dec. 23, 2010.