Echinacea

Echinacea
Echinacea purpurea (L.) Moench
Text by Armando González Stuart, Ph.D., 2005
Botanical family: Asteraceae.
Common names: Of the 9 species contained within the genus Echinacea, 3 are currently employed
medicinally: Echinacea purpurea or purple coneflower, E. pallida or pale coneflower and E.
angustifolia or narrow-leaved Echinacea (Islam and Carter, 2005; Barrett, 2004; Sperber et al., 2004;
Wichtl, 2004; Fugh-Berman, 2003; Hoffmann, 2003; Mahady et al., 2001).
Medicinal parts: The roots, flowers or the whole plant, depending on the species used (McKenna et
al., 2002; Bauer, 1998).
History
Echinacea is one of the best selling medicinal plants on the natural supplement market in the United
States (Bauer R, Woelkart, 2005; Castleman, 2001; Karch, 1999; Tyler, 1998). Native to the central
portion of the United States, Echinacea was used by many Native American tribes for a variety of
ailments, ranging from respiratory infections to snakebite (Foster and Tyler, 2000; Davis and Cupp,
2000). This plant was employed extensively by the eclectic physicians in the U. S. during the
nineteenth century and was officially included in the United States National Formulary until 1950
(Mahady et al., 2001; Presser, 2000).
Although it is originally from the North American continent, most of the recent research on its
medicinal properties has been carried out in Europe (Tyler, 1998).
1
Echinacea has been used by various Native American tribes to treat minor wounds, skin infections, as
well as against arthropod bites, snakebite, and stings (Bartram, 2001; Mahady et al., 2001; Hansel et
al., 2001; Brown, 2001).
Some Echinacea preparations have been adulterated with another closely related plant, Parthenium
integrifolium, commonly known as “Missouri snakeroot” or “prairie dock”. To confound the situation
further, Echinacea is also known by the vernacular name “Missouri snakeroot” (McKenna et al., 2002).
It is quite possible that much of the early research on Echinacea’s medicinal properties was done on
Parthenium instead of Echinacea, due to mistaken identity (McKenna et al., 2002; Bascom, 2002;
Brown, 2001;Bauer, 1998; Duke et al., 2002).
Products containing Echinacea include lollipops, tablets, extracts, capsules, tinctures, teas and
lozenges. Injectable (parenteral) preparations have been banned in some European countries and were
never authorized in the United States (Fetrow and Avila, 2004; Wichtl, 2004)
Active principles
•
Although the 3 medicinal species belong to the same genus, they do not have exactly the same
curative properties or active principles (Bauer and Woelkart, 2005; Wichtl, 2004; Blumenthal,
2003; McKenna et al., 2002; Bauer, 1998).
•
The roots of E. pallida and E. angustifolia contain caffeoyl derivatives such as echinacoside,
which are absent in E. purpurea (Mahady et al., 2001; Bartram, 2001). Echinacoside has both
antibacterial and antiviral effects in vitro (Bauer R, Woelkart, 2005; Mahady et al., 2001).
•
The sesquiterpene lactone esters originally reported for E. purpurea, have subsequently been
attributed to another species within the same botanical family: Parthenium integrifolium
(Sandberg and Corrigan, 2002).
•
In Europe, research done on the species Echinacea purpurea before 1990 may have been done
on another species, E. pallida, due to mistaken identification of the plant (Wichtl, 2004; Weiss
and Fintelmann, 2001; Bauer, 1998).
•
There are conflicting opinions as to the similarity of the medicinal properties between
Echinacea and its common adulterant, Parthenium. Some authors suggest Parthenium has no
medicinal activity (Davis and Cupp 2000), while others suggest the curative properties of this
plant are very similar to those of Echinacea (Duke et al., 2002).
•
Caffeic acid derivatives, such as chicoric acid and chlorogenic acid, which purportedly confer
immunostimulant activity to the plant by increasing cellular phagocytosis activity. (Kraft and
Hobbs, 2004; Wichtl, 2004; Hoffmann, 2003; Mahady et al., 2001; Kuhn and Winston, 2000;
Bauer, 1998), although the exact confirmation of the active principles remains unknown (Weiss
and Fintelmann, 2001; Foster and Tyler, 2000).
2
•
Chicoric acid is a major component in E. purpurea, but is found only in small amounts in the
other two medicinal species; E. pallida and E. angustifolia (Dewick, 2002).
•
Polyacetylenes including ketoalkynes and ketoalkenes may confer immunostimulating
properties to the herb (Dewick, 2002; Kuhn and Winston, 2000).
Applications in herbal therapy
•
Prevention and early-onset treatment of colds.
•
Sinusitis and upper respiratory infections (URI’s).
•
Inflammation of the middle ear (otitis media).
•
Infections of the lower urinary tract.
•
Coadjuvant therapy for recurring vaginal yeast (Candida albicans) infections.
•
Externally, Echinacea preparations are employed against skin infections and carbuncles,
applied as an ointment (Barrett, 2004; Wichtl, 2004; Blumenthal, 2003; Hoffmann, 2003;
Bartram, 2002; Ottariano, 1999; Blumenthal, 1998).
•
The wound healing properties of Echinacea are reported to be due to inhibition of the bacterial
enzyme, hyaluronidase, which enables these organisms to spread within the wound. Caffeic
acid derivatives such as chicoric acid, cynarin, cafteric acid and chlorogenic acid apparently are
responsible for the plant’s anti-hyaluronidase activity. The other medicinal effect is by
stimulation of fibroblasts to produce granulation tissue (Davis and Cupp, 2000; Bauer, 1998).
•
Echinacea’s anti-inflammatory action seems to be due to its high molecular weight
polysaccharide constituents (Bauer R, Woelkart, 2005; Hoffmann, 2003; Tyler 1998; Tragni et
al., 1988).
•
Some studies undertaken in Europe and the United States report that Echinacea may be
effective for the prevention and treatment of colds (Barnes et al. 2002; Weiss and Fintelmann
2000; Blumenthal et al. 1998;), although in some studies, products contained not only
Echinacea, but other plants as well ( Kim et al., 2002; McKenna et al., 2002; Lindenmuth and
Lindenmuth, 2000; Blumenthal et al., 2000), making interpretations of the results difficult to
accredit solely to Echinacea (Rotblatt and Ziment, 2002).
•
A recent review of clinical trials employing Echinacea for the treatment of the common cold
concluded that the therapeutic effectiveness of this plant has not been established (Caruso and
Gwaltney, 2005).
3
Clinical Studies with Echinacea
•
According to Bascom (2002), there have been more than 350 studies related to the efficacy and
safety of different species of Echinacea. Most of these trials have been undertaken in Europe
(Tyler, 1998). Unfortunately the methodological quality of some of these trials has not been
adequate, since not all studies have been randomized or have not included the double-blind
placebo procedure (Fetrow and Avila, 2004; Sperber et al., 2004; Mahady et al., 2001).
•
Another problem encountered in some of the trials is the great variability in the content of the
purported active principles among the different brands (in some cases, even within the same
brand) of Echinacea products sold as over the counter (OTC) medications. Such variation is not
only present among different brands, but apparently also among products of the same brand
(Sperber, et al., 2004; Davis and Cupp, 2000; Bauer, 1998).
•
In a systematic review of 26 controlled clinical trials which employed Echinacea as an
immunomodulator, Melchart et al. (1994), concluded that most of the studies had a low score in
relation to methodology and that insufficient evidence exists as to recommend individual
Echinacea preparations for individual use. The authors stated the need for further well
controlled studies to determine the clinical effectiveness of the plant drug.
•
Another 16 trials consisting of 8 prevention trials and 8 trials on treatment of upper respiratory
tract infections with a total of 3396 participants were reviewed. The selection criteria consisted
of randomized and quasi-randomized trials comparing preparations containing an extract of
Echinacea compared with a placebo, no treatment, or alternate treatment for common colds.
The great range of variation in the different preparations investigated and the lack of
consistency in methodological quality shown in the trials did not meet the criteria for a
quantitative meta-analysis. In general, the results suggested that some Echinacea preparations
may be better than placebo for the treatment of some respiratory infections (Melchart et al.,
2000).
•
Grimm and Muller (1999) undertook an experiment with a total of 109 patients with a history
of more than 3 colds or respiratory infections in the preceding year. In a double-blind study, the
test subjects were randomly assigned to receive 4 mL fluid extract of Echinacea purpurea or 4
mL placebo-juice two times a day. The incidence and severity of colds and respiratory
infections were determined during 8 weeks of follow-up, based on patient reported symptoms
along with the results from a physical examination. No significant differences were found
between treatment groups in the number of infections in each category of severity. The authors
concluded that treatment with fluid extract of Echinacea purpurea did not significantly
decrease the incidence, duration or severity of respiratory infections and colds compared to
placebo.
•
In a randomized, double-blind, placebo-controlled community-based trial set at an American
university, Barret et al. (2002), evaluated the efficacy of dried, encapsulated, whole plant
Echinacea as an early treatment for the common cold on a total of 148 university students
afflicted with common colds of recent onset. After 10 days of treatment, the researchers
4
concluded that unrefined Echinacea did not show any detectable benefit or harm, compared
with placebo in the students who suffered from the common cold.
•
The most reliable data come from research trials testing E. purpurea extracts for the treatment
for acute upper respiratory infections or URI’s (Mahady et al., 2001). Although test results
suggest a modest benefit, the trials have been generally limited both in size and in
methodological quality. In conclusion, although there is a great deal of moderately good-quality
scientific data regarding the effectiveness of E. purpurea, in treating illness or in enhancing the
human immune response, this has not yet been conclusively proven (Bauer and Woelkart,
2005; Islam and Carter, 2005; Barret, 2003; Block and Mead, 2003).
•
Echinacea may also have health implications in veterinary medicine. A double-blind, placebocontrolled, cross-over trial investigated the effects of standardized Echinacea extract on horses.
Eight animals were supplemented with Echinacea or placebo for 42 days, and their response to
supplements recorded. Horses treated with Echinacea increased phagocytic ability of isolated
neutrophils, increased peripheral lymphocyte counts and appeared to stimulate neutrophil
migration from peripheral circulation into the tissues. The Echinacea product used in the study
also increased the size and concentration of peripheral red blood cells, as well as the
concentration of hemoglobin and packed cell volume. The results showed that Echinacea
effectively stimulated equine immunocompetence. Additionally, the Echinacea extract acted as
a hematinic agent (it improved the quality of blood by increasing hemoglobin levels and the
number of erythrocytes).These effects are considered to improve parameters of exercise
physiology and performance in equines (O’Neill et al., 2002).
Table 1. Selected Clinical Trials Employing Echinacea .
Reference
HeinenKammerer et
al., 2005
Turner et al.,
2005
Plant Part / Herbal
Product
Purpose of study
To evaluate whether
treatment of chronic
recurrent respiratory
disease with a
commercial
Echinacea product
was more effective
compared to therapy
Echinacin® commercial without an
herbal product
immunomodulator
To asses the effect of
chemically defined
extracts from E.
Chemically defined
angustifolia roots on
extracts from
subjects
Echinacea angustifolia experimentally
roots
infected with
5
Number of
subjects
Results
995
Effective
437
Not effective
rhinovirus type 39
To evaluate the
effectiveness and
safety of a composite
herbal product in the
Herbal preparation
prevention of
(Chizukit) containing
respiratory tract
Cohen et al.,
echinacea, propolis and infections in children
2004
vitamin C
aged 1-5 years
To determine the
efficacy of a
standardized
preparation of E.
purpurea in reducing
Freeze-dried pressed
symptom severity and
Yale and Liu,
juice from the aerial
duration of the
2004
parts of the plant
common cold
To evaluate the
Echina Gard
ability of Echinacea
(Echinacin)® freezepurpurea to prevent
dried pressed juice from infection with
Sperber et al., the aerial parts of E.
rhinovirus type 39
2004
(RV-39)
purpurea
To determine the
effectiveness of E.
purpurea in reducing
Freeze-dried pressed
the severity and / or
juice from the aerial
duration of URI’s in
Taylor et al.,
parts of E. purpurea
children 2-11 years
2003
mixed into a syrup
old
Lindenmuth
Evaluation of
and
Echinacea Plus® tea,
Echinacea for
Lindenmuth,
made from dried herb
decreasing duration
2000
and root
of cold symptoms
Turner et al.,
N/A
Prevention of the
2000
common cold
Brinkeborn et
Echinaforce® (German Treatment of
al., 1999
product),
symptoms of the
fresh extracts
common cold
Grimm et al.,
Fluid extract
Prevention of the
1999
common cold
Brinkeborn et
Extracts of aerial
Treatment and
al .,1998
parts and root
reduction symptoms
of colds
Melchart et al., Extracts of root
Prevention of the
1998
common cold
Dorn et al.,
Root extract
Treatment and
1997
duration of colds
6
430
Effective
128
Not effective
46
Not effective
407
Not effective
95
117
Effective
Not effective
246
Effective
109
Not effective
199
Effective
302
Not effective
160
Effective
Hoheisel et al.,
1997
Braunig et al.,
1993
Braunig et al.,
1992
Schoneberger
et al., 1992
Pressed juice
Root extract
Root extract
Pressed juice
Treatment and
duration of colds
Treatment and
duration of colds
Treatment of the
common cold
Prevention of the
common cold
120
180
Effective
Effective
160
Effective
108
Not effective
Additional information about clinical trials and the products tested is available in the following
publications: Coates et al. Encyclopedia of Dietary Supplements. New York: Marcel Dekker; 2005;
Ulbricht C, Basch E. Natural Standard: Herb and Supplement Reference. New York: Elsevier; 2005;
Barrett, M. Handbook of Clinically Tested Herbal Remedies, 2 vols.. New York: Haworth Herbal
Press; 2004; Miller SC. Echinacea: The Genus Echinacea. Boca Raton, FL.: CRC Press; 2004;
Blumenthal, M. ABC’s Clinical Guide to Herbs. New York: Thieme; 2003; Bratman S, Girman A.
Handbook of Herbal Supplements and Their Therapeutic Uses. St. Lous: Mosby; 2003; European
Scientific Cooperative On Phytotherapy (ESCOP) Monographs. New York: Thieme; 2003; Bascom A.
Incorporating Herbal Medicine into Clinical Practice. Philadelphia: F. A. Davis; 2002; Yarnell, E. et
al., Clinical Botanical Medicine. New York: Mary Ann Liebert; 2003; Cassileth B, Lucarelli C. HerbDrug Interactions in Oncology. London: BC Decker; 2003; McKenna et al., Botanical Medicines. New
York: Haworth Herbal Press; 2002; Rotblatt M, Ziment I. Evidence-Based Herbal Medicine.
Philadelphia: Hanley and Belfus; 2002; Mahady et al., Botanical Dietary Supplements. The
Netherlands: Swets and Zeitlinger; 2001; Cupp M. Toxicology and Clinical Pharmacology of Herbal
Products. Totowa, New Jersey: Humana Press; 2000.
Safety/Precautions
•
Although toxicological information about Echinacea based products is scarce (Davis and Cupp,
2000; Bauer, 1998), the plant is considered to be safe when taken internally (Block and Mead,
2003; Meletis, 2002; Mahady et al., 2001; Brinker 2000; Presser, 2000; Libster, 2002; Rotblatt
and Ziment, 2002).
•
Single oral or intravenous doses of the expressed juice of Echinacea purpurea proved to be
virtually non-toxic to rats and mice. Tests for mutagenicity carried out in microorganisms and
mammalian cells in vitro and in mice all also gave negative results (Mengs et al., 1991).
•
Cross sensitivity reactions between Echinacea and other members of the daisy or sunflower
family, such as ragweed or chrysanthemum are possible (Mahady et al., 2001; Davis and Cupp,
2000).
•
Some authors suggest that the immune system of people taking Echinacea products for a long
time may be over stimulated and later suppressed (Blumenthal, 2000 ;Weiss and Fintelmann,
2000), although no experimental data exist to confirm this (Bascom, 2002; Mahady et al.,
2001).
7
•
Preliminary testing undertaken in pregnant women did not reveal any teratogenic effects. A
total of 206 women were enrolled in this prospective controlled study, after having used
Echinacea products during pregnancy. Of these, 112 women used the herb in the first trimester
of gestation. The authors concluded that there were no significant statistical differences
between the women taking Echinacea and the control group for any of the principal endpoints analyzed (Gallo et al., 1998; Gallo and Koren, 2001).
•
Echinacea should not be taken during pregnancy. The plant’s effects upon lactation have not
been evaluated (Huntley et al., 2005; Fetrow and Avila , 2004; Sarkar and Koren, 2004; Barnes
et al., 2002; Meletis, 2002).
•
Patients allergic to ragweed or other members of the Composite or Daisy family, such as
Marigold, Arnica or Chamomile, may show cross sensitization to Echinacea products (Mullins,
1998). Injectable preparations were available in Europe, but have been banned in some
countries, due to the potential risk of anaphylactic shock in sensitive individuals (Wichtl, 2004;
Vanaclocha and Cañigueral, 2003; McKenna et al., 2002).
•
It has been suggested that Echinacea preparations could be toxic to the liver, due to the
presence of pyrrolizidine alkaloids in the plant, but this is not accurate, since Echinacea lacks
the 1,2 saturated necine ring associated with hepatoxicity of various pyrrolizidine alkaloids
(Miller, 1999).
•
The unsaturated type pyrrolizidine alkaloids which are potentially hepatotoxic and
carcinogenic are not present in Echinacea (Blumenthal, 2003; Barnes et al., 2002; Duke et al.,
2002; McKenna et al., 2002; Mahady et al., 2001).
•
The German Commission E has contraindicated the use of Echinacea in patients suffering from
HIV infection or autoimmune diseases (Hoffmann, 2003; Schulz et al. 2001; Blumenthal et al.
1998), but some researchers believe that the use of Echinacea in AIDS patients may be useful
and that the contraindications mentioned in the Commission’s monograph on Echinacea are
either theoretical or poorly substantiated (Blumenthal, 2003; Mills and Bone, 2000; Bone,
1997-1998).
•
Although the Commission E monograph on Echinacea mentions that continuous treatment with
Echinacea products should not exceed 8 weeks (Blumenthal, 1998; Schulz et al., 2001) this
statement is not related to toxicity, but to the possibility that the plant’s effectiveness may wane
with time, rendering it less effective (Blumenthal, 2003).
•
There is currently no clinical evidence that Echinacea use is effective in small children,
especially under 12. The use of Echinacea products in infants should be undertaken only under
the direction of a health professional (Hrastinger et al., 2005; Barret, 2004; Taylor et al., 2003).
•
There is one documented case of recurrent erythema nodosum possibly associated with
Echinacea use (Soon and Crawford, 2001).
8
Herb/Drug interactions
•
The possible herb-drug interactions involving Echinacea are for the most part unknown. In
vitro test results have reported that Echinacea could alter the effectiveness or metabolism of
drugs that are substrates of various CYP 3ª4 isozymes (Gorski et al., 2004; Brinker, 2001;
Mahady et al., 2001; Herr, 2002).
•
Echinacea preparations may theoretically reduce the efficacy of immunosuppressant
medications, such as cyclosporine and tacrolimus, for example (Cassileth and Lucarelli, 2003).
Literature cited
Barnes J, Anderson L, Phillipson D. Herbal Medicines 2nd Edition.
London: Pharmaceutical Press; 2002.
Barrett M. Handbook of Clinically Tested Herbal Remedies, 2 Vols.
New York: Haworth Herbal Press; 2004, pp. 303-350.
Barrett B. Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a
randomized controlled trial. J Pediatr. 2004; 145(1):135-6.
Barret, B. Medicinal properties of Echinacea: a critical review.
Phytomedicine 2003; 10(1):66-86.
Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, D'Alessio D. Treatment of the common cold
with unrefined echinacea. A randomized, double-blind, placebo-controlled trial.
Ann Intern Med 2002; 137(12):939-46.
Bartram, T. Bartram’s Encyclopedia of Herbal Medicine.
New York: Marlowe; 2002.
Bascom, A. Incorporating Herbal Medicine Into Clinical Practice.
Philadelphia: F. A. Davis; 2002.
Bauer R, Woelkart K. Echinacea. In: Coates P (Editor) Encyclopedia of Dietary Supplements.
New York: Dekker; 2005; pp.177-187.
9
Bauer, H. Echinacea. In: Bauer and Lawson (Editors) Phytomedicines of Europe.
London: Oxford University Press; 1998.
Block KI, Mead MN. Immune system effects of echinacea, ginseng, and astragalus: a review.
Integr Cancer Ther. 2003;2(3):247-67.
Blumenthal, M. The ABC Clinical Guide to Herbs.
New York: Thieme; 2003.
Blumenthal, M. The Complete Commission E Monographs
Boston: Integrative Medicine Publications; 1998.
Blumenthal M. Expanded Commission E Monographs.
Boston: Integrative Medicine Publications; 2000.
Bone, K. Echinacea; When should it be used?
Eur J Herb Med 1997-1998; 3 (3):13-17.
Brauning B, Knick E. Therapeutical experiences with Echinacea pallida for influenza-like infections
[Article in German]. Natrutheilpraxis 1993; 1: 72-75.
Brauning B, Dorn M, Limburg E. et al. Echinacea purpurea radix for strengthening the immune
response in flu-like infections [in German]. Z Phytother 1992; 13: 7-13
Brinkenborn R, Shah D, Degenring F. Echinaforce ® and other Echinacea fresh plant preparationsin
the treatment of the common cold. A randomnized, placebo controlled, double blind clinical trial.
Phytomedicine 1999; 6 (1):1-6.
Brinkenborn R, Shah D, Geissbuhler S, Degenring F. Echinaforce ® in the treatment of acute colds:
Results from a placebo-controlled, double blind clinical study carried out in Sweden. [in German].
Schweizensche Z Ganz Med1998; 10 (1): 16-19.
Brinker, F. Herb Contraindications and Drug Interactions 3rd ed..
Sandy, Oregon: Eclectic Medical Publications; 2001.
Brinker, F. Toxicology of Botanical Medicine 3rd ed.
Sandy, Oregon: Eclectic Medical Publications; 2000.
Brown, D. New Encyclopedia of Herbs and Their Uses.
London; Dorling-Kinderesly; 2001; pp. 302-303.
Bruneton, J. Pharmacognosy, Phytochemistry and Medicinal Plants 3rd ed.
Paris: Intercept; 1999.
Caruso TJ, Gwaltney JM Treatment of the common cold with echinacea: a structured review. Clin
Infect Dis. 2005; 40(6):807-10.
10
Cassileth B, Lucarelli C. Herb-Drug Interactions in Oncology.
London: BC Decker; 2003.
Castleman, M. The New Healing Herbs 2nd ed.
Emmaus, Pennsylvania: Rodale Press; 2001.
Cohen HA, Varsano I, Kahan E, Sarrell EM, Uziel Y. Effectiveness of an herbal preparation
containing echinacea, propolis, and vitamin C in preventing respiratory tract infections in children: a
randomized, double-blind, placebo-controlled, multicenter study. Arch Pediatr Adolesc Med. 2004;
158(3):217-21.
Davis J, Cupp M. Echinacea. In: Cupp M (Ed). Toxicology and Clinical Pharmacology of Herbal
Products. Totowa, New Jersey: Humana Press; 2000; pp. 85-93.
Dorn M, Knick E, Lewith G. Placebo controlled double blind study of Echinaceapallida radix in upper
respiratory tract infections. Complemnt Ther Med 1997; 5: 40-42.
Duke, J., Bogenschutz, du Cellier, and Duke, P. Handbook of Medicinal Herbs 2nd ed.
CRC Press, Boca Raton, Florida; 2002.
European Scientific Cooperative On Phytotherapy (ESCOP) Monographs: Echinacea species.
New York: Thieme; 2003; pp. 126-141.
Fetrow C, Avila J. Professional’s Handbook of Complementary and Alternative Medicines 3rd ed.
Philadelphia: Lippincott; 2004; pp. 293-299.
Foster S and Tyler V. Tyler’s Honest Herbal
New York: Haworth Herbal Press; 2000.
Gallo M and Koren G. Can herbal products be used safely during pregnancy? Focus on Echinacea.
Can Fam Physician 2001; 47:1727-1728.
Gallo M, Sarkar M, Au W. et al. Pregnancy outcome following gestational exposure to Echinacea: a
prospective controlled study. Arch Intern Med 2000; 160(20):3141-3143.
Gorski JC, Huang SM, Pinto A et al. The effect of echinacea (Echinacea purpurea root) on cytochrome
P450 activity in vivo. Clin Pharmacol Ther. 2004; 75(1):89-100
Grimm W, Muller HH. A randomized controlled trial of the effect of fluid extract of Echinacea
purpurea on the incidence and severity of colds and respiratory infections. Am J Med 1999;
106(2):138-143.
Heinen-Kammerer T, Holtmannspotter C, Schnabel S et al. Effectiveness of echinacin in therapy of
chronic recurrent respiratory disease [Article in German]. Gesundheitswesen. 2005; 67(4):296-301.
Herr, S. Herb-Drug Interaction Handbook 2nd ed.
New York: Church Street Books; 2002.
11
Hoffmann D. Medical Herbalism.
Rochester, VT: Inner Traditions; 2003; pp. 544-545
Hoheisel O, Sandberg M, Bertram S et al. Echinagard treatment shortens the course of the common
cold: a double blind placebo-ontrolled clinical trial. Eur J Clin Res1997; 9: 261-269.
Hrastinger A, Dietz B, Bauer R, Sagraves R, Mahady G. Is there clinical evidence supporting the use
of botanical dietary supplements in children? J Pediatr. 2005 Mar;146(3):311-7.
Huntley AL, Thompson Coon J, Ernst E. The safety of herbal medicinal products derived from
Echinacea species: a systematic review. Drug Saf. 2005;28(5):387-400.
Islam J, Carter R. Use of Echinacea in upper respiratory tract infection.
South Med J. 2005; 98(3):311-8.
Karch, S. The Consumer’s Guide to Herbal Medicine.
New York: Advanced Research Press; 1999.
Kuhn, M., Winston D. Herbal Therapy and Supplements.
Philadelphia: Lippincott; 2000.
Libster, M. Delmar’s Integrative Herb Guide for Nurses.
New York: Delmar-Thompson; 2002.
Lindenmuth GF and Lindenmuth EB. The efficacy of Echinacea compound herbal tea preparation on
the severity and duration of upper respiratory and flu symptoms: a randomized, double-blind placebocontrolled study. J Altern Complement Med 2000; 6(4):327-334.
Mahady G, Fong H, Farnsworth N. Botanical Dietary Supplements: Quality, Safety and Efficacy.
The Netherlands: Swets and Zeitlinger; 2001.
Mahady G, Qato D, Gyllenhaal C. et al. Echinacea: Recommendations for its use in prophylaxis and
treatment of respiratory tract infections. Nutr Clin Care 4 (4) 199-208: 2001.
Mark JD, Grant KL, Barton LL. The use of dietary supplements in pediatrics: a study of echinacea.
Clin Pediatr (Phila). 2001; 40(5):265-269.
McKenna D, Jones, K and Hughes K. Botanical Medicines: The Desk Reference for Major Herbal
Supplements. New York: Haworth Herbal Press; 2002.
Melchart D, Linde K, Fischer P, Kaesmayr J. Echinacea for preventing and treating the common cold
(Cochrane Review). In: The Cochrane Library, Issue 2, 2003. Oxford: Update Software.
Melchart D, Linde K, Worku F, Bauer, R and Wagner H. Immunimodulation with Echinacea- a
systemic review of controlled clinical trials. Phytomedicine1994; 1:245-254.
Meletis, C. Complete Guide to Safe Herbs.
London: Dorling Kindersley; 2002.
12
Mengs U, Clare CB, Poiley JA. Toxicity of Echinacea purpurea. Acute, subacute and genotoxicity
studies. Arzneimittelforschung 1991; 41(10):1076-1081.
Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drugherb interactions. Arch Intern Med. 1998; 158(20):2200-11.
Miller SC. Echinacea: The Genus Echinacea.
Boca Raton, FL: CRC Press; 2004.
Mills S, Bone K. Principles and Practice of Phytotherapy.
London: Churchill-Livingstone; 2000.
Mullins RJ. Echinacea-associated anaphylaxis.
Med J Aust 1998; 168: 170-171.
O'Neill W, McKee S, Clarke AF. Immunological and haematinic consequences of feeding a
standardised Echinacea (Echinacea angustifolia) extract to healthy horses. Equine Vet J. 2002;
34(3):222-7.
Presser, A. Pharmacist’s Guide to Medicinal Herbs.
Petaluma, California: Smart Publications; 2000.
Rotblatt M, Ziment I. Evidence-Based Herbal Medicine.
Philadelphia: Hanley and Belfus; 2002.
Sarkar M, Koren G. The Use of Echinacea in Pregnancy and Lactation: A Critical Review. In:
Echinacea; The Genus Echinacea (SC Miller editor). Boca Raton, FL: CRC Press: 2004; pp. 215-220
Schoneberger D. The influences of immune-stimulating effects of pressed juice from Echinacea
purpurea on the course and severity o colds: results from a double-blind study. [in German].
Forum Immunol 1992; 8: 2-12.
Shulz V, Hansel R, Tyler V, Blumenthal M. Rational Phytotherapy 5 th ed.
Berlin: Springer- Verlag: 2004; pp. 382-388.
Spasov AA, Ostrovskij OV, Chernikov MV, Wikman G. Comparative controlled study of
Andrographis paniculata fixed combination, Kan Jang and an Echinacea preparation as adjuvant, in the
treatment of uncomplicated respiratory disease in children. Phytother Res. 2004; 18(1):47-53.
Sperber SJ, Shah LP, Gilbert RD, Ritchey TW, Monto AS. Echinacea purpurea for prevention of
experimental rhinovirus colds. Clin Infect Dis. 2004; 38(10):1367-71.
Taylor JA, Weber W, Standish L et al. Efficacy and safety of echinacea in treating upper respiratory
tract infections in children: a randomized controlled trial. JAMA. 2003 ;290(21):2824-30.
Tragni E, Galli CL, Tubaro A, et al. Ani inflammatory activity of Echinacea angustifolia fractions
sparated on the basis of molecular weight. Pharmacol Res Comm 1988; 20 (Supplment 5): 845-849.
13
Turner RB, Riker DK, Gangemi JD. Ineffectiveness of Echinacea for the prevention of experimental
rhinovirus colds. Antimicrob Agents Chemother 2000; 44: 1708-1709.
Vanaclocha B, Cañigueral P. Fitoterapia: Vademécum de Prescripción 4th ed.
Barcelona; Masson: 2003; pp. 218-223.
Weiss,V, Fintelmann, J. Herbal Medicine 2nd Ed.
Stuttgart: Thieme, 2000.
Wichtl, M. Herbal Medicines and Phytopharmaceuticals 3rd ed.
Boca Raton, FL: CRC Press; 2004; pp.179-186 .
Yale SH, Liu K. Echinacea purpurea therapy for the treatment of the common cold: a randomized,
double-blind, placebo-controlled clinical trial. Arch Intern Med. 2004; 164(11):1237-41.
Yarnell E, Abascal K, Hooper C. Clinical Botanical Medicine.
New York: Mary Ann Liebert; 2003, pp.192-194.
14