Echinacea Shortens the Course of the Common
Cold
Hoheisel O, Sandberg M, Bertram S, et al. Echinagard
treatment shortens the course of the common cold: a double-blind, placebo-controlled
clinical trial. Eur J Clin Res 1997; 9:261-8.
Summary: A randomized, double-blind,
single-center clinical study examined the effect of the expressed juice
of Echinacea purpurea (Echinagard*) in patients with initial symptoms
of an acute, uncomplicated upper airway infection (common cold). Patients
were adults recruited from a large furniture factory in Sweden. Patients
enrolled had suffered from at least three respiratory infections within
the previous 6 months. Pregnant or lactating women, persons with systemic
immunological diseases and those on immunotherapy, or persons with a
history of hypersensitivity to plants of the Asteraceae family were
excluded. Patients were randomized to receive either echinacea or placebo
- 20 drops in a half glass of water every 2 hours for the first day
and thereafter three times daily for up to 10 days. Patients recorded
subjective symptoms and were interviewed by the attending physician
about their symptoms and the course of illness. The primary variables
were the number of patients reporting a "real" cold (fully
expressed symptoms of the disease) and the time to improvement in each
group.
One hundred twenty patients were enrolled and completed
the study and all were included in the intention-to-treat (ITT) analysis.
Fifty percent of the patients (24 in the echinacea group and 36 in the
placebo group) reported experiencing a "real" cold. In the
ITT analysis, the median time taken to achieve improvement was 0 days
with echinacea and 5 days in the placebo group (the time to improvement
of zero days was assigned to all patients without a "real"
cold). Analysis of time to improvement found that patients taking echinacea
showed a more rapid recovery than those taking placebo (p<0.0001).
In the sub-group of patients with a "real"
cold, the median time to improvement was 4 days for the echinacea group
versus 8 for the placebo group. Patients with a "real" cold
taking echinacea stopped treatment due to improvement after a median
of 6 days compared to 10 days for those on placebo. No specific adverse
events were reported in either group.
*The brand name Echinagard is used in Sweden for the
Echinacin™ product manufactured by Madaus AG of Cologne, Germany.
It is sold in the U.S. under the brand names EchinaGuard™ and EchinaGuard™Pro.
Commentary: The findings of this study
indicate that the use of an expressed juice of the above-ground parts
of Echinacea purpurea, from the first signs of an upper respiratory
tract infection, both inhibits the full expression of the infection
and, when symptoms have developed, speeds up the recovery time. The
study actually demonstrates the ability of echinacea to cut the duration
of the common cold by almost half. Now that's an interesting public
health message!
Effectively treating the common cold remains a challenge
for modern medicine. Many cold and flu medicines aim at reducing congestion
and fever as well as easing coughs. Unfortunately, in addition to side
effects such as fatigue and decreased reaction time, these medicines
may also prolong viral shedding and increase the duration of the disease.1
Alternative therapies aimed at supporting the immune response such as
echinacea and zinc actually shorten the duration of the illness while
reducing risk of recurrence in persons with a history of recurring upper
respiratory tract infections. As noted in my book, Herbal Prescriptions
for Better Health (Prima Publishing, 1996), the use of echinacea extends
to other recurrent infections such as otitis media and vulvovaginal
candidiasis.
This study follows on the heels of another German study
using an extract of Echinacea pallida root in persons with acute upper
respiratory tract infections.² As was the case with the study reviewed
above, the length of illness and severity was reduced in persons taking
echinacea. Interestingly, the current study found a somewhat greater
decrease in duration of illness than the E. pallida study.
Two studies on echinacea for upper respiratory tract
infections and the common cold await analysis and publication. The first,
which was sent to me by David Schardt of the Center for Science in the
Public Interest, is an unpublished study from Canada reporting on the
efficacy of a standardized, encapsulated Echinacea angustifolia extract
in college students with a common cold.3 The study reports no efficacy
for echinacea in shortening the duration or severity of the common cold
when compared to placebo. Two immediate criticisms of this study are
the choice of echinacea product and the fact that a higher dose wasn't
used for the first 24 hours. The product used in this study is an encapsulated
extract standardized to echinacosides. As opposed to the two products
reviewed above, there is no clinical studies to support the efficacy
of this product.
The second study is a 6 month, placebo-controlled trial
testing the expressed juice of Echinacea purpurea (EchinaGuard™)
on incidence of respiratory tract infections in persons with a history
of recurrent respiratory tract infections. This study, which is just
being completed by Bastyr University, is not only well-controlled but
is also including analysis of immunocompetence using the Multitest Merieux.
The results of this study will be an important chapter in the determination
of echinacea's efficacy.
References
- Spector SL. The common cold: current therapy and
natural history. J Allergy Clin Immunol 1995; 95:1133-8.
- Dorn M, Knick E, Lewith G. Placebo-controlled, double-blind
study of Echinacea pallida radix in upper respiratory tract infections.
Comp Ther Med 1997; 5:40-42.
- Galea S, Thacker K. Double-blind prospective trial
investigating the effectiveness of a commonly prescribed herbal remedy
in altering duration, severity and symptoms of the common cold. unpublished,
1996.
Antidepressant Activity of St. John's Wort Extract
- New Mechanisms of Action Proposed
Muller WE, Rolli M, Schafer C, Hafner U. Effects of
hypericum extract (LI 160) in biochemical models of antidepressant activity.
Pharmacopsychiatry 1997; 30(Suppl):102-7.
Summary: Based on the fact that the
mechanism of action for St. John's wort's antidepressant activity is
not understood, the authors tested the standardized St. John's wort
extract LI 160 (Lichtwer Pharma, Berlin, Germany)* in several biochemical
models relevant for the mechanism of action for other antidepressant
drugs. On tests of MAO-A and MAO-B inhibition, LI 160 was found to have
weak action in vitro. The authors conclude that these actions suggest
that MAO-A or MAO-B inhibition cannot explain the antidepressant activity
of LI 160 in vitro.
In various uptake assays, LI 160 was found to be a rather
potent inhibitor of synaptosomal serotonin uptake. Surprisingly, the
extract was also shown to inhibit the synaptosomal uptake of norepinephrine
as well as dopamine with potencies similar to those found with serotonin.
The authors point out that while other antidepressant drugs inhibit
synaptosomal uptake of both serotonin and norepinephrine (e.g. imipramine,
desipramine) and others both dopamine and norepinephrine (e.g. nomifensine,
amineptine), no drug show this action on all three uptake systems.
As is the case with imipramine, LI 160 was also found
to cause a down-regulation of b-adrenoreceptor in the frontal cortex.
However, at comparable doses to those used for imipramine (20 times
the average dose in humans), this reduction was 25% less than that noted
for imipramine. As opposed to imipramine which down-regulates 5-HT2-recptor
density, LI 160 led to an upregulation of 5-HT2-receptor density.
*LI 160 is sold in the U.S. under the tradename of Kira.
Commentary: On March 16th and 17th
of this year, the American Herbal Products Association sponsored the
First International Conference on St. John's wort. The two days were
divided into discussion of cultivation, quality control, extraction
and analytical techniques on the first day followed by pharmacological,
clinical and regulatory presentations on the second day.
In my estimation, the most compelling presentation during
the two days was by Professor Muller of the Department of Psychiatry
at the Biocenter University of Frankfurt and the Department of Psychopharmacology
at the Central Institute of Mental Health in Mannheim, Germany. Professor
Muller presented the findings summarized above. While many of us had
heard rumblings of possible serotonin re-uptake inhibition for St. John's
wort extracts, few of us were prepared for the rather remarkable findings
summarized above.
Working with the LI 160 extract, Professor Muller clearly
demonstrates that the extract has effects in two major biochemical mechanisms
established for antidepressant drugs - inhibition of the synaptosomal
uptake system for serotonin and norepinephrine. Additionally, LI 160
activity was found to also extend to inhibition of dopamine uptake.
This basically implies that LI 160 has a broad spectrum antidepressant
action that places it in a unique position somewhere between SSRIs and
tricyclic antidepressants. It would seem prudent therefore to use St.
John's wort with caution in persons already on tricyclics and SSRIs.
While using St. John's wort to assist with SSRI withdrawal is becoming
increasingly commonplace, persons choosing this course of therapy should
be closely monitored by a healthcare professional.
Professor Muller was also responsible for introducing
research that may possibly point to a "new" active constituent
for St. John's wort extracts - hyperforin. As an addendum to the above
studies, he presented information that demonstrates that hyperforin
has the greatest inhibition of reuptake for the systems noted above.
Professor Muller concluded that St. John's wort extracts should contain
guaranteed levels of hyperforin as opposed to hypericin which showed
minimal activity in his studies.
Professor Muller's work was later confirmed by Dr. Chaterjee
of the Dr. Willmar Schwabe company of Karlsruhe, Germany. Dr. Chaterjee
reports that in animal models of depression, hyperforin is several times
more active than other constituents in St. John's wort. In response
to Professor Muller and Dr. Chaterjee's findings, the Schwabe company
have developed a St. John's wort extract that is standardized to approximately
5% hyperforin. It is important to note that hyperforin is very unstable
and Schwabe has developed a technique that stabilizes the hyperforin
in the extract. Dr. Werner Busse later presented the results of two,
unpublished clinical trials demonstrating the efficacy of this extract
in treating persons with mild to moderate depression. One of these studies
actually compared the extract to an established St. John's wort extract
standardized to 0.3% hypericin. At equal doses of 900 mg daily, the
new extract demonstrated greater effect according to the Hamilton Depression
Scale and self-rating scales over a six week period. Dr. Busse made
no announcement about plans to release this product in the U.S. market.
These results were not accepted warmly by all participants
in the conference. Professor H. Winterhoff of the Department of Pharmacology
and Toxicology of the Westphallen Wilhelms University in Munster, Germany
and Professor A. Nahrstedt of the Department of Pharmaceutical Biology
and Phytochemistry of the same institution (Dr. Nahrstedt is also the
editor-in-chief for Planta Medica), both expressed concern about jumping
on the hyperforin bandwagon at this juncture. Both of them felt that
the actions of hypericin and pseudohypericin cannot be discounted yet.1
You'll have to purchase the tape of their presentations as well as the
rather heated panel discussion that followed to draw your own conclusions.
Needless to say, the issue of active constituents and standardization
of St. John's wort extracts in Germany is a long way from settled.
Finally, in the same supplemental issue of Pharmacopsychiatry,
another study demonstrates the safety of the LI 160 extract compared
to imipramine.² The issue this time is cardiac conduction. It is well
known that tricyclic antidepressants can slow intraventricular conduction
and that patients suffering from pre-existing conductive dysfunction,
particularly bundle-branch block, have an increased risk of developing
symptomatic A-V block while taking tricyclics.
In this study, 209 depressed patients were randomized
to receive either 1800 mg of LI 160 or 150 mg of imipramine daily for
six weeks. EEGs were recorded at baseline and at the end of the six
week treatment period. Persons taking imipramine showed a significant
increase in first degree A-V blocks and abnormalities of repolarization.
Those taking LI 160 had the exact opposite results - a significant reduction
of these pathological findings following six weeks of treatment!
As mentioned in my May TLfDP review of the high-dose
LI 160 study, St. John's wort extracts are emerging as safe alternatives
to prescription antidepressants for a broad spectrum of depressed patients.
The two day conference in Anaheim, California demonstrates that current
and future research of this exiting phytomedicine should lead to wider
acceptance by the medical community in this country.
References
- Butterweck V, Wall A, Lieflander-Wulf U, et al. Effects
of the total extract and fractions of Hypericum perforatum in animal
assays for antidepressant activity. Pharmacopsychiatry 1997; 30(Suppl):117-24.
- Czekalla J, Gastpar M, Hubner WD, Jager D. The effect
of hypericum extract on cardiac conduction as seen in the electrocardiogram
compared to that of imipramine. Pharmacopsychiatry 1997; 30(Suppl):86-8.