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The Commission E Monographs |
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THE COMPLETE GERMAN COMMISSION E MONOGRAPHS
THERAPEUTIC GUIDE TO HERBAL MEDICINES
Copyright © 1999 American Botanical Council
Part One Introduction
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Comments on Specific Monographs
Editor's Notes
Although the Commission E monographs are considered authoritative in their
review of safety and efficacy criteria, we have included an "editor's
note" in brackets when we want to clarify a statement in the monograph, or
when we may question a statement or conclusion of the Commission, or if we wish
to direct the reader to another monograph on a plant in the same genus. For
example, some herbs that are Approved are also found in the Unapproved section,
according to the species or plant part used. Examples include two types of
Echinacea in each section, two monographs for Ginkgo biloba, four for Hawthorn,
and two for Horse Chestnut. However, insofar as we have made such comments on a
case-by-case basis, our review and possible challenge of such statements by
Commission E have not been carried out in a comprehensive manner; we have
commented in areas that we considered worthy of mention. The following specific
comments provide additional information on commonly used herbs. Also we have
included editor's notes in brackets in numerous monographs where we have chosen
to provide additional information to help explain the text (e.g., the four
stages of heart disease in the Hawthorn leaf with flower monograph and the
stages of benign prostatic hyperplasia in Saw Palmetto).
Chamomile
German Chamomile is approved for both internal use (digestive) and external
use. However, there is no approval for chamomile internally for its reputed mild
sedative effects. This is presumably because no scientific literature supported
any central nervous system effects of chamomile when the Commission published
the monograph in 1984 or when it was revised in 1990. However, in 1994 and 1996
two pharmacological studies on apigenin, a constituent in the extract of
chamomile, found that the compound binds at benzodiazepine receptor sites in the
human brain (Viola et al., 1996). This research, although still preliminary,
offers for the first time a molecular-pharmacological rationale for
understanding a potential sedative action for chamomile. Therefore, if the
Commission were still evaluating herbs — which it is not — German Chamomile
flowers could be reviewed in light of this new data; however, chamomile still
would not be approved for mild sedative purposes because the experimental data
cannot be transferred to human experience without clinical confirmation
(Schilcher, 1997b).
Echinacea
Of the four Echinacea monographs, two are positive ( Echinacea pallida
root and E. purpurea leaf) and two are negative ( E. purpurea root
and E. angustifolia root). Echinacea expert Steven Foster has noted that
based on a historical confusion of plant identity and the persistence of
adulterated commercial supplies of E. purpurea root with Parthenium
integrifolium , the assumption was made by some observers that the Commission
decided to place E. purpurea root in a negative category. Work on the
chemistry of vouchered Echinacea species from 1988 onward by R. Bauer and
H. Wagner at the Institute for Pharmaceutical Biology in Munich revealed clear
chemical profiles for E. angustifolia and E. pallida (Bauer and
Wagner, 1991). As a result, it became obvious that earlier pharmacological
studies on E. angustifolia actually involved E. pallida .
Historically, E. pallida and E. angustifolia have been offered to
the trade in mixed lots under the name "Kansas Snake root." Therefore,
lack of current pharmacological and clinical studies on E. angustifolia
root and E. angustifolia/E. pallida aerial (above-ground) parts resulted
in the issuance of a negative monograph until further scientific information
becomes available (Foster, 1996).
However, despite previous problems concerning the botanical identity of Echinacea
species in commercial preparations and research materials, the true reason for
the disparity in approvals is based on the availability of the research on the
respective species. According to Prof. Schilcher, experimental and clinical
studies are available on the flowering tops (herb) and roots of E. purpurea ,
roots of E. pallida, and roots of E. angustifolia . The Commission
decided that only the results from the research conducted on the fresh plant
juice from the flowering herb of E. purpurea and from the water-alcohol
extract of E. pallida roots are adequate for a positive monograph. In the
meantime there have been additional studies based on the alcoholic extract of
the roots of E. purpurea , that in Schilcher's personal opinion should
become a positive monograph (Schilcher, 1997b). Clinical research was carried
out in 1992 on an extract of the root of E. purpurea , suggesting clinical
benefits in patients with colds and flus (Bräunig et al., 1992). The same year
Commission E published a monograph on E. purpurea root as an Unapproved
Component Characteristic, although not all members of the Commission supported
this decision (Schilcher, 1997b).
The monograph on Echinacea Pallida root is an example of a case where
specifications based on a proprietary extract of an herb were approved. This
preparation consists of a "tincture (1:5) with 50 percent (v/v) ethanol
prepared from a native dry extract (50 percent ethanol, 7 to 11:1) corresponding
to 900 mg of the dried plant."
It should also be noted that in Germany, physicians previously had access to
injectable drug products made from either a monopreparation of E. purpurea
herb juice or a fixed combination that contained E. pallida . Thus, the
monographs for E. purpurea herb and E. pallida root both note that
there are adverse side effects associated with intraperitoneal (injectable)
forms of these echinacea products. There are no contraindications or adverse
effects reported for echinacea products taken orally.
Eleuthero (Siberian Ginseng)
The Commission notes an interesting contraindication for the drug made from
the roots and rhizomes of the herb Eleuthero (Siberian ginseng, Eleutherococcus
senticosus , sometimes still referred to in the Chinese literature by its
former Latin binomial, Acanthopanax senticosus ). The monograph states
that it is contraindicated for hypertension. Eleuthero is generally considered
by most herbalists in the U.S. to be milder in activity than the more
stimulating root of Asian Ginseng ( Panax ginseng ). However, there is
documentation in the literature of at least two studies in which it was
recommended that Eleuthero not be given to persons with a blood pressure in
excess of 180/90 mm Hg (Farnsworth, 1985). Presumably, this information prompted
the Commission to note this possible adverse effect in some people and thus the
contraindication.
Ginger
An example of a warning about which we have taken issue can be found in the
monograph on Ginger root. Commission E contraindicates the common spice as a
remedy for morning sickness during pregnancy. However, there is no evidence that
the therapeutic dosage for antinauseant activity cited by Commission E (1 gram
of dried root) produces any harm to either the fetus or the mother. The
Commission presumably based its caution on two studies published in the 1980s in
Japan on 6-gingerol, one of the compounds isolated from ginger rhizome. In vitro
tests indicated that the gingerol had mutagenic activity in vitro at high doses
(Namakura and Tamamoto, 1982; Nagabhushan et al., 1987). However, other
compounds in ginger have been found to exhibit anti-mutagenic activity (Kada et
al., 1978). Ginger is also widely used in Traditional Chinese Medicine (TCM),
but without contraindications in pregnancy. "On the contrary, ginger has
been traditionally used for nausea and vomiting in pregnancy, though as in
typical TCM usage, rarely by itself. There is no lack of remedies for these
conditions using ginger. Also, there is no contraindication of ginger in any of
the recent issues of the Pharmacopoeia of the People's Republic of China (newest
edition, 1995); the dosage is 3-9 grams for both fresh and dried ginger."
(Leung, 1998). A literature review of all available clinical studies on ginger
could find no scientific or medical evidence for Commission E's contraindication
during pregnancy (Fulder and Tenne, 1996). Prof. Schilcher agrees with this
assessment of ginger's presumed safety during pregnancy (Schilcher, 1997b).
Using the fact that ginger is approved by Commission E as a nonprescription
remedy for motion sickness in Germany, in 1995 the European-American
Phytomedicine Coalition (EAPC) filed a citizens petition with the FDA for ginger
to be reviewed as an OTC drug for anti-nausea and motion sickness (Pinco and
Israelsen, 1995). The petition included clinical studies on ginger in
experimental conditions as well as in situ (e.g., with first-time sailors at
sea). It also contained extensive market data in Europe and other countries
where ginger is employed as a medicine. The totality of the materials support
the safety and efficacy of ginger as a medicine. By spring 1998 the FDA had not
yet responded to this petition.
Ginkgo
A monograph for ginkgo leaf and various types of extracts from Ginkgo leaf is
listed as unapproved; a standardized dry extract of Ginkgo biloba leaf is listed
in the approved section. The 1993 and 1994 monographs on Ginkgo biloba
clearly focus on specific extracts or preparations rather than on the plant as a
whole. For instance, the approved Ginkgo extract is the extract on which almost
all the scientific and clinical studies on the effectiveness of Ginkgo biloba
extract have been carried out (Foster, 1996). Thus, only the acetone-water
extract of Ginkgo would be approved. The Commission's evaluation on ginkgo was
based on the review of a 210-page monograph on ginkgo research submitted by the Kooperation
Phytopharmaka in which no effects were documented for dried ginkgo leaf
(Schilcher, 1997b).
In May 1997, the BfArM sent a letter to manufacturers of ginkgo extracts and
other preparations regarding the levels of ginkgolic acid in these products
(Thiele, 1997). The letter stated that, based on the present level of knowledge,
the BfArM considered it necessary to reduce the content of ginkgolic acid in
finished ginkgo preparations to a maximum level of 5 ppm (parts per million). If
proof of this level cannot be documented, "the registration for these
pharmaceuticals will be canceled since in this case, there is the well-founded
suspicion that the pharmaceuticals — when used in accordance with the
instructions [in the monographs] — produce damaging effects which exceed a
justifiable degree according to the knowledge of medical science." (Thiele,
1997.) The discussion on this issue had not yet been finalized by the end of
1997. Numerous responses from members of industry (both pro and con the 5 ppm
proposal) were submitted to the BfArM (Steinhoff, 1997). However, according to
Prof. Schilcher, the Commission did discuss the maximum 5 ppm level and agreed
to the requirement (Schilcher, 1997b).
Hawthorn
In January 1984 all the preparations of Hawthorn berry, leaf, and flower were
approved in one monograph on the basis of historical experience, many
pharmacological studies, about 20 open clinical studies, and many patient case
reports (Schilcher, 1997b). The originally approved monograph indications were
for functional stages I and II of NYHA (New York Heart Association assessment of
the four stages of heart disease). This earlier monograph also included
sensation of pressure in the chest, cardiac degeneration not yet requiring
digitalis ( Altesherz ), and slight forms of bradycardic arrhythmias
(Steinhoff, 1997).
Later, however, the pharmacodynamics (the effects of a substance on the
physiological processes) of a 45 percent ethanol extract or 70 percent methanol
extract of flowering leaf tops with defined content of flavonoids and
proanthocyanidins were elaborated. The other three Hawthorn preparations were
reevaluated: "the flowers, leaves, and fruits as single compounds received
a negative assessment because there no longer seemed to be sufficient scientific
evidence to justify their inclusion." (Steinhoff, 1993/1994a.)
Commenting on the Hawthorn monograph changes, Prof. Schilcher has written
that in 1984 the Commission had an abundance of scientific material, although
none were studies carried out according to GCP (good clinical practices). The
studies (both experimental and clinical) in the past six years confirmed the
previous knowledge of Hawthorn's activity and resulted in a more precise
indication for the approved monograph, i.e., NYHA Stage II only (Schilcher,
1997b). This brought the monographs in line with the 10th edition of the French
Pharmacopeia , which specifies "dried flowering tops" of Crataegus
monogyna . For this reason, there are four Hawthorn monographs: the Approved
flower with leaves, and the three Unapproved for berry, flower, and leaf
individually. These four monographs were published in July 1994 and replaced the
original monograph. Presently, the only approved indication (in the leaf with
flower monograph) is limited to "decreasing cardiac output according to
functional stage II of the NYHA." The approval of the one Hawthorn
preparation based on the extract of leaf with flower is another example of the
trend by the Commission not only to rely on new scientific data for evaluations,
but also to reassess and approve specific, well-defined extract preparations,
often ones that are proprietary. (See pages 34 and 39 for related information.)
Horse Chestnut Seed
The 1994 revision of the Horse Chestnut seed monograph includes a detailed
description of the pharmacokinetics (the absorption/resorption of substances in
the human body) of the approved herb. The 1993 monograph on Horse Chestnut leaf
and flower was written without benefit of detailed pharmacokinetic findings, and
thus the herb was not approved. Also, the approved formulation for Horse
Chestnut was much more stringently defined than earlier. The old monograph
(December 5, 1984) defined the drug as Horse Chestnut seed with 3 percent
triterpene glycosides calculated as aescin, and indicated a daily dose
corresponding to 30-150 mg aescin. The new monograph (April 15, 1994) allows
only a defined extract with an aescin content of 16-21 percent in a slow-release
dosage form.
Sarsaparilla
Sarsaparilla (Unapproved) has been a commonly used botanical in herbal teas
as well as a flavoring for soft drinks in the U.S. for over a century. Oral
ingestion has produced few reports of adverse reactions. It is thus curious that
the Commission would note the "risk" that "Taking sarsaparilla
preparations leads to gastric irritation and temporary kidney impairment."
However, per our note in this monograph, "Contrary to the undocumented
claims of gastric irritation due to saponin content of sarsaparilla root, we can
find nothing in the scientific literature that substantiates this assertion. It
is well known that many commonly consumed vegetables contain saponins and
sarsaparilla root is a common ingredient in soft drinks, e.g., root beer and
many herbal teas. Therefore, we disagree with the Commission that potential
gastric irritation is a problem associated with the ingestion of this plant in
normal quantities."
Prof. Schilcher of the Commission agrees with our assessment; he notes that
the Commission's cautions were based on "a theoretical standpoint and we
have in Germany little experience with sarsaparilla"; he also conjectures
that any gastrointestinal problems potentially attributable to saponins in
sarsaparilla may be a function of dosage (Schilcher, 1997b).
Valerian
In 1994 the EAPC filed a citizens petition to amend the OTC drug monograph
for nighttime sleep-aid drug products to include preparations made from the root
of valerian (Pinco and Israelsen, 1994). The petition included clinical studies
documenting the activity of valerian as a non-habit-forming sedative, plus
extensive market data in Europe and other countries where valerian is employed
as a medicine — both supporting the safety and efficacy of valerian as a
medicine. By spring 1998 the FDA had not yet responded to this petition.
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