Introduction
Monopreparations
The main section of this book is comprised of monographs on
monopreparations, i.e., commercial preparations containing one herb or herbal
extract. Most of the clinical studies on these monopreparations have been
conducted in Western Europe, particularly Germany, where phytotherapy usually
is based on the use of single herbal products. Proprietary monopreparations may
be products made by a patented extraction process or products with a specific
chemical profile resulting from the standardization of specific constituents.
These techniques frequently attempt to provide the consumer with a product of
consistent quality, often containing uniform levels of one or more marker
compounds that in many cases are also the primary active ingredients. This
tends to create a product of consistent activity and efficacy. This proprietary
product section includes one monopreparation called Pycnogenol®. Two
tables beginning on page 398 list the proprietary herbal products mentioned in
this book, both monopreparations and multi-herb products, upon which clinical
research has been conducted.
Multi-herb Products
In European countries, as well as in the traditional herbal
medicine systems of India (Ayurveda), China (traditional Chinese medicine,
TCM), and Japan (Kampo), multi-herb products are used frequently instead of
monopreparations. In fact, in Asia the use of multi-herb products is the rule,
not the exception. The majority of herbal products used in Germany prior to
1990 were products containing fixed combinations of herbs (Schilcher, 1997).
Many multi-herb products contain similar, sometimes identical combinations
based on extensive traditional use or clinical evidence, whereas other
preparations are absolutely unique. The level of clinical evidence supporting
specific multi-herb products varies widely. For several multi-herb products it
has been shown that the therapeutic effect of the combination is greater than
the sum of the individual constituents’ activities, and may result in better
results compared to those of herbal monopreparations or of synthetic drugs.
This section includes only multi-herb products with at least two human studies
supporting their use. Multi-herb products with only one clinical study are
listed in the combination section of the table of clinical studies and in the
Branded Products section of the respective single herb monographs (e.g.,
echinacea, valerian). Please note that this review contains several specific
multi-herb products but does not include all products upon which clinical
research has been conducted. Inclusion of
specific proprietary products in this section and elsewhere in this book is not
meant to serve as an endorsement of particular products, but only as an
acknowledgement of the extent of clinical studies associated with the
respective product.
European Multi-Herb Products and Commission E Fixed Combinations
The German Commission E approved the use of 66 “fixed
combinations”—herbal formulas that represent various commercial herbal products
sold as nonprescription medicines in German pharmacies (Blumenthal et al., 1998). Of the combination
formulas approved by Commission E, 35 are intended for digestive complaints,
while 21 deal with colds, flus, and catarrhal conditions of the upper
respiratory tract (with or without viscous phlegm), dry or spastic cough, and
related conditions. The next largest category of combinations is intended to
treat unrest and insomnia due to nervousness.
The Commission E approved the use of combination formulas
only if each herb in the formula “makes a positive contribution to the
evaluation of the total preparation” i.e., contributes directly to the overall
safety and efficacy of the formula. In approving such formulas, each herb must
also have an individual monograph that is the result of an evaluation of the
available literature on that botanical. The evaluation must focus on safety
primarily and then efficacy according to a “doctrine of reasonable certainty”
(Blumenthal et al., 1998). In
addition, the herbs in each formula must be found in “dosages appropriate for
effectiveness.” Thus, the rationale for the use of herbs in combinations in
Commission E-approved formulas is significantly different from the way herbs
are used in complex formulas in Asian traditional medicine, where individual
herbs are not required to contribute directly to the intended application of
the formula, as stipulated by Commission E, but their inclusion in the formula
is based on a variety of rationale, as noted below.
The most frequently prescribed nonprescription drug in
Germany is a proprietary, multi-herb product named Sinupret®, used
for sinusitis and inflammatory conditions of the respiratory tract (see
Sinupret® monograph below). In 1997, Sinupret® ranked
12th in number of prescriptions among all drug products, with 3.4 million
prescriptions (Schulz et al., 2001).
The following multi-herb products from the European market are also included in
this chapter: Alluna™, Esberitox®, Euvegal®, Mastodynon®,
Phytodolor®, and Prostagutt® forte.
Chinese Multi-Herb Products
China contains one of the world’s oldest systems of
traditional herbal medicine that has been documented in writing, with early
texts dating back as far as 170 B.C.E. (Dharmananda, 2002). Chinese herbal
medicine is based primarily on the combination of numerous herbs into simple or
relatively complex formulas. In TCM, multi-herb products are based on a
sophisticated system of “energetics” in which the herbs are employed based on
their empirically observed properties. Thus, the formulas usually rely on one
“superior” herb to dictate the therapeutic focus of the formula, and then are
primarily based on the “heating” or “cooling” properties of each herb and the
five characteristic flavors (sweet, bitter, spicy, salty, and sour), which
correspond to particular pharmacological activities (Hsu, 1986). While a
thorough explanation of the intricacies of the TCM system of herbal medicine is
not possible here, suffice it to say that many combinations have become
standardized, often employed in modern TCM using the same formulations as found
in classic texts for centuries, while sometimes being slightly modified, based
on the professional judgement of the practitioner. However, from a Western
perspective, few controlled clinical trials have been published in Western
medical journals on TCM herbal formulas. A notable exception was a recent trial
on a Chinese herbal formula to treat irritable bowel syndrome (IBS), published
in a special complementary and alternative medicine edition of the Journal of the American Medical Association
(Bensoussan et al., 1998). In this
three-arm trial, patients received either a standardized formula, a customized
formula prepared for each subject based on the concept of differential
diagnosis, or placebo. The results suggested that the Chinese herbs were
significantly better than placebo in providing relief from the symptoms of IBS,
as measured in the trial.
Indian (Ayurvedic) Multi-Herb Products
Ayurveda is the ancient system of traditional medicine in
India, owing its origins to medical writings found in the RigVeda, a sacred
Sanskrit text that is believed to have been written from 4500 to 1600 B.C.E.
(Kapoor, 1990). In Ayurvedic herbal formulas, the inclusion of multiple herbs
is based on a rationale that is similar to TCM (some authors consider Ayurveda
to be the older, philosophical basis for TCM) but distinctly different from the
European system of herbal medicine. The primary governing concept in Ayurveda
is that the proper combination of herbs can greatly enhance their respective
healing abilities. Ayurvedic herbal formulas begin with an individual herb that
encompasses the primary action considered most appropriate for the individual’s
particular condition. Additional herbs with similar primary actions are
included to support the activity of the formula. For example, in a diaphoretic
formula, used to induce perspiration and treat a common cold, additional herbs
may be added to help enhance mucous discharge from the throat or lungs.
Further, herbs with potential actions that contradict the activity of the main
herbs might be added to balance the formula or prevent it from exhibiting an
excessive or one-sided action. They can also help reduce potential adverse side
effects of some of the main herbs. Stimulant herbs such as black pepper (Piper nigrum), long pepper (P. longum), ginger (Zingiber officinale), and cayenne pepper (Capsicum spp.) may also be included to enhance absorption (Lad and
Frawley, 1986). The rationality of this long-used empirical practice is
validated by modern research demonstrating that the compound piperine in long
pepper and black pepper increases activity of dietary supplements and
conventional pharmaceutical drugs by enhancing the serum concentration, extent
of absorption and bioavailability by inhibiting drug metabolism (i.e.,
breakdown) (Badmaev et al., 2000;
Khajuria et al., 1998; Bano et al., 1991; Atal et al., 1985, 1981).
Liv.52® is an example of an Ayurvedic multi-herb
product and is used for liver dysfunction. In total sales volume, including
statistics for the entire pharmaceutical industry (both nonprescription and
prescription drugs), Liv.52® is the leading brand in India (ORG-MARG
Private Limited, 2001).
Japanese (Kampo) Multi-Herb Products
Kampo, Japan’s traditional herbal medicine, is playing an
increasingly important role in Japanese healthcare and represents a $1 billion
segment of annual drug sales in Japan (Matsumoto et al., 1999). In a recent survey, 96% of responding physicians
indicated that they practice Kampo (Watanabe et al., 2001), and Japan’s Ministry of Health and Welfare approves
148 Kampo prescription drugs for reimbursement under the national health
insurance (Tsumura, 1999).
Kampo is based on TCM, which developed a sophisticated
understanding of the effectiveness and safety of combinations of herbs derived
from long practical experience. Following the introduction of Chinese medicine
to Japan in the fourth century, Japanese practitioners gradually altered the
original formulas. Particularly, after the 17th century, the original formulas
were validated through clinical experience, and the foundation was laid for
uniquely Japanese Kampo medicine. Thus, although Kampo has its roots in China,
it is also a product of Japanese culture and experience.
Like other forms of Asian traditional medicine, Kampo takes
a holistic approach to health, seeking to enhance the body’s natural harmony
and recuperative power. Chronic conditions such as allergies, asthma,
menopausal symptoms, disorders of the elderly, autonomic imbalance, and other
non-specific complaints, and rheumatism are often treated with Kampo, due to
the gentle action and multiple active substances of Kampo formulations. Kampo
is also recommended for patients who respond poorly or have adverse reactions
to Western medicine, as well as for common complaints like colds and gastritis.
Hochu-ekki-to® is a
well-known Kampo formula originally described in the Chinese medical classic Nei Wai Shang Bian Huo Lun (Nai-gai-sho-ben-waku-ron in Japanese) by
Li Dong Yuan (1247 C.E.). This formulation was traditionally prescribed for
patients showing a decline of digestive function and marked fatigability of
extremities. Since inclusion in the above-mentioned text, Hochu-ekki-to®
has undergone more than 700 years of use by healers in the traditional systems
of medicine of China, Japan, and other East Asian countries. Moreover, like
many other Kampo formulations, since it was approved as a prescription drug by
Japan’s Ministry of Health & Welfare in the 1970’s, the extract form, which
is produced according to pharmaceutical GMP standards, has accumulated more
than 20 years of clinical experience as used by conventional physicians as a
component of the modern medical system in Japan. Hochu-ekki-to® is
the second-leading Kampo formulation, with annual sales of $52.3 million (U.S.
dollars) in 1998 (Japan Kampo-Medicine Manufacturers Association, 2001).
Tibetan Formulas
Tibetan medicine has been used for centuries and dates back
to 300 B.C.E. Owing to Tibet’s geographical location, its medicine was deeply
influenced by both the Indian Ayurvedic and the Chinese medical systems, as
well as Persian medicine (which also incorporated tenets of ancient Greek
medicine). The primary text upon which traditional Tibetan medicine is based is
called the Gyu-zhi (The Four Tantras), an Ayurvedic text
written in Sanskrit and translated to Tibetan in the eight century C.E.
(Fallarino, 1994). Like Ayurvedic and Chinese formulas, Tibetan herbal
combinations usually contain a large number of herbs (8–25) intended to restore
balance to the body. The classification of herbal properties in Tibetan
medicine includes six tastes (sweet, sour, salty, bitter, acrid, astringent),
eight properties (heavy, smooth, cool, soft, light, rough, acrid, sharp) and 17
effects (hot, cold, warm, cool, thick, thin, moist, rough, light, heavy,
steady, motive, blunt, tender, dry, soft). Herbs with the opposite effects of
the disease are chosen for each combination. For example, a lung infection is
considered a hot disease, and is therefore treated with a combination
containing Rhodiola rosea, an herb
with cooling properties. Practitioners use a combination of herbs to treat the
condition because the cause of disease is thought to originate from a
combination of disturbances in the body (Khangkar, 1986).
Padma 28® is a product from Tibetan tradition.
This chapter reviews seven clinical studies supporting its possible use for
intermittent claudication, plus one preliminary study suggesting its use for
each of the following conditions: angina pectoris, hypercholesterolemia and
hypertriglyceridemia, and childhood respiratory tract infections.
Proprietary Monographs
With the exception of the monograph on Pycnogenol®,
the monographs in this section cover specific proprietary herbal combination
products and contain information taken primarily from product packages and
other sources. In the cases of some of the combinations sold in Europe and
non-European countries, where they are frequently licensed as nonprescription
drugs, the Primary Uses section includes uses usually approved by the
appropriate agencies of foreign governments. Additional information (Dosage,
Duration of Administration, Action, Contraindications, Pregnancy and Lactation,
Adverse Effects, Drug Interactions, etc.) in these monographs is also derived
from product package labels and/or package inserts, often reflecting the
labeling as approved or required by the government agencies.
The DSHEA Structure-Function Claim section refers to the
claim made on the U.S. label, as authorized by Section 6 of the Dietary
Supplement Health and Education Act of 1994 (DSHEA). Under this law,
manufacturers are authorized to make “statements of nutritional support”
regarding dietary supplement products, including how a supplement can affect
the structure or function of the human body. Such claims are not required to be
pre-approved by the Food and Drug Administration (FDA). The claims must meet
the following criteria: (1) they must be truthful and nonmisleading; (2) the
company must possess scientific information to document the statement; (3) the
company must notify the FDA that it intends to market the product with this
claim within 30 days of introducing the product claim to the market
(post-market notification); (4) the product must be labeled as a “dietary
supplement”; (5) the claims may not make any therapeutic claims, i.e., they
cannot claim to prevent, treat, or cure a disease; and (6) the product must
carry the disclaimer: “This statement has not been evaluated by the Food and
Drug Administration. This product is not intended to diagnose, treat, cure or
prevent any disease.” (DSHEA, 1994). FDA regulations also prohibit the use of
any name of a pathology or disease in a claim, but do allow manufacturers to
make claims that have been previously allowed for nonprescription drugs if the claim does not deal with a disease
state (e.g., antacid, antigas, digestive aid, laxative, nighttime sleep aid,
etc.) (FDA, 2000; Israelsen and Blumenthal, 2000).
Editors’
Note: The
monographs presented in the section on specific proprietary herbal combination
products are presented as some of the best examples of multi-herbal formulas
that have been subjected to various types of human clinical trials. By
including these products in this book, the editors are neither endorsing the
products nor the manufacturers; these products are included as concrete
examples of formulas from various herbal traditions that have been tested in
published clinical trials. Thus, the editors and publisher are merely
acknowledging the research on them as a means to provide healthcare
professionals with examples of complex formulas with potential use in self-care
and healthcare.
References for this proprietary herbal product section begin
on page 390.