|Jennifer Jacobs, M.D.-Cochair|
|John Reed, M.D.- Cochair|
|Michael Balick, Ph.D.||Robert Duggan|
|Steven Birch||Peter Hindebergh, M.D.
|Gerald Bodeker, Ed.D.||Tori Hudson, N.D.|
|Carola Burroughs||Ted Kaptchuk|
|Carlo Calabrese, N.D.||Fredi Kronenberg, Ph.D.|
|Edward Chapman, M.D.||Nancy Lonsdorf, M.D.|
|Deepak Chopra, M.D||Kevin McNamee|
|Effie Chow, Ph.D.||Paul Ortega|
|Patricia D. Culliton, M.A. Dipl.Ac.|
|CONTRIBUTING AUTHORS||Michael Balick, Ph.D.||Richard Pavek|
|James Duke, Ph.D.||Cheryl Pellerin|
|Ted Kaptchuk||John Reed, M.D.|
|Robert S. McCaleb, Ph.D.||James P. Swyers, M.A|
Early humans recognized their dependence on nature in both health and illness. Led by instinct, taste, and experience, primitive men and women treated illness by using plants, animal parts, and minerals that were not part of their usual diet. Physical evidence of use of herbal remedies goes back some 60,000 years to a burial site of a Neanderthal man uncovered in 1960 (Solecki, 1975). In a cave in northern Iraq, scientists found what appeared to be ordinary human bones. An analysis of the soil around the bones revealed extraordinary quantities of plant pollen that could not have been introduced accidentally at the burial site. Someone in the small cave community had consciously gathered eight species of plants to surround the dead man. Seven of these are medicinal plants still used throughout the herbal world (Bensky and Gamble, 1993). All cultures have long folk medicine histories that include the use of plants. Even in ancient cultures, people methodically and scientifically collected information on herbs and developed well defined herbal pharmacopoeias. Indeed, well into the 20th century much of the pharmacopoeia of scientific medicine was derived from the herbal lore of native peoples. Many drugs, including strychnine, aspirin, vincristine, taxol, curare, and ergot, are of herbal origin. About one-quarter of the prescription drugs dispensed by community pharmacies in the United States contain at least one active ingredient derived from plant material (Farnsworth and Morris, 1976).
Middle East medicine. The invention of writing was a focus around which herbal knowledge could accumulate and grow. The first written records detailing the use of herbs in the treatment of illness are the Mesopotamian clay tablet writings and the Egyptian papyrus. About 2000 B.C., King Assurbanipal of Sumeria ordered the compilation of the first known materia medica-an ancient form of today's United States Pharmacopoeia-containing 250 herbal drugs (including garlic, still a favorite of herbal doctors). The Ebers Papyrus, the most important of the preserved Egyptian manuscripts, was written around 1500 B.C. and includes much earlier information. It contains 876 prescriptions made up of more than 500 different substances, including many herbs (Ackerknecht, 1973).
Greece and Rome. One of the earliest materia medica was the Rhizotomikon, written by Diocles of Caryotos, a pupil of Aristotle. Unfortunately, the book is now lost. Other Greek and Roman compilations followed, but none was as important or influential as that written by Dioscorides in the 1st century A.D., better known by its Latin name De Materia Medica. This text contains 950 curative substances, of which 600 are plant products and the rest are of animal or mineral origin (Ackerknecht, 1973). Each entry includes a drawing, a description of the plant, an account of its medicinal qualities and method of preparation, and warnings about undesirable effects.
Muslim world. The Arabs preserved and built on the body of knowledge of the Greco-Roman period as they learned of new remedies from remote places. They even introduced to the West the Chinese technique of chemically preparing minerals. The principal storehouse of the Muslim materia medica is the text of Jami of Ibn Baiar (died 1248 A.D.), which lists more than 2,000 substances, including many plant products (Ackerknecht, 1973). Eventually this entire body of knowledge was reintroduced to Europe by Christian doctors traveling with the Crusaders. Indeed, during the Middle Ages, trade in herbs became a vast international commerce.
East India. India, located between China and the West, underwent a similar process in the development of its medicine. The healing that took place before India's Ayurvedic medical corpus was similar to that of ancient Egypt or China (i.e., sickness was viewed as a punishment from the gods for a particular sin). Ayurvedic medicine emerged during the rise of the philosophies of the Upanishads, Buddhism, and other schools of thought in India. Herbs played an important role in Ayurvedic medicine. The principal Ayurvedic book on internal medicine, the Characka Samhita, describes 582 herbs (Majno, 1975). The main book on surgery, the Sushruta Samhita, lists some 600 herbal remedies. Most experts agree that these books are at least 2,000 years old.
China and Japan. The earliest written evidence of the medicinal use of herbs in China consists of a corpus of 11 medical works recovered from a burial site in Hunan province. The burial itself is dated 168 B.C., and the texts (written on silk) appear to have been composed before the end of the 3rd century B.C. Some of the texts discuss exercise, diet, and channel therapy (in the form of moxibustion-see the "Alternative Systems of Medical Practice" chapter). The largest, clearest, and most important of these manuscripts, called by its discoverers Prescriptions for Fifty-Two Ailments, is predominantly a pharmacological work. More than 250 medicinal substances are named. Most are substances derived from herbs and wood; grains, legumes, fruits, vegetables, and animal parts are also mentioned. Underlying this entire text is the view that disease is the manifestation of evil spirits, ghosts, and demons that must be repelled by incantation, rituals, and spells in addition to herbal remedies.
By the Later Han Dynasty (25-220 A.D.), medicine had changed dramatically in China. People grew more confident of their ability to observe and understand the natural world and believed that health and disease were subject to the principles of natural order. However, herbs still played an important part in successive systems of medicine. The Classic of the Materia Medica, compiled no earlier than the 1st century A.D. by unknown authors, was the first Chinese book to focus on the description of individual herbs. It includes 252 botanical substances, 45 mineral substances, and 67 animal-derived substances. For each herb there is a description of its medicinal effect, usually in terms of symptoms. Reference is made to the proper method of preparation, and toxicities are noted (Bensky and Gamble, 1993).
Since the writing of the Classic of the Materia Medica almost 2,000 years ago, the traditional Chinese materia medica have been steadily increasing in number. This increase has resulted from the integration into the official tradition of substances from China's folk medicine as well as from other parts of the world. Many substances now used in traditional Chinese medicine originate in places such as Southeast Asia, India, the Middle East, and the Americas. The most recent compilation of Chinese materia medica was published in 1977. The Encyclopedia of Traditional Chinese Medicine Substances (Zhong yao da ci dian), the culmination of a 25-year research project conducted by the Jiangsu College of New Medicine, contains 5,767 entries and is the most definitive compilation of China's herbal tradition to date (Bensky and Gamble, 1993).
Traditional Chinese medicine was brought to Japan via Korea, and Chinese-influenced Korean medicine was adapted by the Japanese during the reign of Emperor Ingyo (411-453 A.D.). Medical envoys continued to arrive from Korea throughout the next century, and by the time of the Empress Suiko (592-628 A.D.), Japanese envoys were being sent directly to China to study medicine. Toward the end of the Muromachi period (1333-1573 A.D.) the Japanese began to develop their own form of traditional oriental medicine, called kampo medicine. As traditional Chinese medicine was modified and integrated into kampo medicine, herbal medicine was markedly simplified.
In North America, early explorers traded knowledge with the Native American Indians. The tribes taught them which herbs to use to sharpen their senses for hunting, to build endurance, and to bait their traps. In 1716, French explorer Lafitau found a species of ginseng, Panax quinquefolius L., growing in Iroquois territory in the New World. This American ginseng soon became an important item in world herb commerce (Duke, 1989). The Jesuits dug up the plentiful American ginseng, sold it to the Chinese, and used the money to build schools and churches. Even today, American ginseng is a sizable crude U.S. export.
As medicine evolved in the United States, plants continued as a mainstay of country medicine. Approaches to plant healing passed from physician to physician, family to family. Even in America's recent past, most families used home herbal remedies to control small medical emergencies and to keep minor ailments from turning into chronic problems. During this period there was a partnership between home folk medicine and the family doctor (Buchman, 1980). Physicians often used plant and herbal preparations to treat common ills. Until the 1940s, textbooks of pharmacognosy-books that characterize plants as proven-by-use prescription medicines--contained hundreds of medically useful comments on barks, roots, berries, leaves, resins, twigs, and flowers.
As 20th-century technology advanced and created a growing admiration for technology and technologists, simple plant-and-water remedies were gradually discarded. Today, many Americans have lost touch with their herbal heritage. Few Americans realize that many over-the counter (OTC) and prescription drugs have their origins in medicinal herbs. Cough drops that contain menthol, mint, horehound, or lemon are herbal preparations; chamomile and mint teas taken for digestion or a nervous stomach are time-honored herbal remedies; and many simple but effective OTC ache- and pain-relieving preparations on every druggist's and grocer's shelf contain oils of camphor, menthol, or eucalyptus. Millions of Americans greet the morning with their favorite herbal stimulant-coffee.
Despite the importance of plant discoveries in the evolution of medicine, some regulatory bodies such as the U.S. Food and Drug Administration (FDA)-the main U.S. regulatory agency for food and drugs-consider herbal remedies to be worthless or potentially dangerous (Snider, 1991). Indeed, today in the United States, herbal products can be marketed only as food supplements. If a manufacturer or distributor makes specific health claims about a herbal product (i.e., indicates on the label the ailment or ailments for which the product might be used) without FDA approval, the product can be pulled from store shelves
Despite FDA's skepticism about herbal remedies, a growing number of Americans are again becoming interested in herbal preparations. This surge in interest is fueled by factors that include the following:
The next section discusses the regulatory status of herbal medicine in various countries around the world, particularly in Europe and Asia, as well as in less developed countries. It is followed by an overview of promising European and Asian herbal medicine research and recommendations for making herbal medicine a more viable health care alternative in this country.
The World Health Organization (WHO) estimates that 4 billion people-80 percent of the world population-use herbal medicine for some aspect of primary health care (Farnsworth et al., 1985). Herbal medicine is a major component in all indigenous peoples' traditional medicine and is a common element in Ayurvedic, homeopathic, naturopathic, traditional oriental, and Native American Indian medicine (see the "Alternative Systems of Medical Practice" chapter).
The sophistication of herbal remedies used around the world varies with the technological advancement of countries that produce and use them. These remedies range from medicinal teas and crude tablets used in traditional medicine to concentrated, standardized extracts produced in modern pharmaceutical facilities and used in modern medical systems under a physician's supervision.
Drug approval considerations for phytomedicines (medicines from plants) in Europe are the same as those for new drugs in the United States, where drugs are documented for safety, effectiveness, and quality. But two features of European drug regulation make that market more hospitable to natural remedies. First, in Europe it costs less and takes less time to approve medicines as safe and effective. This is especially true of substances that have a long history of use and can be approved under the "doctrine of reasonable certainty." According to this principle, once a remedy is shown to be safe, regulatory officials use a standard of evidence to decide with reasonable certainty that the drug will be effective. This procedure dramatically reduces the cost of approving drugs without compromising safety. Second, Europeans have no inherent prejudice against molecularly complex plant substances; rather, they regard them as single substances.
The European Economic Community (EEC), recognizing the need to standardize approval of herbal medicines, developed a series of guidelines, The Quality of Herbal Remedies (EEC Directive, undated). These guidelines outline standards for quality, quantity, and production of herbal remedies and provide labeling requirements that member countries must meet. The EEC guidelines are based on the principles of the WHO's Guidelines for the Assessment of Herbal Medicines (1991). According to these guidelines, a substance's historical use is a valid way to document safety and efficacy in the absence of scientific evidence to the contrary. (App. C contains the complete WHO guidelines.) The guidelines suggest the following as a basis for determining product safety:
A guiding principle should be that if the product has been traditionally used without demonstrated harm, no specific restrictive regulatory action should be undertaken unless new evidence demands a revised risk-benefit assessment.... Prolonged and apparently uneventful use of a substance usually offers testimony of its safety.
With regard to efficacy, the guidelines state the following:
For treatment of minor disorders and for nonspecific indications, some relaxation is justified in the requirements for proof of efficacy, taking into account the extent of traditional use; the same considerations may apply to prophylactic use (WHO, 1991).
The WHO guidelines give further advice for basing approval on existing monographs:
If a pharmacopoeia monograph exists it should be sufficient to make reference to this monograph. If no such monograph is available, a monograph must be supplied and should be set out in the same way as in an official pharmacopoeia.
To further the standardization effort and to increase European scientific support, the physiotherapy societies of Belgium, France, Germany, Switzerland, and the United Kingdom founded the European Societies' Cooperative of Phytotherapy (ESCOP). ESCOP's approach to eliminating problems of differing quality and therapeutic use within EEC is to build on the German scientific monograph system (below) to create "European" monographs.
In Europe, herbal remedies fall into three categories. The most rigorously controlled are prescription drugs, which include injectable forms of phytomedicines and those used to treat life threatening diseases. The second category is OTC phytomedicines, similar to American OTC drugs. The third category is traditional herbal remedies, products that typically have not undergone extensive clinical testing but are judged safe on the basis of generations of use without serious incident.
The following brief overviews of phytomedicine's regulatory status in France, Germany, and England are representative of the regulatory status of herbal medicine in Europe.
France, where traditional medicines can be sold with labeling based on traditional use, requires licensing by the French Licensing Committee and approval by the French Pharmacopoeia Committee. These products are distinguished from approved pharmaceutical drugs by labels stating "Traditionally used for ..." Consumers understand this to mean that indications are based on historical evidence and have not necessarily been confirmed by modern scientific experimentation (Artiges, 1991).
Germany considers whole herbal products as a single active ingredient; this makes it simpler to define and approve the product. The German Federal Health Office regulates such products as ginkgo and milk thistle extracts by using a monograph system that results in products whose potency and manufacturing processes are standardized. The monographs are compiled from scientific literature on a particular herb in a single report and are produced under the auspices of the Ministry of Health Committee for Herbal Remedies (Kommission E). Approval of such remedies requires more scientific documentation than traditional remedies, but less than new pharmaceutical drug approvals (Keller, 1991).
In Germany there is a further distinction between "prescription-only drugs" and "normal prescription drugs." The former are available only by prescription. The latter are covered by national health insurance if prescribed by a physician, but they can be purchased over the counter without a prescription if consumers want to pay the cost themselves (Keller, 1991). OTC phytomedicines-used for self-diagnosed, self-limiting conditions such as the common cold, or for simple symptomatic relief of chronic conditions-are not covered by the national health insurance plan.
England generally follows the rule of prior use, which says that hundreds of years of use with apparent positive effects and no evidence of detrimental side effects are enough evidence-in lieu of other scientific data-that the product is safe. To promote the safe use of herbal remedies, the Ministry of Agriculture, Fisheries, and Food and the Department of Health jointly established a database of adverse effects of nonconventional medicines at the National Poisons Unit.
In more developed Asian countries such as Japan, China, and India, "patent" herbal remedies are composed of dried and powdered whole herbs or herb extracts in liquid or tablet form. Liquid herb extracts are used directly in the form of medicinal syrups, tinctures, cordials, and wines.
In China, traditional herbal remedies are still the backbone of medicine. Use varies with region, but most herbs are available throughout China. Until 1984 there was virtually no regulation of pharmaceuticals or herbal preparations. In 1984, the People's Republic implemented the Drug Administration Law, which said that traditional herbal preparations were generally considered "old drugs" and, except for new uses, were exempt from testing for efficacy or side effects. The Chinese Ministry of Public Health would oversee the administration of new herbal products (Gilhooley, 1989).
Traditional Japanese medicine, called kampo, is similar to and historically derived from Chinese medicine but includes traditional medicines from Japanese folklore. Kampo declined when Western medicine was introduced between 1868 and 1912, but by 1928 it had begun to revive. Today 42.7 percent of Japan's Western-trained medical practitioners prescribe kampo medicines (Tsumura, 1991), and Japanese national health insurance pays for these medicines. In 1988, the Japanese herbal medicine industry established regulations to manufacture and control the quality of extract products in kampo medicine. Those regulations comply with the Japanese government's Regulations for Manufacturing Control and Quality Control of Drugs.
Herbal medicines are the staple of medical treatment in many developing countries. Herbal preparations are used for virtually all minor ailments. Visits to Western-trained doctors or prescription pharmacists are reserved for life-threatening or hard-to-treat disorders.
Individual herbal medicines in developing regions vary considerably; healers in each region have learned over centuries which local herbs have medicinal worth. Although trade brings a few important herbs from other regions, these healers rely mainly on indigenous herbs. Some have extensive herbal materia medica. A few regions, such as Southeast Asia, import large amounts of Chinese herbal preparations. But the method and form of herb use are common to developing regions.
In the developing world, herbs used for medicinal purposes are "crude drugs." These are unprocessed herbs-plants or plant parts, dried and used in whole or cut form. Herbs are prepared as teas (sometimes as pills or capsules) for internal use and as salves and poultices for external use. Most developing countries have minimal regulation and oversight
The professional literature of Europe and Asia abounds with efficacy and safety studies of many herbal medicines. It is beyond this report's resources to investigate the validity of this vast literature. The following is an overview of some of the more promising research on herbal remedies around the world.
European phytomedicines, researched in leading European universities and hospitals, are among
the world's best studied medicines. In some cases they have been in clinical use under medical supervision for more than 10 years, with tens of millions of documented cases. This form of botanical medicine most closely resembles American medicine. European phytomedicines are produced under strict quality control in sophisticated pharmaceutical factories, packaged and labeled like American medicines, and used in tablets or capsules.
Examples of well-studied European phytomedicines include Silybum marianum (milk thistle), Ginkgo biloba (ginkgo), Vaccinium myrtillus (bilberry extract), and Ilex guayusa (guayusa). Their efficacy is well documented. Herbs of American origin, such as Echinacea (purple coneflower) and Serenoa repens (saw palmetto), are better studied and marketed in Europe than in the United States. Below is an overview of recent research on these phytomedicines and American herbs.
European clinical trials have shown the effectiveness of bilberry extract for venous insufficiency of the lower limbs in 18- to 75-year-old subjects (Corsi, 1987; Guerrini, 1987). It has been used to treat varicose veins in the legs, where it significantly improved symptoms of varicose syndrome such as cramps, heaviness, calf and ankle swelling, and numbness (Gatta, 1982). These trials revealed no significant side effects, even at 50 percent over the normal dose. In two clinical trials, a standardized bilberry extract was given to 115 women with venous insufficiency and hemorrhoids following pregnancy. Both studies documented improvements of symptoms, including pain, burning, and pruritus, all of which disappeared in most cases (Baisi, 1987; Teglio et al., 1987).
Ginkgo extracts also stimulate circulation in the limbs, reducing coldness, numbness, and cramping. In elderly people, ginkgo improved pain-free walking distance by 30 percent to 100 percent (Foster, 1990). It also lowered high cholesterol levels in 86 percent of cases tested and prevented oxygen deprivation of the heart (Schaffler and Reeh, 1985). The extract seems to affect neurons directly, as shown by a recent French study (Yabe et al., 1992). Another French study proved protection against cell damage, this time by ultraviolet light (Dumont et al., 1992).
A German study documented benefits of long term ginkgo use in reducing cardiovascular risks, including those associated with coronary heart disease, hypertension, hypercholesterolemia, and diabetes mellitus (Witte et al., 1992). By maintaining blood flow to the retina, ginkgo extracts inhibited deteriorating vision in the elderly. An adequate amount of extract may reverse damage from lengthy oxygen deprivation of the retina. The assessment by doctors and patients of the patients' general condition showed a significant improvement after therapy. These results show that visual field damage from chronic lack of blood flow is reversible (Raabe et al., 1991).
Echinacea exhibits interferon like antiviral activity documented through extensive experiments in Germany. For example, in a double-blind, placebo-controlled study of 180 volunteers, Echinacea's therapeutic effectiveness for treating flu-like symptoms was "good to very good" (Braunig et al., 1992). Another study showed that orally administered Echinacea extracts significantly enhanced phagocytes in mice (Bauer et al., 1988). Water-soluble Echinacea components strongly activated macrophages (Stimpel et al., 1984),, enhanced immune system cell motility, and increased these cells' ability to kill bacteria. Other immune system cells were stimulated to secrete the disease-fighting tumor necrosis factor and interleukins 1 and 6 (Roesler et al., 1991). Another study showed that Echinacea polysaccharides increased the number of immunocompetent cells in the spleen and bone marrow and the migration of those cells into the circulatory system. The authors said these effects resulted in excellent protection of mice against consequences of lethal listeria and candida infections (Coeugniet and Elek, 1987).
Another effective herbal drug for treating BPH is made from Prunus africanum and is widely prescribed in France. It is interesting to note that the U.S. government is funding a multicenter study on BPH treatment to find the most cost-effective criteria for surgical versus medical treatment. However, because the study includes neither saw palmetto nor Prunus africanum, it may not reflect the "state of the art" in clinical medicine worldwide.
Since the early 19th century, attempts have been made to understand the actions and properties of traditional Chinese medicine through scientific research. Nearly all of this work has been conducted during the past 60 years, primarily in laboratories in China, Korea, Japan, Russia, and Germany. It was also during this time that most of the drugs used in modern biomedicine were developed. It is therefore not surprising that most of the biomedical research into the effects and uses of traditional Chinese medicinal substances has attempted to isolate their active ingredients and to understand their effects on body tissues.
Several institutions and laboratories at the forefront of medicinal plant research in China are working to identify and study the active ingredients in traditional Chinese herbal remedies. Researchers at the Institute of Materia Medics in Beijing study the use of herbal remedies to prevent and treat the common cold, bronchitis, cancer, and cardiovascular disease and to prevent conception. The institute has isolated compounds such as bergenin from Ardisia japonica, traditionally used to treat chronic bronchitis, and monocrotaline from Crotalaria sessiliflora, used in folk medicine to treat skin cancer. Most of China's 5,000 medicinal plant species are represented in the institute's herbarium. Other Chinese research organizations with major programs on medicinal herbs are the Institute of Chinese Medicine, Beijing; the Institute of Materia Medica, Shanghai; the Institute of Organic Chemistry, Shanghai; the Municipal Hospital of Chinese Traditional Medicine, Beijing; the College of Pharmacy, Nanking; and the Department of Organic Chemistry and Biochemistry, Beijing University (Duke and Ayensu, 1985).
Many herbs in China have been extensively studied by using methods acceptable from a Western perspective. For example, a 1992 article in the Journal of Ethno pharmacology reported that during the preceding 10 years more than 300 original papers on Panax ginseng had been published in Chinese and English (Liu and Xiao, 1992). Ginseng is one of the world's most thoroughly researched herbs. Following is an overview of recent research on ginseng and other herbs in China. Unless otherwise indicated, the data on specific herbs are taken from Chinese Herbal Medicine: Materia Medica, revised edition, compiled and translated by Dan Bensky and Andrew Gamble (1993).
In modern times, ginseng has been extensively studied in China, Japan, and Korea and, to a lesser degree, in the United States. In its various forms, ginseng or its compounds have various physiological effects. These include antis tress capabilities (Cheng et al., 1986; Yuan et al., 1988), antihypoxia effects (Cheng et al., 1988; Han et al., 1979; Qu et al., 1988), alteration of circadian rhythms by modifying neurotransmitters (Lu et al., 1988; Zhang and Chen, 1987), cardiac performance effects (Chen et al., 1982), protection against myocardial infarction in animals (Chen, 1983; Fang et al., 1986), histamine response effects (Zhang et al., 1988), inhibition of platelet aggregation (Shen et al., 1987; Yang et al., 1988), alteration of circadian variation of plasma corticosterone (Li et al., 1988), modulation of immune functions (Qian et al., 1987; Wang et al., 1980), and delay of the effects of aging (Tong and Chao, 1980; Zhang, 1989).
In another study, 6 to 10 thin pieces of sheng jiang placed over the testes were used to treat acute orchitis (inflammation of the testicles). The ginger was changed daily or every other day. All participants felt a hot--to-numbing sensation in the scrotum, while a few reported local erythema and edema. Among 24 patients in the study, average cure time was 3 days. In a control group of four patients, average healing time was 8.5 days. This technique is not recommended for patients with scrotum lesions.
Huang lian preparations have a strong inhibitory effect in vitro against many pathogenic fungi. Capsules of powdered huang lian were given to patients with typhoid fever, with good results. In one report, two cases that were resistant to antimicrobials responded to this herb. In another study, 30 cases of pulmonary tuberculosis were treated with huang lian for 3 months; all improved.
A 10-percent solution of huang lian also was used to treat 44 cases of scarlet fever. It was as effective as penicillin or a combination of penicillin and a sulfa drug. Huang lian also has been successfully used to treat diphtheria; in one study, the fever subsided in 1 to 3 days. Huang lian ointments or solutions promoted healing and reduced infections in first- and second-degree burns. It also has positive effects on blood pressure, smooth muscle, lipid metabolism, and the central nervous system; is effective as an anti-inflammatory; and has been used successfully in gynecology, ophthalmology, and dermatology patients.
In a study of 100 subjects, only 10 percent of the group given a da qing ye decoction twice daily had upper respiratory infections during the study period versus 24 percent of the control group. When a mixture of decoctions of da qing ye and Herba taraxaci mongolici cum radice (pu gong ying) was given to 150 children with measles, signs and symptoms disappeared in 4 to 5 days. In 68 of 100 cases, da qing ye was used successfully to treat infectious hepatitis.
One study was performed with 1,000 subjects to see whether ye ju hua would prevent colds. The subjects were compared with their own histories and against a matched set of 261 controls. A ye ju hua decoction was taken once a month by people with histories of infrequent colds, twice a month by those with three to five colds a year, and weekly by those with frequent colds. Comparison with their own histories showed a 13.2-percent reduction in frequency, but a greater frequency in comparison with the controls. At the same time, another clinical series of 119 cases of chronic bronchitis was observed. Using the same preparation, this group experienced a 38percent reduction in acute attacks in comparison with their seasonally adjusted rate for the previous year.
In another study, powdered bai ji was used to treat 69 cases of bleeding ulcers, and in all cases the bleeding stopped within 6.5 days. In another series of 29 perforated ulcer cases, the powdered herb was successful in 23 cases, 1 required surgery, and the other 4 died (1 went into hemorrhagic shock while under treatment, and the other 3 were in precarious condition on admission).
In other studies, powdered bai ji was given to 60 chronic tuberculosis patients who had not responded to normal therapy. After taking the herb for 3 months, 42 were clinically cured, 13 significantly improved, and 2 showed no change. A sterile ointment made from decocted bai ji and petroleum jelly was used in a local application to treat 48 cases of burns and trauma (less than 11 percent of total body area). Dressings were changed every 5 to 7 days, and all patients recovered within 1 to 3 weeks.
In rats with experimentally induced atherosclerosis, gan cao lowered cholesterol levels and stopped progression of lesions. In several experiments, the herb reduced the toxicity of some substances, including cocaine, and moderately reduced the toxicity of others, including caffeine and nicotine. When decocted with fu zi, it sharply reduced fu zi's toxicity.
In other studies, decoctions and alcohol extracts of dong bei guan zhong strongly stimulated the uterus of guinea pigs and rabbits. It increased the frequency and strength of contractions. Intramuscular injections of dong bei guan zhong preparations were used with more than 91-percent success to treat postpartum, postmiscarriage, and postsurgical bleeding.
When used with Chinese leek seeds, da suan juice and decoctions have a strong inhibitory effect in vitro against many pathogenic bacteria. Da suan can be effective against bacteria that resist penicillin, streptomycin, and chloramphenicol. In one clinical study, 130 patients with bacillary dysentery were given da suan enemas. Of the follow-up colonoscopies, 126 showed that pathological changes were resolved within 6.3 days. In other studies with hundreds of patients, da suan's effectiveness against bacillary dysentery was more than 95 percent. Again, purple-skinned garlic seemed more effective than white-skinned, and fresh bulbs were more effective than old ones. In one clinical study, 17 cases of encephalitis B were treated with an intravenous drip of da suan preparations and supportive care. Except for one fatality, all other cases recovered.
Ayurveda, the oldest existing medical system, is recognized by WHO and is widely practiced. The word comes from two Sanskrit roots: ayus means life or span; veda means knowledge or science. India recently increased research on traditional Ayurvedic herbal medicines after observations that they are effective for conditions to which they have traditionally been applied. For example, the ancient Sanskrit text on Ayurveda, the Sushruta Samhita, noted that Commiphora mukul was useful in treating obesity and conditions equivalent to hyperlipidemia, or increased concentrations of cholesterol in the body. The plant has been used by Ayurveda practitioners for at least 200 years and may have been in use since the writing of the Sushruta Samhita more than 2,000 years ago. In a recent study, the crude gum from Commiphora mukul significantly lowered serum cholesterol in rabbits with high cholesterol levels. The plant substance also protected rabbits from cholesterol-induced atherosclerosis (hardening of the arteries). This finding led to pharmacological and toxicological studies that showed this herbal remedy to be effective in humans, with no adverse side effects. Approval was obtained from the national regulatory authority in India for further clinical trials (Verma and Bordia, 1988). The drug is marketed in India and other countries for treatment of hyperlipidemia (Chaudhury, 1992).
The following other Ayurvedic herbs have recently been studied in India under modern scientific conditions:
In 1977 and 1978, Croom (see Kirkland et al., 1992) spent 2 years documenting plant remedies among the Lumbee Indians, the largest group of Native American Indians east of the Mississippi River. Following are some often-used medicinal plant remedies of the Lumbee:
According to the Handbook of Northeastern Indian Medicinal Plants Native American Indians used about 25 percent of the flora of Maryland for medicinal purposes (Duke, 1986). A few examples of medicinal plant species in Maryland are as follows:
The regulatory lockout of natural remedies has crippled natural products research in U.S. universities and hospitals. There is no dedicated level of support by the Federal Government for herbal medicine research. Herbalists may apply under existing guidelines for approval of new pharmaceutical drugs, but this burden is unrealistic because the total cost of bringing a new pharmaceutical drug to market in the United States is an estimated $140 million to $500 million (Wall Street Journal, 1993). Because botanicals are not patentable (although they can be patented for use), an herbal medicine manufacturer could never recover this expenditure. Therefore, herbal remedies are not viable candidates for the existing drug approval process: pharmaceutical companies will not risk a loss of this magnitude, and herb companies lack the financial resources even to consider seeking approval.
Another major barrier is that the academic infrastructure necessary for proper study of ethno medical systems has seriously eroded in recent decades and must be reinvigorated to accommodate the newly recognized need for preserving traditional medical systems and biological diversity. Pharmacognosy and other academic studies of medicinal plants have declined alarmingly in the United States. North American scientists, once at the forefront of this research, lag behind their European and Japanese colleagues, reducing the likelihood that they will discover useful new medicines from plants. This problem is exacerbated by the fact that much of the discipline of botany has moved away from field studies and into molecular and laboratory approaches. Today only a handful of active fulltime ethnobotanists are trained to catalog information on the medicinal properties of plants.
In contrast to the United States, many European and Asian countries have taken a more holistic approach to researching the efficacy of herbal remedies. In Germany, France, and Japan, the past 20 years have seen a rapid increase in research into and use of standardized, semipurified (still containing multiple individual chemicals) herbal extracts called phytomedicines. In Europe and Japan, phytomedicines treat conditions ranging from serious, life-threatening diseases such as heart disease and cancer to simple symptomatic relief of colds, aches and pains, and other conditions treated by OTC drugs in the United States. Phytomedicines include preventive medicines, an often-neglected area of medicine in the United States. The FDA has approved many plant-derived "heroic" cures, but never a plant-derived preventive medicine.
Much modern-day medicine is directly or indirectly derived from plant sources, so it would be foolish to conclude that plants offer no further potential for the treatment or cure of major diseases. Worldwide, the botanical pharmacopoeia contains tens of thousands of plants used for medicinal purposes. Hundreds, perhaps thousands, of definitive texts, monographs, and tomes on herbal remedies exist. But most of this information is outside current databases and remains unavailable to physicians, researchers, and consumers.
Globally, herbal remedies have been researched under rigorous controls and have been approved by the governments of technologically advanced nations. The scientific validation is good to excellent, and the history of clinical use is even stronger. Many phytomedicines have been used by thousands of physicians in their practices and are consumed under medical supervision by tens of millions of people.
A great deal of literature exists on the use of phytomedicines in Europe and within native medical systems in China, Japan, India, and North America. Much of this literature can be found in a unique database developed and maintained by the University of Illinois at Chicago, College of Pharmacy. The database, NAPRALERT (Natural Products Alert), holds references for more than 100,000 scientific articles and books on natural products (plant, microbial, and animal extracts). NAPRALERT includes considerable data on the chemistry and pharmacology (including human studies) of secondary metabolites of known structure, derived from natural sources. About 80 percent of the references are from post-1975 literature, the rest from pre-1975 literature (see the "Research Databases" chapter for more information on NAPRALERT).
In 1981 the U.S. Department of Agriculture (USDA), in conjunction with the National Cancer Institute, concluded a 25-year study of plants with possible anticancer properties. One result is published in the Handbook of Medicinal Herbs (Duke and Ayensu, 1985). This work lists 365 folk medicinal species and identifies more than 1,000 pharmacologically active phytochemicals. Toxicity estimates are given for many of these biologically active compounds. More recently, Dr. James Duke of USDA published databases on biologically active compounds of more than 1,000 species of plants with potential medicinal uses (Duke, 1992a, 1992b). Duke proposed to FDA a computer-calculated toxicity index to parallel the Ames Human Exposure Rodent Potency (HERP) index for carcinogenicity. He calls his index the Better Understanding of Relative Potency (BURP) index.
Much of the literature on traditional Chinese and other Asian countries' herbal medicine is only now beginning to be translated into English. While much of this information is in the form of folklore, there is a growing body of data from scientifically valid literature on herbal medicine research in China as well as India and Japan. In 1986, the book Chinese Herbal Medicine: Materia Medica was published by Dan Bensky and Andrew Gamble, both of whom are fluent in Chinese dialects and studied herbal medicine in Asia. Revised in 1993 (Bensky and Gamble, 1993), it presents an indepth study of 470 herbs used in traditional Chinese medicine. Each entry details the traditional properties, actions and indications, principal combinations, dosage, and contraindications of the herbs, as well as summaries of abstracts regarding pharmacological and clinical research conducted in Asia. The revised edition also provides a brief description of the appearance of each herb.
Although very little laboratory or clinical research has been performed on Native American Indian herbal remedies, extensive listings of herbs and their uses have been compiled by ethno botanists for several tribes. One source, American Indian Medicine (Vogel, 1970), cites references in the professional ethno botanical literature on herbal medicines for the following tribes: AlabamaKoasati, Arakara, Algonquian, Arapaho, Aztec, Catawba, Cheyenne, Chickasaw, Choctaw, Comanche, Congaree, Creek, Dakota, Delaware, Hoh, Hopi, Houma, Huron, Illinois-Miami, Iroquois, Kwakiutl, Lake St. John Montagnais, Mayan, Menomini, Mescalero Apache, Malecite, Meswaki, Michigan, Mohawk, Mohegan, Natchez, Navajo, Nebraska, Oglala Sioux, Ojibwa, Omaka, Pawnee, Penobscot, Ponca, Potawatomi, Quileute, Rappahannock, San Carlos Apache, Seminole, Sioux, White Mountain Apache, Ute, Winnebago, Yuma, and Zuni. Moerman's database (Moerman, 1982) lists more than 2,000 species of Native American Indian medicinal plants, and Duke (1986) lists more than 700 eastern ones.
These sources-the NAPRALERT database, USDA laboratory research, the Bensky and Gamble book, and the Native American Indian herbal medicinal books-are the foundation on which the U.S. Government, particularly the National Institutes of Health (NIH), can begin substantial research into herbal medicines.
Much unwritten knowledge resides in the hands of healers in many societies where oral transmission of information is the rule. Unfortunately, in many regions this information is endangered because there are no young apprentices to whom elderly healers can pass on their unwritten wisdom; the knowledge that has been refined over thousands of years of experimentation with herbal medicine is being lost. A major research opportunity in this area would be to catalog information on herbal medicines from thousands of traditional healers in cultures where these skills are normally transmitted through an apprentice system. Some organizations have recently increased their efforts to catalog endangered herbal knowledge from traditional medical systems in Latin America, such as those practiced in the rain forests of Belize (Arvigo and Balick, 1993) and Peru (Duke and Martinez, in press).
Basic research into characterizing these plant products and compounds in terms of standardized content and potential toxicity is needed to allow safe and replicable research to document clinical efficacy. Basic science research should be conducted to evaluate research on the biochemical effects of traditional herbal prescriptions from Western, Ayurvedic, oriental, and other traditions (see the "Alternative Systems of Medical Practice" chapter).
Research in phytomedicines in the United States could follow on the results of existing high-quality European and Asian research on plant medicines and should focus on replicating results of key studies or addressing weaknesses in those studies. Reviews of foreign literature and translations of non-English literature would be helpful. Current widespread use of herbal medications as "food supplements" in the United States provides a ready base of users, producers, and practitioners for clinical research in traditional and modern applications of botanical medicine.
Before a comprehensive research agenda is developed, several key issues must be addressed, including the following: the impending loss of knowledge about traditional healing in many societies; the impending loss of large numbers of plant species of potential medicinal value; impediments to the use of herbal remedies outside the cultures in which they originated; and determination of the conditions under which herbal medicines are most appropriate, safe, and effective. Additionally, several regulatory issues hamper research into herbal medicines.
The knowledge of traditional healers in remote Amazonian or Central American regions may have the potential to make a significant contribution to Western society. But few, if any, practitioners of these lesser known medical systems practice outside their native range, and those who still practice within these regions are elderly and often have not found younger disciples.
This loss of knowledge from traditional healers comes at a time when native flora in many areas, especially tropical regions, are being destroyed at an alarming pace. In the United States alone, an estimated 10 percent of all species of flowering plants will be extinct by the year 2000, including an estimated 16 species of medicinally useful plants (Farnsworth et al., 1985).
One hopeful sign is that the U.S. Government recently formed a cooperative biodiversity group including representatives from NIH, the National Institute of Mental Health, the National Science Foundation (NSF), and the U.S. Agency for International Development. This group intends to fund research to locate and catalog medicinally active substances that can be analyzed and used for new pharmaceutical drug development, while working to preserve biological diversity in developing countries.
Basic to the use of medicinal herbs in many societies is the practice of using whole, unrefined plant material. The material may be leaves, buds, flowers, bark, or roots, separately or in combination. In some cases an herbal remedy is a complex mixture of many plants. There is an age-old belief that whole-plant medicines have fewer dangerous side effects and provide a more balanced physiological action than plant derived pharmaceutical drugs whose single ingredient has been isolated, concentrated, and packaged as a pill or liquid.
Herbs and herbal preparations generally are self-administered. Often they are purchased through native herbalists who prescribe one or more herbs or preparations on the basis of medical and health approaches that often include concepts of attaining balance in the client's body, psychology, and spirit (see the "Community Based Medical Practices" section of the "Alternative Systems of Medical Practice" chapter). Consequently, it is often difficult to assess the relative value of herbal remedies versus prescription drugs on a one-to-one basis.
Indeed, herbal remedies of all types, including those from China, are composed of a multitude of ingredients whose interactions with the body are exceedingly complex. A high level of sophistication of research methodology is necessary to describe the interaction between the human body and substances as complex as those contained in many herbal remedies. Only recently has such a rigorous methodology begun to be developed. For example, the Chinese herb Herba hedyotidis diffuse (bai hua she she cao) has been shown clinically effective in the prevention and treatment of a variety of infectious diseases. However, it has not been demonstrated to have a significant inhibitory effect in vitro against any major pathogen. Only as techniques became available to test the immunological system did it become apparent that at least part of the herb's effect was due to its enhancement of the body's immune response (Bensky and Gamble, 1993).
Another complicating factor in researching traditional Chinese herbal medicine is the fact that Chinese medicine characteristically tries to treat the whole body to alleviate disease stemming from one body organ. Therefore, it rarely relies on a single herb to treat an illness. Instead, formulas usually contain 4 to 12 different herbs (Duke and Ayensu, 1985).
Beyond the problem of trying to test herbal preparations that may contain many active ingredients is the question of whether the research eventually will lead to the isolation of single active ingredients that can be packaged and sold separately. Intense debate surrounds the issue of how to conduct clinical trials of herbal medicines according to Western pharmaceutical clinical standards. Critics say there is an inherent problem with the single-active-ingredient approach preferred by pharmaceutical companies that are actively involved in herbal medicine research. The problem, they say, is that isolating a single compound may not be the most appropriate approach in situations where a plant's activity decreases on further fractionation (separation of active ingredients by using solvents) or where the plant contains two or three active ingredients that must be taken together to produce the full effect (Chaudhury, 1992). Beckstrom-Sternberg and Duke (1994) have documented several cases where synergy has been lost by using the single ingredient approach to developing drugs from plants.
A good example of this single-active-ingredient versus whole-plant debate is illustrated by intense interest among pharmaceutical companies in the compound called genistein. Genistein is part of a class of compounds called flavonoids that occur naturally in plants such as kudzu, licorice, and red clover. Soybeans contain high concentrations of genistein, and lima beans reportedly are even higher in genistein than soybeans (Duke, 1993). There is increasing evidence that genistein may inhibit the growth of cancers of the stomach (Yanagihara et al., 1993), pancreas (Ura et al., 1993), liver (Mousavi and Adlercreutz,1993), and prostate (Peterson and Barnes, 1993). Genistein is believed to inhibit the growth of cancers because of its antiangiogenetic properties (i.e., it prevents the growth of new blood vessels-a process known as angiogenesis-to tumors).
Genistein is being intensely studied as a possible preventive or treatment for breast cancer, Which kills an estimated 44,000 women in the United State each year (Duke, 1993) Studies indicate a correlation between a high intake of foods containing genistein (soy products) and a low incidence of hormone-dependent cancers such as breast cancer (Hirayama, 1986) and prostate cancer (Baker, 1992). The growth of certain cancers, especially breast cancers, has been shown to depend on the female sex hormone estrogen. Genistein exhibits estrogenlike activity in plants and is often called a phytoestrogen. In humans it binds to estrogen receptors (Baker, 1992). It has been suggested that these phytoestrogens may compete with endogenous estrogen on the cellular level, further reducing the cellular proliferation and the potentially carcinogenic effects of estrogen (Tang and Adams, 1981).Thus, it may prevent the growth of estrogen-dependent cancer by competing for estogen sites on the tumor cells.
If genistein is developed as an isolated pharmaceutical drug, it may have some action against cancer, but the purified compound may not be as potent as genistein in its natural state, and trials may give misleading results. The reason is that all plant species containing genistein also contain other flavonoid compounds, which may have synergistic effects when ingested with genistein. Formononetin – a precursor of equol, which also occurs with genistein- is said to be more active estrogenically than genistein (Spanuet al., 1993). Although genistein clearly inhibits angiogenesis, several other compu8nds are pseudoestrogens. With thisin mind, the question arises: Is a mixture of genistein, formononetin, and other flavonoids, as occurs in many plants, more estrogenic (and antiangiogenic) than an equivalent quantity of any one of these components? If so, the herabal or dietary approach may make more sense than a genistein “ silver bullet” approach.
Opinions about the safety, efficacy, and appropriateness of medicinal herbs vary widely among medical and health professional in countries where herbal remedies are used. Some countries professionals accept historical, empirical evidence as the only necessary criterion for herbal medicine’s efficacy. Others would ban all herbal remedies as dangerous or of questionable value.
The problem is further complicated by the fact that many “patent medicines” available in world trade often are sold as herbal medicinal preparations when they include non herbal substances. These non herbal additives often includes toxic metals (cinnabar, i.e. mercury) (Kang-Yum and Orasky, 1992), poisonous substance (powdered scorpion) or refined prescription drugs (Catlin et al., 1993). Usually labeled “Chinese herbal medicines,” many of these products are manufactured in Thailand, Taiwan, or Hong Kong and exported to the United States, where they are sold in retail outlets. The Califonia Department of Health Services, in conjunction with the Oriental Herbal Association, recently published a list of 20 popular Asian patient medicines (see app. E) that contain toxic ingredients.
The increased use of plant medicines has potential for improving public health and lowering health care costs. Phytomedicines, if combined with the preventive model of medical practice, could be among the most cost –effective, practical ways to shift the focus of modern health care from disease treatment to prevention. But drug regulatory policy prevents the United States from talking advantage of these phytomedicines for two reasons. The first is the exorbitant expense involved in investigating each chemical compound in a given plant extract before it can be tested fro clinical usefulness. Hence there is an urgent need to rework current research guidelines to allow the whole plant material or combination mixture (an herbal remedy containing more than one plant) to be evaluated instead of requiring separate evaluations of each chemical component of the therapeutic ingredients.
The second reason is that regulatory requirements for proof of safety and efficacy constitute an economic disincentive fro private industry to conduct additional scientific studies. Relaxing regulatory requirements for efficacy for herbal products might make it economically feasible for more private companies to pursuer research into issued of safety and quality control. Even with such regulatory change, some public funding of research is needed to confirm the remedies’ validity. Public funds are needed because private industry has no incentive to develop an herbal product that might displace a patented drug from an approved treatment regime.
The Panel on Herbal Medicine recommends the following:
Adopting a more realistic standard of evidence for established plant medicines would eliminate much of the expense required for approval of new and unknown chemical drugs. Doing so would be similar to having standardized the crude drug senna leaf, used in the United States as an OTC laxative and documented for safety, effectiveness, and quality.
Another option might be to require pharmaceutical companies that are testing a plant-derived, single-ingredient pharmaceutical on a specific condition to demonstrate that it is more effective than the natural product. For example, before a
patent could be issued to a pharmaceutical company for an isolated compound such as genistein, the company would first have to prove that the isolated compound is more effective than genistein consumed in context (as a food). But some market incentive, such as exclusive prescriptive marketing rights, might be needed to allow the pharmaceutical company to recoup its research costs.
With respect to herbs used in popular health care, a proactive FDA role in establishing quality and safety standards would benefit the public and industry. A certification system for herbal content and potency of marketed products could be set up by FDA with USDA and the herbal industry. Such a system could draw on the existing global database and other countries' regulatory experiences. Participation in a voluntary product certification system would be a marketing advantage for ethical producers, allowing them, for example, to make a statement such as "This product meets U.S. government purity and potency standards." New statutory authority also would be necessary to establish a category that would allow traditional usages to be listed on labels according to criteria similar to WHO guidelines.
Finally, if herbal remedy producers were given the option to apply for specific health condition label indications based on new FDA phyto-medicine standards, the United States would have the same three-tiered regulatory system adopted by other developed countries. Such a voluntary system would let consumers make intelligent personal choices about the use of medicinal herb products while mandating safety standards consistent with existing OTC practices for potentially toxic drugs such as aspirin and ibuprofen.
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