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Uses of herbal formulations and their limitations are described,
ALTERNATIVE MEDICINE: HERBALS AND THEIR
Internal Medicine, Boon Hospital Center, Columbia
Ravi K. Puri*
Retired, Group Leader, Environmental Trace Substance Laboratory,
University of Missouri, Rolla, MO, USA.
Alternative medicine was an ambiguous term twenty-five years ago in the Western countries. It was considered as Dernier Cry. Most of the physician· used to make joke on the various systems available for treatments, since the techniques used were neither recognized nor taught in accredited medical institutions. Moreover, adequate scientific data was not available to support the efficacy of the alternative therapies. Hence, majority of the medical practitioners dismissed the idea of accepting alternative medicine at that time.
Despite the dramatic advances in high technology medicine such as gene therapy, laser and plastic surgery, high-resolution body scanning and scientific miracle like vital organ transplantation, it is perplexing that natural healing methods are enjoying a remarkable resurrection. Sales of herbal medicines have grown dramatically since the FDA's decision to categorize them as Dietary Supplements in 1994'. Consumer sales of botanical dietary supplements grew from $1.7 billion in 1994 to $3.4 billion in 1997, with growth expected to
continue at annual rate of 16-18%. In 1998, several mainstream pharmaceutical companies started manufacturing and marketing herbal products. Bayer Consumer Care extended its One-A-Day brand to include a new line of products comprising herbs. Warner-Lambert introduced a line of herbals under the Quanterra brand name and Whitehall-Robbins (American Home Products) launched a new line of herbal products under its Centrum name. Smith Kline Beecham and McNeil are expected to enter the market in future2• Contribution from these large, well financed pharmaceutical houses with established research and development divisions is expected to speed up the progress in phytomedicines.
Many detailed reviews and books have been published on alternative medicine. However, limited information is available about the abuses of herbals sold over the counter. Thus, it was considered desirable, to undertake a bird's eye view of the various alternative medicine systems, their limitations and focus on the most popular herbal drugs, which are sold over the counter as dietary
supplements (Table - 1). The consumers are quite ignorant about the adverse effects of these herbal products. These can be toxic and harmful. if taken along with conventional medication. Some of the herbal products available need to be taken with the approval of the physician on account of their toxic effects due to herbal-drugs interaction. This review is a joint effort of a physician and a pharmacognosist. The most prominent herbals sold over the counter have been discussed with the background of their perspective profession with special emphasis to herbal drugs interaction. It is hoped that their efforts will be beneficial to the consumers, general practitioners, pharmacists and researchers in the field of phytomediclne.
During recent years, there has been a surge in the use of alternative medicine in the USA. The survey showed that patients taking alternative medicine in 1990 visited their alternative practitioners 425 millions times. 40 millions more times than they visited their primary care physician. They spent $13.7 billion on this care and $10.3 billion coming out of their own pocket3.83 million adults used CAM (Complimentary and Alternative Medicine) and spent $27 billion in 19974• Most of them did not reveal the use of alternative treatment to their physician. In a study of unconventional medicine use involving 1539 adults in the US, Eisenberg et al. ' reported thaf34% respondents who used at least one unconventional Hlerapy in the previous year. 72°"-0 did not inform their doctor of their use of therapy. In the U.K., general public increasingly uses phytomedicine to replace conventional riledicine6 In 1996, the UK market for licensed herbal medicine was estimated to be worth £38 million representing over half of the total market for complementary remedies? This will be an underestimate since majority of the herbal medicine sold in the UK consists of unlicensed products. The demands for alternative medicine further increased in the last few years. Articles on alternative
medicines in popular magazines and scientific journals further gave impetus to this Medicine's new age. Additionally, daily newspapers and television regularly address the issue of Alternative Medicine8·". Under the scenario, it is expected that by the year 2010 the supply of alternative medicine clinicians in the USA, particularly chiropractors, naturopaths and oriental medicine practitioners will increase to 124%. The total number of these clinicians, which equaled some 11 % of the US physician's population in 1994, will swell to 17% by 2010':'.
The Office of Alternative Medicine at the NIH
With the increasing demands for alternative medicine in the USA, an Office of the Alternative Medicine (OAM) was established by congress in late 1992 to formally investigate unconventional treatment routes. In 1996, 40% of the American people were using CAM treatments and therapies for a multitude of health problems. As CAM use by the American people has surged many people asked whether the anecdotal reports of success with these treatments are valid. In 1997, a survey suggested that nearly 60 million Americans used herbal medicines. In 1998, the congress responded to this concern by elevating the OAM and expanding its mandate in creating the National Center of Complementary and Alternative Medicine (NCCAM) at the NIH. During that year the Congress provided statutory authorities and a generous budget for the center. In 1998, OAM received $20 million and in 1999, the center support rose to $50 million. The Congress continued to reflect the growing interest in CAM by further increasing the funding for the center to $68.7 million in 200013. Various institutions have been funded to investigate the efficacy of these alternative medicines. OAM received quite substantial money from NIH to investigate the efficacy of these systems. Research funded by the OAM is summarized in Table - 2. In addition, more than .30 US medical schools have added courseson alternative medicine to their curriculum14. Surprisingly, health insurers are beginning to offer coverage of alternative medicine15.
Alternative medicine means the treatment that is not offered by conventional physicians and the main stream medical system. The various alternative medicine systems available for treatment in the USA are listed in Table - 3 and the alternative practices in Table - 4.
Difference from Conventional Medicine
Not only public is showing significant interest in alternative medicine but also many physicians are curious to know and seriously looking into this field. Why is it happening? Is there something of value to a patient or a family physician? Why more and more people are assiduously using alternative medicine? Most probably one way to understand this mystery is to find out as how it differs from conventional medicine. Alternative medicine and conventional medicine systems follow very different approaches. Conventional medicine is diagnosis-led, physicians use symptoms and medical tests to evaluate the problems and prescribe treatment accordingly. Approach of alternative medicine practitioner is holistic IS. Holistic is derived from Greek word means - whole. His focus is to deal the patient as a whole taking into consideration his mental, physical and spiritual aspects. Conventional therapies are aggressive and invasive, whereas alternative medicine tends to take a gentler and slower approach. Conventional medicine focuses on quick-fix, whereas alternative therapies take a long-term approach while making changes in life style. Conventional medicine is patrimonial in their approach to patients. Alternative practitioner tends to work in partnership with patients. They take the traditional role of a healer paying attention to physical, mental and emotional or spiritual concerns17, 18.
Why Alternative Medicine?
Failure to control stress-related, environmental and psychological illness, history of surgical accidents and growing resistance to antibiotics, people are looking for alternative medicine. Moreover, there are some chronic illnesses such as asthma, arthritis, irritable bowel syndrome, migraine, insomnia, immunodeficiency, cancer, which do not have effective conventional treatment. Majority of the patients with cancer or acquired immunodeficiency syndrome are currently using one or more alternative therapies. Negative side effects of conventional treatments are also encouraging people to look for alternative system of-medicine. Above all; after ihe FDA's decision to categorize herbal remedies as food supplements, the popularity of herbal products is increasing day by day. There is no restriction and one can buy over the counter. Advertising and promotion of these products cannot separate myths from reality and give a ray of hope to·some patient. Hence, estimates of herbal medicine sales skyrocketed to between $2 and $3 billion'9
Is Alternative Medicine a Fad?
It has been estimated that 70~90% of the world's population relies on alternative therapies and practices20' Moreover, many types of alternative therapies are a formal approach to healthcare in various societies and cultures around the world. If a particular therapeutic approach has not originated by American healthcare. it does not render it worthless, quackery or fad. Most alternative therapies have evolved from ancient healing system in various cultures around the world and are based on reasonable scientific background21. There must be some truth in it. As science catches up with human behavior, some types of alternative therapies are being found useful.
Despite the dramatic advancement and advantages of conventional medicine herbal drugs have much to offer. Today, herbal drugs are coming back into prominence. Side effects of the conventional medicine such as antibiotics, antimicrobial agents are the major problems. Over the years, some of the infectious organisms have developed resistance to synthetic drugs too. Medicinal chemist is looking for more potent and effective drugs. Hence more complications.
Herbals are used in the art of healing since the time immemorial. The primitive man through trial and error gained knowledge of herbals and passed it on to the next progeny. It is reasonable to assume that for ten thousands of years herbs were perhaps used for the magical powers as well as for their medicinal values. A 60,000 years old burial site excavated in Iraq was found to contain eight different medicinal plants including Ephedra19.
Ancient civilization flourished in 3000 BC onward in Egypt, Middle East, India and China and the use of herbs was refined. The Egyptian Ebers Papyrus (1500 BC) is the earlier recorded information on herbs. In India, 1500 BC Vedas offered sophisticated information on herbs, which was followed by Charaka Samhita, written by a well-known Physician of his time. Ammi visnaga20 and Centella asiatica21 were among the 350 herbals illustrated in this compilation and have recently proven effective for the treatment of asthma and leprosy respectively.
Chinese traditional pharmacopoeia lists over 5700 traditional medicines mostly from plant origin. China now enjoys equal status with Western medicine. Many universities in China teach and practice herbal medicine. Over the last 10 years. Europe has witnessed a rapid growth in Traditional Chinese Herbal Medicine (TCM). Practitioner number is around 11,400, while the annual market is estimated to total $60 million. Development of an authentication center for Europe at Royal Botanic Garden for Traditional Chinese Medicine is in progress to standardize quality control and easy access to authentic reference materiaI22. The center will also focus on credibility of herbal products and patient safety23.
In many traditional cultures all over the world, plants were also used during the religious ceremonies. Amanita muscaria, Cannabis sativa. Lophophora williamsii and related hallucinogens are the few examples. By 500 BC during the developing cultures, medicines commenced to separate from magical and spiritual world and art of healing by herbals got recognition. The Greek philosophers like Hippocrates, Aristotle, Theophrastus contributed significantly towards the use of herbal drugs. With the development of Organic Chemistry, it was revealed 'that the ability of an herbal medicine to affect body system depended upon its chemical constituents. Chemists first started extracting and isolating chemicals from plants in the 18th century. Encouraging results speeded the process and natural product chemist gave the world most useful life saving drugs such as Tubocurarine - a muscle relaxant from Chondrodendron tomentosum, strong painkiller morphine from Papaver somniferum. Ephedrine - antispasmodic from Ephedra, quinine - antimalarial from Cinchona bark, digoxin - cardiac remedy from Digitalis species. Soon discovery of Rauwolfia serpentina and isolation of reserpine for hypertension gave impetus to the search for vlncaleucoblastin, vincristine for Hodgkin's disease from Vinca rosea. Contraceptive pill was synthesized from diosgenin obtained from Dioscorea deltoideae. Discovery of anticancer drug Taxol from yew plant again revived the interest towards herbal medicine.
However, during the period 1975-1985 synthetic drugs dominated pharmaceutical industry. Search for new antimicrobial, antibiotics, antihistamine and antihypertensive agents and related compounds were in progress. Soon developments in
biotechnology dominated the pharmaceutical world. More recently, with the advancement in biotechnology, antibody therapeutic products are available for the treatment of variety of disease conditions, including transplant-related diseases, inflammatory and autoimmune disorders, cardiovascular diseases, infectious diseases and cancer.
Despite the developments in modern medicines, the use of herbals is still increasing. Why? For thousands of years herbs and other products from the natural sources have been used in treating various diseases. Some of those in current use have been an ancient heritage, whereas others have arisen from discoveries and cultural trends in more recent centuries. All therapy referred to as alternative or complementary came from outside the main stream of American medicine. They were not taught in medical school. Now the trend is changing. Now majority of the schools in the USA are offering elective courses in alternative medicines. There is growing interest among physicians and patients to learn more about these. A quiet revolution is taking place. Tens of millions of people are taking herbs such as Ginkgo biloba, ginseng, saw palmetto and many more as shown in Table - 1 to maintain mental and physical health. On the other side, scientists are also investigating supportive evidence for their effective use. Sales of herbal drugs have grown dramatically by 55% during 1999.
Are Herbs Safe?
However, we are ignoring one very significant point regarding the safe use of these herbals. How safe are these? Are these compatible with other drugs patients are taking. What are their side effects? How many doses are required for certain ailments? Most of the consumers and suppliers of herbal remedies believe that these natural products are safe6. This, however, is a misconception. Herbal drugs can produce adverse drug reactions. Further complication is that, these herbals are self prescribed and most of the time patients do not inform the general practitioners about their intake25. If they do tell then most of the general practitioners are not aware of their remedy and discourage them.
Nevertheless, these herbs are not safe26. The rule of the thumb is to consider all substance-based alternative therapies as drugs. These are in the form of crude extracts or plant parts in the form of powder as pills or capsule or tablets. The constituents containing in these parts can combine with the normal prescribed drugs and form complex which can be toxic. These can give synergistic effect and create problems. Sometime these could be antagonistic to the prescribed drugs and cause problems. In some cases existing toxicity of conventional pharmaceutical drugs may be enhanced.
Herbal Drugs Interaction
Technically herbal medicines interact with drugs pharmacokinetically and pharmacodynamically. Pharmcokinetic interaction results in alteration of drugs or natural medicine absorption, metabolism or elimination. These interactions affect drug action by quantitative alterations, either increasing or decreasing the amount of drug available to have an effect.
Absorption is the physical passage of herbs or drugs from the outside to the inside of the body. Majority of the absorption occurs in the intestine, where herbs and drugs must pass through the intestinal wall to enter the blood. Several mechanisms may interfere with the absorption of drugs through the intestine. The absorption of herbs may be adversely affected when the herbs are given together with some drugs, due to the binding in the GI tract. Drugs such as Cholestyramine, Colestipol and Sucralfate may bind to certain herbs, forming an insoluble complex and decrease absorption of both the substances. Absorption of herbs may be further affected when the herbs are given with some drugs, which change the pH of the stomach. Drugs
such as antacid, cimetidine (Tagamet), pepcid (famotidine), Axid (nizatidine), Zantac (ranitidine) and Prilosec (omeprazole) may neutralize, decrease or inhibit the secretion of the stomach acid. This will decrease the pH of the stomach and herbs may not be broken down properly leading to poor absorption in the intestines:
Absorption of the herbs is also affected by GI motility. GI motility is the rate at which the intestines contract to push the content from the stomach to the rectum. Slower GI motility means that the herbs stay in the intestines for a longer period and there will be an increase in absorption. Faster GI motility means that the herbs stay in the intestine for a shorter period of time and there may be a decrease in absorption. Drugs such as Reglan (metoclopramide) and Propulsid (cisapride) increase GI motility and possibly decrease absorption of herbs. An antipsychotic drug such as Haldol (haloperidol) decreases GI motility and may increase absorption of herbs. So when a patient is taking a drug, which affects the GI motility of herbs, he should increase or decrease the dosage of herbs accordingly.
Distribution is another factor, which plays a significant role in the interaction of herbs with drugs. Distribution refers to the process in which herbs or drugs are carried and released to different parts of the body. Interaction occurs during the distribution phase if the drug has a narrow range of safety index and is highly protein bound. For example, warfarin is an anticoagulant medication which is very highly bound to protein and has a very narrow range of safety index. Warfarin interacts with various drugs, vitamins, herbs and foods via different mechanisms. Some known examples that interact with warfarin include aspirin, ibuprofen, vitamin K and green tea. The patients who are taking herbs concurrently with warfarin have to be very careful27.
Metabolism also affects the interaction. The liver inactivates derivatives, metabolizes herbs and drugs. The rate at which the liver metabolizes these herbs and drugs determines the length of time these herbs and drugs stay active in the body. If the liver was induced to speed up the metabolism, the herbs and drugs would be inactivated at a faster rate and overall effectiveness of the ingested substances would be lower. On the other hand, if liver was induced to slow the metabolism, herbs and drugs would be activated at a slow pace and overall effectiveness of the substances would be higher. Drugs such as phenytoin (Dilantin), carbamazepine (Tagretol), phenobarbital and rifampin speed up liver metabolism. Therefore, the herbs may be inactivated faster and their overall effectiveness will be low. Under such scenario, the herbal dose should be higher to get the desired effect.
On the other hand, drugs that inhibit liver metabolism have an immediate onset of action. The rate of liver metabolism may be greatly impaired within a few days. Therefore there will be a higher risk of herbs accumulating inside the body. Drugs such as cimetidine (Tagamet). erythromycin, ethanol, diflucan (fluconazole), Sporonox (itraconazole) and Nizoral (ketoconazole). In this case one may need to lower the dosage of herbs to avoid side effects.
Elimination is another process, which is quite potential in eliminating herbs and drugs from the body. If ttle kidneys were damaged, then the rate of elimination of herbs or drugs by the body would be slowed down leading to an accumulation of herbs or drugs in the body. In this case the dose of the herbal may be lower to avoid side effects. Such drugs that affect the kidneys are amphotericin B, methotrexate, tobramicin and gentimicin. Elderly population has to be more careful since their elimination process is decreased with age.
Pharmacodynamic interactions cause alterations in the way a drug or natural medicine affect a tissue or organ system. These interactions affect drug actions in a qualitative, either through enhancing effects or additive action or antagonizing effects. Examples of both pharmacokinetic and pharmacodynamic interactions are summarized in Table - 5.
The highest risk of clinically significant interaction occur between herbs and drugs that have sympathomimetic, cardiovascular, diuretic, anticoagulant and antidiabetic effects. Herbs with sympathomimiceffects may interfere with antihypertensive and antiseizure drugs. The classic example of sympathomimic herb is Ephedra (Ma Huang) which contains ephedrine and related alkaloids. This herb should be used with great precaution in patients who have hypertension. seizure, diabetes and thyroid conditions2829 Similarly herbs with diuretic effects may have additive or synergistic effects making hypertension more difficult to control. Herbs with anticoagulant effects include herbs that have blood-activating and blood-stasis-removing functions. Such herbs may interfere with anticoagulant drugs such as Coumadin (warfarin) include Salvia miltiorrhizoe. Angelica sinensis, Carthamus tinctorii. Chamomile species, Tanacetum parthenium and Hydrastis canadensis 30 Vitamin E. fish oil can also enhance the effect due to antithrombin activities31. Various examples are discussed32•44 in Table-5. Antidiabetic herbs may interfere with antidiabetic drugs by enhancing hypoglycemic effects. The dose of herbs and drugs should be balanced very carefully to control blood glucose level4s
It is well established that patients taking more than one pharmaceutical medicine can experience drug interaction, which may be detrimental to their health. Though limited information is available in the literature concerning the interaction of herbal with convention medicine, yet it is pertinent to know that certain interactions can be fatal. In recent years, there have been an increasing number of reports of poisoning related to herbal medicine. This may be due to the expanding use of these products or increased awareness among physician and allied professionals of the toxic potential of some of these substances. The WHO database currently lists 8985 adverse drug reaction reports in which herbal preparations are the prime suspects46
Drug interactions not only occur between drugs that may involve interactions with foods and beverages too. For example, alcohol enhances the anticoagulant effect of Warfarin and sedative effect of antidepressants. Verapmil used for the treatment of angina, arrhythmia and hypertension may increase blood alcohol levels. Similarly, grapefruit juice increases the plasma concentration of some dihydropyridine calcium channei blockers such as nifediplne, amlodipine, nicardine, etc used for the treatment of angina and hypertenslon47
Among vegetables, broccoli interferes with warfarin4B On the other hand, cheese, beans and yeast contain tyramine whichmay exert presser eifects on monoamine oxidase inhibitors drugs such as phenelzine used as antidepressant resultin\i in high blood pressure and causing throbbing head-aches49
Herbals in Pregnancy
Women have turned to alternate medicine due to premenstrual syndrome (PMS), menopause and depression. The psychological conception is that herbals are safe containing natural supplements. Black Cohosh (Cimicifuga racemosa) is commonly used for women for menstrual and menopause problems. Adverse effects include nausea, vomiting, dizziness, nervous system and vision disturbance and reduced heart rate. It contains salicylic acid that interferes with anticoagulants. Evening Primrose oil (Oenothera biennis) is used in PMS. The oil may cause gastro-intestinal disturbance. Kava-kava and St. John's wort (Hypericum perforatum) are also used as antidepressants and adverseeffect can cause nausea and vomiting.
Herbal medicine is a combination of many herbs, which contain different chemical constituent? and some of these can be detrimental to pregnancy. There are some herbs, which are teratogenic in nature. Teratogenic herbs are known to cause harm to fetus during pregnancy and thus leading to birth defects or abortion. Herbalist should be consulted before taking herbs. The use of some herbs is prohibited during pregnancy. Prohibited herbs include Abrus precatorius, Achyranthus aspera, Adhatoda vasaka, Hibiscus species, Ricinus communis. and Gossypium species50. It is beyond the scope of this review to list the names of many more. The bottom line is that herbals should be used during pregnancy under the supervision of a herbalist. Nevertheless, consumers often self medicate without consulting an appropriate healthcare professional. This can be unwise decision with serious consequences, especially in pregnancy and later on in breastfeeding mothers.
Herbals and Breastfeeding
The benefits of breastfeeding greatly surpass that achieved by formula feeding. These benefits are two folds, improving the health of both nursling and mother. Nursling will tend to have a lower incidence of ear, respiratory and gastrointestinal infection due to antibodies that are transferred from mother to the child through breast milk5'. Furthermore, breast feeding also decreases the risk of other diseases such as childhood diabetes, Crohn's disease and lymphoma52. According to the Ross Laboratories Mothers' Survey, there has been a significant increase in the initiation of breast-feeding and in maintaining nursing at six month of age53. The following herbs should be used very cautiously during breast-feeding. Symphytum officinale (Comfrey root), a tropical herb containing pyrrolizidine alkaloids has the potential for hepatotoxicity and antimitotic activity. Pyrrolizidine has been found in the breast milk of lactating rats54·55. Tanacetum parthenium (feverfew) used in severe migraine. Main constituent is parthenolide, a sesquiterpene lactone. Thujone a. neurotoxic, is another compound found in Tansy (Feverfew) preparation. Use of this herb in breast-feeding cannot be assured. Purple Cone Flower (Echinacea) is a very popular herb commonly used to boost immune system. It contains nontoxic form of pyrrolizidine. However, it is also not considered safe yet. Ephedra, a potent herb indicated for the alleviation of Asthma-associated bronchoconstriction due the presence of ephedrine. Given the potential cardiovascular risks and addiction complications, the use of this herb is not recommended In breastfeeding. Aloe, Cascara sagrada, Rhubarb and Senna are used as laxatives. Their use is prohibited during breast-feeding due to anthraquinone constituents that may cause potassium deficiency 56 Licorice root is used in the treatment of peptic ulcer/duodenal ulcers. The active components glycyrrhizic and glycyrrhetinic acids account for antiinflammatory and anti-allergic effects. However, the components of licorice root possess mineralocorticoid properties leading to toxic effect such as sodium and water retention, hypokalemia and hypertension which can lead to cardiac arrest5? Rauwolfia serpentina contains reserpine used in hypertension. It is also used as CNS depressant. It is, therefore, contraindicated in breast-feeding. Ginkgo biloba may affect coagulation process in the mother and nurslings55. Ginseng may cause estrogenic side effects as well as platelets changes. Until more information is known, ginseng root should be avoided in lactating mother59 In short, breastfeeding mothers who use herbals should consult a physician or pharmacist who has information concerning the safety of herbal medication60.
Quality Control and Standardization
FDA does not regulate OA/OC and standardization of herbal products since these are sold over the counter as food supplements.
Herbs are not regulated as drugs, so no legal standards exist for their processing, harvesting or packaging. Consumers are depending upon the integrity of the manufacturers. Inspite of the good intentions of majority of the manufactures, it is very difficult to control the quality of the herbal products. Quality control depends upon many factors. Proper identification of the raw material at the time of collection is very important. Misidentification of the herb is detrimental to the quality of the products and manufacturer most of the time is not even aware of this problem. The herbal suppliers, who supply the raw material, are not devoid of the identification's problems, especially in the case of expensive herbs less expensive substitutes are used. So proper authentication of the raw material is very pertinent61. Those companies who are cultivating their own species are better off.
Proper drying and storage of the collected plant parts follow it. Improper drying and storage will definitely impact the active principles. During growth and storage, pesticide residues, microorganism, aflatoxins, radioactive substances and heavy metals can contaminate crude plant material62.
Extraction of the material with pure solvents and concentrating them under proper conditions of temperature affect the quality of the active principles. Organic solvents from plastic containers used for the extraction of herbs often contaminate the final extracts with organic phthalates, which can be toxic. Hence, there are several factors, which have to be controlled to keep the quality of an herbal product.
Standardization is another important and logical issue but not an easy one. Owing to lack of proper standard parameters for the standardization of an herbal preparation, herbal industry is in question. There have been several instances where substandard herbs are reported. Many products containing feverfew had no detectable levels of the active constituent parthenolide - responsible for antimigrain activity. Instead of curing migraine it became a headache for the consumer63 A Consumer Reports study found that level of ginsenosides, the active component in ginseng varied significantly in ten different products brands64 Ziglar65 reported that 60% of the 54 ginseng tested, contained less amount of active constituent and 20 % did not show any trace of the active constituent. A good housekeeping institute analysis of six widely St John's wort supplement capsule and four liquid extracts revealed variation in concentration of the active constituent hypericin and pseudohypericin: The study showed a 17 foid difference between the capsules containing the smallest amount of hypericin and those containing the largest amount, based on manufacture's maximum recommended dosage. A 7 to 8 fold difference from the highest to lowest levels was found in liquid extracts66. Likewise twenty products containing Ephedra were tested at the University of Arkansas. Researchers found many differences in alkaloid content from product to product and between two lots of the same product. One product was devoid of alkaoidal contents67. Another recent report indicated that a leading laboratory had tested five brands of ginger: ginkgo, ginseng, melatonin, saw palmetto, St. John's wort and milk thistle purchased at five stores in Dallas area. Majority of the products did not reveal the stated concentration of the active constituents68. There are many examples of herbal medicines that have been adulterated with other more toxic herbs: potent drugs like phenylbutazone, synthetic corticosteroids and other prescription drugs or heavy metals69, 70.
Thus standardization of herbal product is very essential. Though it is difficult. Herbal preparation is a combination of several herbs and each 'herb comprises of several chemical constituents. In many cases, the overall pharmacological effects are not 'due to single compound but several compounds causing synergistic effects.
This indicates that standardization should calibrate more than one component. It is difficult to quantitate all these constituents in the formulation. Hence, a fingerprint chromatogram of the extracts or preparation obtained by HPLC, gas chromatography or thin layer chromatography is very essential. This fingerprint should represent identity, purity, and therapeutic efficacy of extracts from the same herbal. There is no problem to quantify the single principal active constituent. If a preparation contains more than four herbal extracts, each extract may be characterized before mixing and after mixing to establish the identity of the product. Secondly, toxicity studies are very pertinent to indicate the safety of the product. Simple bioassay for biological standardization of herbal drugs should be incorporated to develop animal models for toxicity and safety evaluation. Finally, clinical trials should also be performed to establish the therapeutic efficacy of the final product. NCCAM recently announced its intention to fund the development of standardized preparation for use in clinical trials of herbs. These include Feverfew, Valerian root, Echinacea. More information is available at the web site7'.
New standardization technology is available. Whitehall-Robins, a division of American Home Products Corporation is launching a new herbal supplement line of six products under the Centrum umbrella. They are utilizing a new standardization technology known as PharmPrint™ that identifies the key constituents in the herb. This unique technology is necessary to (a) Identify, quantify and control the active components of herbal compound. (b) determine the activity of each component in a specific bioassay and (c) ensure the components are present in predetermined quantities for a given manufactured batch. The PharmPrint™ process was initially developed at the University of Southern California in 1970s. After years of testing this process received its first patent in 1996.
The use of alternative medicine such as chiropractic, acupuncture, homeopathy and herbal medicine is in vogue almost throughout the globe. The demand is on increase in the Western countries since 1990. What is going on with the $18 billion consumer-driven market for alternative medicine? A study in 1998 found that several modalities, long considered beyond main stream medicine biofeedback and relaxation, counseling and psychotherapy behavior medicine, diet and exercise are now considered legitimate. Conversely, less than 30 % of these physicians considered acupuncture, herbal medicine, and homeopathic medicine to be legitimate medical practice. Traditional oriental medicine, native American medicine and electromagnetic treatments were even less familiar to and least well accepted by U.S. physicians. The most basic question remains unanswered, which complimentary therapies are effective? Are they safe and natural as claimed? Is there a scientific basis for their action? More clinical trials are required. Rigorous research is needed to investigate the efficacy and safety of the particular alternative therapy. Clinical investigations require financial support. Unlike drug trials, funding for complimentary medicine is scant. Complimentary medicines do not have the backing of universities, hospitals, and full-time researchers. It is also difficult to change the system. Under the scenario, complimentary therapists develop their own professional bodies, academic groups and the facilities to carry out the research72.
National center for alternative and complimentary medicine should develop a broad-based international research program that reaches out to complimentary and alternative researchers and practitioners across the world. Director of international affairs should be appointed who develops a long-range research plan that consists of studies of complimentary and alternative medicine at international level across the globe. Liberal funding should be given to those
countries that are known for the use of herbal medicine and have long history for their potential in health, particularly in the developing countries. However, in the developing countries, traditional medicine is still the only available health service for majority of the population. The question is how effective and safe these treatments are? Very little is known about the safety, efficacy, mechanism of action, cost effectiveness of individual treatments. Most of the time the alternative medicine practitioners are not even fully trained. In some countries, the homeopath, the chiropractitioner, the acupuncturist, etc have not even gone to school to learn the art of healing in their profession. So their hit and trial techniques can be fatal to some patients.
Nevertheless, the real problem starts when alternative treatments are taken along convention pharmaceutical medicine. Majority of the patients do not tell their General Practitioner about the use of alternative medicine particularly herbals. Herbal-drugs interaction is on the alarm by popular and scientific media. Calls for regulation and restriction of herbal products are required. In conclusion, the herbals are to be taken under the supervision of qualified herbalist and these are safe if taken alone without convention medicine. When herbal medicine is used correctly; the chances of side effects are remote. Unfortunately, even the phamacist cannot help the consumers regarding the adverse effect of herbals. The traditional pharmacognosy courses have disappeared from many schools of pharmacy in the US. The developing countries that even believed in traditional medicine are following the West. Today's newly trained pharmacists lack the knowledge of pharmacognosy required to help the consumer of herbals. However, with the rising popularity of herbal preparation the trend is changing. Several school of pharmacy such as Northeast Louisiana, Midwestern and Campbell Universities have initiated courses in herbal medicine73.
The type of herbal medicine used in different countries varies. Thus, the scope of the problem and methods to evaluate the situation and monitor these products for adverse effects vary accordingly. In industrial countries such as the UK, a variety of alternative medicines are used including European herbs, vitamins and Indian and Chinese traditional medicine. Following the five year study assessing the toxicological problems associatedwith the use of traditional and herbal remedies and dietary supplements in the UK, the Medicine Control Agency responded by recognizing the need for vigilance74 In Hong Kong, most traditional medicine is Chinese. Following several reports of severe poisoning related to herbal medicine, the Hong Kong government appointed a working committee to review and make recommendations on the use and practice of traditional Chines medicine.
Indian traditional medicines sometimes contain 'Bhasmas', metal oxides for internal use. In UK 12 cases of poisoning by lead, arsenic and mercury were identified; nine of these were due to traditional remedies containing 'Bhasmas' 74 Some efforts or measures are required to protect people in India from the toxicity caused by 'Bhasmas' and related products. There have been few reports of interaction of drugs with Ayurvedic preparation75. Lead, mercury and arsenic poisoning have been found with the use of Ayurvedic metal-mineral tonics76·78. Presence of toxic metals in selected traditional Chinese Medicinals has also been reported79. More awareness is required in the developing countries where alternative systems are used since the time immemorial. Most of the time the adverse reactions are not known for lack of investigations and proper help.
The rising popularity of use of herbals also poses a direct threat on the survival of wild species. Demand of Gold Seal (Hydrastis canadensis) has become so much that the price has gone upto $150 per kg.lt was a wild plant in Northern America couple of centuries
ago but now a scarcely available species due to over-collection. There are many other species, which fall in this category. The vanishing of plant species as a result of over-collection is not new particularly to those which cannot be cultivated due to ecological variations. Today, while the trend in the use of herbal medicine is increasing day by day, it is very pertinent that manufacturers, suppliers, and practitioners only produce that has been cultivated or wildcrafted in an ecologically sensitive manner to protect the threat to useful species across the planet. .
In view of the above discussion on alternative medicine, it is suggested that conventional and unconventional systems should integrate and get the best of each other. Thus, they can compliment each other. Also high standards and proper training are required in education, practice, quality analysis and quality control and research of alternative medicine. If you want alternative medicine to survive, there should be only one standard throughout the globe. There is no room for variation in science.
Moreover, for the sake of healing the ailing, healers should have open mind to all treatments. Doctors, surgeons, psychotherapists, pharmacists and complimentary practitioners should work together to conquer diseases. Today's crazy treatment may become tomorrow's accepted therapy. The burning examples of penicillin. reserpine, vincristine, vincaleucoblastin and taxol are there to remind us that an experiment of today can be a discovery of tomorrow.