Herbal Medicine

 

Joseph A. Simaan M.D.
Professor and Chairman, Department of Pharmacology
Faculty of Medcine
American University of Beirut
July, 2007

Historical background

Herbal medicine, the most major component of traditional medicine, is as old as recorded history. This is clearly revealed Chinese compendium of medicinal plants, the Pen Tsao of 2300 B.C, the Hamurabi code of medical ethics and treatments of 2200 B.C and the Ebers Papyrus of the ancient Egyptians of 1550 B.C. Beginning in the early 1800, with the explosive development in the science of chemistry, both in its analytical and synthetic methodologies, scientists quickly turned their attention to the active ingredients in plants, historically documented to produce a favorable therapeutic effect. The active ingredients were extracted, purified and the chemical structure disclosed. Pharmaceutical products were then made from those pure chemicals, presented in various pharmaceutical forms and precisely closed. This ushered the modern era of pharmacotherapeutics, based on exploration of pure chemical products as to chemical identity, physico-chemical properties, pharmacodynamic actions, pharmacokinetic behavior in the biological system, toxicological profile and effective and safe application in therapy. Such classical pharmacological agents as morphine, codeine, papaverine, atropine and many others were an outcome of this fertile era of chemistry and pharmacotherapeutics. Needless to say, this relegated the role of traditional medicine and with it herbal medicine, to a secondary and currently practically no role in medicine as it is practiced today. However traditional medicine continued to be practiced to varying degrees and in different cultures. In more recent times there appears to be a revival in the application of traditional medicine, even in culturally advanced societies. In the United States, many studies revealed a surge in the dependence on traditional medicine and in this respect a study by Elsenberg et al in 1997 is revealing (1). Elsenberg et al collected data from a large sample of subjects in the United States and interpolated this data to cover the US population. The data revealed that 12.1% of the adult population had used herbal medicines in the past 12 months as compared to 2.5% in1990 at a cost of $5.1 billion. Parallel to this increased popularity of herbal medicine, concern about efficacy and safety of herbal medicines has also increased and the call for more rigorous control and validation of claims for efficacy and safety of herbal remedies has grown (2). It appears evident that the increase in the dependence on herbal remedies is multifactorial, two of many factors being more prominent, the first being the common belief that natural remedies connot be harmful and the second is vigorous promotion.

 

The risks on health in the use of herbal remedies

1. The use of herbal remedies with unproven therapeutic benefit. Unless a herbal product has been subjected to rigorous testing in well controlled animal experimentation and human trials to disclose a pharmacodynamic effect that is useful in therapy, the use of the preparations can be hazardous. This is particularly true in instances where the herbal product is used as a replacement for formal pharmacotherapeutics in the treatment of serious medical problems such as diabetes mellitus, cardiovascular disease, central nervous system diseases, cancer and others. The disease process will progress to an end point that makes rescue very difficult while patients live under the false impression that the treatment they are receiving is effective.

2. The use of herbal remedies with undisclosed toxicological profile. The common belief that natural products cannot be toxic is deceitful. Every conceivable toxic effect on the biological system, including fatality due to irreversible toxic effects, has been scientifically shown for different plant products. This mandates that no plant product should be administered to patients without a thorough investigation of its toxic potential.

3. Interaction between plant products and concomitantly administered drugs. Currently there is a high level of awareness in pharmacotherapeutics of the potential for drugs to interact with each other when concomitantly administered. The interactions are at the level of important functional components of the biological system, including the plasma proteins, receptors, transporters, ion channels, metabolizing enzymes, drug elimination sites and others. As a consequence of these interactions, a recommended therapeutic dose of a given drug may turn out to be insufficient and consequently subtherapeutic,  thus the benefit of the treatment is not achieved, or excessive, resulting in toxicity. Concomitant administration of drugs and the active chemical ingredients in herbal products is likely to result in interactions with undesirable results. Studies show that in many instances patients on drugs also take herbal preparations (3). The chemicals in a mixture of herbal products may interact to produce toxicity that is not evident when individual herbs are given alone. A commonly ingested food element, grapefruit, exaggerates the effect of around fifty drugs by interfering with their metabolism, many of which are commonly prescribed and many can produce serious toxicities when a higher plasma concentration is exceeded (4). This is true of other botanical products used as herbal medicines (5,6,7)

4. Patient-related factors in the toxicity of herbal preparations. In the practice of pharmacotherapeutics, many patient-related factors are taken into consideration in the choice of therapeutic agents, the prescribed dose and the follow up for effective and safe treatment. This includes age, the disease process and its extent, the state of health of the drug eliminating organs such as the liver and kidney, pharmacogenetic factors and others. Herbal products constitute no exception and their effect on the biological system is determined by these factors (8,9,10).

5. The issue of standardization and purity of herbal preparations. Pharmaceutical preparations contain the active ingredients as pure chemicals in a fixed dose. They are subjected to a wide variety of tests prior to marketing to ensure compliance with applicable standards, particularly the quantity and purity of the active ingredient. This precision in the dosing of the active ingredient sought in a herbal preparation cannot be achieved. Studies have shown that different products containing the same herb in the same amount yielded different concentrations of the active ingredient. Furthermore, herbs are museums of chemicals and the content in a herb of the other chemicals, some of which may be toxic, also varies (11,12). Contaminants including pesticides and microbial toxins have been found in some preparations. Adulterants, including heavy metals and conventional pharmaceuticals are sometimes added to herbal preparations hazardous (13,14,15). In one study 6.5% of randomly studied herbal preparations contained undeclared drugs (16). Herbal preparations advocated for weight loss resulted in fulminant  hepatic failure which was discovered to be due to an undeclared adulterant, N-nitrosofenfluramine (17).

 

Efficacy and safety control at the international level

In its concern for safety and efficacy in the use of herbal preparations, the Word Health Organization (WHO) came out with a document on the “Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines”, issued by the Regional Office for the Western Pacific in 1993. The recommendations of WHO for the study of herbal preparations advocated for therapy are not less rigorous than those applicable for medicines in general. They include verification of the plant species identify, laboratory experiments to verify safety, proof of efficacy particularly when the herbal preparation is recommended for a major treatment and in the case of herbal mixtures, verification of efficacy and safety of individual herbs in the mixture. Efficacy of new herbal products, new indication for an existing herbal preparation or a different dosage form, necessitate clinical studies along the recommendation for the study of modern drugs described in WHO’s Good Clinical Practice (GCP) Protocols in 1995. For old herbal preparations that have been in use for an extended period of time, compilation of the reported literature on their safety and efficacy may lessen the requirement for new animal testing and clinical studies. WHO’s report of a global survey on regulation of herbal medicines, published in 2005, is revealing (18). The report acknowledged the difficulty in the assessment of  safety and efficacy of herbal preparations as compared to conventional pharmaceuticals in that a medicinal plant contains hundreds of natural constituents and a mixed herbal product several times that number. Awareness for the need to regulate herbal medicines is growing. With only 14 member states with laws governing herbal medicines in 1988, the number has grown to 53 member states in 2003 and 42 others were in the process of developing  regulations. In many states, the regulations for registration of herbal medicines are as strict as those for conventional medicines. Some countries that have adopted a common pharmacopocia. Other countries (26 countries) are in the process of developing pharmacopocias.

 

The Lebanese scene

Currently, all herbal preparations sold under different titles as medical herbs, nutritional products, food supplements and others are under the control of a special committee composed of physicians, pharmacists, nutrition specialists and Ministry of Public Health officials, set up by the Council of Ministers in 1998 through the decree 11710 and which functions under the jurisdiction of the Health Engineering section of the Ministry of Public Health. The committee is charged with the process of organizing the importation of products and setting up the required conditions for that purpose, in addition to reviewing requests for importation and taking the appropriate action for approval disapproval, requesting additional information or asking for analysis of products.

 

Recommendations

Where as Lebanon can be considered as one of the countries that has instated a formal control for the importation and registration of herbal and other health-related preparations, assurance must be provided that the system is not being by-passed. The question arises as to whether all the products available in the Lebanese market have been approved. Furthermore, all herbal products advocated for therapeutic purpose with a claim for a therapeutic indication printed on the preparation or that appears in related documents, must be passed on the Technical Committee of the Ministry of Public Health, in charge of evaluation and registration of regular drugs, for evaluation and action. This Committee is expected to apply on herbal medicines with a therapeutic claim, the same criteria applicable to the evaluation of regular drugs in terms of efficacy and safety. This Committee is set up in accordance with section 54 of law number 367, 1994, which governs the Practice of the Pharmacy Profession. Section 36 defines the drug as every product that has a therapeutic, physiologic or prophylactic effect. In this regard, although decree 11710 makes no reference to referral of herbal products with a claim for a therapeutic indication to the Technical Committee for study, the law 367 carries the greater weight and compliance with its terms is mandatory. It is further recommended that all herbal products with a claim a therapeutic indication be treated like regular drugs in terms of promotion. Their promotion in any form of the media should not be allowed.

Herbal products have been in use since the beginning of recorded history and are likely to remain in the future. In fact their use is on the increase as far as many reports, including those of WHO, indicate. Consequently, the need to subject these products to rigorous control assumes great importance.

Refereces

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17. Adachi M, Saito H, Kobayashi H, Horie Y, Kato S, Yoshioka M et al. Hepatic injury
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18. National policy, on traditional medicine and regulation of herbal medicines: report of
      a global survey. World Health Organization, Geneva May 2005