PROBLEMS ASSOCIATED WITH THE USE OF HERBAL MEDICINES

V. PROBLEMS ASSOCIATED WITH THE USE OF HERBAL MEDICINES

Despite the popularity of botanical supplements, many herbal products on the market are of low quality and dubious efficacy. Scientists, clinicians, and consumers are often concerned about safety, effectiveness, and consistency of herbal preparations. Their apprehension about these qualities is due to a plurality of unknowns. These include a variety of poorly controlled factors such as raw herb quality, processing methods used to make the preparations, the complex biochemical heterogeneity of herbs, potential adulteration, unpredictable consequences when herbs are combined, unpredictable con- sequences when herbal remedies are combined with conventional medica- tions, and an apparent lack of scientific validation (24–27). It is not surprising that TCM, a medical paradigm that relies mainly on anecdotal data and tradition of use, frequently cannot withstand the scrutiny of evidence-based medicine.

A. Identification, Harvesting, and Manufacturing Herbal products can have very similar appearances, especially between

subspecies or even varieties within a same family. These can be more difficult to discern if the herb is in the dried form. This poses a great problem as different species, even if they are within the same genus, can have very different chemical constituents (28,29). Misidentification of herbs leading to inappropriate usage of a herb is a cause of morbidity and mortality among consumers. An outbreak of rapidly progressive renal failure was observed in Belgium in 1992–1993 and was related to a slimming regimen involving Chinese herbs, namely Stephania tetrandra and Magnolia officinalis (30,31). Seventy-one cases were reported in 1 month in 1994, 35 of whom were on renal replacement therapy. Renal failure has been progressive in most of the cases despite withdrawal of exposure to the Chinese herbs. Renal biopsies showed an extensive interstitial fibrosis with loss of tubes, predominantly in the outer cortex. Chemical analyses of the Chinese herbs powdered extracts delivered in Belgium demonstrated a misidentification between Stephania tetrandra and another potentially nephrotoxic chinese herb, Aristolochia fangchi. Manu- facturers of herbal products are not required to have good manufacturing practices (GMP) under the current regulations in the United States, Singa- pore, and many other countries. Often, consumers can choose from more than one manufacturing processes or formulations for a given herb. Each method

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may result in a different constituent in the final product, or a different percentage of the active compound (32,33). It is not surprising that incon- sistencies in similar herbal remedies, or even between different batches of a specific herbal remedy, are a problem (33–36).

B. Adulteration Herbal products are subjected to possible adulteration or contamination

because regulations for herbal products are never as stringent as for conven- tional medicines. Adulteration may be intentional, as in the case of an herbal remedy manufactured in China and marketed in Singapore. The product, Slim 10, which is a slimming pill claimed to be totally natural, contained an adulterant, fenfluramine. It has since led to more than 10 cases of drug- induced hepatitis and thyroid disorders. One death related to acute hepatic failure has since occurred, while another consumer escaped certain mortality with a liver transplant. PC-SPES, a drug thought to be useful in prostate cancer, had to be withdrawn because of problems with contamination.

C. Lack of Scientific Evidence for Clinical Efficacy and Safety Except for the handful of phytomedicines known in the West, the risk-benefit

profile of many herbal therapies is not known. Randomized control trials are the gold standard for clinical efficacy and they have been performed only for a handful of commonly used drugs such as gingko, St. John’s wort, ginseng, echinacea, saw palmetto, and kava (10). Little is known about the vast majority of the huge body of herbal extracts and formulae registered in the Chinese pharmacopoeia. The importance of well-organized, long-term clin- ical trials cannot be better illustrated than in the recent issue of hormone replacement therapy and its risks and benefits. Despite the long duration of clinical use of hormone replacement in postmenopausal women, it is only in recent years that certain significant risks have been well recognized and better understood.

D. Drug-herb Herb-Herb Interactions Little more than anecdotal evidence exists regarding interactions between

pharmaceutical and herbal medicines. Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. However, studies on the common herbs indicate that significant herb-drug interactions exists. Thus St. John’s wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon, and theophylline; furthermore, it causes intermenstrual bleeding, delirium, or mild serotonin syndrome, respectively, when used concomitantly with oral

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contraceptives (ethinylestradiol/desogestrel), loperamide, or selective seroto- nin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba ) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic, and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concen- trations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine (37). Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin, and produces hypoglycemia when taken with chlorpropamide. Kava (Piper methysticum ) increases ‘‘off’’ periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazo- lam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea , E. pallida) and saw palmetto (Serenoa repens). Thus, interactions between herbal medicines and synthetic drugs exist and can have serious clinical consequences (38).

E. Inadequate Regulation Since 1994 and the passage of the Dietary Supplement Health and Education

Act (DSHEA), herbal remedies in the United States are classified as dietary supplements and not as drugs or food, and are regulated far less stringently than conventional pharmaceuticals. Under the DSHEA regulations, herbal remedies are commodities sold for ‘‘stimulating, maintaining, supporting, regulating, and promoting’’ health rather than for treating disease. Dietary supplements may carry a statement that ‘‘describes the role of a nutrient or dietary ingredient intended to affect the structure or function in humans’’ or that ‘‘characterizes the documented mechanism by which a nutrient or dietary ingredient acts to maintain such structure or function.’’ DSHEA allows general health or ‘‘structure/function’’ claims but does not permit therapeutic claims. Although dietary supplements are sold to affect physiological func- tioning, they can be removed from the market only if the FDA can prove they are not safe. For botanicals, the DSHEA regulations do not require equiv- alent product standardization for uniformity between production batches because herbal products, as dietary supplements, are considered more similar to foods than to drugs. The regulations also do not require the process that obtains the active component to be identified. Given the different processing methods of a particular herb, inconsistencies in chemical constituents are inevitable.

F. Insufficient Consumer Education If a patient’s perception of herbal therapies is that they are ‘‘safe and natural,’’

like eating fruits to obtain fiber for constipation, the patient may not

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recognize the importance of safety issues associated with some herbal products. Use of herbal remedies can thus be less discerning and more indiscriminate as compared to use of conventional medicine. It is important for consumers to appreciate the fact that though herbal medicines have been in use for a long time, they still bring with them risks of side effects. A good example is ma huang (ephedra), commonly marketed as a natural weight loss product. Ma huang is a Chinese healing herb that has been used for thousands of years. The ephedra plant is a short, bushy shrub. Its stems contain the active constituent from which the stimulant ephedrine is now synthesized. The ephedra plant also produces ephedrine’s stereoisomer, pseudoephedrine. Pseudoephedrine is the favored active ingredient in nondrowsy cold and sinus decongestants (2,39,40). Ephedrine was used traditionally to treat a variety of conditions, including asthma, hypotension, and depression. More effective medications have largely replaced it for treatment of serious disor- ders, but it is still available as an over-the-counter bronchodilator and an energy-enhancer. This is not to be assumed that ma huang is thus a safe herbal remedy. It can have side effects too. These include tremors, nervousness, insomnia, headache, gastrointestinal distress, high blood pressure, irregular heartbeat, hyperglycemia, and kidney stones, as reported (2,41). The Ephedra plant has also been linked to substance abuse. This is so because ephedrine and pseudoephedrine are used to produce the popular illicit stimulant methamphetamine (42,43).