Another situation in which it is helpful to determine whether prod- ucts are similar in therapeutic efficacy is in the pooling of clinical tri- als conducted on different products. A meta-analysis is a statistical review of multiple trials. It is a systematic way to pool data, often from numerous, small, randomized controlled studies, and examine the significance of their findings as a whole. But what is the signifi- cance of pooling data from different botanical preparations, possibly with different chemical profiles and without established bioequi- valence?
Certainly there is a basis for comparing studies conducted on dif- ferent powdered garlic products, but powdered garlic products do not have the same chemical profile as aged garlic or garlic oil. The Agency for Healthcare Research and Quality, an agency in the U.S. Department of Health and Human Services, sponsored a systematic review of garlic through one of its Evidence-Based Practice Centers (EPC). The evidence report separately summarized the effects of gar- lic on cardiovascular-related factors/disease and cancer. Studies on preparations ranging from dehydrated garlic, aged garlic extracts, and garlic oil macerates to distillates, raw garlic, and combination
tablets were all pooled together (Mulrow et al., 2000). This practice of attempting to collectively determine the evidence regarding an herb’s efficacy by pooling all products, regardless of their different specifications, provides misleading results. It reinforces the idea that all garlic products are alike, a concept not supported by chemical analysis.
PERSPECTIVE
The appropriateness of borrowed science is not only a question re- garding truthful advertising but also a question regarding therapeutic benefit for health practitioners and consumers. Often health prac- titioners and patients uncritically substitute one herbal product for another. The consequence of this action could be a lack of the ex- pected therapeutic benefit.
For this situation to change, consumers and health care practitio- ners would need to be aware of the source of the information regard- ing the efficacy of a product. Is the source of evidence traditional use of a tea or tincture, or is it several clinical studies conducted on a spe- cific type of extract? The next question is, does the form of the prod- uct being sold match that of the product with the direct evidence? Of course, certain differences may not influence efficacy, and further re- search is needed to determine what differences are acceptable or un- acceptable. Further, health practitioners and consumers would have to be aware enough of the complexity of herbal preparations to realize that a generic form may provide the same activity, but it also may not. Without evidence of equivalency, health practitioners and consumers would have to be able to distinguish clinically researched products from those that have no direct evidence to support their claims.
At the moment, no regulatory pressure has been placed on manu- facturers to conduct either their own efficacy studies or equivalency tests. Without additional regulation, it is unlikely that most manufac- turers will invest money into such research.
As outlined in this chapter, the concept of herbal product equiva- lence can be approached in a rational and scientific manner. The FIP Herbal Medicinal Products Working Group is exploring the means to do just that. The examination of chemical equivalency is determined by the extent of knowledge regarding the active components. For most herbs, it begins with comparison of the botanical identities, the plant
parts, and agricultural practices and extends to manufacturing prac- tices. Determination of in vitro disintegration and dissolution are first steps toward determining bioequivalency, which ultimately must be determined clinically. It is important to remember that the extent to which the active constituents are known will determine the degree of correlation between dissolution and bioequivalence tests and efficacy.
Until health practitioners and consumers demand more informa- tion on the source of the evidence for efficacy, or until additional reg- ulation is in place, the current problem of borrowed science will con- tinue in the United States. In other words, many U.S. companies will inappropriately attribute science conducted on other products as per- taining to their own.
REFERENCES
Blumenthal M, Busse W, Hall T, Goldberg A, Gruenwald J, Riggins C, Rister S, eds. (1998). The Complete German Commission E Mono- graphs: Therapeutic Guide to Herbal Medicines. Trans. S Klein. Austin, TX: American Botanical Council.
ConsumerLab (2000). Product review: Ginkgo biloba and huperzine A— Memory enhancers. <http://www.consumerlab.com/results/ginkgobiloba. asp>.
Kressmann S, Biber A, Wonnemann M., Schug B, Blume HH, Müller WE (2002). Influence of pharmaceutical quality of active components from Ginkgo biloba preparations. Journal of Pharmacy and Pharmacology 54 (11): 1507-1514.
Kressmann S, Müller WE, Blume HH (2002). Pharmaceutical quality of different Ginkgo biloba brands. Journal of Pharmacy and Pharmacol- ogy 54 (5): 661-669.
Lang F, Keller K, Ihrig M, van Oudtshoorn-Eckard J, Möller H, Srinivasan S, He-ci Y (2003). Biopharmaceutical characterization of herbal medici- nal products: FIP discussion paper, Part 1. Die Pharmazeutische In- dustrie 65 (6): 547-550. Part 2. Die Pharmazeutische Industrie 65 (7): 640-644. Also published in one document in Pharmacopeial Forum 29(4): 1337-1346.
Mulrow CD, Lawrence V, Ackermann R, Ramirez G, Morbidoni L, Aguilar C, Arterburn J, Block E, Chiquette E, Gardener C, et al. (2000). Garlic: Effects on cardiovascular risks and disease, protective effects against cancer and clinical adverse effects. Evidence Report/Technology As-
sessment No. 20, October, AHRQ Publication No. 01-E023. Rockville, MD: Agency for Healthcare Research and Quality.
United States Pharmacopeial Convention (2002). United States Pharmaco- peia 26, National Formulary 21 (USP-NF). Rockville, MD: The United States Pharmacopeial Convention, Inc.
Chapter 7
Determining Efficacy of Herbal Preparations
Determining Efficacy
of Herbal Preparations
Tieraona Low Dog
Herbal medicine has been used since prehistoric times and gave birth to the sciences of botany, pharmacology, and, in part, chemistry. The initial evidence for the efficacy of these medicines was derived from direct human experience and observation. Some of the most ef- fective medicines in our recent past originated from plants, including aspirin (salicylic acid from willow bark and meadowsweet), quinine (from cinchona bark), digoxin (from foxglove), and morphine (from opium poppy). Although many health care practitioners recognize that a number of other botanicals may be of therapeutic benefit, there is an undeniable sense of skepticism given the amount and quality of information currently available.
New information about the safety and efficacy of botanicals is be- coming available on a daily basis. For this reason, both patients and providers utilize the Internet to gather health information; 52 million American adults have used the Web for this purpose (Pew Internet and American Life Project, 2000). Most users like the convenience of using the Web and the fact that they can do their research anony- mously, yet 86 percent of those using the Internet for medical infor- mation worry about getting information from unreliable sources. The Federal Trade Commission (FTC) is charged with enforcing laws that ban “unfair or deceptive acts or practices.” In 1998, the FTC held a “health claims surf day,” during which 80 organizations from 25 countries searched the Internet for treatment and/or cures for cancer, arthritis, heart disease, AIDS, diabetes, and multiple sclerosis. Unfor- tunately, during this one afternoon of searching they found 400 sites making unfounded claims (Rusk, 2001).
So how does a health care provider determine what evidence is available regarding a specific botanical product? How does one as- sess the strength and weight of the existing evidence and apply that to a given patient? Evidence on the efficacy of herbal medicines ranges from historical use data, pharmacological studies, case reports, and uncontrolled clinical studies to the gold standard of randomized, dou- ble-blinded, placebo-controlled clinical studies. The strengths and weaknesses of each type of evidence and the criteria for a quality clinical trial are presented in this chapter.
A long history of traditional use of an herb can be an important source of information about safety and efficacy, especially if the in- formation is corroborated by similar uses in multiple cultures which have apparently discovered that use independently. Objective phar- macological measurements using isolated tissue or cell culture is a well-accepted first step for understanding the biological activity of a particular substance. Animal studies are often used, as they permit generous control over a number of variables and can help to explain potential mechanisms of action. In vitro and animal data can provide important information about both the effectiveness and the safety of an herb; however, they are limited in their ability to accurately predict physiological effects in humans. Special attention must be paid to the experimental concentrations used in in vitro studies. These amounts should correlate with the concentrations expected in the plasma (blood) following human use. Similar attention should also be paid to the doses used in animal studies. In addition, caution must be used in the extrapolation of an activity produced with an isolated constituent of a plant to the activity expected with a whole plant preparation. Es- pecially in the case of in vitro studies, one must determine if the com- ponents in the plant material being studied are altered by gut flora, transported across the intestinal wall, or altered by hepatic first pass metabolism. In addition, any physiological effects due to secondary metabolites must be considered.