Consumer use of herbs and medicinal plant products in the United States over the past two decades has become a mainstream phenomenon. No longer relegated primarily to health food stores, mail order houses, and multilevel marketing organizations, herbs and phytomedicines (advanced medicinal preparations made of herbs) have become one of the fastest growing segments in retail pharmacies, supermarkets, and other mass market outlets. In addition, major health insurance companies are beginning to include herbs as covered modalities of "alternative therapies" and herb products are being considered for use by some managed care organizations.

In general, consumers use herbal products as therapeutic agents for treatment and cure of diseases and pathological conditions, as prophylactic agents to prevent disease over the long term, and as proactive agents to maintain health and wellness. Additionally, herbs and phytomedicinals can be used as adjunct therapy, to support conventional pharmaceutical therapies. This last use is usually found in societies where phytotherapy (the use of herbal medicines in clinical practice) is considerably more integrated with conventional medicine, as in Germany.

Many herbal products are used to treat minor conditions and illnesses (coughs, colds, upset stomach) in much the same manner as conventional FDA-approved over-the-counter (OTC) nonprescription drugs are used. Additionally, a growing number of health consumers often use herbs and other dietary supplements as preventive measures and to increase the body's general wellness and strengthen the immune system (e.g., reduction of cardiovascular risk factors, increase in liver and immune system functions, increase in feelings of wellness). In the former case, consumers often substitute herbs and phytomedicines for conventional OTC nonprescription medications for relatively minor, self-diagnosable, self-treatable, self-limiting illnesses. Unfortunately, there is no appropriate regulatory mechanism to address the safety and efficacy of herbal products as OTC drugs in the U.S., for reasons explained below.

One study of consumer preferences attempted to measure potential use of herbal products by consumers who claimed that they were not yet users of herbs but would consider using them within the next five years. The study, conducted in 1996, indicated that 63 percent of the 1,008 people surveyed said that herbal supplements will be "the answer to many common ailments" or "part of our daily regimen" within five years. The study revealed that consumers would consider taking an herbal remedy for increasing energy (60 percent), preventing colds (56 percent), boosting the immune system (54 percent), and improving sleep (43 percent). Of the 505 men included in the survey, 18 percent would consider taking an herbal supplement to help with prostate problems. When asked what factors would make them decide to use herbs, the respondents cited recommendations by a physician (66 percent), "Because it can't hurt and might help" (41 percent), "Because nothing else has helped my condition" (34 percent), news coverage on herb benefits (26 percent), and friends using herbs (15 percent). Only four percent of respondents said they would never consider using herbs (Anon., 1996).

The size of the herb market in the U.S. was estimated at about $1.6 billion in 1994 (Brevoort, 1996), with some projections reaching around $2 billion in 1996. However, a survey published in early 1997 by Prevention magazine/NBC News estimated that 60 million adult Americans — one-third of all adults — had used herbal medicines in 1996, spending an average of $54 per person annually. This brings the estimated total retail value of herbs sold in the United States to $3.24 billion in 1996 (Johnston, 1997).

The difficulty in determining the actual size of the market for herbs and phytomedicinal products in the U.S. has persisted because these products were formerly sold mostly through channels of distribution normally not subject to econometric tracking services (health food stores, mail order, multi-level marketing organizations). However, with increased sales of herbs in mainstream retail outlets, more accurate statistics are becoming available. As Table 1 shows, the total of herbs sold in the mass-market outlets (grocery stores, pharmacies, and mass merchandiser retail stores) was $441.5 million in 1997. This is a dramatic 79.5 percent increase over total 1996 sales of $246 million (Glovsky, 1998).

An excellent example of the mainstream acceptance of well-researched herbs and phytomedicines can be seen in the huge increase in sales of St. John's Wort, an herb that has made moderate increases in the health food market for the past 10 years but was virtually unknown outside health food stores. Sales for St. John's Wort climbed from relative obscurity in the mass market to fifth place with an impressive $47.8 million for the calendar year, with about 90 percent of those sales being generated during the six-month period after June 27, when the television show 20/20 profiled the herb. The program reported that St. John's Wort was extensively used in Germany and that a meta-analysis of 23 clinical studies published in the British Medical Journal had concluded that St. John's Wort was more effective than placebo in treating cases of mild to moderate depression (Linde et al., 1996). An editorial in the BMJ stated that the phytomedicine produced fewer adverse side effects than conventional prescription drugs, thereby ensuring better patient compliance (DeSmet and Nolen, 1996).

Of the 14 herbs listed as top sellers in Table 1, all but one (Goldenseal root, Hydrastis canadensis ) are the subject of some degree of pharmacological or clinical research, especially in Western Europe. Ten of these herbs are the subjects of positive monographs produced by Commission E as approved nonprescription medications.?

Additional evidence of widespread consumer interest in herbs and other natural products, now legally classified as "dietary supplements" in the United States, can be found in the estimated two million letters, faxes, and phone calls by Americans to members of Congress during 1993 and 1994 in support of legislation that would protect and increase access to the products themselves and information on their responsible use. The Dietary Supplement Health and Education Act of 1994 (DSHEA) created a new legal definition for dietary supplements: vitamins, minerals, herbs or other botanicals, amino acids, and any other "dietary substance for use by man to supplement the diet by increasing total dietary intake," including "a concentrate, metabolite, constituent, extract, or combination" of these ingredients (103d Congress, 1994).

Granting herbs some legal protection as "dietary supplements" in the U.S. was clarified in the Report from the Senate Committee on Labor and Human Resources that accompanied Senate Bill 784, the Hatch-Harkin bill in the Senate, eventually passed as DSHEA. The report said, "Unlike many drugs, the role of herbal dietary supplements is to enhance the diet by adding safe and natural plants and their constituents to support and protect bodily functions and processes. Containing combinations of numerous naturally-occurring plant chemicals, herbs generally act in a wider, more general, less specific way than most single-ingredient pharmaceutical drugs. Their actions are more ‘gentle' than conventional medicines and work usually in more long-term situations." (U.S. Senate, 1994.) The report attributed this information to the now-classic textbook by the late German physician Rudolf F. Weiss, Lehrbuch der Phytotherapie (the sixth edition has been translated into English as Herbal Medicine ), one of the most important textbooks for training physicians in Germany on the clinical uses of herbs and phytomedicines.

Despite some of the regulatory advances heralded by proponents of DSHEA, there are some significant limitations. Section 6 of DSHEA deals only with herbs as dietary supplements, i.e., as foods. Although a limited amount of information regarding an herb's physiological effects can be conveyed on a product label, therapeutic or drug claims are not permitted. That is, DSHEA allows for "statements of nutritional support" or so-called "structure and function claims" (statements indicating how a product will affect the structure or function of the body). However, "health claims" (allowed for conventional foods and dietary supplements in the Nutrition Labeling and Education Act of 1990, (NLEA) are statements that characterize the relationship between a nutrient or food component and a specific disease or health-related condition. The subject of health claims was considered by the seven-member Presidential Commission on Dietary Supplement Labels (CDSL), who proposed criteria and procedures to review and evaluate such claims to the President, Congress, and the Secretary of Health and Human Services. The CDSL has recommended that a standard of "significant scientific agreement" — the standard set for health claims for conventional foods — be applied to dietary supplements, insofar as manufacturers may wish to file for approval of a health claim for a dietary supplement under NLEA. However, this more strict criterion is not relevant to a structure/function claim under DSHEA (CDSL, 1997).

The current OTC drug monograph system in the U.S. has limited ability to review herbs for their potential to increase the body's wellness, to promote resistance to disease, and to act in a proactive manner not directly associated with a pathology. There are few regulatory options for drugs or herbs that have preventive actions. For example, in recent years garlic was one of the best-selling nonprescription medicines in German pharmacies, because the government (i.e., Commission E) recognized the value of garlic preparations as an adjunct therapy when dietary measures have failed to deal with "age related vascular changes." The Commission reviewed numerous clinical studies on garlic preparations that confirmed low-density lipoprotein-lowering activity of the bulb and its preparations, as well as its related ability to lower other cardiovascular risk factors. An indication such as cardiovascular risk is often not amenable to self-diagnosis and self-treatment, is not self-limiting (the condition does not abate within a reasonable period — usually a few days) and, therefore, is currently not subject to consideration under the OTC Drug Review in the U.S.

There are additional limitations of the current OTC drug system in the U.S. with respect to reviewing herbs and phytomedicines. Under FDA policy, novel ingredients that require evaluation for safety and efficacy are new drugs and thus must go through a New Drug Application (NDA). This process is time consuming (average 15 years) and extremely costly; one study in 1996 reported an average cost of $500 million per new drug (PhRMA, 1998). Proponents of rational use of herbs and phytomedicines are quick to point out that without patent protection to ensure market exclusivity, most herbal, phytomedicinal, and pharmaceutical companies are not willing to invest the millions of dollars required for an NDA (Tyler, 1994).

A premise of the OTC Monograph Review process in 1972 was that all ingredients included in the review process be regarded as "old" drugs. Old drugs were treated more leniently than a new drug, which would require an NDA, because old drugs had been on the market in the U.S. "for a material time" (at least five years) and "to a material extent" (at least 10 million doses).

Since the 1970s FDA has taken the position that old drug status extends only to ingredients sold in the U.S. For certain key European phytomedicines to participate in the OTC review process, a group of European and American companies working through the European-American Phytomedicines Coalition (EAPC) filed a petition with the FDA to open the OTC review to old drugs from Europe that have been sold for a material time and to a material extent. The EAPC petition sought to extend this policy to phytomedicines sold for a material time and to a material extent in selected Western countries that have a well developed system of pharmacovigilance (adverse reaction reporting system). Thus, the safety of these European phytomedicines has been well established by common use in countries where reliable epidemiological data is available (Pinco and Israelsen, 1992).

The EAPC petition was filed July 24, 1992. By spring 1998, almost six years after the filing, the FDA had not yet responded directly to the petition. This lack of timely response has given some herbal advocates the impression that the agency (at least those in the Center for Drug Evaluation and Research) is not interested in developing a reasonable mechanism for evaluating herbs as nonprescription drugs. Critics point to statements from FDA that herbs sold for health purposes are essentially drugs. In June 1993 the agency wrote in a proposed rule on NLEA in the Federal Register : "When herbs are consumed primarily for their taste, aroma, or nutritive value, they are foods. If the herbs are intended to be consumed for their medicinal effects, however, they are drugs." (FDA, 1992.) Without the ability for industry to submit herbs for review as old drugs under the OTC Review system, as proposed by the EAPC petition, industry would have no other option but submit them as new drugs , an impossible prospect in light of the high costs associated with new drug approvals.

In 1994 and 1995, in order to add some substance to its 1992 petition, the EAPC filed petitions to amend the nighttime sleep-aid monograph to include valerian root (Pinco and Israelsen, 1994) and the anti-emetic monograph to include the popular herb and spice ginger (Pinco and Israelsen, 1995). Both petitions cited the widespread safe and effective use of these common botanical products in Europe as OTC medications, with no evidence of adverse reaction reports in countries where the reporting of such events (pharmacovigilance) is routine. Both petitions documented the safety and efficacy of the two ingredients as determined by human clinical trials and registrations as medicines in various Western European countries. To date (spring 1998) FDA has not responded to these two petitions. This lack of response has given additional impetus among some members of the herb industry and some scientists with interests in herbal research and education to support the concept of herbs as dietary supplements under DSHEA. Prospects appear uncertain for obtaining OTC drug status for herbs whose safety and efficacy to treat minor, self-limiting conditions has been reasonably established by both scientific data and empirical use.

In October 1996 the FDA issued an advance notice of proposed rulemaking (ANPR) proposing conditions for consideration of OTC drug review that would virtually preclude qualification of European phytomedicines (FDA, 1996). Before the publication of the ANPR the message that members of the herb industry and a number of scientific authorities interpreted from the lack of FDA response to the EAPC petition was that the agency was not really serious in dealing with herbs as drugs . That is, despite previous FDA statements that herbs were really drugs and not foods or dietary supplements, when given an opportunity to evaluate and consider the approval of a few select herbs according to the procedures appropriate for OTC drugs, the agency appeared unable or unwilling to act. With the provisions of the ANPR, the agency proposed regulations consistent with its previous narrow policies regarding herbs. Thus, the potential in the short term for the approval of select herbs and phytomedicines as OTC drugs remains unclear.

With the OTC drug route currently blocked for a subset of herbal products, the herb industry has only one option — to market these products as "dietary supplements" under the terms of DSHEA. In November 1997 the Commission on Dietary Supplement Labels (CDSL), created by DSHEA and appointed by President Clinton in 1995, presented its report to the President, the Congress, and the Secretary of the Department of Health and Human Services. The report recommended that the FDA "give special attention to the feasibility of approving botanical remedies for OTC uses in cases in which sufficient evidence is available. The Commission [CDSL] recommended that FDA convene a botanical products review panel to evaluate petitions concerning such products. Such a panel should include experts with an appropriate scientific background in pharmacognosy as well as experts in other applicable disciplines. In its deliberations this panel should give priority to botanical remedies having the strongest supporting evidence." (CDSL, 1997.) Cited as examples of remedies to consider are the botanicals currently being reviewed by the United States Pharmacopeial Convention (USP) and the extensive monographs by the World Health Organization. The report recommended that FDA "put a high priority on expediting such a review panel." The CDSL report also acknowledged that it did not have any authority in the area of drugs; its recommendations are in the domain of herbs as dietary supplements (CDSL, 1997). As part of public testimony to the CDSL, several herb leaders from various groups presented documentation that herbs were rationally regulated as medicines in leading European countries, particularly Germany, in which the Commission E expert panel process was emphasized (Bayne et al., 1996).

The growing consumer use of these products and increased professional interest in their therapeutic potential require that new regulatory models be considered for evaluating the safety and efficacy of herbs and phytomedicines as drugs. There has never been a greater need for authoritative, reliable information on the use of botanicals. Much of the information on the clinical or pharmacological studies of herbs and phytomedicines is still not being incorporated into curricula at medical and pharmacy schools in the U.S., although a growing number of schools are beginning to offer courses in herbs and phytomedicines, either as the entire course, or as part of a course on "alternative," "unconventional," or the now increasingly preferred "integrative" medicine. Such a course will inevitably attempt to cover the entire range of the sciences and disciplines that encompasses herbal medicine: anthropology and ethnobotany, medical botany, pharmacognosy, phytochemistry, natural products research, pharmacology, plant ecology, and whole systems theory.

In general, health professionals have three basic methods of obtaining scientific information on using these natural products: independent study, including books, articles, and so-called "third party literature" of varying degrees of quality and authority; continuing education courses; and the directions for use and label claims on the products themselves. However, until a regulatory system in the U.S. is developed to review and evaluate the safe and responsible therapeutic uses of herbs and phytomedicines, health professionals will not be able to obtain adequate therapeutic information from product labels. Instead, they will seek guidance from the authoritative information found in the official herbal monographs produced by Commission E and the World Health Organization (WHO), as well as unofficial monographs from professional organizations such as the European Scientific Cooperative on Phytotherapy — ESCOP, the American Herbal Pharmacopoeia — AHP, and the United States Pharmacopeia — USP.