Regulatory Issues

Initially, in the United States, herbal medications were included with conventional pharmaceuticals for the purposes of regulation. In 1962 a distinction was made between drugs and botanicals, with botanicals assigned to the category of food supplements. As a result, herbal medications have a lower threshold of burden of evidence. Subsequently, the Dietary Supplement Health and Education Act (DSHEA; 1994) further delineated regulations pertaining to herbal medications. Herbal medications were defined as compounds containing vitamins, amino acids, herbs, botanical substances, concentrates, or extracts. However, unlike conventional pharmaceuticals, manufacturers are not required to provide the Food and Drug Administration (FDA) with data showing effectiveness and safety—nor are manufacturers required to report adverse events to the FDA. Indeed, the regulatory burden is placed on the FDA to show lack of efficacy or safety. Although manufacturers may not claim effectiveness for specific conditions (e.g., angina), they are allowed to make general claims of health benefits (e.g., promotes heart health).

The FDA has instituted new regulations that improve labeling and manufacturing specifications. The National Center for Complementary and Alternative Medicine (NCCAM) oversees research activities concerning herbal medications. Lastly, the botanical industry itself has established its own regulatory body, the American Herbal Products Association (AHPA).

Other countries also have various degrees of oversight of the marketing and use of herbal medications. European countries have a much longer history of herbal medication use and regulation. The European Union has a much more stringent oversight system. Similar to conventional drugs, herbal medications are reviewed for safety and efficacy and are licensed by the Committee on Herbal Medicinal Products (HMPC), a branch of the European Medicines Agency. Licensed herbal medications can make specific health claims. The HMPC also publishes monographs describing the applications, efficacy, and side effects for each approved herbal medication. Herbal medications appear on formularies and are prescribed by physicians as well as other healthcare providers.

Use of Herbal Medicines

Advocates of herbal medicine can find an herbal preparation applicable to virtually any condition. Several factors contribute to the more widespread use of selected herbal medications by a greater segment of the general population. The general public uses herbal medicine as a supplement or substitute for conventional pharmaceuticals most frequently for the treatment of chronic conditions for which conventional pharmaceuticals provide inadequate relief or produce undesirable side effects. The public often views herbal medication as safer than traditional pharmaceuticals because herbal medicines are derived from natural sources. Because herbal medications are available without prescription in many cases, convenience and personal control of healthcare decisions also motivate use of herbal medications. Major applications of herbal medicines include the treatment of sleep disorders, cardiovascular disorders, depression, chronic pain, prostatic hypertrophy, obesity, erectile dysfunction, and infection (e.g., the common cold). Given the reluctance of patients to share information concerning the use of herbal medications, physicians should use sound judgment and contextual suspicion to inquire about herbal medication use when treating patients with these conditions.

Practice Points

Despite the scant or contradictory evidence supporting the use of herbal medications for many indications, it is clear that the general public has embraced herbal medications. Accordingly, it is important that physicians be knowledgeable about commonly used herbal medications and ask patients about use of these preparations. Many patients are reluctant to divulge their use of alternative or complementary medicines because they fear the reaction of their physicians. Therefore it is important to inquire about herbal medications in a routine nonthreatening manner. If patients acknowledge their use of herbal medications, the physician should determine whether the patient is self-medicating or is receiving guidance from another practitioner (e.g., herbalist, pharmacist). Even if the patient does not acknowledge use of herbal medications, clinicians should proactively discuss possible herbal medication candidates. The physician should present a balanced picture regarding herbal medications by indicating that there is evidence both supporting and refuting their use.

The patient should be informed that just because herbals are natural products, they are not necessarily any safer than conventional drugs.

In addition, it is important to educate patients about the potential for interaction between herbal medications and conventional drugs and other interventions (e.g., surgery).

The physician should refer the patient to reliable sources of patient information on herbals. Most countries maintain a national registry of herbal medications; these registries, which can be found at regulatory agency websites (e.g., NCCAM at the National Institutes of Health [NIH] in the United States and the HMPC monographs in the European Union), serve as valuable sources of information.

Reliability of Herbal Products

There is a great deal of variability in the safety and efficacy of herbal medications. A number of factors contribute to variability in herbal medications, including the following:

Species of plant used (e.g., Echinacea purpurea vs Echinacea angustifolia)

Part of plant used—biologically active ingredients may reside in different parts of the plant (e.g., stem vs leaf)

Growing, harvesting, and storage conditions

Processing methods

Contamination caused by:

Heavy metals, such as lead and mercury

Adulteration with other pharmacologically active substances

Standardization

Often the active ingredient is not known. Thus standards for ingredients and recommended doses are not established. Similarly, standards for labeling may also not have been established.

Even when the active ingredient is known, herbal medicines have shown considerable variability in consistency. In one analysis of 25 ginseng products, the quantity of active ingredients varied from 10% to 300% of the labeled amount. A similar analysis of Echinacea products showed that less than 50% of Echinacea products contained the labeled amount of the herb.

AHPA’s Botanical Safety Handbook provides relative safety ratings for botanicals.

The FDA has initiated Good Manufacturing Guidelines for herbal medications and dietary supplements that will provide standards for labeling.

Efficacy of Herbal Medications

In response to increased demand for herbal products, in 1998 the NIH established NCCAM, which oversees and awards funds for research into complementary and alternative therapies, including herbal medications. In addition, in the European Union, HMPC requires efficacy and safety data before licensing an herbal medication. Nevertheless, compared with mainstream drugs, systematic research into the efficacy of herbal medications is relatively sparse for a number of reasons. The difficulty in obtaining standardized products, lack of knowledge of active principles, and the inability to standardize doses confounds both basic science research and clinical trials. In addition, lack of regulations requiring effectiveness and safety data and lack of patent protection in some countries have limited private investment in herbal research. Moreover, even within existing trials, many conflicting reports exist, perhaps in part because of issues of consistency of products tested (Table 8-1).

TABLE 8-1 Medical Applications of Commonly Used Herbs

Specific Herbal Medications

Full discussion of the wide array of herbal medications used in various forms is well beyond the scope of this text. However, a relatively short list of the most commonly used herbal medications is presented. Table 8-2 presents side effects and drug interactions of some commonly used herbal remedies.

TABLE 8-2 Side Effects and Drug Interactions of Common Herbal Remedies

Herbal Medication	Side Effects	Drug Interactions
Echinacea	Allergic reactions	Potential inhibition of CYP450 isoforms
Ephedra	Excessive adrenergic stimulation Hypertension, myocardial infarction, stroke Excessive CNS stimulation Agitation, sleep disturbances, psychosis	Numerous Synergistic interaction with methylxanthines Synergistic interaction with monoamine oxidase inhibitors Inhibition of antihypertensive effects
Garlic	Odor, diaphoresis, bleeding	Potentiation of anticoagulant and antiplatelet medications Decreased plasma levels of protease inhibitor drug saquinavir
Ginger	No major adverse effects	Potential potentiation of anticoagulant antiplatelet drugs (controversial)
Ginkgo	No major adverse effects	Synergistic interaction with other stimulants (e.g., caffeine)
Ginseng	No major adverse effects	No consistent reports
Kava	Hepatotoxicity	Inhibition of CYP4502E1 Potentiation of other sedatives (benzodiazepines) Inhibition of effects of levodopa in Parkinson’s disease patients
St John’s wort	Mania in bipolar patients Photosensitivity	Many Serotonin syndrome when combined with selective serotonin reuptake inhibitors or tricyclic antidepressants Reduced plasma concentrations of many drugs such as oral contraceptives, statins, warfarin
Soy	Gastrointestinal disturbance	Inhibition of actions of tamoxifen
Saw palmetto	None	No major interactions reported