Concerns and needs for research in herbal supplement pharmacotherapy and safety

Abstract

To the conventionally trained clinician or basic scientist, herbal medicines (or phytomedicinals) represent the most conceptually accessible area of the exploding field known as complementary and alternative medicine. But despite the fact that numerous prescription and OTC pharmaceuticals are also natural products, herbal medicines are defined by U.S. regulatory authorities as dietary supplements and are, in fact, strictly prohibited from promotion as agents to treat, diagnose, or prevent disease. In this review, the argument is made that herbal supplements are indeed drugs, by strict pharmacological definition. However, this regulatory double standard has led to misconceptions among the public and the health care professions alike regarding the safety and efficacy of botanical agents. In cases where herbal remedies are demonstrated effective by double-blind, placebo-controlled, randomized clinical trials, it should logically be appreciated that these agents also pose a risk of toxicity either when taken alone or in combination with prescription or OTC drugs. The most obvious drug-herb interactions are those that can be predicted as additive, dose-dependent extension of the biochemical actions of the offending agents. Less appreciated, but gaining considerable notoriety, are those adverse reactions that cannot be predicted a priori due to pharmacokinetic interactions at the level of altered absorption, metabolism, distribution, and/or excretion. The challenge in pharmaceutical care, particularly where the practitioner may be empathetic with a patient’s desire to use herbal remedies, is to identify a mechanism by which unpredictable side effects and interactions can be evaluated for each specific herbal formulation. Until regulatory legislation dictates that this responsibility lies with herbal manufacturers, the prospective and retrospective studies on herb-drug interactions are left to academic and federal/state researchers and clinicians. In proposing that phytomedicinals be subjected to limited efficacy testing and pharmacodynamic and pharmacokinetic evaluation, the author also cautions that these studies be performed fairly and objectively, in the absence of the blind advocacy or intentional negative bias that characterizes the polarity of stakeholder viewpoints in this health care debate.