Update on Natural Product-Drug Interactions

Gayle Nicholas Scott, PharmD FASCP, BCPS, CGP and Gary W. Elmer, PHD.


Am J Health Syst Pharm. 2002;59(4) 

Abstract and Introduction

The interactions of natural products with drugs are discussed. Interactions between natural products and drugs are based on the same pharmacokinetic and pharmacodynamic principles as drug-drug interactions. Clinically important interactions appear to involve effects on drug metabolism via cytochrome P-450 isoenzymes, impairment of hepatic or renal function, and other possible mechanisms.

Natural products that have been reported to interact with drugs in humans include coenzyme Q10, dong quai, ephedra, Ginko biloba, ginseng, glucosamine sulfate, ipriflavone, melatonin, and St. John's wort. In many cases, more research is needed to confirm these interactions and to determine whether other natural products may also interact with drugs. To effectively counsel patients about interactions involving natural products, pharmacists should be familiar with the most commonly used products and have access to information on more obscure products. In view of the less than stringent provisions of the Dietary Supplement Health and Education Act, pharmacists should consult reliable, independent sources of information on natural products rather than rely on literature provided by manufactured to high quality-control standards.

Natural products can interact with drugs and with other natural products by the same mechanisms as drugs.

The myth that natural products are completely safe is constantly promoted in advertising and creates a need for responsible public education. Although most clinicians can quickly debunk advertising myths with examples of toxic natural products, such as hemlock and cyanide, knowledge of the interactions of natural products with drugs may not be as prevalent. In part because of the disappearance of pharmacognosy from the curricula of most pharmacy schools, the pharmacist who is well aware of a pseudoephedrine-caffeine interaction may not readily recognize the additive toxicity of ephedra (Ephedra sinesis) and guarana (Paullinia cupana).

Since the passage in 1994 of the Dietary Supplement Health and Education Act (DSHEA), which allows natural products to be marketed with minimal FDA scrutiny, dietary supplement sales have grown from $8.8 billion (in 1994) to an estimated $15.7 billion in 2000.[1,2] In a recent survey of medication use in the United States, 40% of respondents reported taking herbal supplements or vitamins on a daily basis, with higher rates among women, whites, and urban dwellers.[3] The DSHEA does not require manufacturers to demonstrate the safety or efficacy of natural products in human trials before marketing. There are no specific requirements for including warnings about known or potential drug interactions on supplement labels, despite improved FDA requirements developed in response to findings by the Commission on Dietary Supplement Labels.[1,4] Consumers need reliable information on interactions between these products and drugs. Pharmacists must be able to recognize such interactions, as well as interactions among natural products. Much of the available information about these interactions is theoretical or is gleaned from case reports, although clinical studies are slowly appearing in the literature.

This article discusses the interactions of natural products with drugs, sources of additional information on such interactions, and strategies for counseling people who use natural products. Natural products are defined here as herbs and supplements including amino acids, vitamins, minerals, and other products of natural origin.