The medical use of plants in their natural and unprocessed form undoubtedly began when the first intelligent animals noticed that certain food plants altered particular body functions. While there is a great deal of historical information about the use of plant-based supplements, there is also much unreliable information as a result of unknown or poor-quality natural product formulations, poorly designed clinical studies that do not account for randomization errors, confounders, and—most importantly—a placebo effect that can contribute 30–50% of the observed response. Since the literature surrounding dietary supplements is evolving, reputable evidence-based resources should be used to evaluate claims and guide treatment decisions. An unbiased and regularly updated compendium of basic and clinical information regarding botanicals is Natural Medicines by Therapeutic Research Center (see References), which includes content review by an international, * The US Food and Drug Administration (FDA) recognizes “herbal medication” and “botanical medication” as “dietary supplements.” For the purposes of this chapter, they are identical.
multidisciplinary, collaborative review committee of experts. The recommendations in this database are limited by the quality of the existing research and the quality of the dietary supplement used at the time of the report. As a result, all statements regarding positive benefits should be regarded as preliminary, and conclusions regarding safety should be considered tentative at this time.
For legal purposes, “dietary supplements” are distinguished from “prescription drugs” derived from plants (morphine, digitalis, atropine, etc) by virtue of being available without a prescription and, unlike “over-the-counter medications,” are legally considered dietary supplements rather than drugs. This distinction eliminates the need for proof of efficacy and safety prior to marketing and also places the burden of proof on the FDA to prove that a supplement is harmful before it can be removed from the market or its use can be restricted. Furthermore, marketed dietary supplements are not tested for dose-response relationships or toxicity, and there is a lack of adequate testing for mutagenicity, carcinogenicity, and teratogenicity. Although manufacturers are prohibited from marketing unsafe or ineffective products, the FDA has met significant challenges from the supplement industry largely due to the strong lobbying effort by supplement manufacturers and the variability in interpretation of the Dietary Supplement Health and Education Act (DSHEA). The DSHEA defines dietary supplements as vitamins, minerals, herbs or other botanicals, amino acids or dietary supplements used to supplement the diet by increasing dietary intake, or concentrates, metabolites, constituents, extracts, or any combination of these ingredients. For the purposes of this chapter, plant-based substances and certain synthetic purified chemicals will be referred to as dietary supplements. Among the purified chemicals, glucosamine, coenzyme Q10, and melatonin are of significant pharmacologic interest. Ephedrine, the active principle in Ma-huang, is discussed in Chapter 9.
This chapter provides some historical perspective and describes the evidence provided by randomized, double-blind, placebo-controlled trials, meta-analyses, and systematic reviews involving several of the most commonly used agents in this class. Health care providers should adhere to the principles of “do no harm” but also, because patients are strongly influenced by popular opinion and media reports, be open to therapies that support “integrative health” safely and responsibly. Unproven therapies that are marketed as “alternatives” to conventional medicine should be viewed with caution, but therapies that are supported by evidence-based medicine and have been assessed for benefits and risks when used in combination with conventional medicine can be viewed favorably, especially if a patient expresses an interest in, and a desire to utilize, dual treatment approaches.
Under the DSHEA, dietary supplements are not considered overthe-counter drugs in the USA but rather food supplements used for health maintenance. Legally, dietary supplements are intended to supplement the diet, but consumers may use them in the same fashion as drugs and even use them in place of drugs or in combination with drugs.