by Amy Anderson
Mankind has sought ways to circumvent its own mortality throughout the course of our history, but disease prevention is a tricky business. In the modern age, the looming threat of chronic disease poses extreme danger to aging individuals and to the health of the U.S. and global economies alike. Scientists across medical disciplines are advocating for a switch from “reactive” to “proactive” action against disease to reduce the number of people becoming ill. The benefits of prevention over treatment are clear; in the United States alone almost $2.7 trillion dollars is spent on health care annually, and three-quarters of that on treatments for chronic diseases. Although the average human lifespan is increasing, the number of years in which a person enjoys good health with minimal handicap have not improved much at all. It seems modern medicine has done a good job of finding ways to keep us alive longer – delaying death for the chronically ill and aging – but has done significantly less to increase the prevalence of health. Perhaps it is because people in developed societies can count on experiencing more chronic illness in their extended life spans that an explosive new market has emerged: supplements to promote long-term health through alternative medicines.
Although the pursuit of good health is a business as old as mankind itself, the nature of our quest has changed in western civilizations. Sedentary lifestyles and processed foods have given rise to an unhealthy population full of people desperately seeking ways to promote their individual well-being without undergoing major lifestyle changes. While the scientific process continues its arduous march, the increasing demand for preventative and chronic disease treatments has created a void that sound medical research has barely begun to fill. In this vacuum, people are increasingly turning to inexpensive, do-it-yourself remedies derived from traditional herbal medicines – often cleverly marketed as “natural” or “homeopathic”. While scientists on the front lines of nutrition and chemoprevention research are only beginning to make inroads into clinical practice, the relatively unregulated business of dietary supplements is rapidly expanding to fill the void.
One might ask, why should we be concerned about alternative medicine and the growing popularity of dietary supplements? Written records of herbal remedies extend back well over five thousand years, detailing innumerable medicinal uses for plants and other well-established traditional practices. Even in this era of modern medicine, cultures which rely almost entirely on “traditional” (also known as “folk” or “indigenous”) practices for primary health care are not uncommon – particularly in Asia and Africa. Although it is undeniable that some traditional medical practices and studies of related plants have formed the foundation of modern day pharmacology and drug discovery, it is the unfortunate truth that numerous others are placebos at best, and harmful at worst.
A major regulatory issue with dietary supplements is that they are classified separately from foods and drugs, even though the boundaries between the three are often significantly overlapped. Any distinctions are further confounded due to the fact that various compounds found in edible plants are the source of most dietary supplements as well as the structural origins of most active drugs (50%-75%), making it possible to classify any number of conceivable products as all three at the same time.
The Food and Drug Administration (FDA) defines a “drug“ rather broadly as requiring two criteria: (1) activity to produce changes in structure and function within the body and (2) intent to diagnosis, cure, mitigate, treat, or prevent a disease when administered. Since bioactive compounds which could affect a change in the body are present in virtually everything we consume, the key component which defines a drug is its intended use. With this definition, we can make a clear distinction between drugs and foods on the basis of intent (if nothing else), since possession of biological “activity” is not limited to products intended as drugs. An extreme example of a food possessing drug-like activity is the grapefruit, whose juice contains a potent inhibitor of the cytochrome P450 CYP3A4 enzyme that can cause dangerous side effects and even death under some circumstances. However, foods with drug-like characteristics are not accounted for under any FDA definition. In fact, the FDA circularly defines food as itself (“articles used for food and drink in man or animal”), and describes drugs as “articles other than food”. Furthermore, the federal definition of a dietary supplement fails to distinguish itself from that of a food or a drug in any way except one – labeling.
To be considered a dietary supplement, the product must be ingested in the form of a pill, capsule, tablet, or liquid. It must contain one or any combination of: a vitamin, a mineral, an herb or botanical, an amino acid, a concentrate, or a metabolite extract. The product must be intended to supplement the diet without being represented as a “conventional food or as a sole item of a meal or diet”. Finally, the product must be labeled as a dietary supplement with a statement that the product has not been evaluated by the FDA and is not intended to diagnose, treat, cure or prevent disease. Considered together, these criteria do not distinguish between foods, drugs, and dietary supplements on the basis of their chemical nature, only on their intended use. The language that the FDA uses to characterize dietary supplements is different than that of a drug and focuses mainly on its physical form and how it is marketed, but the definition fails utterly in making a practical distinction which mutually excludes one type of product from the other. Yet with respect to federal regulations, drugs and dietary supplements are treated entirely differently.
For any conventional drug to come to market, the product must first be registered with the Food and Drug Administration (FDA) by the filing and approval of an Investigational New Drug (IND) application before the manufacturer can even begin mandatory studies to determine safety and efficacy. Producers of dietary supplements are under no such obligation. Often the bioactive ingredient in a supplement is later identified as closely related to or even identical to those in prescription drugs. Even more concerning, the ingredients in a dietary supplement may be uncharacterized and numerous or may be tainted with unknown toxic compounds, such as the potent carcinogen aristolochic acid, a natural botanical compound found as a contaminant in many Chinese herbal remedies.
In 2000, a study in Belgium identified a cohort of patients in end-stage renal failure with concomitant urothelial carcinomena caused by aristolochia toxins. In all cases, these patients had been taking some form of Chinese herbal supplement, with some patients progressing to end stage renal failure in as little as 8 months. In a follow up study, the FDA purchased a limited sample of herbal products marketed in the U.S. and analyzed them for aristolochic acids. Of the 34 products tested, 18 were found to have been inadvertently contaminated with plant material derived from Aristolochia spp. These findings were published in a letter to the supplement industry urging them to “review their current manufacturing practices” and “take adequate steps to identify and report adverse events”. Despite the mortal danger these so-called medicines pose, the FDA continues to have little power to police their distributors, since “under the Federal Food, Drug, and Cosmetic Act, as amended by the Dietary Supplement Health and Education Act, the manufacturer bears the primary responsibility for ensuring that its dietary supplement products are safe.”
The FDA publishes many reports with consumer warnings about the potentially dangers of supplements, including numerous “natural” remedies for weight-loss, muscle growth and recovery, sexual enhancement, joint pain, concussions and other conditions. For example, the makers of OxyELITE Pro – a supplement marketed to men for increasing metabolism and promoting weight loss and muscle gain – has received multiple warnings from the FDA for failing to provide evidence of safety when new ingredients were added to existing formulations of their product. The company has recently been asked to recall and destroy supplements linked to dozens of cases of acute liver failure and hepatitis, including one death and multiple liver transplants. New formulations with untested natural additives have already appeared on the market to replace those that were recalled.
Though many frightening examples exist, it is true that not all dietary supplements necessarily contain poisonous contaminants or mislabeled ingredients. Many may even contain compounds which are generally understood by the scientific community to be beneficial. However, even supplements which aren’t overtly toxic pose a danger when applied indiscriminately. Discounting the possibility of contamination, misidentification, or off-target effects, the “active” ingredient (or often, ingredients) in a dietary supplement may not be therapeutic to all people in all circumstances. Just as approved drugs can be life-saving in a specific circumstance for a specific person at a certain dose, yet lethal in another circumstance, individual, or dose, both the known and unknown ingredients in dietary supplements can affect different people in unpredictable ways. Any medical professional will attest that the effects of a bioactive compound – be it in a drug, food, or dietary supplement – depend greatly on the dose as well as a person’s health and genetic background.
It is said that the road to hell is paved with good intentions, and perhaps so is it with the use of dietary supplements. The bottom line is that the dietary supplement industry manufactures medical products yet is exempt from the strict safety and quality assurance regulations governing the manufacturers of medical products labeled as drugs. Regardless of their formal definition, it is apparent that supplements are being used as drugs and should face the same scientific scrutiny. Without systematic controlled studies to investigate the claims made by supplement manufacturers, a dietary supplement is no safer than an untested drug, and to consume them is to gamble with our health rather than sustain it.