Chapter 37 - Adverse effects, side effects and toxicity of select phytochemicals: A review of clinical studies

National Institutes of Health State-of-the-Science Conference Statement: Multivitamin/Mineral Supplements and Chronic Disease Prevention

Dietary supplements: what is in the public's best interest?

PurposeMagazine advertising has been associated with influencing body image and dietary behaviors. Since enactment of Dietary Supplement Health and Education Act (DSHEA) ten years ago, dietary supplements of unproven value...

In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA). The regulatory framework for dietary supplements created by DSHEA has led to significant misperceptions regarding consumers' understanding of the safety and efficacy of supplements. Research shows that consumers erroneously believe that: (1) supplements are approved by the government, (2) supplements have been tested for safety and effectiveness, (3) the content of supplements is analyzed, and (4) manufacturers are required to disclose known adverse effects to consumers. Furthermore, labelling requirements that are intended to provide transparency to consumers are relatively ineffective. The following four recommendations are offered for reforming DSHEA: (1) only allow structure-function claims that are supported by research evidence, (2) require manufacturers to list known adverse effects on the labels of dietary supplements, (3) require that the Food and Drug Administration analyzes the content of dietary supplements and (4) restrict the definition of dietary ingredients. These recommendations would bring DSHEA to more closely align with consumer expectations regarding the regulation of dietary supplements and would likely provide a safer landscape for the use of supplements. Copyright © 2015 John Wiley & Sons, Ltd.

IN OCTOBER 1994, PRESIDENT CLINTON SIGNED INTO LAW the Dietary Supplement Health and Education Act (DSHEA), and 17 years later, health experts, policy makers, and industry lobbyists continue to spar over the legislation. Classifying dietary supplements as a subcategory of food, DSHEA allowed supplement manufacturers to market products without submitting proof of safety or efficacy to the US Food and Drug Administration (FDA). Currently, for a tainted or otherwise hazardous product to be removed from the supplement marketplace, an agency such as the FDA or the Drug Enforcement Administration must offer evidence that the product is unsafe, contains a controlled substance, or is absent ingredients listed on the product label after the product has appeared in retail outlets. For US health professionals, the fact that more than 150 million US residents use dietary supplements should be a point of concern as many users will almost certainly forgo conventional medical treatment in favor of using products that may offer no medicinal value and taking health advice from medically untrained sales representatives. Counterintuitively, DSHEA became law 5 years after the L-tryptophan amino acid disaster of 1989, in which 38 individuals died and 1500 sustained adverse reactions. When the FDA appeared heavy-handed in its response to the supplement catastrophe, industry lobbyists began applying pressure to lawmakers, especially those with a vested political interest in the economic success of supplement companies. US Senator Orrin Hatch, representing Utah, a major producer of dietary supplements, responded to industry appeals by coauthoring DSHEA and shepherding it through Congress. In doing so, Hatch sought to help manufacturers enjoy the freedom they had profited from during the 1980s after the Proxmire Amendment of 1976 barred the FDA from using potency levels to classify dietary supplements as drugs. To date, no public official has defended the interests of the supplement industry to a similar extent. In 2009, a US Government Accountability Office (GAO) report found that “consumers are not well-informed about the safety and efficacy of dietary supplements and have difficulty interpreting the labels on these products.” In fact, one of the most significant problems with DSHEA is that it allows structure and function claims to appear on product labels; as long as products do not claim to treat, prevent, or cure specific diseases, they can enter and remain in the marketplace. The concern is that consumers may not differentiate between technical descriptions and marketing language and may attempt to use dietary supplements in place of medicines that have been tested in rigorous trials. To that end, a 2010 GAO investigation found that sellers of dietary supplements may actually encourage consumers to substitute supplements for physician-prescribed medications. In preparing its 2010 report, the GAO investigated 22 retailers of herbal dietary supplements, hiring an accredited laboratory to examine 40 single-ingredient supplements for the presence of lead, arsenic, mercury, cadmium, and assorted pesticides. Although none of the supplements qualified as having an acute toxicity hazard, trace amounts of at least 1 contaminant were found in 37 of 40 products. According to the GAO, more troubling than the contaminants was the dubious and potentially hazardous advice offered to investigators who had posed as elderly customers. The GAO gathered written materials from online retailers, observing claims of treating, preventing, and curing conditions such as diabetes, cancer, and cardiovascular disease. Among the more egregious marketing efforts were claims that garlic could be taken in place of high blood pressure medication and that ginkgo biloba could be used to treat Alzheimer disease, depression, and impotence. Studies conducted by the National Center for Complementary and Alternative Medicine have shown that ginkgo biloba, in particular, does not reduce the risk of cancer nor does it prove effective in reducing high blood pressure among older adults. Careful review of National Center for Complementary and Alternative Medicine studies reveals a similar lack of efficacy for garlic, chromium picolinate, and St John’s wort. On occasion, policy makers have attempted to address at least some of the problems associated with dietary supplements. For example, citing the 2009 GAO report, Senators John McCain and Byron Dorgan introduced the Dietary Supplement Safety Act (S 3002) in February 2010. Although this act did not propose significant changes in efficacy assessment, it would have required supplement

Dietary supplements: improving education is not enough

In the United States, traditional Chinese medicines (TCM) are currently sold as dietary supplements, as defined by The Dietary Supplement Health and Education Act (DSHEA). This legislation is unique to the United States and while "structure and function" claims are allowable under DSHEA, disease claims are not. The narrow definition, however, poses a challenge to designing appropriate clinical studies that can provide data for "structure and function" claim substantiation. The process of melding Chinese herbal medicines into the dietary supplement category is complex and there is a need to define a clinical trial paradigm carefully that addresses "structure and function claims" without sacrificing scientific rigor. It is frequently not recognized that TCM favors an amalgamation of several herbs to generate the putative clinical effect. Because of this historical multiherb approach, the reliance on retrospective data to support the potential health benefits of an herb extract has severe limitations. Notwithstanding the immense value of identifying the pharmacological activity of a TCM herb to a chemical suitable for pharmaceutical development, another approach to safe and efficacious herbal products is to develop a standardized herbal extract. This article highlights issues related to the latter approach and will discuss a research-based strategy that may be suitable for validating, in part, the putative health benefits of TCM.

Prior to the 1906 Pure Food and Drug Act, medicine in the United States was in a deplorable state. Predatory patent medicine hucksters preyed on a medically unsophisticated population, hawking worthless and dangerous remedies that promised to cure every disease known to man, including cancer. The practice of selling unproven remedies was known as “quackery.” Quackery was once a well-respected and widely understood term. Virtually all legitimate health professionals deplored quackery, often understanding that it contained elements that were intentionally fraudulent in nature. In 1906, the legal machinery to stop quackery was put into place with the Pure Food and Drug Act. The Food and Drug Administration (FDA) continued to gain the power necessary to control quackery during the ensuing century. However, since the 1990s, unproven products have had an unparalleled resurgence of popularity among the American public. This is partly due to the 1994 Dietary Supplement Health and Education Act (DSHEA), a law that granted unprecedented legitimacy to “dietary supplements,”a broad group of heterogeneous products that had not gone through the prestigious and well-respected FDA OTC review process, and therefore, were wholly lacking in sufficient proof of safety and efficacy. The FDA is the leading agency charged with determining safety and efficacy of nonprescription products, but one of the effects of DSHEA was to nullify its powers in regard to unproven products. FDA cannot require that dietary supplements be proven safe or effective. These unproven products would once have been held up as prime examples of quackery by pharmacy journals and professional organizations. However, in the years since DSHEA, pharmacy’s journals and professional organizations often embrace these products through several means. For instance, they seldom address the issue of quackery in regard to dietary supplements, they recommend their use in editorials and related articles, they help boost their sales by accepting their advertising revenue, they allow their manufacturers to rent booth space at their conventions, and they publish textbook chapters that present uncritical, one-sided, biased views of

The authors conducted two studies to examine the influence of the U.S. Dietary Supplement Health and Education Act (DSHEA) on consumer beliefs about the safety and effectiveness of dietary supplements. Study 1 manipulated information about Food and Drug Administration (FDA) approval in the context of a dietary supplement designed to improve immune system functioning. Study 2 tested the effect of an educational intervention designed to improve knowledge about the DSHEA. Results of Study 1 highlighted deficits in consumer knowledge about FDA regulation of dietary supplements. Results also showed that information about FDA approval failed to have a statistically significant effect on beliefs about safety or effectiveness of the dietary supplement. Results of Study 2 showed that participants who were educated about the regulation of dietary supplements under the DSHEA rated dietary supplements as less safe and less effective than did participants in the control condition. The authors discuss the implications for consumers in the United States and for public policy.

Twenty Years of the Dietary Supplement Health and Education Act—How Should Dietary Supplements Be Regulated? ,

Proposed rule: Current good manufacturing practice in manufacturing, packing, or holding dietary ingredients and dietary supplements

The Dietary Supplement Health and Education Act (DSHEA) of 1994 amended the Federal Food Drug and Cosmetic Act to establish standards concerning dietary supplements. Since 1994, additional amendments to the Federal Food Drug and Cosmetic Act have been added, focusing on adverse event reporting, Supplement Facts labels, current good manufacturing practices, and mandatory recall authority for dietary supplements. This article aims to review the current regulatory paradigm for dietary supplements containing dietary ingredients in the United States, address the positive and negative aspects of the current laws and regulations, and present potential improvements to DSHEA to meet the standard of reasonable certainty of safety for dietary supplements. While aspects of DSHEA have been beneficial, the expanse of technology in online marketing, sales, and manufacturing of dietary supplements has advanced since 1994. Regardless of the legal pathway, updates to DSHEA must address a risk-based safety standard, a publicly available listing of marketed dietary supplements in the United States, and a more efficient and robust mandatory US Federal Food and Drug Administration recall authority.

A s the incidence of diabetes increases to epidemic proportions, people with diabetes are turning more and more to alternative therapies to help manage this condition, despite the availability of numerous traditional therapies. In fact, Americans spent almost $34 billion out of pocket on complementary and alternative products, practitioner visits, and materials in 2007, according to data from the National Health Interview Survey.1 It is important for health care practitioners not only to be aware of what dietary supplements their patients are taking, but also to understand how these supplements work and their possible side effects. First, it is helpful to be familiar with some terminology. The acronym CAM stands for “complementary and alternative medicine.” According to the National Center for Complementary and Alternative Medicine, CAM consists of medical and health care systems, practices, and products that are not generally considered part of conventional medicine. Examples of CAM therapies include acupuncture, biofeedback, chelation therapy, yoga, hypnosis, reiki or energy healing, massage, dietary therapies, meditation, tai chi, and dietary supplements. Complementary medicine is used along with conventional medicine, whereas alternative medicine is used in place of conventional medicine. In the United States, 38% of adults (or 4 in 10) and 12% of children (or 1 in 9) use some form of complementary medicine. People with diabetes are ~ 1.6 times more likely to use CAM therapies than people without diabetes.2 Dietary supplements are one form of oral CAM therapy. The Dietary Supplement Health and Education Act (DSHEA) of 1994 defines a dietary supplement as a “product taken by mouth that contains a dietary ingredient intended to supplement the diet.” These dietary ingredients may consist of “vitamins, minerals, herbs, amino acids, and other botanicals and substances such as enzymes, organ tissues, glandulars, and metabolites.” Dietary supplements can take various forms, …

The Dietary Supplement Health and Education Act (DSHEA) of 1994 defined the FDA’s statutory authority to regulate dietary supplement products as a category of food in the United States. As we celebrate 30 years post-DSHEA, it is important to reflect on its significance for public health, influence on the continuously evolving and expanding product category, the current regulatory framework, and potential opportunities or modernizing oversight to ensure a strong and well-regulated marketplace. An estimated three-fourths of U.S. consumers report use of dietary supplements, and the product market has grown substantially since the passage of DSHEA, from approximately 4,000 products in 1994 to 80,000+ present day. This growth represents a current $60 billion domestic and $200 billion international market for dietary supplements. Scientists, public health officials, health care providers, patients, consumer advocacy organizations, and the U.S. Food and Drug Administration have all called for reform to what has been described as ‘outdated’ regulation of dietary supplements. Advancing at an even faster rate is published scientific evidence in the space. This special issue of the Journal of Dietary Supplements comprises a collection of articles authored by academicians, legal scholars, representatives of U.S. government agencies, and industry scientists that critically examine the successes, challenges, and opportunities for improving specific aspects of DSHEA and domestic health policy. This editorial provides historical context and milestones of dietary supplement regulation in the U.S. post-DSHEA and offers an overview of the research contained within the special issue. Advancing toward a more transparent and safer marketplace requires trustworthy supply chains, increased adherence to quality standards, additional labeling requirements, and enhancement of post-market surveillance. This special issue seeks to contribute to the broader understanding of dietary supplement regulation and its future direction.

Chapter 9 - Dietary supplements