Abstract
This is an excellent book, which fills a need for a high-level science-based review of natural food safety targeted to nonscientists. It is well-written with well-developed topics, balancing social issues with technical concepts for the lay public as well as for legislators and regulators. It is unique among natural food books as it includes discussion of the novel topic of botanic defense mechanisms, including how plants use noxious chemicals to deter predators who may consume/compete with them; these chemicals in turn may present potentially toxic threats for human health. Secondly, it explains the US regulatory frameworks applicable for various product classes, and again, perhaps surprisingly to the public, reveals a patchwork of regulations allowing some products to be marketed without safety studies prior to placement on the commercial market.
The introductory chapter nicely presents the premise of the book. One may assume that natural plant-based products are safer than synthetic chemicals for consumption (the “natural mistake), including herbal remedies, based on a “history of safe use.” A second assumption is that synthetic pesticides are designed to be toxic, so residues on food should be harmful and organic food without residues (or genetic engineering) should be more healthful. But do data and evidence actually support these assumptions? In these days of forcing ourselves to look at our innate biases, it is critical that we take the time to explore these assumptions and demand to see the scientific basis for safety. The author draws from his lifetime of work in food safety and chemical risk assessment and as a regulator at the Food and Drug Administration (FDA), positing that natural foods and supplements are no safer, and in many cases less so, than conventionally produced foods. He explores plant physiology, pesticide safety approval testing processes and regulatory product approvals, and shares his concern for the general absence of safety data on dietary supplements, botanic extracts, and organic food products.
Plants are not always benign. Who among us toxicologists does not appreciate a quick review of plant physiology and a reminder that plants have evolved physical and chemical defense mechanisms to deter insect and larger predator damage? This concept is likely novel to the lay public, and in this second chapter, the author lays out multiple examples to illustrate various scenarios of plant protective measures, such as ricin, warfarin, and nicotine. This point is key to drive the message that there is a potential for plant-based food to be harmful to the health of humans, and that, without synthetic pesticides and with an incentive to increase yield (known to be lower for organic produce than conventional), organic varieties with higher levels of these natural plant protective chemicals are likely to be selected for propagation in the organic food marketplace.
Toxins in the diet can be hard to identify. The phrase “history of safe use” is easily adopted but rarely objectively analyzed. The author discusses the difficulty of identifying adverse effects of a single botanical ingredient in a formulated commercial product, especially a delayed chronic effect with a high background rate in the general population. Aristolochic acid nephropathy is an illustrative example of an adverse effect caused by a plant toxin, as are ephedra cardiovascular effects and Fen-phen cardiac valve pathology. Identification most often occurs by adverse effects reporting to the FDA, which, by definition, is after individuals are harmed. This hardly seems like a modern efficient method to ensure safety of herbals, botanicals, supplements, and cosmetic products.
Chapters 4 through 9 examine the US regulatory system governing various classes of food and drug products. The regulatory regime is first explained for pharmaceuticals within the FDA, then contrasted with unregulated and untested dietary supplements under the Dietary Supplement Health and Education Act (DSHEA) (1994). Perhaps the best example of the “natural is better” fallacy is the 1994 DSHEA, stating that consumers must have access to these products “in order to promote wellness.” The regulation assumes these products are safe based on the “natural mistake” that these remedies have been used for decades or centuries without incurring adverse outcomes (though this premise lacks scientific documentation). Moreover, no safety studies are required before dietary supplements are marketed; rather, it is the responsibility of the regulatory agency to demonstrate that adverse effects are occurring to people consuming the products. The author provides numerous examples of serious adverse effects in Chapter 3 and throughout the book.
Subsequent chapters discuss additional problematic issues with herbal supplements and nutraceuticals, including the inability to obtain complete identities of the chemical components of various formulations, even those used in human clinical trials, and the critical safety issue of drug spiking of nutraceuticals. The author shares his firsthand FDA experience on the presence of intentional spiking of supplements with chemicals and pharmaceuticals in several categories: weight loss, male sexual enhancement, and athletic performance enhancement. This adulteration has resulted in the FDA removing selected products from the market but after individuals suffer medical harm and serious effects. Information resources and links to the FDA website are provided on products known to have adverse effects, along with sites and suggestions on how to report adverse effects to the FDA.
Regulations and approvals of food products, food additives, and pesticide residues are reviewed as a separate category. This chapter presents the provisions of the Organic Food Production Act of 1990 concerning foods not produced using synthetic chemicals (for 3 years immediately preceding the harvest, with exceptions). There are several categories of organic products, each having specific terminology in product labeling. Imported organic products are not required to meet the same standards as those produced domestically. Interestingly, there is no final FDA official definition of “natural”; for many years, this definition has remained in draft form. This chapter contains a strong argument for reassessing one’s preconceived notion that “natural” or “organic” is better or safer than conventionally produced foods. Synthetic pesticides have been well studied as required by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), and allowances based on risk assessment with protective safety margins result in low chemical intakes which confer no significant increase in risk for adverse effects. In contrast, the author reiterates the thesis that organic strains of produce have generally not been studied for adverse effects in humans, and so may have higher risk of adverse effects. This derives from the presence of “natural” chemicals and secondary metabolites which protect the plant and deter competitors/predators. The author argues that “not known to cause adverse effects” is very different than “known not to cause adverse effects.” Genetically modified foods are also explained, with a presentation of the full testing program required for these strains, compared to an absence of testing required for products of standard cross-breeding programs.
The final chapter on the regulatory system again discusses some aspects of dietary supplements and pharmaceuticals, this time including over-the-counter medications and cosmetics, but compares and contrasts these three types of products, highlighting the inconsistencies in our regulatory system.
The last several chapters in the book survey some general but important topics, including the issue of burden of proof in demonstrating safety or risk. This responsibility is critical and expensive; it is one of the reasons why newly developed pharmaceuticals are so expensive in the United States. The author reemphasizes that the United States has a patchwork system of responsibility for the various types of products, and this fact is likely not appreciated by the general public, or for that matter, by legislators. As the topic of evidence of risk can be technically confusing, the following chapter provides discussion on toxic hazard and risk of toxicity.
Suppliers and marketers of natural and organic products can demonize conventional products which have technical data complete with hazard identification studies, using toxicity studies to market their “safer” brand. This ploy uses technical data taken out of context, where the adverse effects are expected to occur only at high concentrations on the dose–response curve under certain conditions. The basic concept of dose–response relationships is presented to the reader. Marketers in the natural product industry have mastered the art of exploiting confusion surrounding the concepts of hazard and risk, the latter of which involves the critical aspect of exposure.
A discussion of healthy dietary and lifestyle factors is a welcome and upbeat chapter where the author identifies many varied aspects of a healthy lifestyle, including diet, activity, and healthy habits. References and links to government resources for dietary guidelines and activity levels are provided.
The final chapter consists of gentle reiteration of the messages to the book’s intended audiences: consumers, legislators, and regulators. The author urges consumers not to automatically accept all the market messaging they receive. Organic or naturally produced food may have some chemical risks from unstudied plant components, whereas synthetic chemical residues in/on conventionally produced food should be present at low levels not conferring risk of harm. If the food budget is limited, choosing conventional produce is a fine choice as the objective of a healthy diet is to consume fresh fruits and vegetables. The author recommends avoiding “quick fix” and “miracle products” in supplements and botanicals, and to read labels and look for the disclaimer “These statements have not been evaluated by the U.S. Food and Drug Administration.”
Regulators and legislators should appreciate that the range of requirements on various products leads to confusion and altered expectations by consumers, and the author advocates for reframing regulations into a simplified but comprehensive law to assure uniform safety standards across product classes. Also critical are additional rigorous identity and purity standards for supplements and botanical products. There is an increased need for food safety testing overall, and for research on health and disease states influenced by dietary constituents, along with improved systems for adverse event reporting.
The shortfalls of the book are few. As a toxicologist, I found the discussion of the dose–response relationship a bit rudimentary. Dose–response is a simple but crucial concept for the entire basis of intake versus effect and specifically for supporting the thesis of conventional food safety using synthetic pesticides. Positive findings at high dose can dictate that the range of doses selected is appropriate, and lower doses will then be informative to selecting no-effect levels or low-effect levels. A more thorough discussion, including diagrams, would be beneficial and comprehensible to the lay public. However, there is a threshold of technical detail which the author did not wish to exceed, and this reviewer appreciates that decision.
Aggregate or cumulative risk assessment is not mentioned in the book; perhaps due to the fact that this method has been utilized by the EPA for years and also that it approaches the limit of technical difficulty of the scientific descriptions in this book intended for the lay public. However, the savvy consumer reading this book may agree that the risk assessment for a food additive or pesticide is acceptable in isolation, but wonders if the aggregate exposure over days, weeks, and years is a concern. Is the ingredient an endocrine disruptor which will not show effects until children are grown to adolescence? This consumer may appreciate a statement as to whether aggregate risk was addressed.
One aspect which the book does not address is the option of personal control, which is highly valued in our current culture. The book discusses several population-driven movements which led to passage of the National Environmental Policy Act (1969), such as after public outrage reflected by Rachel Carson in Silent Spring. This reflected a backlash over environmental damage which individuals cannot control; the exposure to chemicals was being “done to them.” Although consumers currently may be thrilled with the options of using either physician-prescribed medication or self-prescribed supplements or nutraceuticals (reflecting personal choice), they may be horrified to realize that the supplement has had no safety or purity testing conducted upon it (reflecting lack of control). Both aspects of the control issue could be explored.
It is encouraging that, slowly, progress is being made to address scientific and toxicologic needs in the botanical and supplement fields. This reviewer notes the technical work of the American Herbal Pharmacopoeia, and peer-reviewed journal resources such as BMJ Complementary & Alternative Medicine and the American Journal of Essential Oils and Natural Products. Recently announced is the formation of the Botanical Safety Consortium (https://botanicalsafetyconsortium.org/), a public/private partnership with FDA, the National Institute of Environmental Health Sciences (NIEHS), and the non-profit Health and Environmental Sciences Institute (HESI), whose goal is to build an appropriate resource system to assess the toxicological safety for botanical products. The Consortium has defined several Technical Working Groups which currently include genotoxicity, hepatotoxicity, pharmacokinetics, developmental/reproductive toxicity, cardiotoxicity, and systemic toxicity. This reflects the recognition that analytical and safety information for these ingredients is critical and increasingly necessary, and that indeed, Dr MacGregor is on to something with the timely publication of this book.