One of the roles of the public health scientist is to look forward, to identify gaps that need to be addressed in the scientific literature, and to question the scientific framework used to establish or inform policy decisions. As a scientist in the nutrition community, it is my job to seek approaches to establish the health benefits of bioactive food components, and investigate ways that industry can create products that provide value for consumers. There’s been a brewing dialogue in the nutrition science community during the past several years about whether the current framework applied to studying the effects of essential nutrients is the most appropriate. This dialogue needs to continue, but it’s time to add another layer to the conversation, one that both the dietary supplement and functional food industries must consider, both for their own growth and for the benefit of those who use these products.
Moving Beyond Evidence Based Medicine (EBM)
Consider this: For nutrients such as vitamin D, vitamin C and calcium, standard-setting bodies and policymakers recognize their essentiality in the diet—and have established a systematic, but perhaps not necessarily the most appropriate, way of studying them and interpreting the evidence. This has allowed for a means to incorporate essential nutrients into a broad scientific framework for nutrition policy to inform policy decisions—from recommended intake levels, to Tolerable Upper Intake Levels (ULs), to their recognition in the official Dietary Guidelines for Americans. This systematic approach to studying nutrients is also the underpinning of FDA-approved health claims. The approach, most recently articulated in the Institute of Medicine’s (IOM) Dietary Reference Intake (DRI) report for calcium and vitamin D, relies almost exclusively on the randomized, controlled trial (RCT) as the scientific basis for informing nutrition policy decisions. While the appropriateness of this framework itself has generated substantial controversy in the nutrition science community, if we dare to peek beyond essential nutrients, there is an additional gaping hole, the Grand Canyon of nutrition, one which our industry must consider filling.
As our understanding continues to evolve about the role of nutrition in disease prevention and health promotion, we must look not just to essential nutrients, but also to non-essential nutrients, including bioactives such as isoflavones, flavonols, carotenoids and anthocyanidins. Unlike for past generations, whose public health and nutrition policymakers dealt with diseases and conditions of deficiency, our health challenges today center around conditions of excess—excess calories, excess sedentary lifestyle, excess stress, and so on. Thus, optimizing health is no longer solely about avoiding diseases of overt nutrient deficiency, such as rickets and scurvy.
Bioactives are food components that are present in the diet and believed to provide health benefits, particularly for certain populations, but lack an established, widely recognized research framework that would enable scientific bodies like the IOM to establish recommended intakes. Would the DRI framework be the appropriate avenue for these nutrients? And if not, what other scientific approach should be applied to inform broad recommendations for bioactive intake levels? In other words, without DRIs and the accompanying accepted methods that legitimize essential nutrients, how can bioactives ever be taken seriously by policymakers and have the chance to impact consumers’ health?
Let’s take a step back. Bioactives are not considered “essential” nutrients in the traditional sense, because they are not required for the body to function, (i.e., their absence does not produce disease); they are, however, sometimes referred to as “conditionally essential”—especially for specific populations under certain circumstances. For example, there are evidence-supporting benefits associated with lutein for eye health and isoflavones for bone health. However, while little is known about how certain bioactives behave in the body, it is also undoubtedly true that humans have been exposed to them through the diet for millennia, and that we have possibly evolved to a point where we are physiologically dependent on certain bioactive compounds in order to function optimally in our environment. Research suggests there is an inverse relationship between these and other bioactives and chronic disease risk. But if they are not essential nutrients, nor are they drugs, what scientific framework should be applied to help scientific policymakers to accurately and adequately incorporate them into broad-based policy recommendations?
As with the essential nutrients, for bioactives the key to unlocking the policy door is research. The most appropriate way to study nutrients in humans is itself a topic of debate in the scientific community and the discussion is still in its infancy. But more and more nutrition scientists are agreeing that the traditional drug-like model—evidence-based medicine (EBM)—is not the most appropriate way to study nutrients. Since nutrients and drugs behave so differently, it is clear that we must shift the paradigm from an EBM to an evidence-based nutrition (EBN) framework that takes into account the unique homeostatic properties and nuances of essential nutrients and appropriately balances risk and benefit. While an EBM paradigm and its heavy reliance on RCTs is frequently applied to nutrients because an EBN framework has yet to be defined, this approach does not take into account how essential nutrients behave in the body, the complex nutrient networks involved and their subtle effects over time, as opposed to how drugs work, usually in isolation and with acute and powerful action. The question for bioactives is, where do they fall in that equation?
One important element of a hypothetical framework for studying bioactives is that RCT data should not be considered the only accepted form of evidence nor necessarily the gold standard, but instead should be incorporated into the framework in some capacity, resulting in a framework which considers the totality of the available evidence and allows for other types of research that would better lend itself to assessing how nutrients—essential or not—actually work.
It is important to understand and recognize the limitations of RCTs in studying nutrients for disease prevention and health promotion, including huge cost and feasibility issues. For example, studying prevention (or disease risk reduction) where no one has the disease at outset costs orders of magnitude more than studying treatment where all subjects have the disease at outset. In this case, both a larger sample size and longer duration are needed. Add to this the subtle effect that most nutrients exert on the body, which in turn increases the number of subjects needed and duration of the study. Large (tens of thousands) and long-term (years) RCTs present logistical challenges that make them extremely difficult and costly to carry out, even impossible in some cases. Thus the hierarchy approach, whereby RCTs stand at the top of the research pyramid, and are considered the only acceptable standard is most troubling. And while bioactives may fall into a gray zone, it is clear that they behave more like essential nutrients than drugs.
But back specifically to bioactives. The IOM uses a rigorous—some might say limiting—process to establish DRIs, which comprise the Estimated Average Requirement (EARs), Recommended Dietary Allowance (RDAs) and the UL. The process used is one in which a scientific committee evaluates generally the same restrictive portion of the full body of science, omitting that research which does not meet the committee’s gold standards (i.e., EBM). However, at least essential nutrients are on the playing field, with government entities recognizing their potential inherent value. But bioactives, unless we as an industry act, may not stand a chance of getting in the game.
Serving the Greater Good
There is a selfish interest here for our industry, as well as an interest for the greater good. If we truly believe bioactives provide important health benefits for consumers—and I for one do—then we owe it to our industry and to consumers to take this issue seriously.
For companies, the lack of an established and accepted scientific framework to study and evaluate the evidence on bioactives should be a bit concerning. Companies operating in this space need to look beyond their own product portfolios and at the broader picture. Industry should think about what an established framework for studying bioactives could do for the overall market. For instance, if the potential benefits of bioactives were even more widely accepted—and that will only happen with greater acceptance of a broader type of research framework coupled with more financial support—and even more benefits demonstrated, the market for this large category of products would have the potential to grow exponentially. Right now, ingredient suppliers manufacturing bioactives often conduct their own studies on their products in an effort to support product claims. But we need to think bigger. Having widely recognized policy shaped around the bioactives category would further establish credibility, and would have much broader—and more positive—implications for the entire industry.
Until policy is developed, companies in the bioactives market will only have a finite piece of the market, a piece that will shrink over time as competitors enter the arena. However, if we can help develop a recognized way to study bioactives and assess their impact on the body, we will have the opportunity to grow the entire pie, thus providing more opportunity for individual companies to increase their reach. If a bioactive or a non-essential nutrient were to be supported by the right research, making DRIs (or some equivalent) a possibility, the world could open up for the bioactives marketplace in ways industry might not yet think possible.
So as an industry, we have several steps to take. First, we need to continue the work we’ve started on shifting from an EBM research model to an EBN research model—and we must be thinking beyond essential nutrients. With acceptance of the right research framework, we can start the next step—supporting more research. Companies need to think outside of their own self-interest, and help support grander research for the entire category. Only in this way will we be able to have a broader impact on public policy. In other words, individual companies can continue to support small studies that serve to allow them to market competitively their ingredients to manufacturers—or we can pool resources to support research that would open up the possibility of bioactives being accepted for consideration in a larger stadium—the one where the IOM, National Institutes of Health (NIH), U.S. Department of Agriculture (USDA) and Food and Drug Administration (FDA) play—to establish public policy and broad-based recommendations for consumers.
The conversation among researchers in the scientific community about studying bioactives has started, and industry needs to be part of those discussions. But the industry needs to look at that big picture and work cooperatively to increase the visibility and acceptance of bioactives as having a real role in optimizing nutrition and health. For manufacturers, marketers and distributors of bioactive products, elevating the category is vital to achieving a higher level of success. Banding together with your competitors, attending tradeshows and panels on the topic and brainstorming with others in the industry on ways to move the category forward are imperative for growing the market.
References furnished upon request.
CRN is sponsoring a symposium at the American Society of Nutrition’s (ASN) annual meeting at the Experimental Biology (EB) conference in April in Washington, D.C. At this meeting, scientists, including David Heber, UCLA; John Erdman, University of Illinois; Connie Weaver, Purdue University; Elizabeth Johnson, Tufts University; and Paul Coates, the Office of Dietary Supplements, will participate in a panel on establishing a scientific framework to assess the impact of bioactives on humans. If you’re attending EB, you must consider attending this symposium. And if you haven’t yet decided to attend EB, if you’re in the bioactives market, this will be an important presentation for you. For more information, contact CRN at 202-204-7700 or www.crnusa.org.