The Role of Research in Functional Food Development

Research currently underway at academic, industry and government facilities will reveal how a myriad of substances can be used as functional food components. Although additional research is necessary to validate efficacy and establish appropriate dietary levels, researchers have identified functional food components that may improve memory, reduce arthritis, reduce cardiovascular disease and provide other benefits typically associated with drugs.

Functional foods and molecular nutrition represent novel scientific paradigms that challenge traditional nutrition approaches. The risk of adhering rigidly to current paradigms is that health benefits from a broader approach to diet and nutrition will be slow to arrive on our plates. Speeding the arrival of these health benefits requires innovative and paradigm-shifting approaches to nutrients and their role in health, and funding to expand the knowledge base of molecular nutrition.

As we move into the era of nutrigenomics and individualized diets, protecting the privacy of individuals may become an issue. A legal, ethical and societal framework must be developed to ensure genetic information about food and disease is appropriately handled.

Scientists in academia, government and the private sector are all stakeholders in the continuum of research, from basic exploratory studies to clinical application of findings. The challenges are enormous—the need for a continuous supply of scientific hypotheses, researchers with the curiosity and ingenuity to pursue these hypotheses, and funding to support the entire effort. At the same time, funding for research is limited, both within the government and private sectors. Scientific hypotheses are vetted through internal review within the private sector and through grant review boards and study groups for government funding. Regardless of the venue, the review results are judged relative to value of investment.

Early stage research is funded largely through government grants at universities or within the government laboratory system at the National Institutes of Health and the U.S. Department of Agriculture, while private sector funding takes the lead as scientific advances are translated into commercial products. Although early-stage expenses may be considerable, commercialization of a functional food product requires substantial incremental investment.

Without a period of exclusivity during which companies can earn a reasonable return on their investment, the private sector is unlikely to commit the resources necessary to develop a wide range of product choices representing the best that nutritional science and functional foods can offer.

Types of Research Needed Areas for research include better understanding the role and optimal levels of traditional nutrients for specific segments of the population, as well as identifying bioactive substances present in foods and establishing optimal levels. Early nutrition research focused on the range of vitamin and mineral intakes necessary to prevent unmistakable deficiencies. Now, researchers are investigating the optimum intake levels for traditional nutrients and the differences for various subpopulations. Understanding the role of nutrients at the molecular level will result in even more specific recommended dietary allowances for different population subgroups. Similar research is needed to identify the role of other bioactive food components, an area of research that is still in its infancy. Only recently, several government agencies have begun developing a standard definition for “bioactive” food components.

The IFT Expert Panel has identified the areas below as vital to the development of functional foods and worthy of research funding.

Nutrients and Bioactive Substances
Continued basic and applied nutritional research must pursue a more precise understanding of the mechanisms of action for known nutrients, their dose-response relationship, the clinical outcomes and individual variations in response. Diverse health effects are both known and suspected for many nutrients—such as selenium, vitamin E, carotenoids, and the B vitamins—and clinical nutrition journals regularly publish studies exploring the role of known nutrients in health.

Potential and actual health benefits of bioactive food components represent a similar frontier in diet-health research. Researchers have identified numerous phytochemicals with potential roles in health, including sulfur compounds in cruciferous vegetables, polyphenols in teas, and flavonoids in wine, blueberries, and pomegranate.

Epidemiological studies have repeatedly demonstrated that better health and lower incidence of chronic disease are associated with higher intake of whole grains and multiple servings of fruits and vegetables. These beneficial effects cannot be explained by traditional nutrients alone.

Laboratory research has demonstrated diverse roles for bioactive compounds in blocking, reversing or interfering in molecular level processes, which, if left unchecked, would lead to various chronic diseases. Continuing research must identify bioactive compounds and determine their mechanisms of action and effects on health, and this knowledge must then be verified through well designed preclinical and clinical studies.

New and Existing Biomarkers
Identifying specific cause-effect relationships between dietary components and health is challenging and, in some cases, controversial because of the complexity of human biology and physiology. Biomarkers and their relationship to health status are often identified through observational studies or correlations. At best, correlated factors may suggest a complex, multifactorial relationship among diet and health and may be supported by scientific theory that appears credible; at worst, the correlations are the result of another unrelated factor and have no basis in fact.

In functional food research, biomarkers are usually biological endpoints that directly correlate with health status or with exposure to specific food components. Surrogate markers relate directly to disease development and can be used in place of a disease endpoint. In reality, scientists have very few well-defined and accepted biomarkers or surrogate markers. Some of the accepted surrogate markers include elevated low density lipoproteins (LDL)-cholesterol, elevated homocysteine or C-reactive protein for increased risk of coronary heart disease, the presence of colon polyps for increased risk of colon cancer and decreased bone mass for increased risk of osteoporosis.

Many physiological measures are of interest to scientists and consumers as possible indicators of health status. Some of these physiologic measures include inflammatory markers (e.g., cytokine levels and C-reactive protein), blood lipids (e.g., triglyceride level and specific fractions, such as high density lipoproteins [HDL]-cholesterol), blood glucose, plasma insulin, satiety hormones, changes in short-term memory, weight loss or weight maintenance, mood alteration, homocysteine levels, and iron status.

Scientists need to identify additional biomarkers that signal changes in health status and then determine the meaning of changes in those biomarkers relative to a defined health condition. In addition, exposure markers are needed to assess intake, bioavailability and utilization of potential functional food components. The relationship between genes and gene products and disease risk is an emerging area that must be pursued. The effects of diet on biomarkers and the entire human body must be validated through prospective clinical trials.

An expanded database of surrogate markers and exposure biomarkers is essential for these biomarkers to become accepted in medical practice.

Food Vehicles for Bioactive Ingredients
The food vehicle is critical to the overall success of a functional food because it plays an important role in consumer acceptance and compliance. Additional research should identify and tailor foods for delivery of bioactive ingredients. The criteria for such research should include:

• provision of a stable environment for the bioactive ingredient;
• knowledge of the interactions between the bioactive ingredient and other ingredients in the vehicle matrix;
• maximization of the bioactive ingredient’s health benefit;
• maintenance of the bioavailability of the bioactive ingredient; and
• desirable sensory/organoleptic characteristics.

In addition, properly designed packaging has the potential to enhance stability, bioavailability and organoleptic quality. Research will help scientists better understand each of these issues in functional food development.

Food Composition and Dietary Intake Databases
The value of epidemiological studies in establishing diet and health relationships is well recognized. Retrospective cohort studies using dietary intake databases such as the National Health and Nutrition Examination Surveys (NHANES) can be useful in identifying relationships between diet and health. In fact, dietary intake databases helped establish that diets high in fruits and vegetables reduce the risk of certain cancers.

Expanding existing food composition databases will facilitate this work. The Nutrient Data Laboratory at USDA’s Agricultural Research Service has recently undertaken an effort to publish peer-reviewed food composition databases on nutrients with emerging benefits, such as carotenoids, flavonoids, and proanthocyanidins.

The IFT Expert Panel supports efforts to expand USDA food component databases and to update existing databases as better analytical methods become available. It is equally important that the government continue to fund and support the National Center for Health Statistics NHANES research on health status and dietary practices.

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Nutrigenomics and Function of Bioactive Components
The intersection of genomics and molecular nutrition presents opportunities to understand nutrient effects and individual variability in response to diet; this understanding has the potential to revolutionize diet, nutrition and food products, and health care. With the unraveling of mouse and human genomes, the stage is set for rapid advancement. Identification of diet responsive genes and single nucleotide polymorphisms must be followed by clinical validation that dietary intervention modifies gene expression to produce the desired health benefit. Such clinical data will improve the validity of conclusions regarding the role of dietary practices on health status.

Nutrigenomics may disrupt established ways of thinking about nutrition, food, the value chain of the food industry, and the role of industry in health care. Mass customization—the ability to provide nutrient plans and products based on the interaction of genetics and diet for groups and individuals—will soon be scientifically possible. However, such products are well beyond the food industry’s current infrastructure and business model. This new paradigm raises legal and ethical questions based on development and handling of personal genetic data and changes the boundary between foods and drugs from a clear line to a continuum. Meeting these challenges will require new regulatory paradigms and new food industry and health care value chains.

Policies Regarding Ethics, Regulatory, and Legal Implications of Nutrigenomics and Molecular Nutrition Research
Appropriate privacy of genetic information and limitation of decisions that can be made based on knowledge of an individual’s genetic profile has been discussed and debated. Until recently, such discussions focused largely on pharmaceutical applications. However, nutrigenomics has brought the issue into the food arena, and the need for potential policies is being explored. The IFT Expert Panel supports efforts to develop a legal, ethical and societal framework to facilitate personalized nutrition while safeguarding consumer privacy.

Molecular nutrition research has established a druglike role for nutrients, and nutrigenomics renders the effect specific for an individual or group of individuals with particular genetic profiles. However, current food regulatory frameworks do not readily accommodate druglike effects from nutrients and/or personalized nutrient plans based on genetic testing. Drawing on experience with drug development, FDA must develop policies and practices that facilitate the identification of therapeutic effects of foods and enable commercialization of such products.

Expanded Incentives for Health and Nutrition Research
Developing a new functional food is an expensive process. Food companies have traditionally funded research for new food product formulations but for functional foods, the stakes are higher—for both food companies and consumers. Government investment in basic and applied research will promote the development of functional foods, but additional incentives are needed to reward private companies that pioneer new health claims. The research required for a functional food to meet scientific standards for efficacy and safety is a substantial investment, but currently the return on that investment is not exclusive to the company that conducted the research and developed the initial regulatory petition.

As soon as the health claim is adequately documented, competing companies can use the claim. Various groups have examined the issue of incentives for encouraging additional health and nutrition research. The Keystone National Policy Dialogue on Food, Nutrition and Health presented at least four concepts for incentives to the food industry:

• Confidential lead-time prior to public notification, giving the petitioning organization an initial market advantage; • Period of market exclusivity after public notification, giving the petitioning organization a temporary monopoly on the market; • Royalties paid by others to use newly authorized claims, giving the petitioning organization an additional revenue source; and • Reduced research costs via incentives, providing exclusivity, additional tax credits, and government research grants to organizations pursuing health claims research.

FDA’s Food Advisory Committee established a Research/Economic Incentive Working Group (IWG) to examine the Keystone incentives and to pursue additional opportunities. The IWG recognized that FDA cannot provide economic incentives for health claim development and noted that legislative action may be needed to provide meaningful incentives to industry.

The IFT Expert Panel believes that the efficacy of functional foods and claimed benefits must be scientifically supported and believes that patents alone are inadequate as economic incentives because:

• A wealth of hard data and speculation in the public domain describes the role of food in health, complicating and/or precluding patent protection that would be broad enough to be commercially meaningful; and
• Patentability may not ensure commercial insulation sufficient to afford investment recovery and reasonable profit.

A system of economic incentives for companies willing to commercialize emerging nutritional science could have broad ranging effects, from the quality of science developed to whether products are commercialized at all. The lack of exclusivity of health claims encourages companies to limit research and use a structure/function claim instead of an approved health claim. Structure/function claims are more limited and often cannot accurately convey the health effects to consumers.

The IFT Expert Panel believes that appropriate incentives for the food industry would enhance our understanding of the health effects of food and diet, leading to extensive improvements in consumer health.

Possible incentives such as exclusivity, marketing lead time, and confidentiality should be explored. FDA could encourage health claim development by assisting the company in quickly entering the marketplace with a newly authorized health claim. Utilization of authoritative statements via the FDA Modernization Act of 1997 (e.g., whole grain and potassium health claims, nutrient content claim for choline) has helped provide some marketing advantage in the immediate time period following the approval. Legislative bodies should aggressively pursue tax deductions and credits for health and nutrition research.

In addition, to better leverage government and industry investments, the IFT Expert Panel encourages the food industry to support funding for cooperative research, perhaps initially as a pilot program within FDA or USDA. Canada’s National Sciences and Engineering Research Council could serve as a program model in which industry dollars are matched by government dollars to conduct relevant, peer-reviewed research.

Emerging science clearly indicates that the functional foods currently on the market represent a small fraction of the possible products. The scientific literature reports almost daily on new insight into the role of existing nutrients, advances in identifying bioactive compounds and their health benefits, and the intersection of genomics and nutrition science in personalized nutrition. Additional research is needed in many areas to ensure that this emerging science continues to be valid and is rapidly translated into consumer-relevant products. All elements of society stand to benefit from such research.

Recognizing the tremendous health benefits offered by functional foods, the Institute of Food Technologists commissioned an expert panel to review the available scientific literature related to functional food development. The panel’s report is divided into nine sections: Definitions, Introduction, Food and Genes, Current Legal Standards, Scientific Standards, Policy Limitations, Bringing Functional Foods to Market, Role of Research, and Conclusions. Copies of the report are available at Founded in 1939, the Institute of Food Technologists is an international not-for-profit scientific society for food science and technology.