Perspective: Framework for Developing Recommended Intakes of Bioactive Dietary Substances.

Dietary bioactives are food substances that promote health but are not essential to prevent typical deficiency conditions. Examples include lutein and zeaxanthin, omega-3 fatty acids, and flavonoids. When quality evidence is available, quantified intake recommendations linking dietary bioactives with specific health benefits will enable health professionals to provide evidence-based information to consumers. Without evidence-based recommendations, consumers use information from available sources that often lack standards and rigor. This article describes a framework to develop guidance based on quality evidence fully vetted for efficacy and safety by qualified experts, and designed to communicate the amounts of specific dietary bioactive compounds with identified health benefits. The 4-step Framework described here can be adapted by credible health organizations to work within their guideline development process. Standards of practice used in clinical guidelines are adapted to quantify dietary bioactive intake recommendations from foods consumed by the general public, by taking into account that side effects and trade-offs are often needed for medical treatments but are not acceptable for dietary bioactives. In quantifying dietary bioactive recommendations, this Framework establishes 4 decision-making steps: 1) characterize the bioactive, determine amounts in specific food sources, and quantify intakes; 2) evaluate safety; 3) quantify the causal relation between the specific bioactive and accepted markers of health or normal function via systematic evidence reviews; and 4) translate the evidence into a quantified bioactive intake statement. This Framework provides a working model that can be updated as new approaches are advanced.

Dietary Reference Intakes based on chronic disease endpoints: outcomes from a case study workshop for omega 3's EPA and DHA.

Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.

Bioactive nutrients - Time for tolerable upper intake levels to address safety.

There is increasing interest by consumers, researchers, and regulators into the roles that certain bioactive compounds, derived from plants and other natural sources, can play in health maintenance and promotion, and even prolonging a productive quality of life. Research has rapidly emerged suggesting that a wide range of compounds and mixtures in and from plants (such as fruits and vegetables, tea and cocoa) and animals (such as fish and probiotics) may exert substantial health benefits. There is interest in exploring the possibility of establishing recommended intakes or dietary guidance for certain bioactive substances to help educate consumers. A key aspect of establishing dietary guidance is the assessment of safety/toxicity of these substances. Toxicologists need to be involved in both the development of the safety framework and in the evaluation of the science to establish maximum intake/upper limits.

History of Nutrition: The Long Road Leading to the Dietary Reference Intakes for the United States and Canada.

The Dietary Reference Intakes (DRIs) are reference values to guide the planning and assessing of nutrient intakes in the United States and Canada. The DRI framework was conceptualized in 1994, and the first reports were issued from 1997­2004, based on work by expert panels and subcommittees under the guidance of the Food and Nutrition Board of the Institute of Medicine. Numerous conventions, challenges, and controversies were encountered during the process of defining and setting the DRIs, including the definition of the framework, the use of chronic disease endpoints, lack of data on requirements for children and youth, and methods for addressing nonessential bioactive substances with potential health benefits. DRIs may be used to plan and assess the nutrient intakes of both individuals and population groups, but the new paradigm particularly improved methods used for groups. It is now possible to estimate both the prevalence of inadequate intake and the prevalence of potentially excessive intake within a group. The DRIs have served as a potent influence on national nutrition policies, including those related to dietary guidance, food labeling, nutrition monitoring, food assistance programs, and military nutrition standards. Because of this important impact on nutrition policy, the DRIs must be based on the best possible and most up-to-date science. Unfortunately, no updates to specific DRIs are currently planned. Despite the long and challenging road that led to the current DRIs, it must not finish in a dead end. Monetary resources and political will are crucial to maintaining and continuously updating the DRIs.

A randomized trial on the effects of 2010 Dietary Guidelines for Americans and Korean diet patterns on cardiovascular risk factors in overweight and obese adults.

BACKGROUND: Dietary patterns that are considered healthy (eg, the Dietary Approaches to Stop Hypertension diet and Mediterranean diet) may be more successful in reducing typical cardiovascular disease risks compared to dietary patterns considered unhealthy (eg, energy-dense diets such as the typical American diet). OBJECTIVE: This study assessed the effects of a Korean diet, the 2010 Dietary Guidelines for Americans (DGA), and a typical American diet on cardiometabolic risk factors, including lipid levels and blood pressure, in overweight, non-Asian individuals in the United States with elevated low-density lipoprotein cholesterol. DESIGN/INTERVENTION: The study was a three-period crossover, controlled-feeding study from January 2012 to May 2012. Thirty-one subjects were randomly allocated to one of six possible sequential orders for consuming the three diets for 4 weeks, each separated by a 10-day break. Data analysis included 27 subjects on the Korean diet periods and 29 in the DGA and typical American diet periods. Subjects remained weight stable. MAIN OUTCOME MEASURES: Lipid profile, blood pressure, insulin, glucose, and 24-hour urinary sodium were determined at baseline and at the end of each diet period. STATISTICAL ANALYSES PERFORMED: The additive main effects multiplicative interactions model was used to test for a subject by diet interaction. Differences among diets were determined using a mixed-models procedure (PROC MIXED) with random intercept for each subject. RESULTS: Total cholesterol and low-density lipoprotein cholesterol significantly decreased on Korean (P<0.0001 and P<0.01, respectively) and DGA (P<0.01 and P<0.05, respectively) diets, but not on the typical American diet. Although an unfavorable outcome, high-density lipoprotein cholesterol significantly decreased on all three diets (Korean: P<0.0001; DGA: P<0.0001; typical American: P<0.05). No diet had a significant effect on serum triglycerides, but a slight increase in triglycerides in the Korean and decrease in the DGA resulted in a significant difference between these two diets (P<0.01). All three diets caused modest decreases in systolic and diastolic blood pressure, which reached statistical significance for DGA only (P<0.05 and P<0.01, respectively). No diet had significant effect on fasting insulin, whereas fasting glucose decreased significantly on the Korean (P<0.01) and typical American (P<0.05) diets only. Urinary sodium output decreased significantly on DGA (P<0.0001). CONCLUSIONS: After a 4-week feeding period, Korean and DGA diet patterns resulted in positive changes in cardiovascular disease risk factors.

Dietary reference intakes: cases of appropriate and inappropriate uses.

The dietary reference intakes (DRIs) are a set of reference intake levels for nutrients that can be used for planning diets and assessing nutrient inadequacies of individuals and groups. Since the publication of the DRI reports 1997-2004, the reference intake levels have been used for various purposes. While DRIs have been used appropriately for planning and assessing diets for many different situations, there have been instances in which specific DRI categories have not been applied as intended. In this review, cases are described in which DRIs were applied correctly, as well as cases from the growing number of examples in which the wrong DRI was used or DRIs were used incorrectly.

Using criteria to establish nutrient intake values (NIVs).

One of the most important of the nutrient intake values (NIVs) is the average nutrient requirement (ANR). The ANR is defined as an intake value that will be adequate for half of the individuals in a group of people with similar characteristics. It is used to estimate the prevalence of adequacy, and it serves as the basis for the individual nutrient level (INLx). The determination of adequacy is a complex process, with the resulting value of the ANR dependent on the criterion or functional outcome chosen to define nutrient adequacy. Because nutrients have multiple sites of action in human metabolism, it is possible to demonstrate abnormal function in one parameter measured or observed as a result of inadequate intake of a nutrient, while other parameters requiring the same nutrient appear normal or within normal ranges. Thus, depending on the criterion of adequacy selected, the requirement for a given nutrient may be at a lower or a higher intake amount. In harmonizing development of NIVs, it is important to clearly identify the criterion of adequacy selected and the rationale for its selection. Rarely are available data sufficient to provide dose-response information from which to select a level of intake at which half of the individuals demonstrate adequacy and half appear to demonstrate inadequacy. Three levels of intake, of which at least one level of intake is below the requirement for most of the individuals in the sample, and one level of intake is above their requirement, are useful for establishing a level at which half of the group might be considered to demonstrate adequacy. Types of human nutrient studies that may be used to obtain data are discussed, as well as characteristics of the sample size needed to demonstrate adequacy. The variation in requirements is also an important aspect in predicting levels of intake that will have defined probabilities of adequacy for groups (to develop the INLx where x is the defined probability chosen). An analysis of the origins of different types of variability is presented. When estimating energy requirements, a special case of NIVs, important issues must be considered. Additionally, an example of evaluating data used to establish an ANR for vitamin A, and the effect of variability in requirements for vitamin A, is provided.

Establishing new principles for nutrient reference values (NRVs) for food labeling purposes.

Many countries such as The Republic of Korea have established their own nutritional standards, collectively termed Nutrient Reference Values(NRVs), and they vary due to the science which was reviewed, the purposes for which they are developed, and issues related to nutrition and food policy in the country. The current effort by the Codex Alimentarius Committee on Nutrition and Foods for Special Dietary Uses (CNFSDU) to update the NRVs that were established following the Helsinki Consultation in 1988 represents an opportunity to develop a set of reference values reflecting current scientific information to be used or adapted by many countries. This paper will focus on possible approaches to selecting or developing reference values which would serve the intended purpose for nutrition labeling to the greatest extent possible. Within the United States, the Food and Drug Administration (U.S. FDA) is currently reviewing regulations on nutrition labeling to better address current health issues, and is expected to enter into a process in the next few months to begin to explore how best to update nutrient Daily Values (DVs), most of which are still based on the Recommended Dietary Allowances (RDAs) of the Food and Nutrition Board, U.S. National Academy of Sciences, last reviewed and revised in 1968. In this presentation, I review the current purposes in the U.S. for nutrition labeling as identified in the 1938 Food, Drug, and Cosmetic Act as amended, the scientific basis for current nutrition labeling regulations in the United States, and the recommendations made by the recent Committee on Use of Dietary Reference Intakes in Nutrition Labeling of the Institute of Medicine (2003) regarding how to use the DRIs in developing new DVs to be used on the label in the United States and Canada. Based on these reviews, I then provide examples of the issues that arise in comparing one approach to another. Much of the discussion focuses on the appropriate role of nutrient labeling within the Nutrition Facts panel, one of the three major public nutrition education tools in the United States (along with MyPyramid and Dietary Guidelines for Americans).

Which dietary reference intake is best suited to serve as the basis for nutrition labeling for daily values?

The U.S. Food and Drug Administration is currently reviewing regulations on nutrition labeling to better address current health issues as well as updating nutrient daily values (DVs), most of which are still based on recommended dietary allowances (RDAs) established in 1968. In 2003 the Committee on Use of Dietary Reference Intakes in Nutrition Labeling of the Institute of Medicine recommended that the DVs be based on the estimated average requirement (EAR) rather than the RDA and that a population-weighted mean of EARs be used. The rationale given is that the EAR is the best statistical approximation of the nutrient requirement for any one individual in the population, and its use would result in a food appearing more nutritious, as it would provide a greater percentage of the DV if the DV were a smaller amount. Concerns about these recommendations focus on the appropriate role of the Nutrition Facts panel, 1 of the 3 major public nutrition education tools in the United States (along with MyPyramid and Dietary Guidelines for Americans). Providing a benchmark or standard that knowingly has only a 50% chance of meeting a consuming individual's requirement is not appropriate. The DV on a Nutrition Facts panel should provide useful guidance to the individual about how a serving will assist in meeting that person's goal for consumption, and thus it should be based on the RDA or adequate intake, rather than the EAR, and be derived from the highest recommended intake, as has been the practice since 1973.

Dietary reference intakes: concepts and approaches underlying protein and energy requirements.

Nutrient reference values provide guidance for maintaining and enhancing health via standard setting and development of nutritionally improved products to decrease the risk of disease. Since 1941, the Food and Nutrition Board (FNB) of the National Academy of Sciences in the United States has developed and periodically revised recommendations for nutrients; the last (10th) edition of the Recommended Dietary Allowances (RDA) was released in 1989. In 1994 the FNB initiated an expanded approach to develop dietary reference intakes (DRI), quantitative nutrient intakes that include concepts of chronic disease risk and multiple reference values more specifically suited to various applications. In concert with Canadian scientists, 10 DRI reports have been completed since 1997 and are available for review at www.nap.edu. The DRI reports explicitly review possible functional endpoints considered in determining the adequacy of each nutrient, and differentiate between the statistical basis for assessing the adequacy of intakes for individuals and groups and providing recommended intakes, as well as levels of nutrient intake that should not be exceeded. Recommended intakes for infants are based on average volumes of intake by healthy, full-term, exclusively breast-fed infants and nutrient analysis of human milk; the recommended intake also includes nutrients contributed by complementary foods consumed during the second 6-month period of life.