F
Listing of Possible Topics for Research Identified by Individuals During the Workshop
This list, which is based on the transcript of the meeting, reflects suggestions made by presenters. It was prepared for the convenience of the reader. It should not be construed as representing recommendations or consensus statements.
Calcium and Related Nutrients
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Concentration of 25-hydroxyvitamin D—abbreviated as 25-(OH)D—needed for musculoskeletal end points/optimal circulating concentration
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Standardization of 25-(OH)D assays
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Better quantitation of the vitamin D content of foods
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Potential problem of low phosphorus intake, especially by older individuals
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Effect of the increasing use of calcium supplements on the bioavailability of phosphorous
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Effect of anabolic agents for the treatment of osteoporosis on the need for phosphorus
B Vitamins and Choline
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Cataract production as a possible end point for setting the riboflavin Estimated Average Requirement (EAR)
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Peripheral vascular disease function as an end point for niacin optimization
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Genomic effects related to possible new indicators for setting an EAR for biotin
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Possible adverse effects of pyridoxine (vitamin B6) supplementation on the inflammatory response
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Possible adverse effects of unmetabolized folic acid in the serum
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Consideration of genetic variation and relevant parameters in determining the need for individual recommendations for B vitamin requirements.
Antioxidant Nutrients
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Selenoprotein P as a possible indicator for setting the EAR for selenium
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Health risks associated with marginal selenium intake
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Benefits of supplemental selenium as related to selenium status
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Mechanisms responsible for selenium's health effects
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The alpha-tocopherol, gamma-tocopherol, and delta-tocopherol contents of foods
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Biological activity of various vitamin E forms in humans
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The dose-dependence of carotenoid effects on health
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Effects of polymorphisms on the efficacy of antioxidant nutrients
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The role of oxidative stress in chronic disease development of biomarkers of oxidative stress
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Relationships of increased risk for oxidative stress (caused by smoking, intense physical activity, high altitude, and genetic predisposition) to requirements for antioxidant nutrients
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Predictive value of markers of oxidative stress for clinical end points
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Subgroup effects, smoking especially, which persist for antioxidant nutrients
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Should antioxidant nutrients be addressed more comprehensively for DRIs?
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Risk and benefit curves for lutein, zeaxanthin, lycopene, and selenium chemical species and modulators for possible use in setting DRIs
Micronutrients
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Roles of vitamin K in coronary artery disease and in brain function
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Human studies to examine links of neuropsychological outcome measures or other measures of cognitive function with vitamin K status
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End points related to nutrient toxicity
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Vitamin A and gene expression profiles
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Bioavailability and metabolism of menaquinones, and the roles of menaquinones in vitamin K and sphingolipid metabolism
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Classifications of iron-loading syndromes with identification of the central role of hepcidin
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The relationship between iron status and infections such as HIV and tuberculosis
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Status indices related to iron and cognition
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Food-specific bioavailability questions
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Biomarkers of zinc status, primarily genomic or proteomic, to correlate with functional outcomes such as immunity
Macronutrients
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The need, if any, for a Tolerable Upper Intake Level (UL) for functional fiber
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The lowest levels of saturated fat, trans fat and cholesterol that are consistent with a healthy diet and that may cause a low but acceptable amount of harm
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Mechanisms explaining why formerly obese persons may need 60 to 90 minutes of physical activity daily to maintain weight loss
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Behavioral, environmental, policy, and other factors that help people adhere to a physical activity and exercise strategy to help maximize their potential for maintenance of weight loss
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Consideration of differences in body composition and fat-free mass in studies related to energy
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Effects of feeding functional fibers on measurements such as blood cholesterol, C-reactive protein, microflora, stool weight
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Levels of intakes at which the onset of relevant health risks (e.g., obesity, coronary heart disease) occur
Electrolytes and Water
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For persons with kidney dysfunction, the point at which potassium intake poses a risk for harm rather than benefit
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Assessment of the protective effect of potassium-rich diets in blunting the adverse effects of sodium intake—basis for a recommended ratio of sodium intake to potassium intake
Infants and Children
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Analysis of breast milk, collected appropriately
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Nutrient intake data (especially from complementary foods) related to biomarkers that are validated in children
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Studies with stable isotopes and nanotracers to determine vitamin and mineral bioavailability, to investigate kinetics, and possibly to estimate change in pool size on different vitamin intakes
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Doubly-labeled water studies to measure energy expenditure and water turnover
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Determination of vitamin D requirements based on relationships of intake with 25-(OH)D, parathyroid hormone, bone markers, etc.
Tolerable Upper Intake Levels
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Translation of animal data to human health outcomes, which requires knowledge of the mechanisms
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Chronic studies
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Interactions of multiple nutrients and health end points
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Risk/risk models that address the risks of two different materials in a single food and differences in the risks of a single nutrient under various circumstances
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Sharper end points of adverse effects
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Dose–response analyses with larger numbers
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Depletion–repletion studies for adverse effects if feasible and ethical; otherwise, development of methods to obtain better information from cohort studies
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Validated surrogate markers of risk
Applications
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Relative importance of reducing the percentage of the population with inadequate intakes across the different nutrients
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Health and statistical considerations in selecting targets for the percent inadequate across nutrients
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Investigation of frequency questionnaires for systematic bias in intake estimates
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Determination of dietitians’ methods of applying DRIs in their practices
New and Underutilized Research Techniques
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Genotyping, epigenetics, and imprinting—including the assessment of effects of single nucleotide polymorphisms (SNPs) on variability in requirements and/or ULs
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The use of first principles and discovering overlooked earlier findings
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Studying monogastric farm animals, as to find surrogate measures for dose–response studies
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Relationships of DRIs with long-term health
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Use of genetics to help predict who will benefit from a specific dietary treatment
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Use of metabolomics to distinguish individuals with a covert health problem from normal individuals and to analyze composition of food
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Assessment of methods for determining individual risk of chronic disease outcomes
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Delineation of specific genetic variants that contribute to wide interindividual variation in responses to dietary cholesterol and dietary fatty acids—considering low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides.
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Identification of mechanisms whereby early nutritional experiences, such as dietary cholesterol and dietary fat intake, affect the atherosclerotic process and identification of the sensitive periods in development when this may occur.
General
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Setting DRIs for children
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Roles of genetic polymorphisms when revising DRIs
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Differential responses, based on SNPs, to classical depletion– repletion studies
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Development of a framework for establishing impacts and cutoffs for genetic variation that addresses two major points: (1) How prevalent do these polymorphisms have to be to warrant genotype specific recommendations? and (2) What is the penetrance—that is, what is the genetic contribution of variation compared to the overall variation requirement—and is that penetrance sufficient to warrant genotypic-specific results on which to base nutrient recommendations for subgroups?
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A disease prevention approach that involves targeting the molecular antecedents of disease, such as molecular antecedents for cancer
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If a nutrient has beneficial effects at doses much higher than needed for the prevention of deficiency, how should this affect the setting of EARs and RDAs?
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If a nutrient prevents an adverse outcome in one subgroup but not in another, how can this information be incorporated into a DRI process?
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Should the concept of a range of nutrient intake be reconsidered, or is there some other method to incorporate information about disease prevention (including subgroup-specific information) into the DRI process?
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Development of a standard approach for setting an AI
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Should an Adequate Intake (AI) be set for a nutrient that has no known essential functions in humans?
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Can the process of setting ULs be made more systematic—one that consistently uses a decision tree approach?
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Could risk assessment methodology be used to evaluate the lower end rather than just the upper end of nutrient risk?
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New concerns for ULs related to epigenetic effects and genetic rescue
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Can the UL concept be expanded to include a numerical value for nutrients for which an adverse effect or a toxicity has not been clearly established?
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Are separate UL values needed for different forms of a nutrient?
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Methods to apply the DRI process to chronic diseases
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The meaning of “healthy population” in relation to setting DRIs
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Setting ULs for nutrients for which there is a direct progressive relationship between intake and occurrence and/or severity of the adverse effect but for which there is no threshold
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Criteria and methods for adjusting nutrient recommendations, as for age, size
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A basis for expressing DRIs as densities or ratios
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Consumer communication research