. "15 A Research Agenda." Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: The National Academies Press, 2001.
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Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc
Consider the need to protect individuals with extreme or distinct vulnerabilities due to genetic predisposition or disease conditions; and
Weigh the alternatives and set priorities based on expert judgment.
MAJOR KNOWLEDGE GAPS
To derive an Estimated Average Requirement (EAR), the criterion must be known for a particular status indicator or combination of indicators that is consistent with impaired status as defined by some clinical consequence. For the micronutrients considered in this report, there is a dearth of information on the biochemical values that reflect abnormal function. A priority should be the determination of the relationship of existing status indicators to clinical endpoints in the same subjects to determine if a correlation exists. For some micronutrients, either new clinical endpoints or intermediate endpoints of impaired function need to be identified and related to status indicators.
The depletion-repletion research paradigms and balance studies, although not ideal, are still probably the best approach to determining requirements for many of the trace minerals. However, these studies should be designed to meet three important criteria:
An indicator of nutrient status is needed for which a cutoff point has been identified, below which nutrient status is documented to be impaired. (In the case of manganese, serum manganese concentrations appear to be sensitive to large variations in manganese intake; however, there is a lack of information to indicate that this indicator reflects manganese status.)
The depletion and repletion periods and balance studies should be sufficiently long to allow a new steady state to be reached. For iodine and chromium, long-term balance studies are lacking. Study design should allow examination of the effects of initial status on response to maintenance or depletion-repletion.
Repletion regimen intakes should bracket the expected EAR intake to assess the EAR more accurately and to allow for a measure of variance. In addition, an accurate assessment of variance requires a sufficient number of subjects.
A relatively new and increasingly popular approach to determin-