As a result of this approach, the following four areas were identified:
methodological problems related to the assessment of intake of these nutrients and to the assessment of adequacy of intake,
relationships of nutrient intake to public health, and
adverse effects of nutrients.
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 nutrients 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 end-points in the same subjects to determine if a correlation exists. For some nutrients, either new clinical endpoints or intermediate end-points of impaired function have to be identified and related to status indicators.
The depletion-repletion research paradigms that are often used in studies of requirements, although not ideal, are still probably the best approach to determining nutrient requirements. 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 vitamin E, values are based on induced vitamin E deficiency and the correlation with hydrogen peroxide-induced hemolysis and plasma α-tocopherol concentrations, because there is little information relating levels of status indicators to functional sufficiency or insufficiency. Also with vitamin C, there is little information relating levels of status indicators to functional sufficiency or insufficiency, because dose-dependent absorption and renal regulation of ascorbate allow body conservation during low intakes and limitation of plasma levels at high intakes.)
The depletion and repletion periods should be sufficiently long to allow a new steady state to be reached. This can be very problematic for vitamin C because biological half-life ranges from