8 to 40 days and is inversely related to ascorbate body pool. For β-carotene and other carotenoids, no long-term depletion-repletion studies with validated intermediate endpoints exist. Study design should allow examination of the effects of initial status on response to maintenance or depletion-repletion.

  1. 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 determining requirements is kinetic modeling of body pools, using steadystate compartmental analyses. Although this approach is unlikely to supplant depletion-repletion studies, it may be the only technique available to obtain this type of information, despite a number of drawbacks. A number of assumptions that cannot be tested experimentally are often needed, and the estimates obtained for body pool sizes are inherently imprecise. Even if accurate assessments of body pools were possible and were obtained, such information would be useful in setting a requirement only if one could establish the body pool size at which functional deficiency occurs. The amount needed for restoration of biochemical status indicators to baseline values is not necessarily equivalent to the requirement for the nutrient.

For vitamin C, vitamin E, selenium, and β-carotene and other carotenoids, useful data are seriously lacking for setting requirements for infants, children, adolescents, pregnant and lactating women, and the elderly. Studies should use graded levels of nutrient intake and a combination of response indices, and should consider other points raised above. For some of these nutrients, studies should examine whether or not the requirement varies substantially by trimester of pregnancy. In addition, more information is needed for groups at increased risk for oxidative stress, especially those who smoke or who are subjected to second-hand smoke, athletes, and individuals living at high altitudes.

Data are lacking about gender issues with respect to metabolism and requirements of these nutrients. For example, women and children with low intakes of selenium are at higher risk of Keshan disease than are men with similar intakes. Women are at higher risk of macular degeneration even at similar plasma concentrations of carotenoids.

The understanding of the health effects of carotenoids is rudimentary compared with that of the other nutrients in this report.

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