search were assigned the highest priority (other research recommendations are found at the end of Chapter 5, Chapter 6, Chapter 7 through Chapter 8):

  • Studies to provide the basic data for constructing risk curves and benefit curves across the exposures to dietary and supplemental intakes of vitamin C, vitamin E, selenium, β-carotene and other carotenoids. Studies should be designed to determine the relationship of nutrient intakes to validated biomarkers of oxidative stress. These studies should be followed by nested case-control studies to determine the relationship of the biomarkers of oxidative stress to chronic disease. Finally, full-scale intervention trials should be done to establish the preventive potential of a nutrient for chronic disease.

  • Investigations of the gender specificity of the metabolism and requirements for vitamin C, vitamin E, selenium, and β-carotene and the other carotenoids.

  • Studies to validate methods and possible models for determining Dietary Reference Intakes in the absence of data for some life stage groups, such as children, pregnant and lactating women, and older adults.

  • Research to determine the interactions and possible synergisms of vitamin C, vitamin E, selenium, and β-carotene with each other, with other nutrients and other food components, and with endogenous antioxidants. Multifactorial studies are needed to demonstrate in vivo actions as well as synergisms that have been shown in vitro.

  • Studies to develop economical, sensitive, and specific methods to assess the associations of vitamin C, vitamin E, selenium, and β -carotene and the other carotenoids with the causation, prevalence, prevention, and treatment of specific viral or other infections.

  • Investigations of the magnitude and role of genetic polymorphisms in the mechanisms of actions of vitamin C, vitamin E, selenium, and β-carotene and the other carotenoids.

Because of inconsistent data, a Tolerable Upper Intake Level (UL) could not be established for β-carotene, and due to a lack of sufficient data, ULs could not be set for other carotenoids from food. Thus, research is needed concerning the ULs for the carotenoids. In addition, research would be helpful relative to the adverse effects of vitamin C, vitamin E, and selenium. However, it was concluded that higher priority should be given to the areas listed above because of the possibility of adverse effects at intakes consumed from food and supplements in the United States and Canada.

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