Considering these nutrients as a group, only a few studies have been conducted that were explicitly designed to address adverse effects of chronically high intake. Thus, information on which to base Tolerable Upper Intake Levels (ULs) is extremely limited. Although an unexpected result of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was a non-prespecified 50 percent increase in mortality from hemorrhagic stroke in Finnish men who smoked and were supplemented with 50 mg/day of vitamin E, additional randomized trial evidence is needed for confirmation or refutation of this result. Because data on the potential for β-carotene to produce increased lung cancer rates in smokers are conflicting, ongoing studies are needed to help resolve this issue.

Because the various forms of vitamin E are not interconvertible and because plasma concentrations of vitamin E depend on the affinity of hepatic α-tocopherol transfer protein for the various forms, it is recommended that the relative biological potencies of the different forms of vitamin E be reevaluated. Until this is done, the actual concentrations of each of the various vitamin E forms in food and biological samples should be reported separately whenever possible.

Five major types of information gaps were noted: (1) a dearth of studies designed specifically to estimate average requirements in presumably healthy humans; (2) a nearly complete lack of usable data on the nutrient needs of infants, children, adolescents, and pregnant women; (3) a lack of definitive studies to determine the role of these nutrients in reducing the risk of certain chronic diseases; (4) a lack of validated biomarkers to evaluate oxidative stress and the relationship between antioxidant intake and health and disease; and (5) a lack of studies designed to detect adverse effects of chronic high intakes of these nutrients.

Highest priority is thus given to research that has the potential to prevent or retard human disease processes and to prevent deficiencies with functional consequences. The following six areas for re-