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DRI DIETARY REFERENCE INTAKES FOR Vitamin C, Vitamin E, Selenium, and Carotenoids
TABLE 6-6 Sources of Uncertainty Used to Determine UL for Vitamin E
LOAEL to NOAEL
Subchronic to chronic intake
Experimental animal to human
Interindividual variation in sensitivity
Final UF = 2 × 2 × 3 × 3 =
some similarities between the animal and human responses. Another UF of 3 was selected to account for interindividual variation in sensitivity. This value was deemed appropriate based on pharmacokinetic data showing plasma saturation of α-tocopherol concentrations with increasingly higher intakes in humans (Dimitrov et al., 1991, 1996; Jialal et al., 1995; Losowsky et al., 1972; Meydani et al., 1998; Princen et al., 1995). The various UFs are combined to yield an overall UF of 36 to extrapolate from the LOAEL in animals to derive a UL for humans.
Derivation of a UL. The LOAEL of 500 mg/kg/day was divided by the overall UF of 36 to obtain a UL value of 14 mg/kg/day for adult humans. The value of 14 mg/kg/day was multiplied by the average of the reference body weights for male and female adults, 68.5 kg, from Chapter 1 (Table 1-1). The resulting UL for adults is 959 mg/day (which was rounded to 1,000 mg/day):
= 14 / mg / kg / day × 68.5 kg ≈ 1,000 mg /day.
Although adult males and females have different reference body weights, the uncertainties in the estimation of the UL were considerable, and distinction of separate ULs for male and female adults was therefore not attempted. This UL is consistent with the review by Kappus and Diplock (1992) that in humans, side effects occurred at doses of 1,100 to 2,100 mg (2,559 to 4,885 µmol)/day of RRR-α-tocopherol. At high doses all of the stereoisomers of α-tocopherol are considered equivalent given that all forms of vitamin E are absorbed (Kiyose et al., 1997; Meydani et al., 1989; Traber and Kayden, 1989a; Traber et al., 1992, 1994a). Thus, the UL applies to all eight stereoisomers of α-tocopherol.