(Horwitt, 1976) and all rac-α-tocopheryl acetate (historically and incorrectly labeled dl-α-tocopheryl acetate) (Horwitt, 1976) are the forms of synthetic vitamin E used almost exclusively in supplements, food fortification, and pharmacologic agents.

Animal studies show that α-tocopherol is not mutagenic, carcinogenic, or teratogenic (Abdo et al., 1986; Dysmsza and Park, 1975; Krasavage and Terhaar, 1977). Animals fed extremely high doses of α-tocopherol or α-tocopheryl acetate have been shown to experience a variety of adverse effects, but the relevance of some of this information to the human situation is questionable.

Little information exists on the adverse effects to humans that might result from ingestion of other forms of tocopherol, such as γ- or β-tocopherol, in amounts exceeding the levels normally found in foods. One study in humans given supplements of either all rac-α-tocopherol, RRR-α-tocopherol, or mixed tocopherols (α, β, and γ-tocopherol) demonstrated that all supplements yielded the same plasma α- and γ-tocopherol concentrations (Chopra and Bhagavan, 1999). Some data are available from animal studies, however. Clement and Bourre (1997) found that rats fed large amounts of γ-tocopherol had increased concentrations of α-tocopherol in plasma and tissues. Although the fractional absorption of α-tocopherol was decreased when α-tocopherol supplements were given to thoracic ductcannulated rats, no decrease was seen in γ-tocopherol absorption (Traber et al., 1986). Thus, it appears that absorption of the various forms of vitamin E is independent and unaffected by the presence of large amounts of the other forms.

Plasma α-tocopherol concentrations are not informative for assessing adverse effects because plasma concentrations reach a similar plateau (approximately 3 to 4 times unsupplemented concentrations) when humans consume supplements containing at least 200 mg (465 µmol)/day of either RRR- or all rac-α-tocopherol (Chopra and Bhagavan, 1999; Devaraj et al., 1997; Dimitrov et al., 1991, 1996; Jialal et al., 1995; Meydani et al., 1998; Princen et al., 1995). However, since all forms of vitamin E are absorbed, although are not maintained in the plasma (as discussed in the earlier section “Absorption and Transport” [Kiyose et al., 1997; Meydani et al., 1989; Traber and Kayden, 1989a; Traber et al., 1992, 1994a]), they all could contribute to vitamin E toxicity. These observations suggest that at doses at which adverse effects are observed, all the stereoisomers of α-tocopherol should be considered equivalent. A review of vitamin E toxicity studies concluded that humans show few side effects following supplemental doses below 2,100 mg (4,885 µmol)/day of RRR-α-tocopherol (Kappus and Diplock, 1992). However, most



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