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Vitamin E disappearance is accelerated in cigarette smokers due to their increased oxidative stress and is inversely correlated with plasma vitamin C concentrations. Therefore, we hypothesized that ascorbic acid supplementation (500 mg, twice daily; 2 weeks) would normalize smokers' plasma α- and γ-tocopherol disappearance rates and conducted a double-blind, placebo-controlled, randomized crossover investigation in smokers (
n = 11) and nonsmokers (
n = 13) given a single dose of deuterium-labeled α- and γ-tocopherols (50 mg each d
6-
RRR-α and d
2-
RRR-γ-tocopheryl acetate). During the placebo trial, smokers, compared with nonsmokers, had significantly (
P < 0.05) greater α- and γ-tocopherol fractional disappearance rates and shorter half-lives. Ascorbic acid supplementation doubled (
P < 0.0001) plasma ascorbic acid concentrations in both groups and attenuated smokers', but not nonsmokers', plasma α- and γ-tocopherol (
P < 0.05) fractional disappearance rates by 25% and 45%, respectively. Likewise, smokers' plasma deuterium-labeled α- and γ-tocopherol concentrations were significantly higher (
P < 0.05) at 72 h during ascorbic acid supplementation compared with placebo. Ascorbic acid supplementation did not significantly change (
P > 0.05) time of maximal or maximal-labeled α- and γ-tocopherol concentrations. Smokers' plasma F
2α-isoprostanes were ∼26% higher than nonsmokers (
P > 0.05) and were not affected by ascorbic acid supplementation in either group (
P > 0.05). In summary, cigarette smoking increased plasma α- and γ-tocopherol fractional disappearance rates, suggesting that the oxidative stress from smoking oxidizes tocopherols and that plasma ascorbic acid reduces α- and γ-tocopheroxyl radicals to nonoxidized forms, thereby decreasing vitamin E disappearance in humans.