Original ContributionFaster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation
Introduction
Vitamin E is a lipophilic, chain-breaking antioxidant found within biological membranes that protects polyunsaturated fatty acids from lipid peroxidation [1], [2]. α- and γ-tocopherols are present in measurable amounts in human plasma and tissues [3]. γ-Tocopherol, compared to α-tocopherol, is the major tocopherol found in the diet but is generally found in much lesser quantities in humans [4], typically accounting for 10–20% of the total tocopherols found in plasma [5]. This difference in biological activity has been attributed to the specificity of the hepatic α-tocopherol transfer protein since it facilitates the secretion of α-tocopherol from the liver to the plasma [6].
Oxidative stress is often an implicating factor for alterations in dietary antioxidant utilization. However, little is known about the impact of oxidative stress on vitamin E utilization in vivo or in humans. In vitro investigations have generally suggested that vitamin E is depleted with exposure to cigarette smoke [7], [8]. Some clinical investigations indicated that cigarette smokers had lower plasma vitamin E concentrations than nonsmokers [9], [10], whereas others reported no apparent differences among these groups [11], [12], [13]. Data from our laboratory following supplementation with deuterium-labeled α-tocopherols indicated that smokers, compared with nonsmokers, had significantly faster plasma α-tocopherol disappearance and shorter α-tocopherol half-lives. Interestingly, smokers', but not nonsmokers', plasma α-tocopherol disappearance rates were inversely correlated with plasma ascorbic acid concentrations [14]. These findings were not unexpected since in vitro studies have indicated that vitamin C could spare vitamin E from oxidation [15], [16] or recycle tocopheroxyl radicals [17], [18], most likely at the interface of lipophilic membranes [19], [20].
Therefore, we hypothesized that the higher magnitude of oxidative stress experienced by cigarette smokers compared with nonsmokers would lead to more rapid depletion of plasma tocopherols and that ascorbic acid supplementation would attenuate their disappearance. To test this hypothesis, we supplemented smokers and nonsmokers with ascorbic acid or placebo in a randomized double-masked manner for 2 weeks and then orally administered deuterated α- and γ-tocopherols and measured the subjects' plasma tocopherol disappearance rates up to 72 h.
Section snippets
Subjects
This study protocol was approved by the Institutional Review Board for the protection of human subjects at Oregon State University. Participants were recruited by newspaper advertisements in the Corvallis, Oregon area. Participants who responded were enrolled because they met our study participation criteria: 18–35 years, healthy, nonnutritional supplement user >6-months, <7 h/week aerobic exercise, and were cigarette smokers or nonsmokers. Nonsmokers did not reside with anyone who smoked and
Participant characteristics
Nonsmokers (n = 7 male/6 female; 22.8 ± 2.5 years) and smokers (n = 6 male/5 female; 21.2 ± 1.7 years) did not differ (P > 0.05) with respect to age, height, weight, or BMI (24.8 ± 2.7 vs 22.8 ± 4.0 kg/m2). Prior to study randomization, nonsmokers' (62.9 ± 14.6 μmol/L) plasma ascorbic acid concentrations were ∼26% higher than smokers' (50.1 ± 17.6 μmol/L; P < 0.05). Urinary cotinine was measured during each supplementation period. All smokers (2423 ± 1626 ng/mL) had urinary cotinine
Discussion
Supplementation with ascorbic acid for 2 weeks effectively reduced the elevated plasma α- and γ-tocopherol disappearance rates observed in cigarette smokers. Consistent with our earlier study [14], we anticipated that smokers would have greater plasma tocopherol disappearance rates. Previously we observed that vitamin E disappeared faster in smokers with lower plasma ascorbic acid concentrations, suggesting that ascorbic acid supplementation would decrease tocopherol disappearance.
Ascorbic acid
Acknowledgments
We are especially grateful to the study participants for their cooperation during this investigation. The authors also thank the Natural Source Vitamin E Association for partial support of the purchase of the LC/MS. Special thanks to Wendy McMahan of the Montine lab for providing the F2α-isoprostane analysis and to the National Institutes of Health for providing the financial support to M.G.T. (NIH DK 59576) and T.J.M. (AG05144 and AG16835), and from the National Institute of Environmental
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