TitleLower plasma alpha-carboxyethyl-hydroxychroman after deuterium-labeled alpha-tocopherol supplementation suggests decreased vitamin E metabolism in smokers.
Publication TypeJournal Article
Year of Publication2005
AuthorsBruno RS, Leonard SW, Li J, Bray TM, Traber MG
JournalAm J Clin Nutr
Date Published2005 May
KeywordsAdult, alpha-Tocopherol, Antioxidants, Chromans, Humans, Oxidative Stress, Smoking, Stereoisomerism

BACKGROUND: Cigarette smoking increases the fractional disappearance rates of alpha-tocopherol and is associated with increased oxidative stress, but its effects on alpha-tocopherol metabolism are unknown.

OBJECTIVE: We hypothesized that smokers would have less alpha-tocopherol available and consequently lower plasma alpha-carboxyethyl-hydroxychroman (alpha-CEHC), the alpha-tocopherol metabolite produced by a cytochrome P450-mediated process.

DESIGN: Smokers and nonsmokers (n = 10 per group) were supplemented with deuterium-labeled alpha-tocopheryl acetates (75 mg each d3-RRR-alpha-tocopheryl and d6-all-rac-alpha-tocopheryl acetate) from day -6 to day -1, and plasma tocopherols and CEHCs were measured (day -6 through day 17).

RESULTS: After 6 d of supplementation, plasma d3- and d6-alpha-tocopherol concentrations did not differ significantly between groups. Plasma d3- and d6-alpha-CEHCs were detectable only from day -5 to day 5. Before supplementation, unlabeled alpha- and gamma-CEHCs were approximately 60% and 40% lower, respectively, in smokers than in nonsmokers (P < or = 0.05). In addition, d0-, d3-, and d6-alpha-CEHC areas under the curves were approximately 50% lower in smokers (P < 0.05), and smokers had lower maximal d3-alpha-CEHC (P = 0.004) and d6-alpha-CEHC (P = 0.0006) concentrations. Notably, 2.9-4.7 times as much alpha-CEHC was produced from all-rac-alpha-tocopherol than from RRR-alpha-tocopherol. During supplementation, smokers had about one-half (P < 0.05) the plasma total, d6-, or d3-alpha-CEHC concentrations that nonsmokers did given similar alpha-tocopherol concentrations.

CONCLUSIONS: Smoking did not increase alpha-tocopherol disappearance through P450-mediated tocopherol metabolism. Therefore, the mechanism of increased alpha-tocopherol disappearance in smokers likely operates through oxidation pathways, which is consistent with alpha-tocopherol's antioxidant function. Consequently, evaluating the molecular mechanism or mechanisms responsible for tocopherol metabolism under conditions of oxidative stress and the mechanisms that regulate alpha-tocopherol status is warranted.

Alternate JournalAm. J. Clin. Nutr.
PubMed ID15883428
Grant ListDK59576 / DK / NIDDK NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States