Lower plasma alpha-carboxyethyl-hydroxychroman after deuterium-labeled alpha-tocopherol supplementation suggests decreased vitamin E metabolism in smokers.
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.


METHODS
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.
Bruno
Richard S
RS
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
Leonard
Scott W
SW
Li
Jun
J
Bray
Tammy M
TM
Traber
Maret G
MG
D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D002839:Chromans / Q000097:blood*; D006801:Humans; D018384:Oxidative Stress; D012907:Smoking / Q000378:metabolism*; D013237:Stereoisomerism; D024502:alpha-Tocopherol / Q000378:metabolism*
D000975:Antioxidants; D002839:Chromans; C483420:carboxyethyl-hydroxychroman; D024502:alpha-Tocopherol