Vitamin E dose-response studies in humans with use of deuterated RRR-alpha-tocopherol.
BACKGROUND
Supplemental vitamin E does not raise plasma alpha-tocopherol concentrations more than approximately 3-fold.


OBJECTIVE
To elucidate the mechanism for the limitation in plasma alpha-tocopherol, we undertook human supplementation trials using incrementally increased doses of deuterated vitamin E.


METHODS
Plasma was obtained from 6 healthy, young adults (4 men and 2 women) during 3 sequential supplementation trials with doses of 15, 75, and 150 mg RRR-alpha-tocopheryl acetate labeled with deuterium (d3-RRR-alpha-tocopheryl acetate). A defined diet was provided on the day of deuterated vitamin E administration, but otherwise subjects ate ad libitum.


RESULTS
The areas under the curves calculated from the plasma d3-RRR-alpha-tocopherol concentrations increased linearly with dose--a 10-fold increase in dose resulted in a 10-fold increase in area under the curve. d3-RRR-alpha-Tocopherol absorption and incorporation into plasma did not decrease with increasing dose. At 11 h, the 15-, 75-, and 150-mg doses resulted in 8+/-4%, 21+/-10%, and 37+/-20% labeling, respectively, of plasma vitamin E. Plasma total (labeled plus unlabeled) alpha-tocopherol concentrations before supplementation were 12+/-3 micromol/L and over the 96 h after the dose averaged 13.3+/-2.6, 15.4+/-3.0, and 16.7+/-4.9 micromol/L for the 15-, 75-, and 150-mg doses, respectively.


CONCLUSIONS
d3-RRR-alpha-Tocopherol was incorporated into the plasma in preference to circulating plasma RRR-alpha-tocopherol. This could occur if the newly absorbed d3-RRR-alpha-tocopherol was preferentially used to replenish circulating vitamin E.
Department of Medicine, New York University Medical Center, New York, USA. Maret.Traber@orst.edu
M G
MG
Traber
D
D
Rader
R V
RV
Acuff
R
R
Ramakrishnan
H B
HB
Brewer
H J
HJ
Kayden
D000042:Absorption; D000328:Adult; D003903:Deuterium; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D014810:Vitamin E / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics
D014810:Vitamin E; D003903:Deuterium