Absorption and transport of deuterium-substituted 2R,4′R,8′R-α-tocopherol in human lipoproteins

Abstract

Oral administration of a single dose of tri- or hexadeuterium substituted 2R,4′R,8′R-α-tocopheryl acetate (d₃- or d₆-α-T-Ac) to humans was used to follow the absorption and transport of vitamin E in plasma lipoproteins. Three hr after oral administration of d₃-α-T-Ac (15 mg) to 2 subjects, plasma levels of d₃-α-T were detectable; these increased up to 10 hr, reached a plateau at 24 hr, then decreased. Following administration of d₆-α-T-Ac (15–16 mg) to 2 subjects, the percentage of deuterated tocopherol relative to the total tocopherol in chylomicrons increased more rapidly than the corresponding percentage in whole plasma. Chylomicrons and plasma lipoproteins were isolated from 2 additional subjects following administration of d₃-α-T-Ac (140 or 60 mg). The percentage of deuterated tocopherol relative to the total tocopherol increased most rapidly in chylomicrons, then in very low density lipoproteins (VLDL), followed by essentially identical increases in low and high density lipoproteins (LDL and HDL, respectively) and lastly, in the red blood cells. This pattern of appearance of deuterated tocopherol is consistent with the concept that newly absorbed vitamin E is secreted by the intestine into chylomicrons; subsequently, chylomicron remnants are taken up by the liver from which the vitamin E is secreted in VLDL. The metabolism of VLDL in the circulation results in the simultaneous delivery of vitamin E into LDL and HDL.