Impaired discrimination between stereoisomers of alpha-tocopherol in patients with familial isolated vitamin E deficiency.

We assessed whether patients with familial isolated vitamin E deficiency could discriminate between natural (RRR-) and synthetic (SRR-) stereoisomers of alpha-tocopherol labeled with six (d6) or three (d3) deuterium atoms, respectively. After oral administration of 20 mg of each of the stereoisomers, patients (seven) and controls (seven) had similar concentrations of both in chylomicrons, similar initial increases of both, and similar rates of decrease of d3-SRR-alpha-tocopherol in plasma. Patients and controls differed in their abilities to maintain plasma d6-RRR-alpha-tocopherol concentrations. Controls maintained plasma d6-RRR-alpha-tocopherol concentrations by preferentially secreting it in very low density lipoprotein (VLDL). Three of seven patients did not discriminate between the two stereoisomers and their plasma and lipoprotein d6-RRR-alpha-tocopherol concentrations declined rapidly. The remaining patients were intermediate between non-discriminators and controls in their ability to discriminate and maintain plasma d6-RRR-alpha-tocopherol concentrations. The degree of discrimination between the two stereoisomers in the patients was correlated with the age of onset of the neurologic disability (r2 = 0.64, P < 0.03). Estimates based on the rate of decrease of plasma d6-RRR-alpha-tocopherol in non-discriminators suggest that the entire plasma alpha-tocopherol pool of normal subjects is replaced daily. We suggest 1) that a hepatic alpha-tocopherol binding protein, which preferentially incorporates RRR-alpha-tocopherol into VLDL, is required to maintain plasma RRR-alpha-tocopherol concentrations; 2) that non-discriminators are lacking this protein, or have a marked defect in the RRR-alpha-tocopherol binding region of the protein; and 3) that patients who discriminate, but have difficulty maintaining plasma RRR-alpha-tocopherol concentrations, have a less severe defect, or perhaps a defect in the transfer function of the protein.