Background: Vitamin E supplementation has been recommended for persons with familial hypobetalipoproteinemia (FHBL), a rare disorder of lipoprotein metabolism that leads to low serum a-tocopherol and decreased LDL-cholesterol and apolipoprotein (apo) B. We examined the effect of truncated apoB variants on vitamin E metabolism and oxidative stress in persons with FHBL.Methods: We studied 9 individuals with heterozygous FHBL [mean (SE) age, 40 (5) years; body mass index (BMI), 27 (10) kg/m(2)] and 7 normolipidemic controls [age, 41 (5) years; BMI, 25 (2) kg/m(2)]. We also studied 3 children-2 with homozygous FHBL (apoB-30.9) and 1 with abetalipoproteinemia-who were receiving a-tocopherol supplementation. We used HPLC with electrochemical detection to measure alpha- and gamma-tocopherol in serum, erythrocytes, and platelets, and gas chromatography-mass spectrometry to measure F-2-isoprostanes and tocopherol metabolites in urine as markers of oxidative stress and tocopherol intake, respectively.Results: Compared with controls, persons with FHBL had significantly lower fasting plasma concentrations of total cholesterol [2.4 (0.2) vs 4.7 (0.2) mmol/L], triglycerides [0.5 (0.1) vs 0.9 (0.1) mmol/L], LDL-cholesterol [0.7 (0.1) vs 2.8 (0.3) mmol/L], apoB [0.23 (0.02) vs 0.84 (0.08) g/L], a-tocopherol [13.6 (1.0) vs 28.7 (1.4) mu mol/L], and gamma-tocopherol [1.0 (0.1) vs 1.8 (0.3) mu mol/L] (all P < 0.03). Erythrocyte a-tocopherol was decreased [5.0 (0.2) vs 6.0 (0.3) mu mol/L; P < 0.005]; but we observed no differences in lipid-adjusted serum tocopherols, erythrocyte gamma-tocopherol, platelet alpha- or gamma-tocopherol, urinary F-2-isoprostanes, or tocopherol metabolites.Conclusion: Taken together, our findings do not support the recommendation that persons with heterozygous FHBL receive vitamin E supplementation. (c) 2006 American Association for Clinical Chemistry.