Assessment of tocopherol metabolism and oxidative stress in familial hypobetalipoproteinemia.

BACKGROUND Vitamin E supplementation has been recommended for persons with familial hypobetalipoproteinemia (FHBL), a rare disorder of lipoprotein metabolism that leads to low serum alpha-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/m2] and 7 normolipidemic controls [age, 41 (5) years; BMI, 25 (2) kg/m2]. We also studied 3 children-2 with homozygous FHBL (apoB-30.9) and 1 with abetalipoproteinemia-who were receiving alpha-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 F2-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], alpha-tocopherol [13.6 (1.0) vs 28.7 (1.4) micromol/L], and gamma-tocopherol [1.0 (0.1) vs 1.8 (0.3) micromol/L] (all P < 0.03). Erythrocyte alpha-tocopherol was decreased [5.0 (0.2) vs 6.0 (0.3) micromol/L; P < 0.005], but we observed no differences in lipid-adjusted serum tocopherols, erythrocyte gamma-tocopherol, platelet alpha- or gamma-tocopherol, urinary F2-isoprostanes, or tocopherol metabolites. CONCLUSION Taken together, our findings do not support the recommendation that persons with heterozygous FHBL receive vitamin E supplementation.