Assessment of tocopherol metabolism and oxidative stress in familial hypobetalipoproteinemia

Clin Chem. 2006 Jul;52(7):1339-45. doi: 10.1373/clinchem.2006.068692. Epub 2006 May 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abetalipoproteinemia / drug therapy
  • Abetalipoproteinemia / genetics
  • Abetalipoproteinemia / metabolism
  • Adult
  • Apolipoproteins B / genetics
  • Biomarkers / urine
  • Blood Platelets / metabolism
  • Child, Preschool
  • Erythrocytes / metabolism
  • F2-Isoprostanes / urine
  • Female
  • Heterozygote
  • Humans
  • Hypobetalipoproteinemias / genetics
  • Hypobetalipoproteinemias / metabolism*
  • Infant
  • Male
  • Oxidative Stress*
  • Tocopherols / blood
  • Tocopherols / metabolism*
  • Tocopherols / urine
  • Vitamins / administration & dosage
  • Vitamins / blood
  • Vitamins / urine
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / blood
  • alpha-Tocopherol / urine
  • gamma-Tocopherol / blood

Substances

  • Apolipoproteins B
  • Biomarkers
  • F2-Isoprostanes
  • Vitamins
  • gamma-Tocopherol
  • alpha-Tocopherol
  • Tocopherols