Assessment of tocopherol metabolism and oxidative stress in familial hypobetalipoproteinemia.

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.

• Authors: Michael W Clarke, Amanda J Hooper, Henrietta A Headlam, Jason H Y Wu, Kevin D Croft, John R Burnett
• Journal: Clinical chemistry (Clin Chem) Vol. 52 Issue 7 Pg. 1339-45 (Jul 2006) ISSN: 0009-9147 [Print] England
• PMID: 16728468 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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