Urinary α-tocopherol metabolites in α-tocopherol transfer protein-deficient patients

Abstract

Patients with α-tocopherol transfer protein (α-TTP) defects experience neurological symptoms characteristic of vitamin E deficiency and depend on continuous high α-tocopherol supplements. We investigated the excretion of 2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman (α-CEHC), a urinary metabolite of α-tocopherol, as a putative marker for the α-tocopherol status of α-TTP-deficient patients and control subjects. In three patients vitamin E supplementation was stopped for short periods of time, during which plasma α-tocopherol concentrations and urinary α-CEHC excretion were measured. In the patients, plasma α-tocopherol decreased below normal (<5 μmol/l) but α-CEHC excretion remained above the range of unsupplemented control subjects (0.118–0.306 mg/day, n = 6). In healthy subjects, however, α-CEHC excretion was increased only after surpassing a plasma α-tocopherol threshold of 30–40 μmol/l. Such a threshold did not exist in patients. The general mechanism of α-tocopherol degradation did not appear to differ between patients and control subjects. The presumed mechanism of ω- and subsequent β-oxidation was supported by the detection of α-CPHC, an α-CEHC homolog with a side chain longer by 3 carbon atoms, both in supplemented patients and in control subjects.—Schuelke, M., A. Elsner, B. Finckh, A. Kohlschütter, C. Hübner, and R. Brigelius-Flohé. Urinary α-tocopherol metabolites in α-tocopherol transfer protein-deficient patients. J. Lipid Res. 2000. 41: 1543–1551.

Keywords

• α-tocopherol
• α-tocopherol metabolites
• α-CEHC
• α-tocopherol transfer protein
• AVED patients