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

Patients with alpha-tocopherol transfer protein (alpha-TTP) defects experie nce neurological symptoms characteristic of vitamin E deficiency and depend on continuous high alpha-tocopherol supplements. We investigated the excre tion of 2,5,7,8-tetramethyl-2 (2'-carboxyethyl)-6-hydroxychroman (alpha-CEH C), a urinary metabolite of alpha-tocopherol, as a putative marker for the alpha-tocopherol status of alpha-TTP-deficient patients and control subject s. In three patients vitamin E supplementation was stopped for short period s of time, during which plasma alpha-tocopherol concentrations and urinary alpha-CEHC excretion were measured. In the patients, plasma alpha-tocophero l decreased below normal (<5 mu mol/l) but alpha-CEHC excretion remained ab ove the range of unsupplemented control subjects (0.118-0.306 mg/day, n = 6 ), In healthy subjects, however, alpha-CEHC excretion was increased only af ter surpassing a plasma alpha-tocopherol threshold of 30-40 mu mol/l. Such a threshold did not exist in patients. The general mechanism of alpha-tocop herol degradation did not appear to differ between patients and control sub jects. The presumed mechanism of omega- and subsequent beta-oxidation was s upported by the detection of alpha-CPHC, an alpha-CEHC homolog with a side chain longer by 3 carbon atoms, both in supplemented patients and in contro l subjects.