Urinary excretion of 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman is a major route of elimination of γ-tocopherol in humans

Abstract

Little is known of the post-absorptive, metabolic fate of γ-tocopherol, the major form of vitamin E in North American diets. The objective of this study was to determine the extent of urinary excretion of 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman (γ-CEHC), a recently identified metabolite of γ-tocopherol. A method for measurement of urinary γ-CEHC was developed, using gas chromatography–mass spectrometry (GC–MS) with a deuterated internal standard, 2,7,8-trimethyl-2-(β-carboxyethyl)-(3,4-2H2)-6-hydroxychroman (d2-γ-CEHC). This standard was synthesized by dehydrogenation of 6-acetyl-γ-CEHC followed by deuteration of the resulting 3,4-double bond. The use of d2-γ-CEHC resulted in accurate determinations of the concentration of d0-γ-CEHC in human urine. Urine samples containing added d2-γ-CEHC were treated with β-glucuronidase, extracted with an organic solvent, and analyzed by GC–MS. Analysis of 24-h urine pools from healthy subjects revealed γ-CEHC concentrations, normalized against creatinine, ranging from 2.5 to 31.5 μmol/g creatinine, or a total of 4.6 to 29.8 μmol per day. These results correspond to 2–12 mg γ-tocopherol excreted daily as γ-CEHC in the urine. Given an estimated mean intake of γ-tocopherol of 20 mg/day, catabolism of γ-tocopherol to γ-CEHC, followed by glucuronide conjugation and urinary excretion, is a major pathway for elimination of γ-tocopherol in humans.—Swanson, J. E., R. N. Ben, G. W. Burton, and R. S. Parker. Urinary excretion of 2,7,8-trimethyl-2-(β-carboxyethyl)-6-hydroxychroman is a major route of elimination of γ-tocopherol in humans. J. Lipid Res. 1999. 40: 665–671.

Keywords

• vitamin E
• γ-chroman acid
• tocopherol metabolism
• LLU-α