Novel urinary metabolite of alpha-tocopherol, 2,5,7,8-tetramethyl-2(2’-carboxyethyl)-6-hydroxychroman, as an indicator of an adequate vitamin E supply?

Abstract

Previously, the metabolism of alpha-tocopherol was considered to involve the opening of the chroman structure because of its oxidation to tocopherylquinone. In contrast, we describe here 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) as the major urinary metabolite of alpha-tocopherol that appears in human urine after vitamin E supplementation. It is formed directly from alpha-tocopherol without previous oxidative splitting of the chroman ring. The correlation of alpha-tocopherol intake, plasma alpha-tocopherol concentrations, and urinary excretion of alpha-CEHC in human volunteers supplemented with RRR-alpha-tocopherol dosages ranging from 0 to 800 mg/d was examined. HPLC and gas chromatography-mass spectroscopy analysis revealed that alpha-CEHC was only excreted when a plasma threshold of 7-9 mumol alpha-tocopherol/g total lipid was exceeded. This concentration was obtained by a daily intake of approximately 50-150 mg alpha-tocopherol. We suggest that alpha-CEHC excretion indicates a saturated binding capacity of vitamin E in the plasma and thus may be considered to be a marker of optimum vitamin E intake.

Conventional cell culture media do not adequately supply cells with antioxidants and thus facilitate peroxide-induced genotoxicity

“…1A) revealed, that the a-tocopherol content was consistently lower than that of human serum, which usually ranges between 20 and 30/zM. 27 Some of the 10 different sera tested (Fig. 1A) even had a-tocopherol contents of less than 10 nM, which was our detection limit.…”

Regulatory mechanisms to control tissue α-tocopherol

“…Together, these data suggest the modest increase in lung α-CEHC levels is likely a result of plasma delivery and not metabolism of α-tocopherol in situ. Presumably, the increase in kidney α-CEHC levels is due to its excretory function [2,27]. However, since CYP4F1 is constitutively expressed in the kidney, α-tocopherol metabolism within the kidney may be an additional source of kidney α-CEHC.…”

“…Only α-tocopherol, not the others, is maintained in human plasma and tissues, as a result of the function of the hepatic α-tocopherol transfer protein (α-TTP) [1]. Unlike other fat-soluble vitamins, vitamin E is not accumulated in the body to toxic levels, suggesting that mechanisms, i.e., metabolism and excretion, prevent excess accumulation [2].…”

α-Tocopherol incorporation in mitochondria and microsomes upon supranutritional vitamin E supplementation

“…The data furthermore showed that the a-tocopheryl quinone arising from excessive oxidative degradation of a-tocopherol can potentially interfere with mitochondrial electron transfer (Gregor et al 2006). Searching for urinary metabolites of vitamin E, another metabolite of a-tocopherol, 2,5,7,8-tetramethyl-2(2 0 -carboxyethyl)-6-hydroxychroman (a-CEHC), was identified (Schultz et al 1995). The metabolites of vitamin E are the CEHC products of the respective forms of vitamin E, that is, a-, b-, c-, and d-CEHC, and the various non-a-tocopherol forms are metabolized in preference to a-tocopherol (Swanson et al 1999;Sontag and Parker 2002).…”