Novel metabolites and roles for α-tocopherol in humans and mice discovered by mass spectrometry–based metabolomics

Abstract

Background: Contradictory results from clinical trials that examined the role of vitamin E in chronic disease could be a consequence of interindividual variation, caused by factors such as xenobiotic use. Cometabolism of vitamin E with other pharmaceutical products could affect the bioavailability of the drug. Thus, it is necessary to understand fully the metabolic routes and biological endpoints of vitamin E. Objective: The objective was to uncover novel metabolites and roles of vitamin E in humans and mouse models. Design: Human volunteers (n = 10) were fed almonds for 7 d and then an a-tocopherol dietary supplement for 14 d. Urine and serum samples were collected before and after dosing. C57BL/6 mice (n = 10) were also fed a-tocopherol-deficient and -enriched diets for 14 d. Urine, serum, and feces were collected before and after dosing, and liver samples were collected after euthanization. Ultraperformance liquid chromatography electrospray ionization time-of-flight mass spectrometry and multivariate data analysis tools were used to analyze the samples. Results: Three novel urinary metabolites of a-tocopherol were discovered in humans and mice: a-carboxyethylhydroxychroman (a-CEHC) glycine, a-CEHC glycine glucuronide, and a-CEHC taurine. Another urinary metabolite, a-CEHC glutamine, was discovered in mice after a-CEHC gavage. Increases in liver fatty acids and decreases in serum and liver cholesterol were observed in mice fed the a-tocopherol-enriched diet. Conclusion: Novel metabolites and metabolic pathways of vitamin E were identified by mass spectrometry-based metabolomics and will aid in understanding the disposition and roles of vitamin E in vivo.Am J Clin Nutr 2012;96:818-30.

Complexity of vitamin E metabolism

“…While glucoside conjugates of γ-CEHC [156] and α-CEHC glutamine [176] have been only found in mice, taurine, glycine or glycine glucuronides conjugates were found [139,141] ICM Ether glucuronides Human and mouse urine [176] Sulfates Human urine [177] SCM Glucosides, glutamine Mouse [156,176] Taurine, glycine or glycine glucuronides…”

“…In humans, the majority of CEHCs are excreted via urine as glucuronides [136,147,152,155] , whereas sulfates were found only in trace amounts [177] or in significant amounts [135,136,176] . In addition, other conjugates are known for α-CEHC, such as taurine, glycine or glycine glucuronide conjugates [176] . In mice, glucuronides and sulfates of α-, γ-, δ-CEHC have been found [136,156,176] .…”

“…Human and mouse urine [176] Sulfates Rats [178] in murine urine as well as in urine of humans [176] . The glucoside conjugate of γ-CEHC was found by Cho et al [156] and appeared to be the main conjugated form of γ-CEHC in mice.…”

“…This was confirmed in studies by Hashiguchi et al [175] . α-5'-COOH ether glucuronides [176] in urine of both humans and mice as well as α-5'-COOH sulfate in human urine [177] are known conjugates of ICMs. More is known about the conjugates of the SCMs.…”

“…In addition, other conjugates are known for α-CEHC, such as taurine, glycine or glycine glucuronide conjugates [176] . In mice, glucuronides and sulfates of α-, γ-, δ-CEHC have been found [136,156,176] .…”