• Jiao Luo, Yasufumi Hashimoto, Leon G Martens, Fleur L Meulmeester, Nadia Ashrafi, Dennis O Mook-Kanamori, Frits R Rosendaal, J Wouter Jukema, Ko Willems van Dijk, Kevin Mills, Saskia le Cessie, Raymond Noordam, and Diana van Heemst.
• Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: j.luo@lumc.nl.
• Nutrition. 2022 Jan 1; 93: 111440.

AbstractVitamin E (α-tocopherol [α-TOH]) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-h urine quantified by liquid chromatography with tandem mass spectrometry. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) and vitamin E metabolites (outcomes), adjusted for demographic factors. We analyzed 474 individuals (55% women, 45% men) with a mean (SD) age of 55.7 (6.0) y. Out of 147 metabolomic measures, 106 were associated (P < 1.34 × 10-3) with serum α-TOH (median β [interquartile range] = 0.416 [0.383-0.466]), predominantly lipoproteins associated with higher α-TOH. The associations of metabolomic measures with urinary α-CEHC have directions similar to those with α-TOH, but effect sizes were smaller and non-significant (median β [interquartile range] = 0.065 [0.047-0.084]). However, associations of metabolomic measures with urinary α-TLHQ were markedly different from those with both serum α-TOH and urinary α-CEHC, with negative and small-to-null relations to most very-low-density lipoproteins and amino acids. Therefore, our results highlight the differences in the lipoproteins involved in the transportation of circulating α-TOH and oxidized vitamin E metabolites. This indicates that circulating α-TOH may be representative of the enzymatic but not the antioxidative function of vitamin E.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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