Vitamin E (alpha-tocopherol [alpha-TOH] ) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology... Show moreVitamin E (alpha-tocopherol [alpha-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 alpha-TOH and its urinary enzymatic (alpha-CEHC) and oxidized (alpha-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 x 10(3)) with serum alpha-TOH (median beta [interquartile range] = 0.416 [0.383-0.466]), predominantly lipoproteins associated with higher alpha-TOH. The associations of metabolomic measures with urinary alpha-CEHC have directions similar to those with alpha-TOH, but effect sizes were smaller and non-significant (median beta [interquartile range] = 0.065 [0.047-0.084]). However, associations of metabolomic measures with urinary alpha-TLHQ were markedly different from those with both serum alpha-TOH and urinary alpha-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 alpha-TOH and oxidized vitamin E metabolites. This indicates that circulating alpha-TOH may be representative of the enzymatic but not the antioxidative function of vitamin E. (C) 2021 The Author( s). Published by Elsevier Inc. Show less
A limited understanding of intersubject and intrasubject variability hampers effective biomarker translation from in vitro/in vivo studies to clinical trials and clinical decision support.... Show moreA limited understanding of intersubject and intrasubject variability hampers effective biomarker translation from in vitro/in vivo studies to clinical trials and clinical decision support. Specifically, variability of biomolecule concentration can play an important role in interpretation, power analysis, and sampling time designation. In the present study, a wide range of 749 plasma metabolites, 62 urine biogenic amines, and 1,263 plasma proteins were analyzed in 10 healthy male volunteers measured repeatedly during 12 hours under tightly controlled conditions. Three variability components in relative concentration data are determined using linear mixed models: between (intersubject), time (intrasubject), and noise (intrasubject). Biomolecules such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, platelet-derived growth factor C, and cathepsin D with low noise potentially detect changing conditions within a person. If also the between component is low, biomolecules can easier differentiate conditions between persons, for example cathepsin D, CD27 antigen, and prolylglycine. Variability over time does not necessarily inhibit translatability, but requires choosing sampling times carefully. Show less
