Het hoofddoel van dit proefschrift is het ontrafelen van de causale rol van oxidatieve stress, gemeten door antioxidanten spiegels in bloed en mitochondriaal DNA-kopieaantal (mtDNA-CN), bij het... Show moreHet hoofddoel van dit proefschrift is het ontrafelen van de causale rol van oxidatieve stress, gemeten door antioxidanten spiegels in bloed en mitochondriaal DNA-kopieaantal (mtDNA-CN), bij het ontstaan van chronische ziekten. In dit proefschrift is de nadruk gelegd op het onderzoek naar cardiometabole ziekten en verwante risicofactoren door het toepassen van conventionele epidemiologische technieken in combinatie met Mendeliaanse Randomisatie. De studies beschreven in dit proefschrift hebben antwoord gegeven op twee hoofdvragen na toepassing van innovatieve epidemiologische onderzoeksmethoden op populatieniveau, namelijk: 1) of mitochondriale disfunctie een causale risicofactor is in de ontwikkeling van atherosclerotische cardiovasculaire ziekten en verwante risicofactoren, en 2) of antioxidanten in de voeding klinisch relevante voordelen opleveren bij de preventie van atherosclerotische cardiovasculare ziekten. Daarnaast werpt dit proefschrift licht op de rol van ontsteking, welke een bron kan zijn van verhoogde oxidatieve stress , bij neurologische aandoeningen. Show less
Luo, J.; Hashimoto, Y.; Martens, L.G.; Meulmeester, F.L.; Ashra, N.; Mook-Kanamori, D.O.; ... ; Heemst, D. van 2022
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
Luo, J.; Meulmeester, F.L.; Martens, L.G.; Ashrafi, N.; Mutsert, R. de; Mook-Kanamori, D.O.; ... ; Heemst, D. van 2021
Background & aims: Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (alpha-tocopherol, alpha-TOH) competitively reacts with lipid peroxyl... Show moreBackground & aims: Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (alpha-tocopherol, alpha-TOH) competitively reacts with lipid peroxyl radicals to mitigate oxidative damage, and forms oxidized vitamin E metabolites. Accordingly, we aimed to investigate the associations between alpha-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population. Methods: This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. alpha-TOH metabolites in blood (alpha-TOH and alpha-CEHC-SO3) and urine [sulfate (SO3) and glucuronide (GLU) of both alpha-TLHQ (oxidized) and alpha-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MSeMS). Measures of glucose homeostasis (HOMA-B, HOMA-IR, Insulinogenic index and Matsuda index) were obtained from fasting and postprandial blood samples. Multivariable linear regression analyses were performed to assess the associations of alpha-TOH metabolites and measures of glucose homeostasis. Results: We included 498 participants (45% men) with mean (SD) age of 55.8 (6.1) years who did not use glucose-lowering medication. While blood alpha-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (alpha-TLHQ-SO3/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher alpha-TLHQ-SO3 was associated with 0.92 (95% CI: 0.87, 0.97) fold lower HOMA-IR and 1.06 (1.01, 1.11) fold higher Matsuda index, respectively. Similar results were obtained for the urinary alpha-TLHQ to alpha-CEHC ratio as a measure of oxidized-over-enzymatic conversion of alpha-TOH. Conclusion: Higher urinary levels of oxidized alpha-TOH metabolites as well as higher oxidized-to-enzymatic alpha-TOH metabolite ratio, but not circulating alpha-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating alpha-TOH, estimates of the conversion of alpha-TOH might be informative in relation to health and disease. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ Show less
Silva, S.L. da; Vellas, B.; Elemans, S.; Luchsinger, J.; Kamphuis, P.; Yaffe, K.; ... ; Stijnen, T. 2014
