Urinary oxidized, but not enzymatic vitamin E metabolites are inversely associated with measures of glucose homeostasis in middle-aged healthy individuals

Jiao Luo,Fleur L Meulmeester,Leon G Martens,Nadia Ashrafi,Renée De Mutsert,Dennis O Mook-Kanamori,Frits R Rosendaal,Ko Willems Van Dijk,Saskia Le Cessie,Kevin Mills,Raymond Noordam,Diana Van Heemst

doi:10.1016/j.clnu.2021.01.039

Abstract

Damage induced by lipid peroxidation has been associated with impaired glucose homeostasis. Vitamin E (α-tocopherol, α-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 α-TOH metabolites (oxidized and enzymatic) in both circulation and urine and measures of glucose homeostasis in the general middle-aged population. This cross-sectional study was embedded in the population-based Netherlands Epidemiology of Obesity (NEO) Study. α-TOH metabolites in blood (α-TOH and α-CEHC-SO3) and urine [sulfate (SO3) and glucuronide (GLU) of both α-TLHQ (oxidized) and α-CEHC (enzymatic)] were quantified by liquid chromatography coupled with tandem mass spectrometry (LC/MS-MS). 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 α-TOH metabolites and measures of glucose homeostasis. 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 α-TOH was not associated with measures of glucose homeostasis, urinary oxidized metabolites (α-TLHQ-SO3/GLU) were associated with HOMA-IR and Matsuda index. For example, a one-SD higher α-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 α-TLHQ to α-CEHC ratio as a measure of oxidized-over-enzymatic conversion of α-TOH. Higher urinary levels of oxidized α-TOH metabolites as well as higher oxidized-to-enzymatic α-TOH metabolite ratio, but not circulating α-TOH or enzymatic metabolites, were associated with lower insulin resistance. Rather than circulating α-TOH, estimates of the conversion of α-TOH might be informative in relation to health and disease.

Highlights

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease, characterized by synovial hyperplasia, production of autoantibodies, destruction of cartilage and bone, and malformation and destruction of multiple joints [1]
The aim of this review is to evaluate the evidence to date regarding the ideal dietary approach for the management of RA in order to reduce oxidative stress, counteract inflammation and alteration in immune system, and to construct a food pyramid for patients with RA
This research was conducted based on the keywords: “Rheumatoid Arthritis” AND “Energy intake” AND “Body Mass Index” AND “Body composition” AND “Physical Activity”; 28 articles were sourced: 6 caseecontrol studies, 4 observational study, 2 cohort studies, 1 position paper, 4 narrative reviews, 2 meta-analysis, 1 systematic review, 2 systematic reviews & meta-analysis, 2 guidelines, 1 1ongitudinal study, 1 cross-sectional study, 1 in vitro study and 1 comment on an article

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease, characterized by synovial hyperplasia, production of autoantibodies, destruction of cartilage and bone, and malformation and destruction of multiple joints [1]. The pathogenesis of RA is complicated and involves both genetic and external factors [2]. Similar to other autoimmune diseases, RA involves an aberrant pathway of T cell activation in both the initial and progression phases of the disease [3]. It has become clear that pathogenesis of RA cannot be explained in terms of a classical antigen-driven expansion of effector T cells, but that disease progression involves a more complex autoimmune response. It is largely accepted that RA is closely associated with CD4þ T effector cells (both Th-1, 2, 17) which can be detected in RA synovial joints [4]. Patients with RA have a premature immune aging phenotype including accumulation of CD4þ CD28À T cells, telomeric shortening in hematopoietic stem cells, proliferation defects of naïve CD4 T cells, premature loss of naïve CD4 T cells telomeres, loss of telomerase in T cells, and impaired DNA damage repair due to ATM insufficiency [5]

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