Current evidence of the role of vitamin E in prolonging a healthy life

This is a narrative review of the evidence of α-tocopherol importance in human health, especially with regards to its vitamin role. α-Tocopherol is a potent peroxyl radical scavenger, and this role is prominent in its efficacy in maintaining the metabolic health of tissues. Vitamin E deficiency is discussed as a tool to understand the impact of α-tocopherol’s absence promoting increased lipid peroxidation and polyunsaturated fatty acid depletion. Downstream deficiency consequences include impacts on choline and one-carbon metabolism, glucose and energy metabolism, and their interactions with critical thiols, such as glutathione. Importantly, human vitamin E deficiency, caused by genetic defects in the α-tocopherol transfer protein (α-TTP), provides important clues for the necessity of α-tocopherol for the peripheral nervous system. Moreover, α-TTP expression in the liver, brain, eyes, and placenta illustrates that these tissues are especially vulnerable and require this specific α-tocopherol delivery mechanism for their protection. Although clinical trial evidence is limited and equivocal about the health benefits of vitamin E supplements, there is epidemiologic evidence of the long-term benefits of increased α-tocopherol intakes in ’healthy’ diets (high in vegetables and fruits, fish, nuts, and seeds, as well as fiber). Significance statement The elaborate regulation of α-tocopherol concentrations by the human body suggests that the consistent consumption of the recommended amounts of dietary α-tocopherol (15 mg) over a lifetime are protective of the at-risk tissues, as well as providing protection from chronic diseases

α-Tocopherol disappearance rates from plasma depend on lipid concentrations: studies using deuterium-labeled collard greens in younger and older adults

BACKGROUND: Little is known about α-tocopherol’s bioavailability as a constituent of food or its dependence on a subject’s age. OBJECTIVE: To evaluate the α-tocopherol bioavailability from food, we used collard greens grown in deuterated water (²H collard greens) as a source of deuterium-labeled (²H) α-tocopherol consumed by younger and older adults in a post hoc analysis of a vitamin K study. DESIGN: Younger (mean ± SD age: 32 ± 7 y; n = 12 women and 9 men) and older (aged 67 ± 8 y; n = 8 women and 12 men) adults consumed a test breakfast that included 120 g ²H collard greens (1.2 ± 0.1 mg ²H-α-tocopherol). Plasma unlabeled α-tocopherol and ²H-α-tocopherol were measured by using liquid chromatography–mass spectrometry from fasting (>12 h) blood samples drawn before breakfast (0 h) and at 24, 48, and 72 h and from postprandial samples collected at 4, 5, 6, 7, 9, 12, and 16 h. RESULTS: Times (12.6 ± 2.5 h) of maximum plasma ²H-α-tocopherol concentrations (0.82% ± 0.59% total α-tocopherol), fractional disappearance rates (0.63 ± 0.26 pools/d), half-lives (30 ± 11 h), and the minimum estimated ²H-α-tocopherol absorbed (24% ± 16%) did not vary between age groups or sexes (n = 41). Unlabeled α-tocopherol concentrations were higher in older adults (26.4 ± 8.6 μmol/L) than in younger adults (19.3 ± 4.2 μmol/L; P = 0.0019) and correlated with serum lipids (r = 0.4938, P = 0.0012). In addition, ²H-α-tocopherol half-lives were correlated with lipids (r = 0.4361, P = 0.0044). CONCLUSIONS: Paradoxically, α-tocopherol remained in circulation longer in participants with higher serum lipids, but the ²H-α-tocopherol absorbed was not dependent on the plasma lipid status. Neither variable was dependent on age. These data suggest that plasma α-tocopherol concentrations are more dependent on mechanisms that control circulating lipids rather than those related to its absorption and initial incorporation into plasma. This trial was registered at clinicaltrials.gov as NCT0036232.Keywords: cholesterol, pharmacokinetics, age, bioavailability, vitamin E, triacylglyceride

A Metabolomic Analysis of Omega-3 Fatty Acid-Mediated Attenuation of Western Diet-Induced Nonalcoholic Steatohepatitis in LDLR[superscript -/-] Mice

Background: Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease and a risk factor for cirrhosis, hepatocellular carcinoma and liver failure. Previously, we reported that dietary docosahexaenoic acid (DHA, 22:6,n-3) was more effective than eicosapentaenoic acid (EPA, 20:5,n-3) at reversing western diet (WD) induced NASH in LDLR-/- mice. Methods: Using livers from our previous study, we carried out a global non-targeted metabolomic approach to quantify diet-induced changes in hepatic metabolism. Results: Livers from WD + olive oil (WD + O)-fed mice displayed histological and gene expression features consistent with NASH. The metabolomic analysis of 320 metabolites established that the WD and n-3 polyunsaturated fatty acid (PUFA) supplementation had broad effects on all major metabolic pathways. Livers from WD + O-fed mice were enriched in saturated (SFA) and monounsaturated fatty acids (MUFA), palmitoylsphingomyelin, cholesterol, n-6 PUFA, n-6 PUFA-containing phosphoglycerolipids, n-6 PUFA-derived oxidized lipids (12-HETE) and depleted of C20-22 n-3 PUFA-containing phosphoglycerolipids, C20-22 n-3 PUFA-derived oxidized lipids (18-HEPE, 17,18-DiHETE) and S-lactoylglutathione, a methylglyoxal detoxification product. WD + DHA was more effective than WD + EPA at attenuating WD + O-induced changes in NASH gene expression markers, n-6 PUFA and oxidized lipids, citrate and S-lactosyl glutathione. Diet-induced changes in hepatic MUFA and sphingolipid content were associated with changes in expression of enzymes involved in MUFA and sphingolipid synthesis. Changes in hepatic oxidized fatty acids and S-lactoylglutathione, however, correlated with hepatic n-3 and n-6 C20-22 PUFA content. Hepatic C20-22 n-3 PUFA content was inversely associated with hepatic α-tocopherol and ascorbate content and positively associated with urinary F2- and F3-isoprostanes, revealing diet effects on whole body oxidative stress. Conclusion: DHA regulation of hepatic SFA, MUFA, PUFA, sphingomyelin, PUFA-derived oxidized lipids and Slactoylglutathione may explain the protective effects of DHA against WD-induced NASH in LDLR-/- mice

Novel liquid chromatography–mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos

To test the hypothesis that embryogenesis depends upon α-tocopherol (E) to protect embryo polyunsaturated fatty acids (PUFAs) from lipid peroxidation, new methodologies were applied to measure α-tocopherol and fatty acids in extracts from saponified zebrafish embryos. A solid phase extraction method was developed to separate the analyte classes, using a mixed mode cartridge (reverse phase, π–π bonding, strong anion exchange), then α-tocopherol and cholesterol were measured using standard techniques, while the fatty acids were quantitated using a novel, reverse phase liquid chromatography–mass spectrometry (LC–MS) approach. We also determined if α-tocopherol status alters embryonic lipid peroxidation products by analyzing 24 different oxidized products of arachidonic or docosahexaenoic (DHA) acids in embryos using LC with hybrid quadrupole-time of flight MS. Adult zebrafish were fed E- or E+ diets for 4 months, and then were spawned to obtain E- and E+ embryos. Between 24 and 72 hours post-fertilization (hpf), arachidonic acid decreased 3-times faster in E- (21 pg/h) compared with E+ embryos (7 pg/h, P<0.0001), while both α-tocopherol and DHA concentrations decreased only in E- embryos. At 36 hpf, E- embryos contained double the 5-hydroxy-eicosatetraenoic acids and 7-hydroxy-DHA concentrations, while other hydroxy-lipids remained unchanged. Vitamin E deficiency during embryogenesis depleted DHA and arachidonic acid, and increased hydroxy-fatty acids derived from these PUFA, suggesting that α-tocopherol is necessary to protect these critical fatty acids.KEYWORDS: Embryogenesis, Neurogenesis, Hybrid quadrupole-time of flight MS, Arachidonic acid, Vitamin EThis is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Elsevier. The published article can be found at: http://www.journals.elsevier.com/redox-biolog

The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome

Metabolic syndrome (MetS) is a constellation of cardiometabolic risk factors, which together predict increased risk of more serious chronic diseases. We propose that one consequence of dietary overnutrition is increased abundance of Gram-negative bacteria in the gut that cause increased inflammation, impaired gut function, and endotoxemia that further dysregulate the already compromised antioxidant vitamin status in MetS. This discussion is timely because “healthy” individuals are no longer the societal norm and specialized dietary requirements are needed for the growing prevalence of MetS. Further, these lines of evidence provide the foundational basis for investigation that poor vitamin C status promotes endotoxemia, leading to metabolic dysfunction that impairs vitamin E trafficking through a mechanism involving the gut-liver axis. This report will establish a critical need for translational research aimed at validating therapeutic approaches to manage endotoxemia—an early, but inflammation-inducing phenomenon, which not only occurs in MetS, but is also prognostic of more advanced metabolic disorders including type 2 diabetes mellitus, as well as the increasing severity of nonalcoholic fatty liver diseases