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Vitamin E: Function and Metabolism
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Vitamin E: Function and Metabolism

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 21727

Special Issue Editor

Dr. Manfred L. Eggersdorfer

E-Mail Website
Guest Editor
Department of Internal Medicine, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
Interests: micronutrients; nutrient intake and status; biomarker; impact of inadequate intake on health; healthy ageing

Special Issue Information

Dear Colleagues,

Vitamin E is a fat-soluble vitamin with several forms, but alpha-tocopherol is the only one used by the human body. Its main role is to act as an antioxidant, scavenging loose electrons—so-called “free radicals”—that can damage cells. Free radicals form as a result of normal body processes. They cause damage that shortens the life of your cells. Vitamin E is a powerful antioxidant that may help reduce free radical damage and slow the aging process of cells. Its deficiency is associated with ataxia, neuropathy, anaemia and several other health conditions.

Vitamin E is considered the most important fat-soluble antioxidant of cellular membranes and circulating lipoproteins, with important applications in prevention and adjuvant treatment of some chronic and degenerative diseases, such as atherosclerosis, Alzheimer’s disease, neuroinflammation and neurotoxicity associated with epilepsy. In addition to its antioxidant function, vitamin E and its related long-chain metabolites are PXR agonists with the dimethyl configurations of the chroman ring as the most active ones. PXR is a nuclear receptor involved in the modulation of metabolic enzymes and transporters in the metabolism of xenobiotics and endobiotics such as steroids and β-amyloid peptides that are associated with the pathogenesis of Alzheimer’s disease. These metabolites also exhibit potential anti-inflammatory effects, inhibiting COXs and 5-LOX. 5-LOX is responsible for the production of leukotrienes which are potent proinflammatory mediators involved in DNA oxidative damage, allergic and autoimmune reactions, and several pathophysiological conditions such as cardiovascular and liver diseases, neurodegeneration and cancer.

This Special Issue examines in detail, and provides an update on, the molecular targets, protective effects and modes of action of vitamin E and its metabolites, as well as their roles in prevention and treatment of human diseases both in preclinical animal models and clinical trials.

 

Dr. Manfred Eggersdorfer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Tocopherol status
  • Vitamin E deficiency
  • Vitamin E prevalence
  • Vitamin E status
  • Fat-soluble vitamin
  • Free radicals
  • Metabolites

Published Papers (5 papers)

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Research

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18 pages, 5271 KiB  
Article
Effects of Gamma-Tocotrienol on Intestinal Injury in a GI-Specific Acute Radiation Syndrome Model in Nonhuman Primate
by Sarita Garg, Tarun K. Garg, Stephen Y. Wise, Oluseyi O. Fatanmi, Isabelle R. Miousse, Alena V. Savenka, Alexei G. Basnakian, Vijay K. Singh and Martin Hauer-Jensen
Int. J. Mol. Sci. 2022, 23(9), 4643; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094643 - 22 Apr 2022
Cited by 14 | Viewed by 1799
Abstract
The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated [...] Read more.
The gastrointestinal (GI) system is highly susceptible to irradiation. Currently, there is no Food and Drug Administration (FDA)-approved medical countermeasures for GI radiation injury. The vitamin E analog gamma-tocotrienol (GT3) is a promising radioprotector in mice and nonhuman primates (NHP). We evaluated GT3-mediated GI recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques were divided into two groups; eight received vehicle and eight GT3 24 h prior to 12 Gy TBI. Proximal jejunum was assessed for structural injuries and crypt survival on day 4 and 7. Apoptotic cell death and crypt cell proliferation were assessed with TUNEL and Ki-67 immunostaining. Irradiation induced significant shortening of the villi and reduced mucosal surface area. GT3 induced an increase in crypt depth at day 7, suggesting that more stem cells survived and proliferated after irradiation. GT3 did not influence crypt survival after irradiation. GT3 treatment caused a significant decline in TUNEL-positive cells at both day 4 (p < 0.03) and 7 (p < 0.0003). Importantly, GT3 induced a significant increase in Ki-67-positive cells at day 7 (p < 0.05). These data suggest that GT3 has radioprotective function in intestinal epithelial and crypt cells. GT3 should be further explored as a prophylactic medical countermeasure for radiation-induced GI injury. Full article
(This article belongs to the Special Issue Vitamin E: Function and Metabolism)
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12 pages, 2391 KiB  
Article
A Redox-Silent Analogue of Tocotrienol May Break the Homeostasis of Proteasomes in Human Malignant Mesothelioma Cells by Inhibiting STAT3 and NRF1
by Kyota Ishii, Momoka Fusegi, Tatsuki Mori, Kosuke Teshima, Nanako Ninomiya, Kakeru Kohno, Ayami Sato, Tatsuya Ishida, Yuichi Miyakoshi and Tomohiro Yano
Int. J. Mol. Sci. 2022, 23(5), 2655; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052655 - 28 Feb 2022
Cited by 4 | Viewed by 1871
Abstract
6-O-Carboxypropyl-alpha-tocotrienol (α-T3E) is a multi-target redox-silent analogue of tocotrienol that exhibits cytotoxicity against many cancer cells, including malignant mesothelioma (MM) cells. α-T3E has several molecular targets to effectively induce cytotoxicity against MM cells; however, the mechanisms underlying this cytotoxicity remain unclear. [...] Read more.
6-O-Carboxypropyl-alpha-tocotrienol (α-T3E) is a multi-target redox-silent analogue of tocotrienol that exhibits cytotoxicity against many cancer cells, including malignant mesothelioma (MM) cells. α-T3E has several molecular targets to effectively induce cytotoxicity against MM cells; however, the mechanisms underlying this cytotoxicity remain unclear. In the present study, we demonstrated that the α-T3E-dependent disruption of the homeostasis of proteasomes strongly induced endoplasmic reticulum (ER) stress, which resulted in effective cytotoxicity against MM cells. The α-T3E-dependent disruption of the homeostasis of proteasomes depended on decreases in proteasome subunits via the inactivation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid 2 related factor-1 (NRF1), which inhibited protease activity, such as chymotrypsin-like activity, in proteasomes. The α-T3E-dependent inhibition of this activity also induced severe ER stress and ultimately resulted in effective cytotoxicity against MM cells with chemoresistance. The present results indicate that α-T3E acts as an effective anti-mesothelioma agent by disrupting the homeostasis of proteasomes through the simultaneous inactivation of STAT3 and NRF1. Full article
(This article belongs to the Special Issue Vitamin E: Function and Metabolism)
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Review

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13 pages, 999 KiB  
Review
Beneficial Effects of Vitamin E Supplementation on Endothelial Dysfunction, Inflammation, and Oxidative Stress Biomarkers in Patients Receiving Hemodialysis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Thi Thuy Uyen Nguyen, Ji-hyun Yeom and Won Kim
Int. J. Mol. Sci. 2021, 22(21), 11923; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111923 - 03 Nov 2021
Cited by 12 | Viewed by 2738
Abstract
Inflammation and oxidative stress are closely related to cardiovascular complications and atherosclerosis, and have the potential to lead to an increase in death in patients receiving hemodialysis. Vitamin E has antioxidant and anti-inflammatory properties. We conducted a systematic review and meta-analysis to assess [...] Read more.
Inflammation and oxidative stress are closely related to cardiovascular complications and atherosclerosis, and have the potential to lead to an increase in death in patients receiving hemodialysis. Vitamin E has antioxidant and anti-inflammatory properties. We conducted a systematic review and meta-analysis to assess the effects of vitamin E supplementation on endothelial dysfunction, inflammation, and oxidative stress biomarkers in adult patients receiving hemodialysis. We searched the MEDLINE, EMBASE, Web of Science, and Cochrane Library databases and identified randomized controlled trials of adult patients receiving hemodialysis until 30 August 2021. A total of 11 trials with 491 randomized patients were included. The pooled data indicated that vitamin E supplementation significantly decreased intercellular adhesion molecule-1 [standardized mean difference (SMD): −1.35; 95% confidence interval (CI): −2.57, −0.13; p = 0.03, I2 = 89%], vascular cell adhesion molecule-1 (SMD: −1.08; 95% CI: −2.05, −0.11; p = 0.03, I2 = 81%), C-reactive protein (SMD: −0.41; 95% CI: −0.75, −0.07; p = 0.02, I2 = 64%), and malondialdehyde (SMD: −0.76; 95% CI: −1.26, −0.25; p = 0.003, I2 = 77%) levels, but not interleukin-6 levels compared to those in the control group. Our results suggest that vitamin E supplementation may help alleviate oxidative stress and both vascular and systemic inflammation in patients receiving hemodialysis. Full article
(This article belongs to the Special Issue Vitamin E: Function and Metabolism)
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15 pages, 1201 KiB  
Review
Enjoy Carefully: The Multifaceted Role of Vitamin E in Neuro-Nutrition
by Liesa Regner-Nelke, Christopher Nelke, Christina B. Schroeter, Rainer Dziewas, Tobias Warnecke, Tobias Ruck and Sven G. Meuth
Int. J. Mol. Sci. 2021, 22(18), 10087; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810087 - 18 Sep 2021
Cited by 12 | Viewed by 3671
Abstract
Vitamin E is often associated with health benefits, such as antioxidant, anti-inflammatory and cholesterol-lowering effects. These properties make its supplementation a suitable therapeutic approach in neurodegenerative disorders, for example, Alzheimer’s or Parkinson’s disease. However, trials evaluating the effects of vitamin E supplementation are [...] Read more.
Vitamin E is often associated with health benefits, such as antioxidant, anti-inflammatory and cholesterol-lowering effects. These properties make its supplementation a suitable therapeutic approach in neurodegenerative disorders, for example, Alzheimer’s or Parkinson’s disease. However, trials evaluating the effects of vitamin E supplementation are inconsistent. In randomized controlled trials, the observed associations often cannot be substantiated. This could be due to the wide variety of study designs regarding the dosage and duration of vitamin E supplementation. Furthermore, genetic variants can influence vitamin E uptake and/or metabolism, thereby distorting its overall effect. Recent studies also show adverse effects of vitamin E supplementation regarding Alzheimer’s disease due to the increased synthesis of amyloid β. These diverse effects may underline the inhomogeneous outcomes associated with its supplementation and argue for a more thoughtful usage of vitamin E. Specifically, the genetic and nutritional profile should be taken into consideration to identify suitable candidates who will benefit from supplementation. In this review, we will provide an overview of the current knowledge of vitamin E supplementation in neurodegenerative disease and give an outlook on individualized, sustainable neuro-nutrition, with a focus on vitamin E supplementation. Full article
(This article belongs to the Special Issue Vitamin E: Function and Metabolism)
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17 pages, 1429 KiB  
Review
Tocopherols and Tocotrienols—Bioactive Dietary Compounds; What Is Certain, What Is Doubt?
by Kacper Szewczyk, Aleksandra Chojnacka and Magdalena Górnicka
Int. J. Mol. Sci. 2021, 22(12), 6222; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126222 - 09 Jun 2021
Cited by 84 | Viewed by 10496
Abstract
Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the [...] Read more.
Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers’ interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research. Full article
(This article belongs to the Special Issue Vitamin E: Function and Metabolism)
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