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IUBMB Life Apr 2019Vitamin E is an essential nutrient that was discovered in the 1920s. Many of the physiological functions of vitamin E, including its antioxidative effects, have been... (Review)
Review
Vitamin E is an essential nutrient that was discovered in the 1920s. Many of the physiological functions of vitamin E, including its antioxidative effects, have been studied for nearly 100 years. Changes in redox balance induced by both endogenously and exogenously generated reactive oxygen species (ROS) are involved in various diseases, and are also a phenomenon that is considered essential for survival. Vitamin E is known to regulate redox balance in the body due to its high concentration among the lipid soluble vitamin groups, and exists ubiquitously in the whole body, including cell membranes and lipoproteins. However, it has been reported that the beneficial properties of vitamin E, including its antioxidative effects, are only displayed in vitro, and not in vivo. Therefore, there exists an ongoing debate regarding the biological functions of vitamin E and its relationship with redox balance. In this review, we introduce the relationship between vitamin E and redox interactions with (i) absorption, distribution, metabolism, and excretion of vitamin E, (ii) oxidative stress and ROS in the body, (iii) mechanism of antioxidative effects, (iv) non-antioxidant functions of vitamin E, and (v) recent recognition of the field of oxidative stress research. Understanding the recent findings of the redox interaction of vitamin E may help to elucidate the different antioxidative phenomena observed for vitamin E in vitro and in vivo. © 2019 IUBMB Life, 71(4):430-441, 2019.
Topics: Antioxidants; Humans; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Vitamin E
PubMed: 30681767
DOI: 10.1002/iub.2008 -
Nutrients Nov 2018Vitamin E is a fat-soluble antioxidant that can protect the polyunsaturated fatty acids (PUFAs) in the membrane from oxidation, regulate the production of reactive... (Review)
Review
Vitamin E is a fat-soluble antioxidant that can protect the polyunsaturated fatty acids (PUFAs) in the membrane from oxidation, regulate the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and modulate signal transduction. Immunomodulatory effects of vitamin E have been observed in animal and human models under normal and disease conditions. With advances in understating of the development, function, and regulation of dendritic cells (DCs), macrophages, natural killer (NK) cells, T cells, and B cells, recent studies have focused on vitamin E's effects on specific immune cells. This review will summarize the immunological changes observed with vitamin E intervention in animals and humans, and then describe the cell-specific effects of vitamin E in order to understand the mechanisms of immunomodulation and implications of vitamin E for immunological diseases.
Topics: Animals; Antioxidants; Humans; Immunity, Cellular; Vitamin E
PubMed: 30388871
DOI: 10.3390/nu10111614 -
International Journal of Nanomedicine 2020Vitamin E belongs to the family of lipid-soluble vitamins and can be divided into two groups, tocopherols and tocotrienols, with four isomers (alpha, beta, gamma and... (Review)
Review
Vitamin E belongs to the family of lipid-soluble vitamins and can be divided into two groups, tocopherols and tocotrienols, with four isomers (alpha, beta, gamma and delta). Although vitamin E is widely known as a potent antioxidant, studies have also revealed that vitamin E possesses anti-inflammatory properties. These crucial properties of vitamin E are beneficial in various aspects of health, especially in neuroprotection and cardiovascular, skin and bone health. However, the poor bioavailability of vitamin E, especially tocotrienols, remains a great limitation for clinical applications. Recently, nanoformulations that include nanovesicles, solid-lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and polymeric nanoparticles have shown promising outcomes in improving the efficacy and bioavailability of vitamin E. This review focuses on the pharmacological properties and pharmacokinetics of vitamin E and current advances in vitamin E nanoformulations for future clinical applications. The limitations and future recommendations are also discussed in this review.
Topics: Biological Availability; Drug Compounding; Humans; Nanostructures; Vitamin E
PubMed: 33324057
DOI: 10.2147/IJN.S276355 -
Molecular Carcinogenesis Apr 2020α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of... (Review)
Review
α-Tocopherol (α-T) is the major form of vitamin E (VE) in animals and has the highest activity in carrying out the essential antioxidant functions of VE. Because of the involvement of oxidative stress in carcinogenesis, the cancer prevention activity of α-T has been studied extensively. Lower VE intake or nutritional status has been shown to be associated with increased cancer risk, and supplementation of α-T to populations with VE insufficiency has shown beneficial effects in lowering the cancer risk in some intervention studies. However, several large intervention studies with α-T conducted in North America have not demonstrated a cancer prevention effect. More recent studies have centered on the γ- and δ-forms of tocopherols and tocotrienols (T3). In comparison with α-T, these forms have much lower systemic bioavailability but have shown stronger cancer-preventive activities in many studies in animal models and cell lines. γ-T3 and δ-T3 generally have even higher activities than γ-T and δ-T. In this article, we review recent results from human and laboratory studies on the cancer-preventive activities of different forms of tocopherols and tocotrienols, at nutritional and pharmacological levels. We aim to elucidate the possible mechanisms of the preventive actions and discuss the possible application of the available information for human cancer prevention by different VE forms.
Topics: Animals; Antioxidants; Carcinogenesis; Dietary Supplements; Humans; Neoplasms; Oxidation-Reduction; Oxidative Stress; Tocopherols; Vitamin E
PubMed: 32017273
DOI: 10.1002/mc.23160 -
IUBMB Life Apr 2019Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality, all around the world. Vitamin E is an important nutrient influencing key cellular and... (Review)
Review
Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality, all around the world. Vitamin E is an important nutrient influencing key cellular and molecular mechanisms as well as gene expression regulation centrally involved in the prevention of CVD. Cell culture and animal studies have focused on the identification of vitamin E regulated signaling pathways and involvement on inflammation, lipid homeostasis, and atherosclerotic plaque stability. While some of these vitamin E functions were verified in clinical trials, some of the positive effects were not translated into beneficial outcomes in epidemiological studies. In recent years, the physiological metabolites of vitamin E, including the liver derived (long- and short-chain) metabolites and phosphorylated (α-, γ-tocopheryl phosphate) forms, have also provided novel mechanistic insight into CVD regulation that expands beyond the vitamin E precursor. It is certain that this emerging insight into the molecular and cellular action of vitamin E will help to design further studies, either in animal models or clinical trials, on the reduction of risk for CVDs. This review focuses on vitamin E-mediated preventive cardiovascular effects and discusses novel insights into the biology and mechanism of action of vitamin E metabolites in CVD. © 2019 IUBMB Life, 71(4):507-515, 2019.
Topics: Animals; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cardiovascular System; Humans; Vitamin E
PubMed: 30779288
DOI: 10.1002/iub.2020 -
IUBMB Life Apr 2019Vitamin E, a potent lipid-soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients...
Vitamin E, a potent lipid-soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients known to modulate immune function. Vitamin E deficiency has been demonstrated to impair normal functions of the immune system in animals and humans, which can be corrected by vitamin E repletion. Although deficiency is rare, vitamin E supplementation above current dietary recommendations has been shown to enhance the function of the immune system and reduce risk of infection, particularly in older individuals. The mechanisms responsible for the effect of vitamin E on the immune system and inflammation have been explored in cell-based, pre-clinical and clinical intervention studies. Vitamin E modulates T cell function through directly impacting T cell membrane integrity, signal transduction, and cell division, and also indirectly by affecting inflammatory mediators generated from other immune cells. Modulation of immune function by vitamin E has clinical relevance as it affects host susceptibility to infectious diseases such as respiratory infections, in addition to allergic diseases such as asthma. Studies examining the role of vitamin E in the immune system have typically focused on α-tocopherol; however, emerging evidence suggests that other forms of vitamin E, including other tocopherols as well as tocotrienols, may also have potent immunomodulatory functions. Future research should continue to identify and confirm the optimal doses for individuals at different life stage, health condition, nutritional status, and genetic heterogeneity. Future research should also characterize the effects of non-α-alpha-tocopherol vitamin E on immune cell function as well as their potential clinical application. © 2018 IUBMB Life, 71(4):487-494, 2019.
Topics: Animals; Asthma; Cell Membrane; Humans; Immune System; Inflammation; Pneumonia; Signal Transduction; Vitamin E
PubMed: 30501009
DOI: 10.1002/iub.1976 -
Free Radical Biology & Medicine Jul 2014The vitamin E family consists of four tocopherols and four tocotrienols. α-Tocopherol (αT) is the predominant form of vitamin E in tissues and its deficiency leads to... (Review)
Review
The vitamin E family consists of four tocopherols and four tocotrienols. α-Tocopherol (αT) is the predominant form of vitamin E in tissues and its deficiency leads to ataxia in humans. However, results from many clinical studies do not support a protective role of αT in disease prevention in people with adequate nutrient status. On the other hand, recent mechanistic studies indicate that other forms of vitamin E, such as γ-tocopherol (γT), δ-tocopherol, and γ-tocotrienol, have unique antioxidant and anti-inflammatory properties that are superior to those of αT in prevention and therapy against chronic diseases. These vitamin E forms scavenge reactive nitrogen species, inhibit cyclooxygenase- and 5-lipoxygenase-catalyzed eicosanoids, and suppress proinflammatory signaling such as NF-κB and STAT3/6. Unlike αT, other vitamin E forms are significantly metabolized to carboxychromanols via cytochrome P450-initiated side-chain ω-oxidation. Long-chain carboxychromanols, especially 13'-carboxychromanols, are shown to have stronger anti-inflammatory effects than unmetabolized vitamins and may therefore contribute to the beneficial effects of vitamin E forms in vivo. Consistent with mechanistic findings, animal and human studies show that γT and tocotrienols may be useful against inflammation-associated diseases. This review focuses on non-αT forms of vitamin E with respect to their metabolism, anti-inflammatory effects and mechanisms, and in vivo efficacy in preclinical models as well as human clinical intervention studies.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Humans; Vitamin E
PubMed: 24704972
DOI: 10.1016/j.freeradbiomed.2014.03.035 -
Nutrients May 2022Vitamin E deficiency (VED) is associated with clinical repercussions in preterm newborns (PTN), but low levels are also found in full-term newborns (TN). As this... (Review)
Review
Vitamin E deficiency (VED) is associated with clinical repercussions in preterm newborns (PTN), but low levels are also found in full-term newborns (TN). As this inadequacy can compromise neurogenesis in childhood, studies are needed to assess whether there is a difference in vitamin E status among newborns according to gestational age to provide support for neonatal monitoring protocols. This systematic review presents a synthesis of the available information on the vitamin E status among PTN and TN. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Observational studies that evaluated alpha-tocopherol levels were searched in the databases reported in the protocol registered in PROSPERO (CRD42021165152). The Newcastle-Ottawa Scale was used to assess the methodological quality. Overall, 1809 articles were retrieved; 10 were included in the systematic review. In the PTN, the alpha-tocopherol levels ranged from 3.9 to 8.5 mmol/L, while in TN, they were 4.9 to 14.9 mmol/L, and VED ranged from 19% to 100% in newborns. Despite substantial heterogeneity in research methodology and VED classification, the results suggest that the alpha-tocopherol levels among preterm and full-term newborns is below the recommended levels. Our findings demonstrate that further investigations are needed to standardize this classification and to monitor vitamin E status in birth and postnatal with adequate bias control.
Topics: Gestational Age; Humans; Infant; Infant, Newborn; Vitamin E; Vitamin E Deficiency; alpha-Tocopherol
PubMed: 35684057
DOI: 10.3390/nu14112257 -
Free Radical Biology & Medicine Feb 2022Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of...
Asthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of allergy early in life and modify responses to allergen after allergen sensitization. Seemingly varied outcomes from vitamin E are consistent with the differential functions of the isoforms of vitamin E. Mechanistic studies demonstrate that the vitamin E isoforms α-tocopherol and γ-tocopherol have opposite functions in regulation of allergic inflammation and development of allergic disease, with α-tocopherol having anti-inflammatory functions and γ-tocopherol having pro-inflammatory functions in allergy and asthma. Moreover, global differences in prevalence of asthma by country may be a result, at least in part, of differences in consumption of these two isoforms of tocopherols. It is critical in clinical and animal studies that measurements of the isoforms of tocopherols be determined in vehicles for the treatments, and in the plasma and/or tissues before and after intervention. As allergic inflammation is modifiable by tocopherol isoforms, differential regulation by tocopherol isoforms provide a foundation for development of interventions to improve lung function in disease and raise the possibility of early life dietary interventions to limit the development of lung disease.
Topics: Animals; Asthma; Hypersensitivity; Tocopherols; Vitamin E; alpha-Tocopherol; gamma-Tocopherol
PubMed: 34785320
DOI: 10.1016/j.freeradbiomed.2021.10.037 -
IUBMB Life Apr 2019Although vitamin E has been recognized as a critical micronutrient to neuronal health for more than half a century, vitamin E transport and regulation in the brain... (Review)
Review
Although vitamin E has been recognized as a critical micronutrient to neuronal health for more than half a century, vitamin E transport and regulation in the brain remain a mystery. Currently, the majority of what is known about vitamin E transport has been delineated in the liver. However, clues from the pathogenesis of neurological-related vitamin E deficient diseases point to compromised neuronal integrity and function, underlining the critical need to understand vitamin E regulation in the CNS. Additionally, most of the same molecular players involved in vitamin E transport in the liver are also found in CNS, including sterol SRB1, TTP, and ABCA/ABCG, suggesting similar intracellular pathways between these organ systems. Finally, based on chemical similarities, intracellular CNS shuttling of vitamin E likely resembles cholesterol's use of ApoE particles. Utilizing this information, this review will address what is currently known about trafficking vitamin E across the blood brain barrier in order to ensure an adequate supply of the essential nutrient to the brain. Although debatable, the health of the brain in relation to vitamin E levels has been demonstrated, most notably in oxidative stress-related conditions such as ataxias, Alzheimer's disease, and Parkinson's disease. Future vitamin E research is vital in understanding how the regulation of the vitamin can aid in the prevention, treatment, and curing of neurological diseases. © 2018 IUBMB Life, 71(4):424-429, 2019.
Topics: Animals; Biological Transport; Blood-Brain Barrier; Brain; Carrier Proteins; Central Nervous System; Humans; Mice; Vitamin E; Vitamin E Deficiency; alpha-Tocopherol
PubMed: 30556640
DOI: 10.1002/iub.1993