Role of Antioxidant Vitamins in Oral Submucous Fibrosis: A Narrative Review.

Oral submucous fibrosis (OSMF) has a high rate of malignant transformation and is an insidious chronic inflammatory disease. Though this disorder seems to be multifactorial in origin, betel quid chewing appears to be the main etiologic factor. Various treatment strategies have been attempted but none proven to cure the disorder because of its multimodal pathogenesis. Reactive oxygen species (ROS) appear to have a role in cancer formation. As OSMF is an oral premalignant disorder and found to be associated with carcinogens like areca nut and tobacco, it is believed to have some relationship with ROS. Tissue damage due to ROS along with other mechanisms may result in the complex pathophysiology of OSMF. The antioxidant system in the body helps to prevent damage caused by highly reactive ROS and helps in the repair of tissues. To study the levels of oxidative stress and antioxidant vitamins in OSMF condition, the present review was done. We carried out a thorough literature search to identify original reports and studies determining the status of oxidative stress and antioxidant vitamins in OSMF condition using several databases including Google Scholar, PubMed, and Scopus. Our review observed that the oxidative stress increased in the condition of OSMF as shown by an increase in malonaldehyde (MDA) and a decrease in antioxidant vitamins like vitamin A, vitamin C, and vitamin E. Also, after the intake of antioxidant vitamins, there was symptomatic improvement in OSMF patients. With the help of identifying oxidative stress and antioxidant status, we can assess the clinical stage of OSMF and can develop a comprehensive treatment plan.

Atypical retinopathy in ataxia with vitamin E deficiency: report of a sibship.

Typical retinitis pigmentosa (RP) may not be the only retinal phenotype encountered in ataxia with vitamin E deficiency (AVED). The following short case series describes a novel form of retinopathy in AVED. We describe two patients with AVED belonging to the same consanguineous sibship. Both presented an unusual retinopathy consisting of scattered, multifocal, nummular, hyperautofluorescent atrophic retinal patches. The retinopathy remained stable under vitamin E supplementation. We hypothesize these changes to be the result of arrested AVED-related RP following early supplementation with α-tocopherol acetate.

Serum Metabolic Characterization of Vitamin E Deficiency in Holstein Cows during the Transition Period Based on Proton Nuclear Magnetic Resonance Spectroscopy.

Vitamin E, a potent antioxidant, is a necessary and complex micronutrient for cows. During the transition period, vitamin E deficiency (VED) is among the highest prevalent micronutrient deficits in dairy cows. It may eventually result in oxidative stress and immunological malfunction, and it increases the risk of peripartum disorders. At present, detailed data on blood metabolites in VED cows are limited. Consequently, the purpose of this research was to examine the alterations in the serum metabolic profile of VED cows throughout the early postpartum period. Using comprehensive 1H nuclear magnetic resonance (1H NMR), the alterations in serum metabolic activities of VED cows were analyzed. In total, 28 multiparous Holstein cows were assigned according to serum α-tocopherol (α-Toc) concentrations into normal (α-Toc ≥ 4 µg/mL, n = 14) and VED (α-Toc < 3 µg/mL, n = 14) groups at 21 days postpartum, and their blood samples were collected for biochemical and 1H NMR analyses. A t-test on independent samples as well as multivariate statistics were used to assess the findings. In comparison with normal cows, VED cows showed significantly worse body condition scores, milk yield, and dry matter intake (p < 0.05). Significantly higher levels of serum non-esterified fatty acids, aspartate aminotransferase, low-density lipoprotein, and malonaldehyde were found in VED-affected cows, as well as lesser concentrations of serum albumin, high-density lipoprotein, and total antioxidant capacity in comparison with normal cows (p < 0.01), while other vitamins and minerals concentrations showed no distinction between the groups (p > 0.05). Furthermore, 24 upregulated serum metabolites were identified under VED conditions. The metabolomics pathway analysis of these metabolites demonstrated that a global metabolic response to VED in cows was represented by changes in 11 metabolic pathways, comprising energy, carbohydrate, and amino acid metabolism. From these results, we conclude that VED cows were more likely to experience a negative energy balance characterized by alterations of common systemic metabolic processes and develop oxidative stress, inflammation, and ultimately liver injury. This study provides the first evidence of metabolic changes in cows with VED.

Association Between Vitamin Deficiencies and Ophthalmological Conditions.

Vitamin deficiencies can have adverse effects on health, including on the visual system. The ocular manifestations of a vitamin deficiency are related to the underlying biochemical function of the particular nutrient. While vitamin deficiencies are not common in developed counties, they are still prevalent in parts of the developing world and in specific, vulnerable populations. Vitamin deficiencies can cause or contribute to many ophthalmological conditions and eye diseases may even be the first presenting finding of a vitamin deficiency. As such, it is important for ophthalmologists to be aware of the ocular manifestations of vitamin deficiencies, especially given that the complications can be severe and effectively treated if identified early. This review summarizes the literature on the main vitamins known to have characteristic ocular manifestations: vitamins A, B1, B2, B9, B12, C, D, E and K. The function, epidemiology, manifestations, workup, and management of each vitamin is discussed in detail.

Vitamin E and cardiovascular diseases: an interest to public health?

Cardiovascular diseases (CVD) are the leading cause of death worldwide. From this perspective, the role of vitamin E and its metabolites in preventing CVD has been studied, being supported by the findings that low vitamin E concentrations are associated with an increased risk of cardiovascular events. Despite this, no studies have analysed the co-existence of vitamin E deficiency (VED) and CVD on the basis of population studies. Facing that, this study summarises information on the relationship between vitamin E status and CVD, providing a basis for understanding the determining and protective factors for its development. VED may be a public health problem since it has been observed to vary from 0·6% to 55·5% worldwide, with higher percentages in Asia and Europe, where CVD mortality rates stand out. Intervention studies with α-tocopherol supplementation do not confirm cardioprotective action of vitamin E, which may reflect that α-tocopherol alone does not provide cardiovascular protection to individuals, but the consumption of all isomers found in food. Considering that low concentrations of α-tocopherol can lead to a higher susceptibility to diseases involving oxidative stress in the population, in addition to the high and growing prevalence of CVD and VED, it is essential to investigate or reinterpret the mechanisms of action of vitamin E and its metabolites in the cardiovascular process to better understand the co-existence of CVD and VED. It is also important to implement public health policies and programmes aimed at promoting the consumption of natural food sources of vitamin E and healthy fats.

Twendee X, a mixed antioxidant supplement, improves cognitive function, coordination, and neurotrophic factor expression in long-term vitamin E-deficient mice.

Oxidation products gradually accumulate during senescence, enhancing the risk of onset of many severe diseases. One such disease is dementia, and the number of cases of dementia, including Alzheimer's disease, has been increasing world-wide. These diseases can be prevented via attenuation of age-related physiological dysfunction; one preventive approach is the ingestion of antioxidants such as vitamin C and vitamin E. Many antioxidants are readily available commercially. Ingestion of mixed antioxidants is expected to provide further beneficial effects for human health. In this study, we used vitamin E-deficient mice as an animal model of increased oxidative stress and assessed the effects of dosing with mixed antioxidants. Administration of a commercial mixed antioxidant formula, Twendee X significantly improved cognitive function and coordination compared to untreated vitamin E-deficient animals. Furthermore, the levels of brain-derived neurotrophic factor and nerve growth factor were significantly increased in the cerebral cortex of Twendee X-dosed vitamin E-deficient mice compared to untreated animals. These results indicate that intake of a mixed antioxidant supplement may be beneficial to human health, even after oxidative stress has begun. In the next stage, it will be necessary to compare with other antioxidants and consider whether it is effective in the aged model.

The low prevalence rate of vitamin E deficiency in urban adults of Wuhan from central China: findings from a single-center, cross-sectional study.

BACKGROUND: Vitamin E is an essential nutrient in human body famous for its antioxidant and non-antioxidant functions. However, little is known about vitamin E deficiency status in urban adults of Wuhan from central China. Our aim is to describe the distribution of both circulating and lipid-adjusted serum vitamin E concentration in urban adults of Wuhan. METHODS: We hypothesized that the prevalence rate of vitamin E deficiency would be low in Wuhan in consideration of the Chinese food composition. A cross-sectional study with 846 adults was performed in a single-center. Concentrations of vitamin E were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: The median (interquartile range, IQR) of serum vitamin E concentration was 27.40 (22.89-33.20) µmol/L while that of serum vitamin E concentration adjusted by total cholesterol or the sum of cholesterol (TC) and triglyceride (TG) (the sum of cholesterol and triglyceride, TLs) were 6.20 (5.30-7.48) and 4.86 (4.10-5.65) mmol/mol, respectively. No significant difference of the circulating and TC-adjusted vitamin E concentration was found between male and female except for vitamin E/TLs. However, concentrations of vitamin E increased significantly (r = 0.137, P < 0.001) with age, but lipid-adjusted concentrations of vitamin E did not. On analysis of risk factors, the subjects characterized by hypercholesterolemia are more likely to exhibit higher circulating but lower lipid-adjusted vitamin E level due to adequacy of the serum carriers for delivery of vitamin E. Only 0.47% of the population were below 12 µmol/L of vitamin E defined as functional deficiency. CONCLUSION: The prevalence rate of vitamin E deficiency in urban adults of Wuhan is low, which is important and useful to clinicians for clinical decision-making in public health practice.

Clinical and genetic study of ataxia with vitamin E deficiency: A case report.

BACKGROUND: Ataxia with vitamin E deficiency (AVED) is a type of autosomal recessive cerebellar ataxia. Clinical manifestations include progressive cerebellar ataxia and movement disorders. TTPA gene mutations cause the disease. CASE SUMMARY: We report the case of a 32-year-old woman who presented with progressive cerebellar ataxia, dysarthria, dystonic tremors and a remarkably decreased serum vitamin E concentration. Brain magnetic resonance images showed that her brainstem and cerebellum were within normal limits. Acquired causes of ataxia were excluded. Whole exome sequencing subsequently identified a novel homozygous variant (c.473T>C, p.F158S) of the TPPA gene. Bioinformatic analysis predicted that F185S is harmful to protein function. After supplementing the patient with vitamin E 400 mg three times per day for 2 years, her symptoms remained stable. CONCLUSION: We identified an AVED patient caused by novel mutation in TTPA gene. Our findings widen the known TTPA gene mutation spectrum.

[Physiological Function and Congenital Deficiency of α-TTP, a Determinant of Vitamin E Transport in the Body -One Portion of the Research for Which the Pharmaceutical Society of Japan Award Was Given].

This review summarizes one portion of the research for which the author received the Pharmaceutical Society of Japan Award. The complete title of the awarded research is "Pharmacological Studies on Metabolism and Functions of Biomembrane Lipids". Because the awarded research is a very broad study, this review describes the discovery, physiological functions, and congenital defects of α-tocopherol transfer protein (α-TTP), a critical factor in determining the transport of vitamin E in the body, which has been the focus of the author's work throughout his research career.

Vitamin E Levels in Preterm and Full-Term Infants: A Systematic 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.

Deficiency of vitamins C and E in women of childbearing age in Brazil: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Despite the several options available for supplements containing vitamins C and E, evidence regarding the prevalence of deficiency or insufficiency of these vitamins is weak. OBJECTIVES: To estimate the prevalence of deficiency or insufficiency of vitamins C and E and associated factors among women of childbearing age, in Brazil. DESIGN AND SETTING: Systematic review and meta-analysis conducted at a Brazilian public university. METHODS: A search from index inception until May 2020 was conducted. Meta-analyses were performed using inverse variance for fixed models, with summary proportions calculation using Freeman-Tukey double arcsine (base case). Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. RESULTS: Our review identified 12 studies, comprising 1,316 participants, especially breastfeeding women. There was at least one quality weakness in all studies, mainly regarding sampling method (i.e. convenience sampling) and small sample size. The prevalence of vitamin C deficiency ranged from 0% to 40%. Only vitamin E deficiency was synthetized in meta-analyses, with mean prevalences of 6% regardless of the alpha-tocopherol cutoff in plasma, and 5% and 16% for cutoffs of < 1.6-12.0 mmol/l and < 16.2 mmol/l, respectively. The cumulative meta-analysis suggested that a trend to lower prevalence of vitamin E deficiency occurred in recent studies. CONCLUSIONS: Although the studies identified in this systematic review had poor methodological and reporting quality, mild-moderate vitamin C and E deficiencies were identified, especially in breastfeeding women. Thus, designing and implementing policies does not seem to be a priority, because the need has not been properly dimensioned among women of childbearing age in Brazil. REGISTRATION NUMBER IN PROSPERO: CRD42020221605.

Ataxia with vitamin E deficiency in the Philippines†: A case report of two siblings.

Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.

Vitamin E: How much is enough, too much and why!

α-Tocopherol (α-T) is a required dietary nutrient for humans and thus is a vitamin. This narrative review focuses on vitamin E structures, functions, biological determinants and its deficiency symptoms in humans. The mechanisms for the preferential α-T tissue enrichment in the human body include the α-T transfer protein (TTPA) and the preferential metabolism of non-α-T forms. Potential new α-T biomarkers, pharmacokinetic data, and whether there are better approaches to evaluate and set the α-T dietary requirement are discussed. Finally, the possible role of α-T supplements in delay of chronic diseases and the evaluation of vitamin E safety are considered.

α-Tocopherol transfer protein (α-TTP).

α-Tocopherol transfer protein (α-TTP) is so far the only known protein that specifically recognizes α-tocopherol (α-Toc), the most abundant and most biologically active form of vitamin E, in higher animals. α-TTP is highly expressed in the liver where α-TTP selects α-Toc among vitamin E forms taken up via plasma lipoproteins and promotes its secretion to circulating lipoproteins. Thus, α-TTP is a major determinant of plasma α-Toc concentrations. Familial vitamin E deficiency, also called Ataxia with vitamin E deficiency, is caused by mutations in the α-TTP gene. More than 20 different mutations have been found in the α-TTP gene worldwide, among which some missense mutations provided valuable clues to elucidate the molecular mechanisms underlying intracellular α-Toc transport. In hepatocytes, α-TTP catalyzes the vectorial transport of α-Toc from the endocytotic compartment to the plasma membrane (PM) by targeting phosphatidylinositol phosphates (PIPs) such as PI(4,5)P2. By binding PIPs at the PM, α-TTP opens the lid covering the hydrophobic pocket, thus facilitating the release of bound α-Toc to the PM.

Expanding role of vitamin E in protection against metabolic dysregulation: Insights gained from model systems, especially the developing nervous system of zebrafish embryos.

This review discusses why the embryo requires vitamin E (VitE) and shows that its lack causes metabolic dysregulation and impacts morphological changes at very early stages in development, which occur prior to when a woman knows she is pregnant. VitE halts the chain reactions of lipid peroxidation (LPO). Metabolomic analyses indicate that thiols become depleted in E- embryos because LPO generates products that require compensation using limited amino acids and methyl donors that are also developmentally relevant. Thus, VitE protects metabolic networks and the integrated gene expression networks that control development. VitE is critical especially for neurodevelopment, which is dependent on trafficking by the α-tocopherol transfer protein (TTPa). VitE-deficient (E-) zebrafish embryos initially appear normal, but by 12 and 24 h post-fertilization (hpf) E- embryos are developmentally abnormal with expression of pax2a and sox10 mis-localized in the midbrain-hindbrain boundary, neural crest cells and throughout the spinal neurons. These patterning defects indicate cells that are especially in need of VitE-protection. They precede obvious morphological abnormalities (cranial-facial malformation, pericardial edema, yolksac edema, skewed body-axis) and impaired behavioral responses to locomotor activity tests. The TTPA gene (ttpa) is expressed at the leading edges of the brain ventricle border. Ttpa knockdown using morpholinos is 100% lethal by 24 hpf, while E- embryo brains are often over- or under-inflated at 24 hpf. Further, E- embryos prior to 24 hpf have increased expression of genes involved in glycolysis and the pentose phosphate pathway, and decreased expression of genes involved in anabolic pathways and transcription. Combined data from both gene expression and the metabolome in E- embryos at 24 hpf suggest that the activity of the mechanistic Target of Rapamycin (mTOR) signaling pathway is decreased, which may impact both metabolism and neurodevelopment. Further evaluation of VitE deficiency in neurogenesis and its subsequent impact on learning and behavior is needed.

Sensory Axonopathy Associated With Vitamin E Deficiency.

Vitamin E deficiency can be observed in patients with malabsorption syndromes or inherited diseases such as ataxia. It is unusual for it to be a result of dietary insufficiency due to its presence in a wide variety of foods. Patients with vitamin E deficiency can present with neuromuscular disorders such as ataxia, hyporeflexia, spinocerebellar syndrome, as well as loss of vibration and proprioceptive sensation. Herein, we are presenting a case in which a previously healthy adult with no family history of genetic defects and malabsorption syndrome presented with a characteristic sensory axonopathy associated with vitamin E deficiency without any evidence of fat malabsorption. Patient reported a markedly improvement of symptoms after three-month supplementation of vitamin E. The unique part of this case was that the patient presented with neuropathic pain associated with vitamin E deficiency without any family history of inherited deficiency or any malabsorption syndrome.

Vitamin E status in healthy population in Asia: A review of current literature.

Vitamin E is a lipid soluble antioxidant which mainly circulates as α-tocopherol in the human plasma. Its deficiency is associated with ataxia, neuropathy, anaemia and several other health conditions. Although substantial data on vitamin E status has been published worldwide, there is paucity of data on the extent of deficiency from most Asian countries, including India. Part of the problem is lack of validated biomarkers for vitamin E and no consensus on cut offs for defining deficiency and sufficiency. Thus, interpretation of the data on the vitamin E status is difficult. Limited available data from 31 studies on vitamin E status in healthy people from Asia, the most populated continent, has been collated for the purpose of this review. Broadly, the results suggest inadequate vitamin E status in most age groups, with the prevalence of deficiency reaching 67%, 80%, 56% and 72% in infants, children and adolescents, adults, elderly and pregnant women, respectively, based on varying cut offs. The findings are not surprising as both, vitamin E intakes and its status have not received too much attention in the past. Lack of conclusive data accentuates the need for more research on the vitamin E status across all age groups and to define age, gender and physiological state specific cut offs for vitamin E levels.

Brown Bowel Syndrome: An Exceedingly Rare Condition with Longstanding Malabsorption and an Unusual Cause of Colon Pseudo-Obstruction.

Brown bowel syndrome (BBS) is an exceedingly rare condition usually associated with longstanding malabsorption of any etiology. As a result of vitamin E deficiency and subsequent mitochondrial degeneration due to oxidative stress induced by free radicals, lipofuscin granules accumulate in the smooth muscles of the gastrointestinal tract resulting in myopathy and dysmotility with underlying disease aggravation. The current study reports a BBS case in a 64-year-old female patient who had undergone jejunoileal bypass surgery as a bariatric procedure. The patient was admitted with signs of malabsorption and ileus in computed tomography imaging. Endoscopic workup revealed no stenosis or obstruction. The colon histologically showed periodic acid-Schiff-positive lipofuscin granules in the lamina muscularis mucosa consistent with BBS. The vitamin E level in the patient was extremely low. Moreover, clinical improvement was documented following high-dose substitution. BBS should be considered in patients with malabsorption of any cause especially with signs of gastrointestinal dysmotility. Vitamin E substitution may improve clinical status and prevent further deterioration.

Vitamin E deficiency and associated factors among Brazilian school children / Deficiência de vitamina E e fatores associados entre crianças escolares brasileiras

ABSTRACT: Objective: Brazilian national data show a significant deficiency in pediatric vitamin E consumption, but there are very few studies evaluating laboratory-proven nutritional deficiency. The present study aimed to settle the prevalence of vitamin E deficiency (VED) and factors associated among school-aged children attended at a primary health unit in Ribeirão Preto (SP). Methods: A cross-sectional study that included 94 children between 6 and 11 years old. All sub-jects were submitted to vitamin E status analysis. To investigate the presence of factors associated with VED, socio-economic and anthropometric evaluation, determination of serum hemoglobin and zinc levels, and parasitological stool exam were performed. The associations were performed using Fisher's exact test. Results: VED (α-tocopherol concentrations <7 µmol/L) was observed in seven subjects (7.4%). None of them had zinc deficiency. Of the total of children, three (3.2%) were malnourished, 12 (12.7%) were anemic, and 11 (13.5%) presented some pathogenic intestinal parasite. These possible risk factors, in addition to maternal-work, maternal educational level, and monthly income, were not associated with VED. Conclusions: The prevalence of VED among school-aged children attended at a primary health unit was low. Zinc deficiency, malnutrition, anemia, pathogenic intestinal parasite, maternal-work, maternal educational level, and monthly income were not a risk factor for VED. (AU)

RESUMO: Objetivo: Determinar a prevalência da deficiência de vitamina E (DVE) e os fatores associados a essa deficiência em escolares atendidos em uma unidade básica de saúde de Ribeirão Preto (SP). Métodos: Estudo transversal que incluiu 94 crianças entre 6 e 11 anos de idade, atendidas em uma unidade básica de saúde. Todos os indivíduos foram submetidos à análise do status de vitamina E. Para investigar a presença de fatores associados à DVE, foi realizada avaliação socio-econômica e antropométrica, determinação dos níveis séricos de hemoglobina e zinco, e exame parasitológico de fezes. As associações foram realizadas por meio do teste exato de Fisher. Resultados: A DVE (concentrações de α-tocoferol <7 µmol/l) foi observada em sete indivíduos (7,4%). Nenhum sujeito apresentou deficiência sérica de zinco. Do total de crianças, três (3,2%) eram desnutridas, 12 (12,7%) anêmicas e 11 (13,5%) apresentavam algum parasita intestinal patogênico. Estes possíveis fatores de risco, além do trabalho materno, escolaridade materna e renda mensal, não foram associados à DVE (p>0,05). Conclusão: A prevalência de DVE em escolares atendidos em uma unidade básica de saúde foi baixa. Desnutrição, anemia, parasitose intestinal, renda mensal e trabalho e nível educacional maternos não se apre-sentaram como fatores de risco para a DVE. (AU)