Equine neuroaxonal dystrophy/degenerative myeloencephalopathy in Gypsy Vanner horses.

BACKGROUND: Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a neurodegenerative disease that primarily affects young, genetically predisposed horses that are deficient in vitamin E. Equine NAD/EDM has not previously been documented in Gypsy Vanner horses (GVs). OBJECTIVES: To evaluate: (1) the clinical phenotype, blood vitamin E concentrations before and after supplementation and pedigree in a cohort of GV horses with a high prevalence of neurologic disease suspicious for eNAD/EDM and (2) to confirm eNAD/EDM in GVs through postmortem evaluation. ANIMALS: Twenty-six GVs from 1 farm in California and 2 cases from the Midwestern U.S. METHODS: Prospective observational study on Californian horses; all 26 GVs underwent neurologic examination. Pre-supplementation blood vitamin E concentration was assessed in 17- GVs. Twenty-three were supplemented orally with 10 IU/kg of liquid RRR-alpha-tocopherol once daily for 28 days. Vitamin E concentration was measured in 23 GVs after supplementation, of which 15 (65%) had pre-supplementation measurements. Two clinically affected GVs from California and the 2 Midwestern cases had necropsy confirmation of eNAD/EDM. RESULTS: Pre-supplementation blood vitamin E concentration was ≤2.0 µg/mL in 16/17 (94%) of GVs from California. Post-supplementation concentration varied, with a median of 3.39 µg/mL (range, 1.23-13.87 µg/mL), but only 12/23 (52%) were normal (≥3.0 µg/mL). Normalization of vitamin E was significantly associated with increasing age (P = .02). Euthanized horses (n = 4) had eNAD/EDM confirmed at necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: GVs could have a genetic predisposition to eNAD/EDM. Vitamin E supplementation should be considered and monitored in young GVs.

Evening primrose oil enriched with gamma linolenic acid and D/L-alpha tocopherol acetate attenuated carbon tetrachloride-induced hepatic injury model in male rats via TNF-α, IL-1ß, and IL-6 pathway.

The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4)-induced liver damage model was assessed in this study. Twenty male Albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded. Serum liver enzymes, hepatic malondialdehyde (MDA), hepatic reduced glutathione (GSH) and the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) were assessed. The binding affinities of γ-linolenic acid and D/L-alpha tocopherol constituents with IL-1ß, IL-6 and TNF-α were investigated using molecular docking simulations. Histopathological and electron microscopic examinations of the liver were performed. The results indicated that CCl4 elevated serum liver enzyme and hepatic MDA levels, whereas GSH levels were diminished. The upregulation of IL-1ß, IL-6, and TNF-α gene expressions were induced by CCl4 treatment. The PO/CCl4-treated group showed amelioration of hepatic injury biomarkers and oxidative stress. Restoration of histopathological and ultrastructural alterations while downregulations the gene expressions of TNF-α, IL1-ß and IL-6 were observed. In conclusion, evening primrose oil enriched with γ-linolenic acid and D/L-alpha tocopherol acetate elicited a potential amelioration of CCl4-induced hepatic toxicity.

Vitamin E Supplementation and Cardiovascular Health: A Comprehensive Review.

This article conducts a thorough investigation into the potential role of vitamin E in preventing cardiovascular diseases (CVDs) in the context of shifting mortality patterns from infectious diseases to the continued prominence of CVDs in modern medicine. The primary focus is on vitamin E's antioxidant properties and its specific ability to counter lipid peroxidation, a pivotal process in the early stages of atherosclerosis, a precursor to CVDs. The research spans a wide range of methodologies, including in vitro, in vivo, clinical, and experimental studies, examining how vitamin E affects critical aspects of cardiovascular health, such as signaling pathways, gene expression, inflammation, and cholesterol metabolism. It also explores vitamin E's influence on complex processes like smooth muscle cell development, oxidative stress reduction, foam cell formation, and the stability of atherosclerotic plaques. In the context of clinical studies, the article presents findings that both support and yield inconclusive results regarding the impact of vitamin E supplementation on CVDs. It acknowledges the intricate interplay of factors such as patient selection, pathophysiological conditions, and genetic variations, all of which can significantly influence the efficacy of vitamin E. The article underscores the need for ongoing research, with a specific focus on understanding the regulatory metabolites of vitamin E and their roles in modulating cellular processes relevant to CVDs. It highlights the potential for innovative therapeutic approaches based on a deeper comprehension of vitamin E's multifaceted effects. However, it also candidly addresses the challenges of translating clinical trial findings into practical applications and emphasizes the importance of considering diverse variables to optimize therapeutic outcomes. In summary, this meticulously conducted study provides a comprehensive examination of vitamin E's potential as a preventive agent against CVDs, recognizing the complexity of the subject and the need for continued research to unlock its full potential in cardiovascular health.

The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant.

Oral vaccines represent many advantages compared to standard vaccines. They hold a simple method of administration and manufacturing process. In addition to these, the way they can induce immune responses makes these a promising technology for the pharmaceutical industry and represents a new hope to society. Physiologically based pharmacokinetics (PBPK) has been used in support of drug development to predict the pharmacokinetics of the compound, considering the patient's physiology. Despite PBPK studies now being widely used, there are very few models in the literature that support vaccine development. Therefore, the goal of this article was to determine how PBPK could support vaccine development. The first PBPK model for an oral vaccine using alpha-tocopherol as a vaccine adjuvant was built. LogP is the parameter that influences the delivery of alpha-tocopherol into the tissues more. Having a high LogP means it accumulates in adipose tissue and is slowly metabolized. The ideal formulation to include alpha-tocopherol in an oral vaccine would incorporate nanoparticles in a capsule, and the dosage of the compound would be 150 mg in a volume of 200 mL. This article aims to determine if alpha-tocopherol, as a well-known adjuvant for intramuscular injection vaccines, could be used as an adjuvant to oral vaccines. This model was built considering the conditions and requirements needed for designing an oral vaccine. This implies making sure the antigen and adjuvants reach the main target by overcoming the challenges of the gastrointestinal tract. The main parameters that would need to be included in a formulation using alpha-tocopherol as an adjuvant were determined.

PLGA nanoparticle loaded with antioxidants and photosensitizer for ROS shock mediated phototherapy of triple negative breast cancer.

The potential use of antioxidants for photodynamic therapy (PDT) is investigated in this study. PDT causes reactive oxygen species (ROS)-mediated cell death; on the contrary, antioxidants scavenge ROS. The use of a photosensitizer along with an antioxidant photosensitizer compensates for the loss of ROS due to the use of antioxidant, eventually leading to cell death. In this work, for PDT and photothermal therapy (PTT), we have combined the photosensitizer IR 792 perchlorate dye with the antioxidants alpha-tocopherol (A) andp-coumaric acid (C) encapsulated in a polymeric nanocarrier (AC IR NPs). We have reported the synthesis of AC IR NPs using poly lactic-co-glycolic acid (PLGA) by nanoprecipitation method. The size of the polymeric nanoparticles was found to be 80.4 ± 15.6 nm, with a spherical morphology observed by scanning electron microscopy and transmission electron microscopy. The synthesized AC IR NPs demonstrated good biocompatibility in fibroblast cell lines (L929). Furthermore, the efficacy assessment of the as prepared nanosystemin vitroon breast cancer cell lines (4T1) revealed a significant cell death of nearly 80%. This could be attributed to the ROS generation leading to oxidative stress and inhibition of metastasis. This study provides evidence that the combination of antioxidant drugs along with photosensitizers have the potential to be an effective therapy for treating triple negative breast cancer.

Vitamin E and Its Molecular Effects in Experimental Models of Neurodegenerative Diseases.

With the advancement of in vivo studies and clinical trials, the pathogenesis of neurodegenerative diseases has been better understood. However, gaps still need to be better elucidated, which justifies the publication of reviews that explore the mechanisms related to the development of these diseases. Studies show that vitamin E supplementation can protect neurons from the damage caused by oxidative stress, with a positive impact on the prevention and progression of neurodegenerative diseases. Thus, this review aims to summarize the scientific evidence of the effects of vitamin E supplementation on neuroprotection and on neurodegeneration markers in experimental models. A search for studies published between 2000 and 2023 was carried out in the PubMed, Web of Science, Virtual Health Library (BVS), and Embase databases, in which the effects of vitamin E in experimental models of neurodegeneration were investigated. A total of 5669 potentially eligible studies were identified. After excluding the duplicates, 5373 remained, of which 5253 were excluded after checking the titles, 90 articles after reading the abstracts, and 11 after fully reviewing the manuscripts, leaving 19 publications to be included in this review. Experiments with in vivo models of neurodegenerative diseases demonstrated that vitamin E supplementation significantly improved memory, cognition, learning, motor function, and brain markers associated with neuroregeneration and neuroprotection. Vitamin E supplementation reduced beta-amyloid (Aß) deposition and toxicity in experimental models of Alzheimer's disease. In addition, it decreased tau-protein hyperphosphorylation and increased superoxide dismutase and brain-derived neurotrophic factor (BDNF) levels in rodents, which seems to indicate the potential use of vitamin E in preventing and delaying the progress of degenerative lesions in the central nervous system.

Effects of the Melatonin and Vitamin E (Alpha-Tocopherol Acetate) as Antioxidants on Biochemical Blood Parameters, Lipid Profile, and Muscle Vitamin E Concentration in Awassi Lambs Fed a High-Energy Diet and Normal Diet.

Health specialists currently suggest low-cholesterol diets, suggesting that cholesterol in the form of high-density lipoprotein (HDL) reduces the risk of chronic atherosclerosis. The large volume of literature describes the biological roles of vitamin E and its application to preventing disease and improving the health and productive performances of farm animals. The present study aimed to evaluate the effects of vitamin E (Alpha-tocopherol acetate) supplementation and melatonin implants on biochemical blood, lipid profile and muscle vitamin E content of Awassi male lambs fed by a high and normal diet in Iraq. The lambs were divided into teen groups as control normal energy diet T1 (NED) T2 (HED) concentrated lamb fattening feed. Two levels of melatonin (18 and 36 mg implant) were applied to T3, T4, T5, and T6 treatment and 2 levels of Vitamin E (Alpha-tocopherol acetate) diet 200 mg/kg, 400 mg/kg to T7. T8. T9 and T10, respectively. Results from the present study indicate that Vitamin E 200, 400 mg/lamb/day and melatonin implantation 18 mg, 36 mg/lamb/day significantly (P<0.05) increased total protein in serum while decreasing globulin level, glucose concentration in serum, melatonin implantation 36 mg/lamb and vitamin E 400 mg/lamb/day recorded significantly (P<0.05). The same effect on decreasing cholesterol concentration in serum 42.6mg\dl, 40.5 mg\dl, respectively, compared to non-treated groups. Vitamin E 200 mg/kg/lamb recorded the lowest AST level in serum, 43.3. Lambs implanted with Melatonin 36 mg/lamb and fed a high-energy diet (T8) resulted in a significant decrease of serum ALT activity (P<0.05) in comparison to other treated groups 12.7 U/L was achieved. Lambs fed a normal energy diet with vitamin E 200 mg/kg/lamb (T4) exceeded other treated groups, decreasing ALT serum levels by 9.35 U/L. Interestingly, muscle vitamin E concentrations for lambs received 200, 400 mg/lamb/day on the 2nd, 7th and 14th days of the storage period, and fed high energy diet (T10) or normal energy diet (T5) were significantly higher compared to control group (T1, T6).

Can antioxidant treatment replace delay in bracket bonding? An in vitro study.

BACKGROUND: Deterioration in shear bond strength has been reported after immediate bracket bonding following hydrogen peroxide bleaching. This study compared the effectiveness of three antioxidant agents, namely, alpha-tocopherol, green tea extract, and sodium ascorbate, in reversing the bleaching effect and as possible alternatives to delayed bonding. METHODS: A total of 105 extracted human premolars were arbitrarily assigned to 7 groups (n = 15 each), including group 1 as the unbleached control group and six experimental groups, which were bleached with 40% hydrogen peroxide in three sessions of 15 min each. In experimental group 2, bonding was performed immediately after bleaching, whereas in groups 3 and 4, bonding was delayed for 1 and 2 weeks, respectively; meanwhile, the specimens were immersed in artificial saliva at 37 °C. Groups 5, 6, and 7 were treated immediately after bleaching with 10% of alpha-tocopherol, green tea extract, and sodium ascorbate solutions, respectively, for 15 min. Specimens were processed using 500 thermal cycles between 5 and 55 °C, with a dwell time of 30 s after 24 h of bracket bonding, and then tested for shear bond strength. The adhesive remnant index was examined to evaluate fracture mode. One-way analysis of variance, Kruskal-Wallis H, and post hoc Tukey's honestly significant difference tests were used to compare the data. Significant results were subjected to pairwise comparisons with Bonferroni's correction-adjusted of p values ≤ 0.050. RESULTS: Shear bond strength was significantly lower (p < 0.001) in the immediate bonding and 1-week delay groups than in the control group. However, no significant difference was detected among the 2-week delay, antioxidant-treated, and control groups (p > 0.05). CONCLUSIONS: Application of 10% alpha-tocopherol, green tea extract, or sodium ascorbate for 15 min could restore shear bond strength after 40% hydrogen peroxide bleaching as an alternative to delay in bracket bonding.

Consumption and supplementation of vitamin E in breast cancer risk, treatment, and outcomes: A systematic review with meta-analysis.

BACKGROUND: Robust evidence have shown diet or dietary components in playing a direct role on cancer chemoprevention such as breast cancer (BC), and also prevention against cancer therapy side effects. In this context, vitamin E isoforms have been associated with tumor suppression pathways, mainly related to proliferation, invasion, metastasis, tumor metabolism and chemoresistance. OBJECTIVE: Therefore, we performed a systematic review with meta-analysis to assess the effects of vitamin E consumption and/or supplementation on breast cancer risk, treatment, and outcomes. METHODS: The studies were selected in the electronic databases PubMed, Science Direct, Scopus and Web of Science. RESULTS: A total of 22 articles were selected, which nine manuscripts we perform the meta-analysis. The summary effect estimate did not indicate any significant association between consumption versus non-consumption of total vitamin E and breast cancer risk. After assessing the effects of vitamin E supplementation on breast cancer risk, only two had data for comparison and vitamin E supplementation presented no impact on breast cancer risk. However, the summary effect estimate from the included studies indicated that vitamin E consumption was inversely associated with breast cancer recurrence in the control group. There are no significant results regarding dietary or supplemental vitamin E intake and BC risk reduction. CONCLUSION: Finally, regarding recurrence, survival, and mortality, the results indicated that vitamin E consumption was inversely associated with breast cancer recurrence, although no association was found for breast cancer mortality.

The effect of Vitamin E supplementation on inflammatory biomarkers and oxidative stress in patients with chronic kidney disease on hemodialysis: A systematic review

Hemodialysis, along with chronic kidney disease (CKD), intensifies the inflammatory process and oxidative stress in patients undergoing treatment. In this context, Vitamin E supplementation can mitigate the deleterious effects resulting from these processes. This is a systematic review whose objective was to evaluate the effect of Vitamin E supplementation on inflammatory biomarkers and oxidative stress in patients with CKD on hemodialysis. This review was prepared according to the methodology for systematic reviews and meta-analyses (PRISMA) and the search was performed in Pubmed, Cochrane Library, Scopus and Web of Science databases. The risk of bias of the included studies was assessed with the Cochrane Risk of Bias Tool. Twelve studies developed between 2006 and 2020 were included in this review. Most of them (n= 11) used vitamin E doses ranging from 400 IU to 888 IU and the supplementation time ranged from 2 weeks to 12 months. Of all the 12 articles included, 25% (n= 3) analyzed supplementation on biomarkers of oxidative stress and 25% (n= 3) addressed these parameters simultaneously. A positive effect was observed in 58.4% of the studies (n= 7). Thus, Vitamin E supplementation can be effective in mitigating the inflammatory process and oxidative stress, however, it is worth noting that the effect depends on the dose and time of supplementation.

La hemodiálisis, junto con la enfermedad renal crónica (ERC), intensifica el proceso inflamatorio y el estrés oxidativo en los pacientes en tratamiento. En este contexto, la suplementación con vitamina E puede mitigar los efectos nocivos resultantes de estos procesos. Esta es una revisión sistemática cuyo objetivo fue evaluar el efecto de la suplementación con vitamina E sobre biomarcadores inflamatorios y estrés oxidativo en pacientes con ERC en hemodiálisis. La revisión se elaboró según la metodología para revisiones sistemáticas y metanálisis (PRISMA) y la búsqueda se realizó en las bases de datos Pubmed, Cochrane Library, Scopus y Web of Science. El riesgo de sesgo de los estudios incluidos se evaluó con la Herramienta Cochrane de Riesgo de Sesgo (Cochrane Risk of Bias Tool). En esta revisión se incluyeron doce estudios desarrollados entre 2006 y 2020. La mayoría (n= 11) utilizó dosis de vitamina E que oscilaban entre 400 UI y 888 UI y el tiempo de suplementación osciló entre 2 semanas y 12 meses. De los 12 artículos incluidos, 25% (n= 3) analizaba la suplementación en biomarcadores inflamatorios, 50% (n= 6) en biomarcadores de estrés oxidativo y 25% (n= 3) en estos parámetros simultáneamente. Se observó un efecto positivo en 58,4% de los estudios (n= 7). Por lo tanto, la suplementación con vitamina E puede ser efectiva para mitigar el proceso inflamatorio y el estrés oxidativo, sin embargo, vale la pena señalar que el efecto depende de la dosis y el tiempo de suplementación.

A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice.

The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse.

Vitamin E depletion is associated with subclinical axonal degeneration in juvenile horses.

BACKGROUND: Phosphorylated neurofilament heavy, a marker of neuroaxonal damage, is increased in horses with equine neuroaxonal dystrophy. However, the temporal dynamics of this biomarker during the post-natal risk period are not understood. OBJECTIVE: To measure serum and cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile foals across the post-natal window of susceptibility for equine neuroaxonal dystrophy. STUDY DESIGN: Case-control in vivo experimental study. METHODS: Concentrations of phosphorylated neurofilament heavy were measured using frozen serum and cerebrospinal fluid collected from 13 foals raised in a vitamin E deficient environment from 1 to 6 months of age. Four of these foals were produced by equine neuroaxonal dystrophy-affected dams, developed clinical signs consistent with equine neuroaxonal dystrophy and had a diagnosis confirmed by histopathology. The remaining nine foals, produced by healthy mares, were vitamin E depleted and remained clinically healthy. An additional cohort of foals, produced by healthy mares, were supplemented with vitamin E (α-tocopherol; α-TOH) from birth and sampled similarly. RESULTS: Serum α-TOH concentrations were significantly higher in vitamin E supplemented healthy foals. Serum phosphorylated neurofilament heavy concentrations did not differ significantly between groups at any time point. Cerebrospinal fluid phosphorylated neurofilament heavy concentrations increased with age in healthy vitamin E depleted foals (p < 0.001); an effect that was not observed in healthy vitamin E supplemented foals. MAIN LIMITATIONS: A genetically susceptible cohort supplemented with vitamin E was not available for comparison. CONCLUSION: We demonstrate that vitamin E depletion may elevate cerebrospinal fluid phosphorylated neurofilament heavy in otherwise healthy juvenile foals by 6 months of age. We highlight an important cofactor to consider when interpreting cerebrospinal fluid phosphorylated neurofilament heavy concentrations in juvenile horses.

Effects of the combination of vitamins C and E supplementation on oxidative stress, inflammation, muscle soreness, and muscle strength following acute physical exercise: meta-analyses of randomized controlled trials.

Background:The combined supplementation of vitamins C and E potentially can mitigate oxidative stress (OS) and accelerate recovery following exercise. However, there is little evidence and a lack of consensus on the effects of these vitamins for this purpose. The objective of this systematic review was to summarize the evidence on the effects of the combined supplementation of vitamins C and E in OS, inflammatory markers, muscle damage, muscle soreness, and musculoskeletal functionality following acute exercise. Methods: The search was carried out from inception until March 2021, on MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and SPORT Discus. We included placebo-controlled randomized clinical trials (RCTs) that evaluated the effects of combined supplementation of vitamins C and E in OS, inflammatory markers, muscle damage, muscle soreness, and muscle strength following a single bout of exercise. Random-effect meta-analyses were used to compare pre to post-exercise mean changes in subjects who received supplementation with vitamins C and E or placebo versus controls. Data are presented as standard mean difference (SMD) and 95% confidence interval (95% CI). Results: Eighteen RCTs, accounting for data from 322 individuals, were included. The use of vitamins attenuated lipid peroxidation (SMD= -0.703; 95% CI= -1.035 to -0.372; p < 0.001), IL-6 (SMD= -0.576; 95%CI= -1.036 to -0.117; p = 0.014), and cortisol levels (SMD= -0.918; 95%CI= -1.475 to -0.361; p = 0.001) immediately, and creatine kinase levels 48 h following exercise (SMD= -0.991; 95%CI= -1.611 to -0.372; p = 0.002). Supplementing the combination of vitamins had no effects on protein carbonyls, reduced/oxidized glutathione ratio, catalase, interleukin-1Ra, C-reactive protein, lactate dehydrogenase, muscle soreness, and muscle strength. Conclusion: Prior supplementation of the combination of vitamins C and E attenuates OS (lipid peroxidation), the inflammatory response (interleukin-6), cortisol levels, and muscle damage (creatine kinase) following a session of exercise.

Docosahexaenoic acid in regio- and enantiopure triacylglycerols: Oxidative stability and influence of chiral antioxidant.

Docosahexaenoic acid (DHA) is essential for health but easily oxidized. Yet the influence of DHA's exact location (sn-1, sn-2, or sn-3) in triacylglycerols on oxidative stability is currently unknown. This is the first study comparing oxidative stability of DHA in regio- and enantiopure triacylglycerols with or without RRR-α-tocopherol. Headspace solid-phase micro-extraction with gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy were applied. DHA in sn-2 was the most stable with or without added RRR-α-tocopherol resulting in differences in hydroperoxide formation. Without antioxidant, stability of DHA in sn-1 and sn-3 was mainly similar, with slight tendency towards better stability in sn-3. With RRR-α-tocopherol higher stability in sn-1 compared to sn-3 was observed. This points to diastereomeric interactions between RRR-α-tocopherol and DHA in sn-1. These results are highly relevant for enzymatic restructuring processes of DHA-rich fish or microalgae oil concentrates aimed for food supplements or food fortification.

Gamma-tocopherol, a major form of vitamin E in diets: Insights into antioxidant and anti-inflammatory effects, mechanisms, and roles in disease management.

γ-Tocopherol (γT) is a major form of vitamin E in the US diet and the second most abundant vitamin E in the blood and tissues, while α-tocopherol (αT) is the predominant vitamin E in tissues. During the last >25 years, research has revealed that γT has unique antioxidant and anti-inflammatory activities relevant to disease prevention compared to αT. While both compounds are potent lipophilic antioxidants, γT but not αT can trap reactive nitrogen species by forming 5-nitro-γT, and appears to show superior protection of mitochondrial function. γT inhibits ionophore-stimulated leukotrienes by blocking 5-lipoxygenase (5-LOX) translocation in leukocytes, decreases cyclooxygenase-2 (COX-2)-catalyzed prostaglandins in macrophages and blocks the growth of cancer cells but not healthy cells. For these activities, γT is stronger than αT. Moreover, γT is more extensively metabolized than αT via cytochrome P-450 (CYP4F2)-initiated side-chain oxidation, which leads to formation of metabolites including 13'-carboxychromanol (13'-COOH) and carboxyethyl-hydroxychroman (γ-CEHC). 13'-COOH and γ-CEHC are shown to be the predominant metabolites found in feces and urine, respectively. Interestingly, γ-CEHC has natriuretic activity and 13'-COOH inhibits both COX-1/-2 and 5-LOX activity. Consistent with these mechanistic findings of γT and metabolites, studies show that supplementation of γT mitigates inflammation and disease symptoms in animal models with induced inflammation, asthma and cancer. In addition, supplementation of γT decreased inflammation markers in patients with kidney diseases and mild asthma. These observations support that γT may be useful against inflammation-associated diseases.

Effect of Statin Therapy on the Plasma Concentrations of Retinol, Alpha-Tocopherol and Coenzyme Q10 in Children with Familial Hypercholesterolemia.

PURPOSE: Familial hypercholesterolemia (FH) requires early treatment. However, statins, which are regarded the first-line therapy, have an influence on redox balance. Antioxidant vitamins are important for many metabolic processes in the developing body. There are few data available on the long-term safety of statin use in children. The aim of this study was to evaluate the influence of statin treatment in children with FH on plasma concentrations of antioxidant vitamins: retinol, alpha-tocopherol and coenzyme Q10. METHODS: The first study group consisted of 13 children aged 10-18 years treated with simvastatin for at least 6 months, and the second group comprised 13 age- and sex-matched children with hypercholesterolemia, in whom pharmacological treatment had not been applied yet. Analyses were performed using a high-performance liquid chromatograph coupled with a MS detector. RESULTS: The analysis did not reveal significant differences in the concentration of retinol, alpha-tocopherol or coenzyme Q10 between the studied groups. The adjustment of the concentrations of the vitamins to the cholesterol level also indicated no significant differences. We found no deficits in antioxidant vitamins in patients treated with statins, or any risk of adverse effects associated with an increase in their concentration. CONCLUSION: There is no rationale for additional supplementation using antioxidant vitamins or modification of low-fat and low-cholesterol diet in pediatric patients treated with statins.

Vitamin E for the management of major depressive disorder: possible role of the anti-inflammatory and antioxidant systems.

OBJECTIVES: Vitamin E has various functions in humans, including antioxidant, anti-inflammatory, anti-cancer, and anti-atherogenic actions, as well as direct effects on enzymatic activities and modulation of gene transcription. In addition to these functions, vitamin E is also important for the central nervous system, and its role in the prevention and/or treatment of some neurological diseases has been suggested. In particular, the role of vitamin E in the modulation of major depressive disorder (MDD) is an issue that has emerged in recent studies. Many factors have been implicated in the pathophysiology of this disorder, including inflammation, oxidative, and nitrosative stress. METHODS: This narrative review discusses the involvement of inflammation, oxidative, and nitrosative stress in the pathophysiology of MDD and presents clinical and preclinical studies that correlate vitamin E with this psychiatric disorder. RESULTS: We gathered evidence from clinical studies that demonstrated the relationship between low vitamin E status and MDD symptoms. Vitamin E has been reported to exert a beneficial influence on the oxidative and inflammatory status of individuals, factors that may account for the attenuation of depressive symptoms. Preclinical studies have reinforced the antidepressant-like response of vitamin E, and the mechanisms underlying its effect seem to be related to the modulation of oxidative stress and neuroinflammation. CONCLUSION: We suggest that vitamin E has potential to be used as an adjuvant for the management of MDD, but more studies are clearly needed to ascertain the efficacy of vitamin E for alleviating depressive symptoms.

A systematic review and meta-analysis on the impact of oral vitamin E supplementation on apolipoproteins A1 and B100.

BACKGROUND AND AIM: Cardiovascular diseases (CVDs) are the number one cause of mortality worldwide. Apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), and ApoB/ApoA1 ratio are considered as predictors of CVD alongside with lipid profile. Evidence suggest that nutrients with antioxidant properties, especially vitamin E, are essential for a healthy cardiovascular system. The aim of present meta-analysis was to determine the effect alpha-tocopherol on ApoA1 and ApoB levels. METHODS: PubMed-Medline and SCOPUS databases and Google Scholar were searched up to July 2021. Random-effects model was employed to perform meta-analysis. In order to find heterogeneity sources, subgroup analysis was performed. Trim and fill analysis was performed in case of presence of publication bias. Quality assessment was performed using Cochrane Collaboration's tool. RESULTS: Seven eligible studies, involving 1284 individuals were included. Mean age of participants ranged between 25.4 and 59 years. There was no significant effect of vitamin E supplementation on Apo A1 (SMD = 0.22 IU/d; 95% CI: -0.38, 0.28; P = 0.481) and Apo B levels (SMD = -0.62 IU/d; 95% CI: -1.94, 0.70; P = 0.360). CONCLUSION: No remarkable effect of vitamin E supplementation was observed on ApoA1 and ApoB levels in adults. Additional studies investigating the influence of vitamin E on apolipoproteins as primary outcome with larger sample size are suggested.

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.

Sex-Specific Reduction in Inflammation of Osteoarthritic Human Chondrocytes and Nutraceutical-Dependent Extracellular Matrix Formation.

INTRODUCTION: The aim of this study was to investigate the ability of osteoarthritic human chondrocytes to produce articular cartilage (AC) tissues with a reduced inflammatory environment in response to 4 anti-inflammatory nutraceuticals: alpha-tocopherol (Alpha), gallic acid (G), ascorbic acid (AA), and catechin hydrate (C). METHODS: Chondrocytes isolated from patients who underwent total knee arthroplasty surgeries were divided into groups (9 male; mean age, 66.2 ± 3.5 years and 11 female; mean age, 64.2 ± 3.1 years). Cells were cultured based on sex and supplemented with either a negative control (NC) medium or NC plus one of the nutraceuticals at a concentration of 50 µM. At day 21, cultures were characterized histologically, biochemically, and for gene expression of vital markers. RESULTS: At day 21, 62.3% and 66.2% reduction in nitric oxide (NO) content was evident for female and male cells, respectively. G-treatment of female cells resulted in the lowest expression of nitric oxide synthase-2 (NOS2), matrix metalloproteinase-13 (MMP13), and collagen type-10 (COL10). Alpha-treatment of male cells resulted in the lowest expression of NOS2, bone morphogenic protein-2, MMP13, COL10 and tumor necrosis factor alpha induced protein-6 (TNFAIP6) relative to NC. AA and Alpha treatment resulted in the highest glycosaminoglycan (GAG) content for female and male cultures, respectively. CONCLUSION: A sex-dependent response of osteoarthritic chondrocytes to nutraceutical treatment was evident. Our results suggest the use of G for female cells and Alpha for male cells in OA applications seems to be favorable in reducing inflammation and enhancing chondrocytes' ability to form AC tissues.