Nano vitamin E improved the antioxidant capacity of broiler chickens.

Vitamin E (VE) is a potent nutritional antioxidant that is critical in alleviating poultry oxidative stress. However, the hydrophobic nature and limited stability of VE restrict its effective utilization. Nanotechnology offers a promising approach to enhance the bioavailability of lipophilic vitamins. The objective of this experiment was to investigate the effects of different sources and addition levels of VE on the growth performance, antioxidant capacity, VE absorption site, and pharmacokinetics of Arbor Acres (AA) broilers. Three hundred and eighty-four 1-d-old AA chicks were randomly allocated into four groups supplemented with 30 and 75 IU/kg VE as regular or nano. The results showed that dietary VE sources had no significant impact on broiler growth performance. However, chickens fed 30 IU/kg VE had a higher average daily gain at 22 to 42 d and 1 to 42 d, and lower feed conversion ratio at 22 to 42 d than 75 IU/kg VE (P < 0.05). Under normal feeding conditions, broilers fed nano VE (NVE) displayed significantly higher superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) enzyme activities and lower malonic dialdehyde (MDA) concentration (P < 0.05). Similarly, NVE had a higher antioxidant effect in the dexamethasone-constructed oxidative stress model. It was found that nanosizing technology had no significant effect on the absorption of VE in the intestinal tract by examining the concentration of VE in the intestinal tract (P > 0.05). However, compared to broilers perfused with regular VE (RVE), the NVE group displayed notably higher absorption rates at 11.5 and 14.5 h (P < 0.05). Additionally, broilers perfused with NVE showed a significant increase in the area under the concentration versus time curve from zero to infinity (AUC0-∞), mean residence time (MRT0-∞), elimination half-life (t1/2z), and peak concentration (Cmax) of VE in plasma (P < 0.05). In summary, nanotechnology provides more effective absorption and persistence of VE in the blood circulation for broilers, which is conducive to the function of VE and further improves the antioxidant performance of broilers.

With the rapid development of intensive farming, factors such as high temperature, harmful gases, high-fat and high-protein diets, and changes in feeding methods have become causes of oxidative stress in animals. Studies have shown that oxidative stress decreases livestock feed intake and slows growth in animals, thereby affecting the quality of livestock products. Antioxidants and micronutrients are commonly added to animal feed to reduce the effects of oxidative stress. Since the progress in nanotechnology, nanovitamins have gained extensive recognition due to their novel qualities, including a high level of adsorption capacity and low toxicity. Therefore, the present study compared the effects of dietary supplementation with different sources of vitamin E (regular, RVE vs. nano, NVE) and varying inclusion levels on the growth performance, antioxidant capacity, VE absorption sites, and pharmacokinetics in AA broilers. The results indicated that supplementing broiler diets with NVE provides superior antioxidant benefits compared to RVE. This improvement is attributed to the enhanced absorption efficiency and extended half-life of NVE, both contributing to increased antioxidant performance of broilers.

The association of dietary antioxidants and the inflammatory potential of the diet with poor physical function and disability in older Australian men: the Concord Health and Ageing in Men Project.

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed tests, and activities of daily living (ADL) and instrumental activities of daily living (IADL) questionnaires, at baseline and 3-year follow-up (n 616). Logistic regression analysis was used to identify associations between diet and incident poor physical function and disability. Both poor antioxidant intake and high E-DII scores at baseline were significantly associated with poor grip strength and ADL disability at 3-year follow-up. No significant associations with walking speed or IADL disability were observed. Individual micronutrient analysis revealed a significant association between the lowest two quartiles of vitamin C intake and poor grip strength. The lowest quartiles of intake for vitamins A, C, E and Zn were significantly associated with incident ADL disability. The study observed that poor antioxidant and anti-inflammatory food intake were associated with odds of developing disability and declining muscle strength in older men. Further interventional research is necessary to clarify the causality of these associations.

Efecto de la Vitamina E en Células Peritubulares de Testículos de Ratones Mus musculus Tratados con Ácido Valproico Durante el Estado Fetal y Pubertad / Effect of Vitamin E on Peritubular Cells from Testis of Mus musculus Mice Treated with Valproic Acid During the Fetal Stage and Puberty

El ácido valproico (VPA) es un fármaco antiepiléptico teratógenico que, al ser administrado durante etapas tempranas del embarazo, puede producir alteraciones en el desarrollo embriofetal, las que se manifiestan tanto a nivel del sistema nervioso como del testículo. No obstante, se ha reportado que la administración de vitamina E (VE) podría revertir dichas alteraciones. El objetivo del presente estudio fue determinar el efecto protector de la VE a nivel testicular en fetos y ratones púberes expuestos a VPA durante la fase embrionaria de su desarrollo. Se utilizó un total de 30 ratones hembra adultas gestantes (Mus musculus) cepa BALB/c, las cuales se dividieron en 6 grupos. El estudio contempló el análisis de fetos machos a los 17,5 días post-coital (dpc) y machos juveniles a las 6 semanas post-natal. A los grupos 1 y 4 se les administró 0,3 mL de solución fisiológica (grupos control para 17,5 dpc y 6 semanas postnatal, respectivamente). A los grupos 2 y 5 se les suministró la cantidad de 600 mg/kg de VPA (grupos VPA), en tanto que a los grupos 3 y 6 se les aplicó la misma dosis de VPA complementada con 200 UI de VE (grupos VPA+VE). Se describió la histología normal y patológica del compartimento peritubular del testículo. En los grupos VPA se evidenció una degeneración de la pared peritubular, y atrofia de túbulos seminíferos, así como exfoliación de las células germinales. Por el contrario, en los grupos VPA+VE tales signos no fueron observados y la morfología presentó aspecto normal solo con algunas alteraciones focales. Estos resultados corroboran el hecho que la administración de VE contrarresta en parte, los efectos deletéreos que ocasiona el VPA.

SUMMARY: Valproic acid (VPA) is a teratogenic antiepileptic drug that, when administered during the early stages of pregnancy, can produce alterations in embryo-fetal development, which manifest both at the level of the nervous system and the testicle. However, it has been reported that the administration of vitamin E (VE) could reverse these alterations. The study aimed to determine the protective effect of VE at the testicular level in fetuses and pubertal mice exposed to VPA during the embryonic phase of their development. 30 pregnant adult female mice (Mus musculus) BALB/c strain were used, which were divided into 6 groups. The study included the analysis of male fetuses at 17.5 days post-coital (dpc) and juvenile males at 6 weeks post-natal. Groups 1 and 4 were administered 0.3 mL of physiological solution. Groups 2 and 5 were given 600 mg/kg of VPA (VPA groups), while groups 3 and 6 were given the same dose of VPA supplemented with 200 IU of VE (VPA+VE). The normal and pathological histology of the peritubular compartment of the testis was described. In the VPA groups, degeneration of the peritubular wall, and atrophy of the seminiferous tubules, as well as exfoliation of the germ cells, were evident. On the contrary, in the VPA+VE groups such signs were not observed and the morphology presented a normal appearance with only some focal alterations. These results corroborate the fact that the administration of VE partially counteracts the deleterious effects caused by VPA.

Vitamin E suppresses aortic ultrastructural alterations induced by toxic doses of monosodium glutamate / La vitamina E suprime las alteraciones ultraestructurales aórticas inducidas por dosis tóxicas de glutamato monosódico

SUMMARY: An association between certain food additives and chronic diseases is reported. Current study determined whether administering toxic doses of the food additive monosodium glutamate (MSG) into rats can induce aortopathy in association with the oxidative stress and inflammatory biomarkers upregulation and whether the effects of MSG overdose can be inhibited by vitamin E. MSG at a dose of (4 mg/kg; orally) that exceeds the average human daily consumption by 1000x was administered daily for 7 days to the rats in the model group. Whereas, rats treated with vitamin E were divided into two groups and given daily doses of MSG plus 100 mg/ kg vitamin E or MSG plus 300 mg/kg vitamin E. On the eighth day, all rats were culled. Using light and electron microscopy examinations, a profound aortic injury in the model group was observed demonstrated by damaged endothelial layer, degenerated smooth muscle cells (SMC) with vacuoles and condensed nuclei, vacuolated cytoplasm, disrupted plasma membrane, interrupted internal elastic lamina, clumped chromatin, and damaged actin and myosin filaments. Vitamin E significantly protected aorta tissue and cells as well as inhibited MSG-induced tissue malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The highest used vitamin E dosage was more effective. Additionally, a significant correlation was observed between the aortic injury degree and tissue MDA, TNF-α, IL-6, and superoxide dismutase (SOD) levels (p=0.001). Vitamin E effectively protects against aortopathy induced by toxic doses of MSG in rats and inhibits oxidative stress and inflammation.

RESUMEN: Se reporta una asociación entre ciertos aditivos alimentarios y enfermedades crónicas. El objetivo de este estudio fue determinar si la administración de dosis tóxicas del aditivo alimentario glutamato monosódico (MSG) en ratas puede inducir aortopatía en asociación con el estrés oxidativo y la regulación positiva de los biomarcadores inflamatorios y si el efecto de una sobredosis de MSG se puede inhibir con vitamina E. Se administró MSG diariamente durante 7 días una dosis de (4 g/kg; por vía oral) que excede el consumo diario humano promedio, en 1000x a las ratas del grupo modelo. Mientras que las ratas tratadas con vitamina E se dividieron en dos grupos y se administraron dosis diarias de MSG más 100 mg/kg de vitamina E o MSG más 300 mg/kg de vitamina E. Todas las ratas fueron sacrificadas en el octavo día. Usando exámenes de microscopía óptica y electrónica, se observó una lesión aórtica profunda en el grupo modelo demostrada por una capa endotelial dañada, células musculares lisas degeneradas (SMC) con vacuolas y núcleos condensados, citoplasma vacuolado, membrana plasmática rota, lámina elástica interna interrumpida, cromatina agrupada y filamentos de actina y miosina dañados. La vitamina E protegió significativamente el tejido y las células de la aorta, además de inhibir el malondialdehído tisular (MDA) inducido por MSG, la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-α). La dosis más alta de vitamina E utilizada fue más efectiva. Además, se observó una correlación significativa entre el grado de lesión aórtica y los niveles tisulares de MDA, TNF-α, IL-6 y superóxido dismutasa (SOD) (p=0,001). La vitamina E efectivamente protege contra la aortopatía inducida por dosis tóxicas de MSG en ratas e inhibe el estrés oxidativo y la inflamación.

Risk of Colorectal Cancer in a Brazilian Population is Differentially Associated with the Intake of Processed Meat and Vitamin E.

The incidence and mortality rates of colorectal cancer (CRC) in Northeast Brazil are increasing. To study the association between CRC and diet, data were obtained from 64 patients with CRC and 123 sex- and age-matched controls. The dietary details were recorded using a validated food frequency questionnaire. Nutrient intake was calculated using Dietsys software (National Cancer Institute, Maryland, USA). In a binary logistic regression model of dietary components (model 1), the chance of CRC increased by 0.2% (odds ratio [OR] = 1.002; 95% confidence interval [CI]: 1.000-1.004) for each gram of processed meat intake per week (p < 0.010). Consumption of eggs decreased the chance by 0.1% per gram (OR = 0.999; 95% CI: 0.998-1.000; p < 0.050). The use of oil (including olive oil) for served food decreased the chance by 1.8% (OR = 0.982; 95% CI: 0.970-0.992) for each time consumed (p < 0.010). In a model of nutritional factors (model 2), intake of vitamin E decreased the chance by 16.8% (OR = 0.832; 95% CI: 0.725-0.940) for each milligram intake per week (p < 0.010). In model 1 and 2 smoking increased the chance of CRC by 10.294 (95%CI: 4.240-27.670) and 2.496 (95% CI: 1.425-3.566) times (p < 0.010; p < 0.010), respectively.

Exploring the potential neurotoxicity of vaping vitamin E or vitamin E acetate.

Serious adverse health effects have been reported with the use of vaping products, including neurologic disorders and e-cigarette or vaping product use-associated lung injury (EVALI). Vitamin E acetate, likely added as a diluent to cannabis-containing products, was linked to EVALI. Literature searches were performed on vitamin E and vitamin E acetate-associated neurotoxicity. Blood brain barrier (BBB) penetration potential of vitamin E and vitamin E acetate were evaluated using cheminformatic techniques. Review of the literature showed that the neurotoxic potential of inhalation exposures to these compounds in humans is unknown. Physico-chemical properties demonstrate these compounds are lipophilic, and molecular weights indicate vitamin E and vitamin E acetate have the potential for BBB permeability. Computational models also predict both compounds may cross the BBB via passive diffusion. Based on literature search, no experimental nonclinical studies and clinical information on the neurotoxic potential of vitamin E via inhalation. Neurotoxic effects from pyrolysis by-product, phenyl acetate, structurally analogous to vitamin E acetate, suggests vitamin E acetate has potential for central nervous system (CNS) impairment. Cheminformatic model predictions provide a theoretical basis for potential CNS permeability of these inhaled dietary ingredients suggesting prioritization to evaluate for potential hazard to the CNS.

Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial.

Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.

Vitamin E-Enhanced Liners in Primary Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

OBJECTIVE: Adding vitamin E to highly cross-linked polyethylene liners is frequently performed in clinical practice, aiming at reducing liner wear, increasing liner survival, and delaying revision surgery. This study is aimed at evaluating the revision rate, total femoral head penetration, and postoperative clinical function of highly cross-linked polyethylene liners with and without vitamin E in total hip arthroplasty. METHODS: We conducted a systematic literature search to identify the use of highly cross-linked vitamin E liners compared to other liners in patients who received total hip arthroplasty (THA) before April 2021. The study quality assessment and data collection were conducted by two independent reviewers. Studies were artificially grouped, and vitamin E-enhanced liners (VE-PE) were compared with vitamin E-free liners (non-VE-PE). Analyses were executed using Review Manager version 5.4.1. RESULTS: From the preliminary screening of 568 studies, fourteen studies met the research criteria. Compared to non-VE-PE, using VE-PE reduced the all-cause revision rate (odds ratio = 0.54; 95% confidence interval (CI) 0.40, 0.73; P < 0.0001). The total femoral head penetration of the VE-PE was lower than that of the non-VE-PE (mean difference = -0.10; 95% CI -0.17, -0.03; P = 0.007). However, there was no difference in clinical function, including the Harris Hip Score and EuroQol Five-Dimension Questionnaire scores. CONCLUSION: Compared to the liners without vitamin E, the addition of vitamin E to liners could reduce the all-cause revision rate by approximately 46% in the short-term follow-up. In addition, even though addition of vitamin E could also slow down femoral head penetration, there is no contribution to clinical function.

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of ß-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

Tocotrienol-Rich Vitamin E (Tocovid) Improved Nerve Conduction Velocity in Type 2 Diabetes Mellitus Patients in a Phase II Double-Blind, Randomized Controlled Clinical Trial.

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

Hepatoprotective, antioxidant and anti-inflammatory potentials of Vit-E/C@SeNPs in rats: Synthesis, characterization, biochemical, radio-biodistribution, molecular and histopathological studies.

This study aimed to synthesize a nano-structure between selenium, Vit. C, and Vit. E (Vit-E/C@SeNPs) as a promising protective and therapeutic agent for hepatocellular carcinoma. Vit-E/C@SeNPs were characterized using TEM and DLS and its zetapotential was measured to evaluate its stability. DPPH assay and SRB test were performed to estimate its antioxidant capacity and cytotoxicity, respectively. A radiosynthesis of 99mTc-Vit-E/C@SeNPs was done for further in-vivo pharmacokinetic studies on normal and solid tumor induced mice. Further, in-vivo studies were conducted to investigate Vit-E/C@SeNPs efficacy against hepatocellular damage in Wistar albino rats induced by diethylnitrosamine (DEN) / Carbon Tetra chloride (CCl4). The synthesis results showed spherical Vit-E/C@SeNPs with core size of 50 nm, radical scavenging activity (%RSC) of 75.9%, and IC50 of 27.9 µg/ml. The biochemical analysis results showed that the lower liver function biomarker values (ALT, AST, ALP, total bilirubin and GGT) has gone for the Vit-E/C@SeNPs prevention and treated group, which also showed significant depletion of liver tissue l-MDA, and obvious increase in GSH concentration and CAT activity and marked improvement in the histological feature of liver tissue. Additionally, a significant up-regulation of mRNA gene expression levels of inflammatory gene (TGFß1, NFκB, iNOS, PPAR-γ and TNFα) and Apoptotic gene (P53) were determined by using Quantitative real-time PCR (qPCR). The values down regulate and tend to normal in prevention and control group. All of these introduce Vit-E/C@SeNPs as a promising agent as protective and therapeutic agent against DEN/ CCl4-induced hepatocellular damage (Hepatocellular carcinoma).

Brefeldin A delivery nanomicelles in hepatocellular carcinoma therapy: Characterization, cytotoxic evaluation in vitro, and antitumor efficiency in vivo.

Hepatocellular carcinoma (HCC) is one of the major cancers with high mortality rate. Traditional drugs used in clinic are usually limited by the drug resistance and side effect and novel agents are still needed. Macrolide brefeldin A (BFA) is a well-known lead compound in cancer chemotherapy, however, with poor solubility and instability. In this study, to overcome these disadvantages, BFA was encapsulated in mixed nanomicelles based on TPGS and F127 copolymers (M-BFA). M-BFA was conferred high solubility, colloidal stability, and capability of sustained release of intact BFA. In vitro, M-BFA markedly inhibited the proliferation, induced G0/G1 phase arrest, and caspase-dependent apoptosis in human liver carcinoma HepG2 cells. Moreover, M-BFA also induced autophagic cell death via Akt/mTOR and ERK pathways. In HepG2 tumor-bearing xenograft mice, indocyanine green (ICG) as a fluorescent probe loaded in M-BFA distributed to the tumor tissue rapidly, prolonged the blood circulation, and improved the tumor accumulation capacity. More importantly, M-BFA (10 mg/kg) dramatically delayed the tumor progression and induced extensive necrosis of the tumor tissues. Taken together, the present work suggests that M-BFA has promising potential in HCC therapy.

Topical cream containing nanoparticles with vitamin E to prevent radiodermatitis in women with breast cancer: a clinical trial protocol.

OBJECTIVE: Little is known about the efficacy of products aiming to prevent radiodermatitis, which affects between 90-95% of women with breast cancer. The use of antioxidants is promising, however, there is a lack of evidenceon their effectiveness. Here, the authors present a clinical trial protocol to evaluate the effects of applying a cream containing nanoparticles with vitamin E to prevent radiodermatitis in patients with breast cancer. METHOD: The protocol recommends that 108 women with breast cancer, receiving radiotherapy, are included in this triple-blinded, randomized, controlled study at an oncology hospital. Patients will be divided in three groups of 36 individuals each: group A will receive a cream with lipid nanoparticles and vitamin E, group B will receive a cream without nanoparticles nor vitamin E, and group C will receive a cream with nanoparticles without vitamin E. The primary endpoints will evaluate the incidence, degree, and time of onset of radiodermatitis. The secondary endpoints will focus on the quality of life, symptoms, and local temperature. Patients will be assessed three times a week, from the start of their radiotherapy treatment to two weeks after the last session. This protocol was approved by the research ethics committee of the institutions involved and registered on an international trials database.

Antioxidant Supplementation Does Not Affect Bone Turnover Markers During 60 Days of 6° Head-Down Tilt Bed Rest: Results from an Exploratory Randomized Controlled Trial.

BACKGROUND: Immobilization and related oxidative stress are associated with bone loss. Antioxidants like polyphenols, omega-3 fatty acids, vitamins, and micronutrients may mitigate these negative effects on bone metabolism through scavenging of free radicals. OBJECTIVES: We hypothesized that antioxidant supplementation during 60 days of 6° head-down tilt bed rest (HDBR) would reduce bone resorption and increase bone formation compared to nonsupplemented controls. METHODS: This exploratory randomized, controlled, single-blind intervention study conducted in a parallel design included 20 healthy male volunteers (age, 34 ± 8 years; weight, 74 ± 6 kg). The study consisted of a 14-day adaptation phase [baseline data collection (BDC)], followed by 60 days of HDBR and a 14-day recovery period (R). In the antioxidant group, volunteers received an antioxidant cocktail (741 mg/d polyphenols, 2.1 g/d omega-3 fatty acids, 168 mg/d vitamin E, and 80 µg/d selenium) with their daily meals. In the control group, volunteers received no supplement. Based on their body weight, all volunteers received an individually tailored and strictly controlled diet, consistent with DRIs. We analyzed biomarkers of calcium homeostasis, bone formation, and bone resorption during BDC, HDBR, and R, as well as for 30 days after the end of HDBR. Data were analyzed by linear mixed models. RESULTS: The antioxidant supplement did not affect serum calcium, parathyroid hormone, urinary C-telopeptide of type I collagen (CTX), urinary N-telopeptide of type I collagen, serum ß-C-telopeptide of type I collagen (ß-CTX), bone alkaline phosphatase, aminoterminal propeptide of type I collagen, osteocalcin, or urinary calcium excretion. In both groups, typical bed rest-related changes were observed. CONCLUSIONS: Supplementation of an antioxidant cocktail to a diet matching the DRIs did not affect bone resorption or formation during 60 days of HDBR in healthy young men. This trial was registered at clinicaltrials.gov as NCT03594799.

Efficacy of combining pentoxiphylline and vitamin E versus vitamin E alone in non-alcoholic steatohepatitis- A randomized pilot study.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease. Vitamin E (VE), an anti-oxidant, has shown improvement in NAFLD activity score (NAS) but not fibrosis. Pentoxiphylline (PTX), an anti-TNF-alpha agent, has been reported to reduce hepatic inflammation and fibrosis. We evaluated combination of these drugs in NASH patients. METHODS: In a prospective study, consecutive histologically proven patients with NASH were randomized to receive either PTX, 400 mg thrice daily and VE 400 IU twice daily (group PTVE, n = 36) or VE alone (group VE, n = 33). Clinical, dietary and biochemical follow-up was done till 12 months. Primary end-point was change in alanine aminotransferase (ALT)  levels.   RESULTS: Both groups were comparable at baseline. On a strict diet and lifestyle modification regimen, both groups had similar reduction in body mass index and waist circumference. There was a similar reduction in ALT levels in the two groups. Metabolically, patients in PTVE group had greater reduction in fasting insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) than VE group (p = 0.05). Tumor necrosis factor alpha (TNFα) levels were also significantly lower in PTVE group from 6 months onwards. Twelve (10%) patients had repeat liver biopsy (7 in group PTVE, 5 in group VE) with no difference in reduction of NAS score (p = 0.45). However, there was a significant fibrosis regression in PTVE compared to VE group (p = 0.003). CONCLUSIONS: These data show greater efficacy of a combination of PTX and VE in achieving fibrosis regression compared to VE alone with better metabolic homeostasis and amelioration of the pro-inflammatory status. TRIAL REGISTRATION: Clinical Trials Registry no. NCT01384578.

The role of biofactors in the prevention and treatment of age-related diseases.

The present demographic changes toward an aging society caused a rise in the number of senior citizens and the incidence and burden of age-related diseases (such as cardiovascular diseases [CVD], cancer, nonalcoholic fatty liver disease [NAFLD], diabetes mellitus, and dementia), of which nearly half is attributable to the population ≥60 years of age. Deficiencies in individual nutrients have been associated with increased risks for age-related diseases and high intakes and/or blood concentrations with risk reduction. Nutrition in general and the dietary intake of essential and nonessential biofactors is a major determinant of human health, the risk to develop age-related diseases, and ultimately of mortality in the older population. These biofactors can be a cost-effective strategy to prevent or, in some cases, even treat age-related diseases. Examples reviewed herein include omega-3 fatty acids and dietary fiber for the prevention of CVD, α-tocopherol (vitamin E) for the treatment of biopsy-proven nonalcoholic steatohepatitis, vitamin D for the prevention of neurodegenerative diseases, thiamine and α-lipoic acid for the treatment of diabetic neuropathy, and the role of folate in cancer epigenetics. This list of potentially helpful biofactors in the prevention and treatment of age-related diseases, however, is not exhaustive and many more examples exist. Furthermore, since there is currently no generally accepted definition of the term biofactors, we here propose a definition that, when adopted by scientists, will enable a harmonization and consistent use of the term in the scientific literature.

Implant survival of 2,723 vitamin E-infused highly crosslinked polyethylene liners in total hip arthroplasty: data from the Finnish Arthroplasty Register.

Background and purpose - The use of crosslinked polyethylene in total hip arthroplasty (THA) has decreased wear remarkably. It has been suggested that the antioxidative effects of vitamin E may enhance the wear properties of polyethylene even further. This study evaluates revision rates between vitamin E-infused polyethylene liners (E1 and E-poly, ZimmerBiomet, Warsaw, IN, USA) versus moderately crosslinked polyethylene (ModXLPE) liners from the same manufacturer used in primary THA.Patients and methods - We conducted a study based on data from the Finnish Arthroplasty Register. The study group consisted of 2,723 THAs with a vitamin E-infused liner and a reference group of 2,707 THAs with a moderately crosslinked polyethylene liner. Survivorship, revision risk, and re-revision causes were compared between groups.Results - The 7-year survival of the vitamin E-infused polyethylene liner group and of the reference group with revision for any reason as the endpoint was comparable (94% [95% CI 92.9-94.9] and 93% [CI 91.9-93.9], respectively). The adjusted hazard ratio (HR) for any revision was similar between the groups (0.7 [CI 0.4-1.1]). When revision for aseptic loosening was studied as the endpoint, the survival for the study group was 99% (CI 98.6-99.4) and for the reference group 99% (CI 98.7-99.5), and the risk of revision was comparable between the study groups (HR 1.3 [CI 0.7-2.5]).Interpretation - After an observation period of 7 years vitamin E-infused liners shows results equal to results obtained with crosslinked polyethylene liners.

Vitamin E pretreated Wharton's jelly-derived mesenchymal stem cells attenuate CCl4-induced hepatocyte injury in vitro and liver fibrosis in vivo.

Oxidative microenvironment in fibrotic liver alleviates the efficacious outcome of mesenchymal stem cells (MSCs)-based cell therapy. Recent evidence suggests that pharmacological pretreatment is a rational approach to harness the MSCs with higher therapeutic potential. Here, we investigated whether Vitamin E pretreatment can boost the antifibrotic effects of Wharton's jelly-derived MSCs (WJMSCs). We used rat liver-derived hepatocytes injured by CCl4 treatment in co-culture system with Vitamin E pretreated-WJMSCs (Vit E-WJMSCs) to evaluate the hepatoprotective effect of Vit E-WJMSCs. After 24 h of co-culturing, we found that Vit E-WJMSCs rescued injured hepatocytes as hepatocyte injury-associated medium (AST, ALT, and ALP) and mRNA (Cyp2e1, Hif1-α, and Il-1ß) markers reduced to normal levels. Subsequently, CCl4-induced liver fibrosis rat models were employed to examine the antifibrotic potential of Vit E-WJMSCs. After 1 month of cell transplantation, it was revealed that Vit E-WJMSCs transplantation ceased fibrotic progression, as evident by improved hepatic architecture and functions, more significantly in comparison to naïve WJMSCs. In addition, Vit E-WJMSCs transplantation decreased the expressions of fibrosis-associated gene (Tgf-ß1, α-Sma, and Col1α1) markers in the liver parenchyma. Intriguingly, the results of tracing experiments discovered that more WJMSCs engrafted in the Vit E-WJMSCs treated rat livers compared to naïve WJMSCs treated livers. These findings implicate that pretreatment of WJMSCs with Vitamin E improves their tolerance to hostile niche of fibrotic liver; thereby further enhancing their efficacy for hepatic fibrosis.

Application of Partial Hydrogenation for the Generation of Minor Tocochromanol Homologs and Functional Evaluation of Hydrogenated Tocotrienol-rich Vitamin E Oil in Diabetic Obese Mice.

Recent research has identified minor homologs of vitamin E with one or two double bonds in the side-chain, namely tocomonoenol (T1) and tocodienol (T2), in natural products. We first explored the effectiveness of partial hydrogenation for generating minor tocochromanols from tocotrienol (T3). During hydrogenation with pure α-T3 as a substrate, the side-chain was partially saturated in a time-dependent manner, and a large amount of α-T1 and α-T2 was obtained. To investigate the beneficial effects of the hydrogenated product, we fed diabetic obese KK-A y mice with a hydrogenated T3 mixture (HT3). Feeding HT3 revealed tissue-specific accumulation of tocochromanols, ameliorated hyperglycemia and improved ratio of high-density lipoprotein cholesterol to total cholesterol in serum, with invariant body weight and fat mass. Hence, we propose that hydrogenation is a useful method for generating T1 and T2 homologs, which can be applied to explore the structure-related function of tocochromanols.