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International Journal of Molecular... Jun 2021Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils,... (Review)
Review
Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers' interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research.
Topics: Antioxidants; Diet; Humans; Tocotrienols; alpha-Tocopherol; gamma-Tocopherol
PubMed: 34207571
DOI: 10.3390/ijms22126222 -
Equine Veterinary Education Apr 2021Vitamin E is essential for neuromuscular function. The primary treatment, oral supplementation with natural ('RRR') α-tocopherol, is not effective in all horses. The...
Vitamin E is essential for neuromuscular function. The primary treatment, oral supplementation with natural ('RRR') α-tocopherol, is not effective in all horses. The objectives of this pilot study were to evaluate the safety and efficacy of a subcutaneously administered RRR-α-tocopherol preparation. Horses were randomly assigned in a cross-over design to initially receive RRR-α-tocopherol (5000 IU/450 kg of 600 IU/mL) subcutaneously (n = 3) or orally (n = 3) or were untreated sentinels (n = 2). Tissue reactions following injection in Phase I of the study necessitated adjustment of the preparation with reduction of the RRR-α-tocopherol concentration to 500 IU/mL in Phase 2. Following an 8-week washout period, horses received the reciprocal treatment route with the new preparation (5000 IU/450 kg of 500 IU/mL). Serum, CSF and muscle α-tocopherol concentrations were determined by high-performance liquid chromatography over a 14-day period during each phase. Serum and CSF α-tocopherol concentrations increased significantly postinjection only when the 500 IU/mL product was administered (P<0.0001). There was no significant difference in the muscle concentration of α-tocopherol following either treatment. All eight horses had marked tissue reaction to subcutaneous injection, regardless of product concentration. Whilst we have demonstrated that this route may be a useful alternative to oral supplementation, the marked tissue reaction makes use of such products limited at this time to only the most refractory of cases.
PubMed: 34326575
DOI: 10.1111/eve.13308 -
Respiratory Research Jun 2022Oxidative stress plays a key role in the pathogenesis of respiratory diseases; however, studies on antioxidant vitamins and respiratory outcomes have been conflicting.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oxidative stress plays a key role in the pathogenesis of respiratory diseases; however, studies on antioxidant vitamins and respiratory outcomes have been conflicting. We evaluated whether lower serum levels of vitamins A, C, D, and E are associated with respiratory morbidity and mortality in the U.S. adult population.
METHODS
We conducted a pooled analysis of data from the 1988-1994 and 1999-2006 National Health and Nutrition Examination Survey (participants aged ≥ 20 years). We estimated covariate-adjusted odds ratios (aOR) per interquartile decrease in each serum vitamin level to quantify associations with respiratory morbidity, and covariate-adjusted hazard ratios (aHR) to quantify associations with respiratory mortality assessed prospectively through 2015. Vitamin supplementation and smoking were evaluated as potential effect modifiers.
RESULTS
Lower serum vitamin C increased the odds of wheeze among all participants (overall aOR: 1.08, 95% CI: 1.01-1.16). Among smokers, lower serum α-tocopherol vitamin E increased the odds of wheeze (aOR: 1.11, 95% CI: 1.04-1.19) and chronic bronchitis/emphysema (aOR: 1.13, 95% CI: 1.03-1.24). Conversely, lower serum γ-tocopherol vitamin E was associated with lower odds of wheeze and chronic bronchitis/emphysema (overall aORs: 0.85, 95% CI: 0.79-0.92 and 0.85, 95% CI: 0.76-0.95, respectively). Lower serum vitamin C was associated with increased chronic lower respiratory disease (CLRD) mortality in all participants (overall aHR: 1.27, 95% CI: 1.07-1.51), whereas lower serum 25-hydroxyvitamin D (25-OHD) tended to increase mortality from CLRD and influenza/pneumonia among smokers (aHR range: 1.33-1.75). Mortality from influenza/ pneumonia increased with decreasing serum vitamin A levels in all participants (overall aHR: 1.21, 95% CI: 0.99-1.48). In pooled analysis, vitamin C deficiency and 25-OHD insufficiency were associated with mortality from influenza/pneumonia, increasing mortality risk up to twofold.
CONCLUSIONS
Our analysis of nationally representative data on over 34,000 participants showed that lower serum levels of vitamins A, C, D, and α-tocopherol vitamin E are associated with increased respiratory morbidity and/or mortality in U.S. adults. The results underscore the importance of antioxidant vitamins in respiratory health.
Topics: Adult; Antioxidants; Ascorbic Acid; Bronchitis, Chronic; Emphysema; Humans; Influenza, Human; Morbidity; Nutrition Surveys; Vitamin A; Vitamins; alpha-Tocopherol
PubMed: 35681205
DOI: 10.1186/s12931-022-02059-w -
Current Developments in Nutrition Jun 2021α-Tocopherol (αT) is essential for fetal development. One study has shown that the human placenta preferentially transfers the natural stereoisomer, -αT. But prenatal...
BACKGROUND
α-Tocopherol (αT) is essential for fetal development. One study has shown that the human placenta preferentially transfers the natural stereoisomer, -αT. But prenatal supplements generally contain synthetic αT (S-αT).
OBJECTIVES
We aimed to determine if umbilical cord plasma is enriched for -αT in racially diverse neonates from both uncomplicated and complicated pregnancies and if cord -αT enrichment is impacted by maternal αT stereoisomer profile.
METHODS
We measured αT and αT stereoisomers in plasma from a randomly selected subset of 66 predominantly black and Hispanic maternal-fetal pairs from the Camden Study involving control (= 28) and complicated pregnancies (= 38). We collected maternal plasma at study entry (week 16 gestation; w16) and week 28 gestation (w28) and cord plasma at birth.
RESULTS
-αT was the predominant stereoisomer in all maternal and cord plasma samples, but S-αT stereoisomers were found in most samples and comprised a high percentage of αT in some maternal-neonate pairs. Cord plasma had a higher percentage -αT (< 0.05) and lower percentage S-αT (< 0.0001) than w28 plasma. Pregnancy status did not impact maternal or cord plasma concentrations of αT, -αT, or S-αT; except plasma from complicated pregnancies was higher in S-αT at w28 than at w16 (< 0.05). Maternal w28 αT did not correlate with cord αT. However, both maternal w28 αT and S-αT positively correlated with both cord S-αT ( = 0.340, = 0.0049; = 0.538, < 0.00001) and percentage S-αT ( = 0.399, = 0.001; = 0.786, < 0.00001) but negatively correlated with cord percentage -αT ( = -0.399, = 0.0009; = -0.786, < 0.00001).
CONCLUSIONS
The proportion of -αT was higher in cord compared with maternal plasma in both uncomplicated and complicated pregnancies. Our data suggest that maternal S-αT raises cord S-αT and decreases the proportion of -αT in the neonatal circulation. Because the bioactivities of -αT and S-αT differ, this warrants future research to determine the importance of our observations to neonatal αT status.
PubMed: 34104848
DOI: 10.1093/cdn/nzab073 -
Nutrients Jun 2021Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a...
Recent cohort studies indicate a potential role of the antioxidant α-tocopherol in reducing bone loss and risk of fractures, especially hip fractures. We performed a Mendelian randomization investigation of the associations of circulating α-tocopherol with estimated bone mineral density (eBMD) using heel ultrasound and fractures, identified from hospital records or by self-reports and excluding minor fractures. Circulating α-tocopherol was instrumented by three genetic variants associated with α-tocopherol levels at < 5 × 10 in a genome-wide association meta-analysis of 7781 participants of European ancestry. Summary-level data for the genetic associations with eBMD in 426,824 individuals and with fracture (53,184 cases and 373,611 non-cases) were acquired from the UK Biobank. Two of the three genetic variants were strongly associated with eBMD. In inverse-variance weighted analysis, a genetically predicted one-standard-deviation increase of circulating α-tocopherol was associated with 0.07 (95% confidence interval, 0.05 to 0.09) g/cm increase in BMD, which corresponds to a >10% higher BMD. Genetically predicted circulating α-tocopherol was not associated with odds of any fracture (odds ratio 0.97, 95% confidence interval, 0.91 to 1.05). In conclusion, our results strongly strengthen a causal link between increased circulating α-tocopherol and greater BMD. Both an intervention study in those with a low dietary intake of α-tocopherol is warranted and a Mendelian randomization study with fragility fractures as an outcome.
Topics: Aged; Aged, 80 and over; Bone Density; Female; Fractures, Bone; Genetic Predisposition to Disease; Genome-Wide Association Study; Heel; Humans; Male; Mendelian Randomization Analysis; Meta-Analysis as Topic; Odds Ratio; Polymorphism, Single Nucleotide; Ultrasonography; White People; alpha-Tocopherol
PubMed: 34198753
DOI: 10.3390/nu13061940 -
Biochemistry and Biophysics Reports Dec 2021One of the neuropathological hallmarks of Alzheimer's disease (AD)-causing neurodegeneration and consequent memory deterioration, and eventually, cognitive decline-is...
One of the neuropathological hallmarks of Alzheimer's disease (AD)-causing neurodegeneration and consequent memory deterioration, and eventually, cognitive decline-is amyloid-β (Aβ) aggregation forming amyloid plaques. Our previous study showed the potential of a tocotrienol-rich fraction-a mixture of naturally occurring of vitamin E analogs-to inhibit Aβ aggregation and restore cognitive function in an AD mouse model. The current study examined the effect of three vitamin E analogs-α-tocopherol (α-TOC), α-tocotrienol (α-T3), and γ-tocotrienol (γ-T3)-on Aβ aggregation, disaggregation, and oligomerization in vitro. Thioflavin T (ThT) assay showed α-T3 reduced Aβ aggregation at 10 μM concentration. Furthermore, both α-T3 and γ-T3 demonstrated Aβ disaggregation, as shown by the reduction of ThT fluorescence. However, α-TOC showed no significant effect. We confirmed the results for ThT assays with scanning electron microscopy imaging. Further investigation in photo-induced cross-linking of unmodified protein assay indicated a reduction in Aβ oligomerization by γ-T3. The present study thus revealed the individual effect of each tocotrienol analog in reducing Aβ aggregation and oligomerization as well as disaggregating preformed fibrils.
PubMed: 34541343
DOI: 10.1016/j.bbrep.2021.101131 -
Journal of Traditional and... Jul 2022The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic...
BACKGROUND AND AIM
The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic oxidative status of middle-aged rats with Freund's adjuvant-induced polyarthritis, a model for rheumatoid arthritis. Intraperitoneally administered free α-tocopherol provided the reference for comparison.
EXPERIMENTAL PROCEDURE
Two protocols of treatment were followed: intraperitoneal administration of free α-tocopherol (100 mg/kg i.p.) or oral administration of free and nanoencapsulated α-tocopherol (100 mg/kg p.o.). Animals were treated during 18 days after arthritis induction.
RESULTS
Free (i.p.) and encapsulated α-tocopherol decreased the hind paws edema, the leukocytes infiltration into femorotibial joints and the mRNA expression of pro-inflammatory cytokines in the tibial anterior muscle of arthritic rats, but the encapsulated compound was more effective. Free (i.p.) and encapsulated α-tocopherol decreased the high levels of reactive oxygen species in the brain and liver, but only the encapsulated compound decreased the levels of protein carbonyl groups in these organs. Both free (i.p.) and encapsulated α-tocopherol increased the α-tocopherol levels and the ratio of reduced to oxidized glutathione in these organs.
CONCLUSION
Both intraperitoneally administered free α-tocopherol and orally administered encapsulated α-tocopherol effectively improved inflammation and systemic oxidative stress in middle-aged arthritic rats. However, the encapsulated form should be preferred because the oral administration route does not be linked to the evident discomfort that is caused in general by injectable medicaments. Consequently, α-tocopherol-loaded polycaprolactone nanoparticles may be a promising adjuvant to the most current approaches aiming at rheumatoid arthritis therapy.
PubMed: 35747358
DOI: 10.1016/j.jtcme.2021.12.003 -
Antioxidative Effect of Dihydrosphingosine (d18:0) and α-Tocopherol on Tridocosahexaenoin (DHA-TAG).Journal of Agricultural and Food... Oct 2023Sphingoid bases have shown promise as effective antioxidants in fish oils together with α-tocopherol, and the effect has been attributed to products resulting from...
Sphingoid bases have shown promise as effective antioxidants in fish oils together with α-tocopherol, and the effect has been attributed to products resulting from amino-carbonyl reactions (lipation products) between the sphingoid base amine group and carbonyl compounds from lipid oxidation. In this study, the synergistic effect of dihydrosphingosine (d18:0) and α-tocopherol was studied on pure docosahexaenoic acid (DHA) triacylglycerols with an omics-type liquid- and gas-chromatographic mass spectrometric approach to verify the synergistic effect, to get a comprehensive view on the effect of d18:0 on the oxidation pattern, and to identify the lipation products. The results confirmed that d18:0 rapidly reacts further in the presence of lipid oxidation products and α-tocopherol. α-Tocopherol and d18:0 showed an improved antioxidative effect after 12 h of oxidation, indicating the formation of antioxidants through carbonyl-amine reactions. Imines formed from the carbonyls and d18:0 could be tentatively identified.
Topics: Antioxidants; alpha-Tocopherol; Docosahexaenoic Acids; Sphingosine; Oxidation-Reduction
PubMed: 37751317
DOI: 10.1021/acs.jafc.3c02668 -
Molecules (Basel, Switzerland) Jan 2022Our research aimed to show acrylamide's influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing...
Our research aimed to show acrylamide's influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing inflammation via supplementation with α-tocopherol. For this purpose, an in ovo model was used where the embryos were exposed to acrylamide, α-tocopherol and a cocktail of these substances. After 48 h of exposure, we collected brain samples and performed biochemical assays to examine the effect of the chosen substances on oxidative stress (malondialdehyde-MDA and reduced glutathione-GSH) and acetylcholinesterase activity (AChE). The results showed that acrylamide decreased AChE activity in the examined brain samples by about 25% in comparison to the control group, and this effect was decreased by administering α-tocopherol. The concentration of malondialdehyde significantly increased in the group given acrylamide, while, in the group with α-tocopherol, the observed concentration was lower in comparison to the control group. Moreover, a decrease in glutathione concentration was observed after the administration of acrylamide; however, the protective effect of α-tocopherol was only slightly visible in this case. In conclusion, α-tocopherol minimizes the harmful effects of acrylamide on AchE, and it can minimize the concentration of MDA.
Topics: Acrylamide; Animals; Antioxidants; Brain; Chick Embryo; Chickens; Eggs; Inflammation; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; alpha-Tocopherol
PubMed: 35164231
DOI: 10.3390/molecules27030965 -
Biomedicine & Pharmacotherapy =... Jun 2024Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E,...
Spinal cord injury (SCI) is a type of central nervous system (CNS) injury in which ferroptosis is becoming a promising target for treatment. Alpha-tocopherol (Vitamin E, Vit E) is a compound with anti-ferroptosis activity. The mechanism of alpha-tocopherol in regulating ferroptosis after SCI has not been deeply studied. In this study, rats with SCI were treated by Alpha-tocopherol based on bioinformatic analysis and molecular docking prediction. Behavioral tests and histological findings showed that Alpha-tocopherol promoted neural function recovery and tissue repairment in rats with SCI. Subsequently, regulatory effects of Alpha-tocopherol on Alox15 and ferroptosis were detected and then localized by immunofluorescence. In vitro, alpha-tocopherol improved the ROS accumulation, iron overload, lipid peroxidation and mitochondrial dysfunction. The effects of Alpha-tocopherol on the expression of Alox15, Ptgs2 and 4Hne were validated in vitro. Finally, the inhibitory effects of Alpha-tocopherol on Alox15 and ferroptosis were weakened by the mutation of 87th residue of Alox15. In summary, alpha-tocopherol could alleviate SCI-induced ferroptosis by downregulating Alox15 to promote neural function recovery in rats with SCI. Findings in this study could help further our understanding on SCI-induced ferroptosis and provide a novel insight for treating SCI.
Topics: Animals; Ferroptosis; alpha-Tocopherol; Spinal Cord Injuries; Recovery of Function; Down-Regulation; Rats; Arachidonate 15-Lipoxygenase; Rats, Sprague-Dawley; Lipid Peroxidation; Male; Reactive Oxygen Species; Arachidonate 12-Lipoxygenase; Disease Models, Animal; Molecular Docking Simulation
PubMed: 38754264
DOI: 10.1016/j.biopha.2024.116734