Vitamin E comprises eight structurally related isoforms, including α-, β-, γ-, and δ-tocopherols and their corresponding tocotrienols. These isoforms differ in the degree of methylation of the chromanol ring and the saturation of the side chain, structural features that critically influence their bioavailability, antioxidant capacity, and neuroprotective functions. This mini review systematically summarizes recent advances in the antioxidant and neuroprotective roles of vitamin E isoforms, with particular emphasis on their distinct mechanisms of action in the nervous system. Evidence from cell-based studies, animal models, and human investigations indicates that the neuroprotective effects of vitamin E isoforms vary considerably. Tocotrienols, characterized by their unsaturated side chains, exhibit enhanced membrane mobility and broader biological activity, demonstrating superior neuroprotective properties through modulation of signaling pathways, maintenance of mitochondrial function, and inhibition of abnormal tau hyperphosphorylation. In addition, different tocopherol isoforms show complementary roles in scavenging reactive oxygen species and/or reactive nitrogen species. Despite substantial experimental evidence, clinical data remain limited, and challenges such as differences in bioavailability and incomplete understanding of isoform-specific mechanisms persist. Overall, vitamin E should be regarded not as a single molecule but as a family of functionally complementary isoforms, whose synergistic actions may play a crucial role in maintaining brain health and in the prevention and treatment of neurodegenerative diseases.

Curcumin and α-tocopherol (vitamin E) are lipophilic antioxidants limited by poor stability. To overcome this, both compounds were co-encapsulated in tannic acid-crosslinked gelatine-sodium alginate microcapsules via complex coacervation, comparing Ultra-Turrax (UT) and ultrasonication (US) homogenisation across core-to-wall ratios (1/1, 1/2, 1/3). Ultrasonication at a 1/3 ratio yielded the highest encapsulation efficiencies (94.3% curcumin, 91.0% vitamin E, vs. ∼41-44% untreated). These US microcapsules were smaller (227 nm), less porous (36.7%), and demonstrated progressive pH-dependent release over 72 h without an initial burst. Antioxidant activity was fully retained during simulated gastrointestinal digestion. Overall, ultrasonication-assisted complex coacervation provides an effective route for developing robust gelatine-alginate delivery systems for food and pharmaceutical formulations.

The development of novel olive cultivars with enhanced vitamin E levels in their virgin olive oil is a major goal in olive breeding programs. This study reports the cloning and characterization of an olive cDNA, which encodes tocopherol methyltransferase (TMT) that catalyzes the last reaction of tocopherol biosynthesis. Sequence analysis and bacterial functional expression confirmed that the gene encodes an active TMT enzyme. Expression profiling across different olive tissues and cultivars revealed a cultivar-dependent spatial and temporal regulation of TMT transcripts. When combined with tocopherol profiling, the data suggest that OeTMT is implicated in the biosynthesis of the α-tocopherol present in olive mesocarp and, consequently, in the olive oil. Additionally, the α-tocopherol biosynthesis in the olive mesocarp appears to be transcriptionally regulated in response to environmental factors, including water status, temperature, light, and wounding, indicating that OeTMT could play a role in the response to abiotic stress.

Ataxia with vitamin E deficiency (AVED) is a rare autosomal-recessive neurological disorder caused by biallelic pathogenic variants in TTPA. Early vitamin E supplementation may prevent or limit irreversible neurological damage, but diagnosis is often delayed. Multi-nucleotide variants (MNVs) in TTPA have rarely been described and may be misinterpreted when adjacent substitutions are evaluated independently. We investigated a 34-year-old woman with childhood-onset progressive ataxia using clinical, biochemical, neuroimaging, and electrophysiological assessments. Serum vitamin E levels were measured longitudinally during supplementation. Whole-exome sequencing, read-level inspection, and Sanger sequencing were used to identify and confirm a homozygous TTPA complex allele, NM_000370.3:c. 296G > A;299 A > C, predicted to result in NP_000361.1:p. Gly99_Tyr100delinsAspSer, and to assess familial segregation. Population-database review, in silico prediction, and exploratory structure-based analysis were performed to evaluate its potential clinical relevance. The patient had markedly reduced baseline serum vitamin E levels of 0.8 µg/mL, which increased to 7.5 µg/mL after 12 months of supplementation. This biochemical correction was temporally accompanied by qualitatively observed improvements in gait stability, coordination, speech, and fine motor performance. Read-level analysis supported the presence of both substitutions on the same allele, and Sanger sequencing confirmed the homozygous complex allele in the patient and heterozygous carrier status in both parents. The affected residues are conserved and located within the CRAL-TRIO domain of α-tocopherol transfer protein. Exploratory structure-based analysis suggested altered local residue interactions; however, no functional assay was performed, and effects on protein stability, α-tocopherol binding, or transfer could not be established. This report expands the molecular spectrum of AVED by describing a homozygous TTPA complex allele and highlights the importance of MNV-aware interpretation of closely spaced substitutions. Vitamin E supplementation resulted in biochemical correction and was accompanied by possible partial clinical improvement despite initiation in adulthood. Functional studies are required to determine the precise effect of this allele on α-tocopherol transfer protein function.

Lactic fermentation can restructure food matrices and modulate the molecular distribution of nutrients and bioactive compounds, thereby altering their technological and functional performance in complex food systems. In this study, Agaricus bisporus flour was used as a model mushroom matrix to investigate how fermentation-drive compositional remodeling influences the physicochemical and functional properties of gluten-free bread. Native and lactic-fermented mushroom flours were incorporated into a rice-corn-tapioca system, and their effects on dough expansion, crumb structure, nutritional composition, fatty acid profile, free sugar profiles, and antioxidant signatures assessed. Fermentation markedly altered the mushroom flour matrix, leading to reduced dough gas retention and denser crumb structures, consistent with microstructural modifications affecting viscoelastic behavior. More importantly, fermentation induced clear composition shifts, including redistribution of free sugars, modulation of fatty acid profiles, and increased α-tocopherol retention, indicating microbial metabolism-mediated molecular reorganization. These changes were directly associated with enhanced antioxidant capacity in the final breads, particularly in samples enriched with fermented flour. Multivariate analysis further confirmed that fermentation status, rather than incorporation level, was the main driver of variation across compositional and functional parameters, especially those related to lipid oxidation protection, sugar metabolism, and antioxidant potential. These findings demonstrate that lactic fermentation acts as a matrix-engineering strategy capable of redefining the structure-function role of A. bisporus flour in gluten-free bread, offering mechanistic insights into how fermented fungal ingredients can be leveraged to design nutritionally enhanced and functionally optimized cereal-free products.

Plants exposed to high light (HL) must dissipate excess excitation energy while preventing photooxidative damage to the photosynthetic apparatus. Tocopherols are major lipophilic antioxidants in chloroplasts, but whether replacement of α-tocopherol by γ-tocopherol preserves HL acclimation and NPQ-associated photoprotection remains unclear. Here, we investigated the response of Arabidopsis wild-type Col and the α-tocopherol-deficient mutant vte4-4, which accumulates γ-tocopherol instead of α-tocopherol, to acute HL stress. Under HL, vte4-4 showed more severe visible leaf damage than Col, together with higher malondialdehyde and jasmonic acid accumulation and a significant loss in the PSII reaction center protein D1. The mutant also displayed weaker induction of non-photochemical quenching (NPQ), stronger decreases in Fv/Fm and ΦEo, and more pronounced alterations in OJIP-derived parameters due to HL stress. Although vte4-4 increased the total VAZ pool under HL, its lower Z/(VAZ) and higher A/(VAZ) ratios respect to Col indicate a qualitative impairment in xanthophyll-cycle operation rather than defective pigment accumulation. This phenotype was associated with lower HL-induced PsbS accumulation, loss of VDE protein and low AsA/DHA ratio, suggesting a redox limitation affecting both photooxidative buffering and VDE-dependent zeaxanthin formation. Together, our results indicate that γ-tocopherol accumulation is not sufficient to sustain wild-type-like HL acclimation in the absence of α-tocopherol. We propose that α-tocopherol functions not only as a membrane antioxidant, but also as a component of the photoprotective network that supports efficient NPQ engagement and preserves PSII performance under high light stress.

Pesticide use in extensive agriculture generates complex exposures for wildlife, however, early-life effects in reptiles remain underexplored. In this study, we evaluated whether embryonic exposure at manufacturer-recommended concentration for field use: glyphosate (GLY at 1 and 2%), 2,4-D (at 0.06 and 0.12%), chlorantraniliprole (CAP at 0.015 and 0.03%), imidacloprid (IMI at 0.1 at 0.2%) and three mixtures at the lowest concentrations (M1: GLY+2,4-D; M2: CAP + IMI; M3: M1+M2) disrupt lipid metabolism, lipoperoxidation and corticosterone levels in Caiman latirostris hatchlings. Hatching success declined under 2,4-D 0.06%, CAP 0.03%, and IMI 0.2%. Residual yolk showed alterations in polyunsaturated fatty acids, together with yolk-cholesterol and α-tocopherol depletion, particularly under CAP 0.03% and in the complex mixtures M1, M2, and M3. Changes in plasma lipid profiles, hepatic aminotransferase activities as well as alteration of NADPH-producing gene expression in blood were observed in M2 and M3. Higher lipoperoxidation levels were observed at the highest concentration across single compounds and in M1 and M3; whereas corticosterone increased in 2,4-D 0.12%. These findings demonstrate that early life stages of caimans are highly sensitive to these xenobiotics, affecting lipid metabolism and associated physiological processes. Moreover, mixtures induced stronger and more complex responses than single compounds, leading to metabolic disruption during early development. Our findings highlight the importance of evaluating realistic agrochemical mixtures to better assess their ecological risk.

Long-term exposure to ambient particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5) has been associated with optic neuropathy and retinal neurodegeneration, but experimental evidence remains limited. We assessed two certified environmental particulate reference materials in primary mouse retinal cells and after repeated ocular-surface exposure in mice. For the in vitro analyses, technical replicate wells were first averaged within each independent cell isolation, and each experimental condition was then normalized to the corresponding control from the same biological replicate. Particulate exposure produced condition-dependent changes in 2',7'-dichlorofluorescin diacetate (DCFDA) fluorescence and ATP-dependent viability, with statistically significant effects concentrated in selected retinal glial-cell conditions. After within-experiment normalization and multiplicity adjustment, direct comparisons did not demonstrate a statistically significant protective effect of α-tocopherol or N-acetylcysteine on particulate-associated responses, and retinal glial-cell coculture did not significantly improve RGC survival relative to monoculture. In postnatal mice, topical particulate administration was associated with inner retinal thinning and lower RGC-marker-positive cell counts. In adult Thy1-CFP mice, neither sample-specific nor post hoc pooled within-mouse comparisons with contralateral saline-treated eyes were statistically significant. A separate post hoc exploratory between-animal comparison showed fewer CFP-positive cells in pooled particulate-treated eyes than in independent bilateral-saline controls (mean difference, -14.4 cells; 95% CI, -28.1 to -0.7; P = 0.040). These findings support cellular and retinal susceptibility under the conditions used, but they do not establish particle transport to the retina, a causal oxidative mechanism, or quantitative risk from ambient PM2.5 exposure in humans.

BackgroundDehydroepiandrosterone sulfate (DHEAS) has been consistently linked to cardiovascular and skeletal health; however, the relationship between circulating antioxidant concentrations, including vitamins, and DHEAS levels in older adults has been insufficiently examined.AimTo assess associations between serum DHEAS and five antioxidants: β-cryptoxanthin, total lycopene, α-tocopherol, γ-tocopherol, and retinol.MethodsData from the Midlife in the United States (MIDUS3) Biomarker Project (2017-2022) were analyzed in a cross-sectional design. Analyses evaluated associations between DHEAS, antioxidant levels, and demographic and metabolic characteristics, including age, sex, smoking history, creatinine, HbA1c, total cholesterol, body mass index, dietary quality, alcohol intake, physical activity, and sleep quality. Multivariable linear regression models adjusting for all antioxidants and potential confounders were conducted following square-root transformation of DHEAS.SummaryThe analytical sample comprised 747 participants (55.8% female) with a mean age of 66.0 years (SD = 9.64). In adjusted models, higher α-tocopherol concentrations were associated with lower DHEAS levels (β = -0.09; 95% CI: [-0.172 to -0.009], P < 0.031) whereas retinol demonstrated a positive association with DHEAS (β = 0.081; 95% CI: [0.009-0.154], P = 0.029). None of the other antioxidants had a significant association with serum DHEAS. Increasing age, female sex, and poorer sleep quality were significantly associated with lower DHEAS concentrations. In conclusion, in older adults, serum retinol levels are positively associated with DHEAS concentrations, whereas α-tocopherol shows an inverse association. Conversely, no significant associations were observed between serum DHEAS levels and β-cryptoxanthin, total lycopene, or γ-tocopherol.

Consumers and producers are increasingly interested in how finishing practices impact beef nutrient density. This study compared ribeye steaks from grass-fed cattle (n = 237) and grain-fed cattle (n = 71) sourced from 112 North American operations and retailers using targeted metabolomics. Grain-fed beef contained 15-35% higher vitamins B1, B5, and B6 (all p ≤ 0.05), reflecting vitamin-mineral premixes and/or enhanced microbial synthesis under amylolytic rumen conditions. In contrasts, grass-fed beef contained ∼88% higher α-tocopherol and ∼ 53% higher β-carotene (both p ≤ 0.01). Of 195 detected phytonutrients and related metabolites, 43 differed significantly between systems; 35 were higher in grass-fed beef, including hippuric acid (+78%), p-cresol sulfate (+37%), and cinnamoylglycine (+93%; all, p < 0.001), while 8 were higher in grain-fed beef, including 4-hydroxyphenylacetic acid (+275%) and 3-phenyllactic acid (+150%; both p < 0.001). Correlation analyses indicate that botanically diverse and well-rested pastures were associated with higher α-tocopherol and total phytonutrient concentrations in grass-fed beef, while higher phenylpropanoic/phenyllactic compounds associated with grain finishing.

The increasing number of cases of E-cigarette or vaping product use-associated lung injury (EVALI) has raised concerns regarding their safe use, particularly because of the association of vaping additives with lung dysfunction. While the mechanisms by which vaping additives affect the LS film are unclear, labored breathing is a hallmark of EVALI, suggesting disruption of LS mechanics. We hypothesize that the accumulation of vape additives in the lungs alters their lipid packing and rheological properties. We investigate how two common vape additives, cannabidiol (CBD) and α-tocopherol (vitamin E), alter the interfacial mechanics of dipalmitoylphosphatidylcholine (DPPC) monolayers subjected to cyclic deformations mimicking breathing. Quasi-static surface properties were evaluated through compression/expansion isotherms using a Langmuir-Pockels trough with movable ribbon barriers, while epifluorescence microscopy was employed to visualize domain morphology. More importantly, since lung compliance depends on the dynamic restructuring of LS components at the alveolar surface, dilatational rheology was probed via oscillatory barrier deformations. Our results showed that both additives affected the surface activity and rheology of DPPC films in a concentration-dependent manner. However, the extent of impact also depended on the chemical composition of the additive, with vitamin E showing a larger impact than CBD at all concentrations studied. Further, when both additives were present, our results suggest that vitamin E plays a dominant role. This difference may be attributed to the bulkier molecular structure of vitamin E. Overall, our findings highlight that long-term exposure to vaping can disrupt film structure, altering its interfacial mechanics and thus reducing film stability.

The effects of dietary vitamin E level and source on the reproductive performance of female red hybrid tilapia, Oreochromis sp., was investigated. Broodstock diets were formulated with added α-tocopheryl acetate (α-ToAc) at 0 (T0), 60 (T60) or 600 (T600) mg per kg diet, which represented sub-optimal, at optimal or ten times above optimal levels, respectively, of vitamin E requirement reported for maximum growth of hybrid tilapia. A fourth diet was supplemented with a palm oil-derived tocotrienols-rich fraction (TRF) designed to contribute α-tocopherol (α-T) at 60 mg per kg diet (PalmE60). TRF consisted of a mixture of co-existing α-T with tocotrienols (T3; 75.5% of total vitamin E). Six pre-spawning female tilapia (individually color-tagged) and two males were placed in each breeding tank. Each diet was fed to two tanks of broodfish for 12 weeks. Irrespective of level or source, vitamin E supplementation significantly improved (P < 0.05) reproductive performance. The average number of eggs produced at each spawning per broodfish was increased by 77.9%, 65.8% and 40.4% when fed T600, PalmE60 and T60, respectively, compared to T0 diet. Absolute fecundity of broodfish fed the T600 or PalmE60 diet was significantly higher compared to the T60 diet. The mobilization of α-T from the peripheral tissues to the ovaries of broodfish fed the T0 or T60 diet confirmed that vitamin E supplementation beyond dietary levels estimated for growth was necessary to optimize spawning performance of tilapia. This is the first report that palm TRF could provide vitamin E to meet the reproductive needs of broodfish.