Vitamin E can promote spermatogenesis by regulating the expression of proteins associated with the plasma membranes and protamine biosynthesis.

Vitamin E is generally believed to promote the production of ovine sperm mainly through its antioxidant effect. Our previous studies have shown that some non-antioxidant genes may also be key in mediating this process. The objective of this study was to identify key candidate proteins that were differentially expressed in response to a treatment with Vitamin E. Prepubertal ovine testicular cells were isolated and divided into two groups. They were either treated with 800 µM Vitamin E (based on our previous results) or used as a non-treated control. After 24 h, all the cells were harvested for proteomic analysis. We found 115 differentially expressed proteins, 4 of which were up-regulated and 111 were down-regulated. A GO term enrichment analysis identified 127 Biological Process, 63 Cell Component and 26 Molecular Function terms that were enriched. Within those terms, 13, 11 and 26 terms were significantly enriched, respectively. Terms related to membrane and enzyme activity including the inner acrosomal membrane, signal peptidase complex, cysteine-type endopeptidase activity, etc., were also markedly enriched, while none of the KEGG pathways were enriched. We found that many of the differentially expressed proteins, such as CD46 (membrane cofactor protein), FLNA (Filamin A), DYSF (Dysferlin), IFT20 (Intraflagellar transport 20), SPCS1 (Signal peptidase complex subunit 1) and SPCS3 (Signal peptidase complex subunit 3) were related to the acrosomal and plasma membranes. A parallel reaction monitoring (PRM) analysis verified that Vitamin E improved spermatogenesis by regulating the expression of FLNA, SPCS3, YBX3 and RARS, proteins that are associated with the plasma membranes and protamine biosynthesis of the spermatozoa.

Mapping of quantitative trait loci for antioxidant molecules in tomato fruit: Carotenoids, vitamins C and E, glutathione and phenolic acids.

The nutritional value of a crop lies not only in its protein, lipid, and sugar content but also involves compounds such as the antioxidants lycopene, ß-carotene and vitamin C. In the present study, wild tomato Solanum pimpinellifolium LA 1589 was assessed for its potential to improve antioxidant content. This wild species was found to be a good source of alleles for increasing ß-carotene, lycopene, vitamin C and vitamin E contents in cultivated tomato. Characterization of an LA 1589 interspecific inbred backcross line (IBL) mapping population revealed many individuals with transgressive segregation for the antioxidants confirming the usefulness of this wild species for breeding of these traits. Molecular markers were used to identify QTLs for the metabolites in the IBL population. In total, 64 QTLs were identified for the antioxidants and their locations were compared to the map positions of previously identified QTLs for confirmation. Four (57 %) of the carotenoid QTLs, four (36 %) of the vitamin QTLs, and 11 (25 %) of the phenolic acid QTLs were supported by previous studies. Furthermore, several potential candidate genes were identified for vitamins C and E and phenolic acids loci. These candidate genes might be used as markers in breeding programs to increase tomato's antioxidant content.

Metabolic engineering of soybean seeds for enhanced vitamin E tocochromanol content and effects on oil antioxidant properties in polyunsaturated fatty acid-rich germplasm.

Soybean seeds produce oil enriched in oxidatively unstable polyunsaturated fatty acids (PUFAs) and are also a potential biotechnological platform for synthesis of oils with nutritional omega-3 PUFAs. In this study, we engineered soybeans for seed-specific expression of a barley homogentisate geranylgeranyl transferase (HGGT) transgene alone and with a soybean γ-tocopherol methyltransferase (γ-TMT) transgene. Seeds for HGGT-expressing lines had 8- to 10-fold increases in total vitamin E tocochromanols, principally as tocotrienols, with little effect on seed oil or protein concentrations. Tocochromanols were primarily in δ- and γ-forms, which were shifted largely to α- and ß-tocochromanols with γ-TMT co-expression. We tested whether oxidative stability of conventional or PUFA-enhanced soybean oil could be improved by metabolic engineering for increased vitamin E antioxidants. Selected lines were crossed with a stearidonic acid (SDA, 18:4Δ6,9,12,15)-producing line, resulting in progeny with oil enriched in SDA and α- or γ-linoleic acid (ALA, 18:3Δ9,12,15 or GLA, 18:3Δ6,9,12), from transgene segregation. Oil extracted from HGGT-expressing lines had ≥6-fold increase in free radical scavenging activity compared to controls. However, the oxidative stability index of oil from vitamin E-enhanced lines was ~15% lower than that of oil from non-engineered seeds and nearly the same or modestly increased in oil from the GLA, ALA and SDA backgrounds relative to controls. These findings show that soybean is an effective platform for producing high levels of free-radical scavenging vitamin E antioxidants, but this trait may have negative effects on oxidative stability of conventional oil or only modest improvement of the oxidative stability of PUFA-enhanced oil.

Gene expression analysis of ovine prepubertal testicular tissue vitrified with a novel cryodevice (E.Vit).

PURPOSE: Testicular tissue cryopreservation prior to gonadotoxic therapies is a method to preserve fertility in children. However, the technique still requires development, especially when the tissue is immature and rather susceptible to stress derived from in vitro manipulation. This study aimed to investigate the effects of vitrification with a new cryodevice (E.Vit) on cell membrane integrity and gene expression of prepubertal testicular tissue in the ovine model. METHODS: Pieces of immature testicular tissue (1 mm3) were inserted into "E.Vit" devices and vitrified with a two-step protocol. After warming, tissues were cultured in vitro and cell membrane integrity was assessed after 0, 2, and 24 h by trypan blue exclusion test. Controls consisted of non-vitrified tissue analyzed after 0, 2, and 24 h in vitro culture (IVC). Expression of genes involved in transcriptional stress response (BAX, SOD1, CIRBP, HSP90AB1), cell proliferation (KIF11), and germ- (ZBDB16, TERT, POU5F1, KIT) and somatic- (AR, FSHR, STAR) cell specific markers was evaluated 2 and 24 h after warming. RESULTS: Post-warming trypan blue staining showed the survival of most cells, although membrane integrity immediately after warming (66.00% ± 4.73) or after 2 h IVC (59.67% ± 4.18) was significantly lower than controls (C0h 89.67% ± 1.45). Extended post-warming IVC (24 h) caused an additional decrease to 31% ± 3.46 (P < 0.05). Germ- and somatic-cell specific markers showed the survival of both cell types after cryopreservation and IVC. All genes were affected by cryopreservation and/or IVC, and moderate stress conditions were indicated by transcriptional stress response. CONCLUSIONS: Vitrification with the cryodevice E.Vit is a promising strategy to cryopreserve prepubertal testicular tissue.

Deciphering the genetic basis for vitamin E accumulation in leaves and grains of different barley accessions.

Tocopherols and tocotrienols, commonly referred to as vitamin E, are essential compounds in food and feed. Due to their lipophilic nature they protect biomembranes by preventing the propagation of lipid-peroxidation especially during oxidative stress. Since their synthesis is restricted to photosynthetic organisms, plant-derived products are the major source of natural vitamin E. In the present study the genetic basis for high vitamin E accumulation in leaves and grains of different barley (Hordeum vulgare L.) accessions was uncovered. A genome wide association study (GWAS) allowed the identification of two genes located on chromosome 7H, homogentisate phytyltransferase (HPT-7H) and homogentisate geranylgeranyltransferase (HGGT) that code for key enzymes controlling the accumulation of tocopherols in leaves and tocotrienols in grains, respectively. Transcript profiling showed a correlation between HPT-7H expression and vitamin E content in leaves. Allele sequencing allowed to decipher the allelic variation of HPT-7H and HGGT genes corresponding to high and low vitamin E contents in the respective tissues. Using the obtained sequence information molecular markers have been developed which can be used to assist smart breeding of high vitamin E barley varieties. This will facilitate the selection of genotypes more tolerant to oxidative stress and producing high-quality grains.

Genome-wide association study of vitamin E using genotyping by sequencing in sesame (Sesamum indicum).

BACKGROUND: At least eight structurally related forms of vitamin E occur in nature, four tocopherols and four tocotrienols, all of which are potent membrane-soluble antioxidants. In this study, we detected two major isoforms in sesame (Sesamum indicum L.) seed: γ-tocopherol and ß-tocotrienol. The objective of this study is to investigate the genetic basis of these vitamin E isoforms. METHODS: We  conducted a genome-wide association study (GWAS) using 5962 genome-wide markers, acquired from 96 core sesame accessions. The GWAS was performed using generalized linear (GLM) and mixed linear (MLM) models. RESULTS: LG08_6621957, on chromosome 8, was detected as having a significant association with γ-tocopherol in both models. It explained 20.9% of γ-tocopherol variation in sesame. For ß-tocotrienol, no significant loci were detected according to the two models, but one locus, SLG03_13104062, explained 17.8% of the phenotypic variation. Based on structure and phylogenetic studies, the 96 accessions were clearly clustered into two subpopulations. CONCLUSION: This study on sesame demonstrates and provides an evidence that genotyping by sequencing (GBS) based GWAS can be used to identifying important loci for small growing crops. The significant SNPs or genes could be useful for improving the vitamin E content in sesame breeding programs.

Vitamin E Metabolic Effects and Genetic Variants: A Challenge for Precision Nutrition in Obesity and Associated Disturbances.

Vitamin E (VE) has a recognized leading role as a contributor to the protection of cell constituents from oxidative damage. However, evidence suggests that the health benefits of VE go far beyond that of an antioxidant acting in lipophilic environments. In humans, VE is channeled toward pathways dealing with lipoproteins and cholesterol, underlining its relevance in lipid handling and metabolism. In this context, both VE intake and status may be relevant in physiopathological conditions associated with disturbances in lipid metabolism or concomitant with oxidative stress, such as obesity. However, dietary reference values for VE in obese populations have not yet been defined, and VE supplementation trials show contradictory results. Therefore, a better understanding of the role of genetic variants in genes involved in VE metabolism may be crucial to exert dietary recommendations with a higher degree of precision. In particular, genetic variability should be taken into account in targets concerning VE bioavailability per se or concomitant with impaired lipoprotein transport. Genetic variants associated with impaired VE liver balance, and the handling/resolution of oxidative stress might also be relevant, but the core information that exists at present is insufficient to deliver precise recommendations.

Effects of δ-tocotrienol on ochratoxin A-induced nephrotoxicity in rats.

Ochratoxin A (OTA), is a natural contaminant of the food chain worldwide involved in the development of different type of cancers in animals and humans. Several studies suggested that oxidative damage might contribute to increase the cytotoxicity and carcinogenicity capabilities of OTA. The aim of this study was to evaluate the possible protective effect of δ-tocotrienol (Delta), a natural form of vitamin E, against OTA-induced nephrotoxicity. Male Sprague-Dawley rats were treated with OTA and/or Delta by gavage for 14 days. Our results shown that OTA treatment induced the increase of reactive oxigen species production correlated to a strong reduction of Glomerular Filtration Rate (GFR) and absoluted fluid reabsorption (Jv) with conseguent significant increase in blood pressure. Consistent, we noted in the kidney of rats treated with OTA, an increase in malondialdheyde and dihydroethidium production and a reduction of the activity of the catalase, superoxide dismutase, and glutathione peroxidase. Conversly, in the rat group subjected to the concomitant treatment OTA plus Delta, we observed the restored effect, compared the OTA treatment group, on blood pressure, GFR, Jv, and all activities of renal antioxidant enzymes. Finally, as far as concern the tissue damage induced by OTA and measured evaluating fibronectin protein levels, we observed that in OTA plus Delta group this effect is not restored. Our findings releval that a mechanism underlying the renal toxicity induced by OTA is the oxidative stress and provide a new rationale to use a Delta in order to protect, at least in part, against OTA-induced nephrotoxicity.

Maize w3 disrupts homogentisate solanesyl transferase (ZmHst) and reveals a plastoquinone-9 independent path for phytoene desaturation and tocopherol accumulation in kernels.

Maize white seedling 3 (w3) has been used to study carotenoid deficiency for almost 100 years, although the molecular basis of the mutation has remained unknown. Here we show that the w3 phenotype is caused by disruption of the maize gene for homogentisate solanesyl transferase (HST), which catalyzes the first and committed step in plastoquinone-9 (PQ-9) biosynthesis in the plastid. The resulting PQ-9 deficiency prohibits photosynthetic electron transfer and eliminates PQ-9 as an oxidant in the enzymatic desaturation of phytoene during carotenoid synthesis. As a result, light-grown w3 seedlings are albino, deficient in colored carotenoids and accumulate high levels of phytoene. However, despite the absence of PQ-9 for phytoene desaturation, dark-grown w3 seedlings can produce abscisic acid (ABA) and homozygous w3 kernels accumulate sufficient carotenoids to generate ABA needed for seed maturation. The presence of ABA and low levels of carotenoids in w3 nulls indicates that phytoene desaturase is able to use an alternate oxidant cofactor, albeit less efficiently than PQ-9. The observation that tocopherols and tocotrienols are modestly affected in w3 embryos and unaffected in w3 endosperm indicates that, unlike leaves, grain tissues deficient in PQ-9 are not subject to severe photo-oxidative stress. In addition to identifying the molecular basis for the maize w3 mutant, we: (1) show that low levels of phytoene desaturation can occur in w3 seedlings in the absence of PQ-9; and (2) demonstrate that PQ-9 and carotenoids are not required for vitamin E accumulation.

Evaluation of Biosynthesis, Accumulation and Antioxidant Activityof Vitamin E in Sweet Corn (Zea mays L.) during Kernel Development.

Sweet corn kernels were used in this research to study the dynamics of vitamin E, by evaluatingthe expression levels of genes involved in vitamin E synthesis, the accumulation of vitamin E, and the antioxidant activity during the different stage of kernel development. Results showed that expression levels of ZmHPT and ZmTC genes increased, whereas ZmTMT gene dramatically decreased during kernel development. The contents of all the types of vitamin E in sweet corn had a significant upward increase during kernel development, and reached the highest level at 30 days after pollination (DAP). Amongst the eight isomers of vitamin E, the content of γ-tocotrienol was the highest, and increased by 14.9 folds, followed by α-tocopherolwith an increase of 22 folds, and thecontents of isomers γ-tocopherol, α-tocotrienol, δ-tocopherol,δ-tocotrienol, and ß-tocopherol were also followed during kernel development. The antioxidant activity of sweet corn during kernel development was increased, and was up to 101.8 ± 22.3 µmol of α-tocopherol equivlent/100 g in fresh weight (FW) at 30 DAP. There was a positive correlation between vitamin E contents and antioxidant activity in sweet corn during the kernel development, and a negative correlation between the expressions of ZmTMT gene and vitamin E contents. These results revealed the relations amongst the content of vitamin E isomers and the gene expression, vitamin E accumulation, and antioxidant activity. The study can provide a harvesting strategy for vitamin E bio-fortification in sweet corn.

Advances in Genetic Improvement for Tocotrienol Production: A Review.

Tocotrienols are forms of vitamin E that are present in several important food crops. Compared to tocopherols, less research has been conducted on these compounds because of their low bioavailability and distribution in plant tissues. Both tocotrienols and tocopherols are known for their antioxidant and anticancer activities, which are beneficial for both humans and animals. Moreover, tocotrienols possess certain properties which are not found in tocopherols, such as neuroprotective and cholesterol-lowering activities. The contents of tocotrienols in plants vary. Tocotrienols constitute more than 70% and tocopherols less than 30% of the total vitamin E content in palm oil, which is the best source of vitamin E. Accumulation of tocotrienols also occurs in non-photosynthetic tissues, such as the seeds, fruits and latex of some monocotyledonous and dicotyledonous plant species. The use of biotechnological techniques to increase the tocotrienol content in plants, their biological functions, and benefits to human health are discussed in this review.

Lethal dysregulation of energy metabolism during embryonic vitamin E deficiency.

Vitamin E (α-tocopherol, VitE) was discovered in 1922 for its role in preventing embryonic mortality. We investigated the underlying mechanisms causing lethality using targeted metabolomics analyses of zebrafish VitE-deficient embryos over five days of development, which coincided with their increased morbidity and mortality. VitE deficiency resulted in peroxidation of docosahexaenoic acid (DHA), depleting DHA-containing phospholipids, especially phosphatidylcholine, which also caused choline depletion. This increased lipid peroxidation also increased NADPH oxidation, which depleted glucose by shunting it to the pentose phosphate pathway. VitE deficiency was associated with mitochondrial dysfunction with concomitant impairment of energy homeostasis. The observed morbidity and mortality outcomes could be attenuated, but not fully reversed, by glucose injection into VitE-deficient embryos at developmental day one. Thus, embryonic VitE deficiency in vertebrates leads to a metabolic reprogramming that adversely affects methyl donor status and cellular energy homeostasis with lethal outcomes.

Genetic Variations Involved in Vitamin E Status.

Vitamin E (VE) is the generic term for four tocopherols and four tocotrienols that exhibit the biological activity of α-tocopherol. VE status, which is usually estimated by measuring fasting blood VE concentration, is affected by numerous factors, such as dietary VE intake, VE absorption efficiency, and VE catabolism. Several of these factors are in turn modulated by genetic variations in genes encoding proteins involved in these factors. To identify these genetic variations, two strategies have been used: genome-wide association studies and candidate gene association studies. Each of these strategies has its advantages and its drawbacks, nevertheless they have allowed us to identify a list of single nucleotide polymorphisms associated with fasting blood VE concentration and α-tocopherol bioavailability. However, much work remains to be done to identify, and to replicate in different populations, all the single nucleotide polymorphisms involved, to assess the possible involvement of other kind of genetic variations, e.g., copy number variants and epigenetic modifications, in order to establish a reliable list of genetic variations that will allow us to predict the VE status of an individual by knowing their genotype in these genetic variations. Yet, the potential usefulness of this area of research is exciting with regard to personalized nutrition and for future clinical trials dedicated to assessing the biological effects of the various isoforms of VE.

Vitamin E-Labeled Polyethylenimine for in vitro and in vivo Gene Delivery.

A series of Vitamin E (vitE)-labeled PEIs (PEI-vitEn) were synthesized and showed excellent complexation ability with plasmid DNA (pDNA). The cellular uptake of PEI-vitEn/pDNA complexes was greatly enhanced with the increase of vitE labeling, which is much better than that of control PEI25 in three different cell lines. PEI-vitE6 showed the best performance in gfp pDNA delivery and following GFP expression in HEK-293A cells. In addition, in vivo gene delivery in living mice also confirmed that PEI-vitE6 showed low toxicity and efficiently delivered gfp pDNA to the cells of liver and lung tissues for gene expression.

Genetically Programmed Changes in Photosynthetic Cofactor Metabolism in Copper-deficient Chlamydomonas.

Genetic and genomic studies indicate that copper deficiency triggers changes in the expression of genes encoding key enzymes in various chloroplast-localized lipid/pigment biosynthetic pathways. Among these are CGL78 involved in chlorophyll biosynthesis and HPPD1, encoding 4-hydroxyphenylpyruvate dioxygenase catalyzing the committed step of plastoquinone and tocopherol biosyntheses. Copper deficiency in wild-type cells does not change the chlorophyll content, but a survey of chlorophyll protein accumulation in this situation revealed increased accumulation of LHCSR3, which is blocked at the level of mRNA accumulation when either CGL78 expression is reduced or in the crd1 mutant, which has a copper-nutrition conditional defect at the same step in chlorophyll biosynthesis. Again, like copper-deficient crd1 strains, cgl78 knock-down lines also have reduced chlorophyll content concomitant with loss of PSI-LHCI super-complexes and reduced abundance of a chlorophyll binding subunit of PSI, PSAK, which connects LHCI to PSI. For HPPD1, increased mRNA results in increased abundance of the corresponding protein in copper-deficient cells concomitant with CRR1-dependent increased accumulation of γ-tocopherols, but not plastoquinone-9 nor total tocopherols. In crr1 mutants, where increased HPPD1 expression is blocked, plastochromanol-8, derived from plastoquinone-9 and purported to also have an antioxidant function, is found instead. Although not previously found in algae, this metabolite may occur only in stress conditions.

Subgenome-specific assembly of vitamin E biosynthesis genes and expression patterns during seed development provide insight into the evolution of oat genome.

Vitamin E is essential for humans and thus must be a component of a healthy diet. Among the cereal grains, hexaploid oats (Avena sativa L.) have high vitamin E content. To date, no gene sequences in the vitamin E biosynthesis pathway have been reported for oats. Using deep sequencing and orthology-guided assembly, coding sequences of genes for each step in vitamin E synthesis in oats were reconstructed, including resolution of the sequences of homeologs. Three homeologs, presumably representing each of the three oat subgenomes, were identified for the main steps of the pathway. Partial sequences, likely representing pseudogenes, were recovered in some instances as well. Pairwise comparisons among homeologs revealed that two of the three putative subgenome-specific homeologs are almost identical for each gene. Synonymous substitution rates indicate the time of divergence of the two more similar subgenomes from the distinct one at 7.9-8.7 MYA, and a divergence between the similar subgenomes from a common ancestor 1.1 MYA. A new proposed evolutionary model for hexaploid oat formation is discussed. Homeolog-specific gene expression was quantified during oat seed development and compared with vitamin E accumulation. Homeolog expression largely appears to be similar for most of genes; however, for some genes, homoeolog-specific transcriptional bias was observed. The expression of HPPD, as well as certain homoeologs of VTE2 and VTE4, is highly correlated with seed vitamin E accumulation. Our findings expand our understanding of oat genome evolution and will assist efforts to modify vitamin E content and composition in oats.

Selenium- or Vitamin E-Related Gene Variants, Interaction with Supplementation, and Risk of High-Grade Prostate Cancer in SELECT.

BACKGROUND: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E. METHODS: We undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics. RESULTS: We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome. CONCLUSION: Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks. IMPACT: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. Cancer Epidemiol Biomarkers Prev; 25(7); 1050-8. ©2016 AACR.

Titanium dioxide nanoparticles (100-1000 mg/l) can affect vitamin E response in Arabidopsis thaliana.

In the present study we analyze the effect of seed treatment by a range of nano-TiO2 concentrations on the growth of Arabidopsis thaliana plants, on the vitamin E content and the expression of its biosynthetic genes, as well as activity of antioxidant enzymes and lipid peroxidation. To conduct the mechanistic analysis of nano-TiO2 on plants growth and antioxidant status we applied nanoparticles concentrations that are much higher than those reported in the environment. We find that as the concentration of nano-TiO2 increases, the biomass, and chlorophyll content in 5-week-old Arabidopsis thaliana plants decrease in a concentration dependent manner. In opposite, higher nano-TiO2 concentration enhanced root growth. Our results indicate that a high concentration of nano-TiO2 induces symptoms of toxicity and elevates the antioxidant level. We also find that the expression levels of tocopherol biosynthetic genes were either down- or upregulated in response to nano-TiO2. Thermoluminescence analysis shows that higher nano-TiO2 concentrations cause lipid peroxidation. To the best of our knowledge, this is the first report concerning the effect of nano-TiO2 on vitamin E status in plants. We conclude that nano-TiO2 affects the antioxidant response in Arabidopsis thaliana plants. This could be an effect of a changes in vitamin E gene expression that is diminished under lower tested nano-TiO2 concentrations and elevated under 1000 µg/ml.

Tocopherols and tocotrienols in serum and liver of dairy cows receiving conjugated linoleic acids or a control fat supplement during early lactation.

The fat-soluble vitamin E comprises the 8 structurally related compounds (congeners) α-, ß-, γ-, and δ-tocopherol (with a saturated side chain) and α-, ß-, γ-, and δ-tocotrienol (with a 3-fold unsaturated side chain). Little is known regarding the blood and liver concentrations of the 8 vitamin E congeners during the transition from pregnancy to lactation in dairy cows. We thus quantified tocopherols (T) and tocotrienols (T3) in serum and liver and hepatic expression of genes involved in vitamin E metabolism in pluriparous German Holstein cows during late gestation and early lactation and investigated whether dietary supplementation (from d 1 in milk) with conjugated linoleic acids (CLA; 100g/d; each 12% of trans-10,cis-12 and cis-9,trans-11 CLA; n=11) altered these compared with control-fat supplemented cows (CTR; n=10). Blood samples and liver biopsies were collected on d -21, 1, 21, 70, and 105 (liver only) relative to calving. In both groups, the serum concentrations of αT, γT, ßT3, and δT3 increased from d -21 to d 21 and remained unchanged between d 21 and 70, but were unaffected by CLA. The concentrations of the different congeners of vitamin E in liver did not differ between the CTR and the CLA groups. In both groups, the concentrations of the vitamin E forms in liver changed during the course of the study. The hepatic mRNA abundance of genes controlling vitamin E status did not differ between groups, but α-tocopherol transfer protein and tocopherol-associated protein mRNA increased with time of lactation in both. In conclusion, the concentrations of vitamin E congeners and the expression of genes related to vitamin E status follow characteristic time-related changes during the transition from late gestation to early lactation but are unaffected by CLA supplementation at the dosage used.

Genetic variants reflecting higher vitamin e status in men are associated with reduced risk of prostate cancer.

Vitamin E (α-tocopherol) plays a key role in the regulation of cell growth and differentiation and has been studied as a potential chemopreventive agent for prostate cancer. The association of serum vitamin E concentrations with cancer risk may be modified by genetic variations in vitamin E-related genes. We examined whether variants in vitamin E-related genes were associated with risk of prostate cancer in a nested case-control study using 483 prostate cancer cases and 542 matched controls of European ancestry from a large U.S. multicenter trial that had available measurements of serum vitamin E concentrations and genotyping of 3 genome-wide association study meta-analysis-identified single-nucleotide polymorphisms (SNPs) associated with circulating vitamin E. ORs and 95% CIs were calculated using unconditional logistic regression adjusted for age, family history of prostate cancer, and serum total cholesterol. Findings suggest lower prostate cancer risk for men whose genotypes reflect higher vitamin E (i.e., α-tocopherol) status. An SNP (rs964184) near budding-site selection protein 13 (yeast) (BUD13), zinc finger protein 259 (ZNF259), and apolipoprotein A5 (APOA5) on 11q23.3 was significantly associated with prostate cancer risk (per-allele OR = 0.75; 95% CI: 0.58, 0.98; P-trend = 0.03). The association between rs964184 and prostate cancer risk was stronger among homozygous carriers of the minor allele (OR = 0.27; 95% CI: 0.09, 0.83). Another variant, rs11057830 in scavenger receptor class-B member 1 (SCARB1) on 12p24.31, approached statistical significance (OR = 0.32; 95% CI: 0.10, 1.01, P = 0.05; 2 minor allele copies). This study suggests that polymorphisms near BUD13/ZNF259/APOA5, involved in vitamin E transport and metabolism, may be associated with lower risk of prostate cancer. This trial was registered at clinicaltrials.gov as NCT00002540.