Form Of Α-tocopherol Research Articles

Scientific opinion on the tolerable upper intake level for vitamin E.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin E. As α-tocopherol is recognised as the only essential form of vitamin E, the Panel restricted its evaluation to α-tocopherol. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of vitamin E, namely risk of impaired coagulation and bleeding, cardiovascular disease and prostate cancer. The effect on blood clotting and associated increased risk of bleeding is considered as the critical effect to establish an UL for vitamin E. No new evidence has been published that could improve the characterisation of a dose-response. The ULs for vitamin E from all dietary sources, which were previously established by the Scientific Committee on Food, are retained for all population groups, i.e. 300 mg/day for adults, including pregnant and lactating women, 100 mg/day for children aged 1-3 years, 120 mg/day for 4-6 years, 160 mg/day for 7-10 years, 220 mg/day for 11-14 years and 260 mg/day for 15-17 years. A UL of 50 mg/day is established for infants aged 4-6 months and a UL of 60 mg/day for infants aged 7-11 months. ULs apply to all stereoisomeric forms of α-tocopherol. ULs do not apply to individuals receiving anticoagulant or antiplatelet medications (e.g. aspirin), to patients on secondary prevention for CVD or to patients with vitamin K malabsorption syndromes. It is unlikely that the ULs for vitamin E are exceeded in European populations, except for regular users of food supplements containing high doses of vitamin E.

Design and Investigation of New Water-Soluble Forms of α-Tocopherol with Antioxidant and Antiglycation Activity Using Amphiphilic Copolymers of N-Vinylpyrrolidone.

Water-soluble forms of α-tocopherol (TP) as an effective antioxidant were obtained by encapsulating it into nanoparticles (NPs) of amphiphilic copolymers of N-vinylpyrrolidone with triethylene glycol dimethacrylate (CPL1-TP) and N-vinylpyrrolidone with hexyl methacrylate and triethylene glycol dimethacrylate (CPL2-TP) synthesized by radical copolymerization in toluene. The hydrodynamic radii of NPs loaded with TP (3.7 wt% per copolymers) were typically ca. 50 or 80 nm depending on copolymer composition, media, and temperature. Characterization of NPs was accomplished by transmission electron microscopy (TEM), IR-, and 1H NMR spectroscopy. Quantum chemical modeling showed that TP molecules are capable to form hydrogen bonds with donor groups of the copolymer units. High antioxidant activity of both obtained forms of TP has been found by the thiobarbituric acid reactive species and chemiluminescence assays. CPL1-TP and CPL2-TP effectively inhibited the process of spontaneous lipid peroxidation as well as α-tocopherol itself. The IC50 values of luminol chemiluminescence inhibition were determined. Antiglycation activity against vesperlysine and pentosidine-like AGEs of TP water-soluble forms was shown. The developed NPs of TP are promising as materials with antioxidant and antiglycation activity and can be used in various biomedical applications.

Citrus is a Multivitamin Treasure Trove: A Review

Citrus is popularly known as the source of beneficial and essential nutrients for human health, including vitamins. The current review revealed the content of multivitamins, not only vitamin C but also vitamins A, B, and E that are not widely acknowledged within Citrus. Numerous Citrus genotypes contain vitamin C, with the grapefruit (Citrus paradisi) being the richest, and citron (C. medica) the poorest. Vitamin A in the form of β-carotene, α-carotene, and β-cryptoxanthin is commonly found within Citrus, especially in several colored flesh species such as grapefruit, mandarin (C. reticulate), and orange (C. sinensis). In terms of vitamin B, orange and grapefruit are proven to contain B-complex, including thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), inositol (B8) and folate (B9). Vitamin E in the form of α-tocopherol was detected in leaf kaffir lime (C. hystrix) and orange (C. sinensis), lemon (C. limon), mandarin (C. reticulate), and tangerine (C. nobilis) fruit. This review summarizes the nutritional content of Citrus; Citrus contains not only vitamin C but also other vitamins beneficial to human health, therefore Citrus consumption is highly recommended.

The potential of Strychnos madagascariensis (Poir.) as a source of vegetable oil

A study was undertaken to quantify screw press-extractable oil in the seed coat of Strychnos madagascariensis (Poir.) fruits harvested from trees in the northern coastal plain of KwaZulu-Natal province of South Africa and to determine the physiochemical properties and fatty acid composition of the oil. The seed coat constituted 19.36% of the dry fruit biomass and contained w/w 42% oil. Thus, the oil yield of the dried fruit was approx. 8.13%. Monounsaturated oleic acid accounted for between ca.70–73% of the total fatty acids in the Strychnos oil. Palmitic acid was present in amounts ranging between 15.05 and 16.27%. Also present, but in smaller amounts were cis linoleic acid (5.76–6.03%), stearic acid (1.64–4.65%), n3 linolenic acid (1.26–1.90%), and palmitoleic acid (1.10–1.65%). The oil contained trace amounts of arachidic acid (0.45–0.54%) and eicosenoic acid (approx.0.325%). Vitamin E was present in appreciable amounts, mostly in the form of α-tocopherol (approx. 5.8–14.4 mg/100 g oil) and β-tocotrienol (approx. 8.1–15.6 mg/100 g oil) homologues. The downside was that the oil had high acid values (161–181.32 mg KOH/g) and free fatty acid content (66–81 g oleic acid/100 g oil). There were 141 volatile compounds detected in the Strychnos oil, the most dominant of which were butyl-butyrate (20%), butyl hexanoate (8.2%) and glycerol (6.1–6.7%). Overall, the results indicate that Strychnos madagascariensis has potential as a source of vegetable oil.

New water-soluble forms of α-tocopherol: preparation and study of antioxidant activity in vitro

Water-soluble forms of α-tocopherol (vitamin E) possessing antioxidant activity in vitro were obtained by encapsulating in N-vinylpyrrolidone with triethylene glycol dimethacrylate polymer particles and were characterized by various physicochemical methods. Quantum-chemical modeling of a structure of α-tocopherol with the copolymer moiety and its theoretical absorption spectra modeling were carried out.

How Management System Affects the Concentration of Retinol and α-Tocopherol in Plasma and Milk of Payoya Lactating Goats: Possible Use as Traceability Biomarkers.

Simple SummaryThe milk production systems in goats are mainly intensive and semi-extensive. In the former, the goats are housed and are fed a total mixed ration with vitamin supplementation. In the latter, the feeding of the goats is based on grazing, although with some supplementation with compound feed. Retinol and α-tocopherol that appear in these animals come from the feeding regime, since the animal cannot synthesize them. The objective of this study was to verify if the vitamins provided in different management systems of Payoya lactating goats are good markers of the production system. For this purpose, the content of carotenoids, retinol and α-tocopherol in the milk and plasma of the goats was quantified. Results showed an inverse relationship of the amount of these vitamins between milk and plasma. On the other hand, the metabolism of different vitamins depends on their origin (natural/synthetic), with natural α-tocopherol and synthetic retinol showing the highest amount in milk. Finally, it was found that these compounds can be good traceability tools which allows to guaranty to the consumer the origin of the products derived from these animals.The retinol and α-tocopherol concentrations were quantified (μg/mL) using high-performance liquid chromatography (HPLC) in both plasma and milk of goats from three management systems. The aim was to investigate if the compounds pass from feed to animals’ fluids and to evaluate their potential use as feeding regime biomarkers. A total of 45 Payoya dams were distributed in three groups according to management system during the first month of lactation: mountain grazing (MG), cultivated meadow (CM) and total mixed ration (TMR). TMR group had higher concentrations of retinol in both plasma (25.92 ± 3.61 at 30 days postpartum) and milk (8.26 ± 0.79 at 10 days postpartum), and they were also the unique animals whose milk contained detectable concentrations of α-tocopherol (3.15 ± 0.19 at parturition). However, MG and CM goats showed higher plasma concentrations of α-tocopherol (64.26 ± 14.56 and 44.65 ± 5.75 at 30 days postpartum, respectively). These results could imply differences in the bioavailability of supplemented vitamin A and natural β-carotene and between the natural/synthetic forms of α-tocopherol. An inverse relationship between the fluids (plasma/milk) in the contents of α-tocopherol and retinol was observed as lactation progressed. Since 80% of the animals were correctly classified using a discriminant analysis based on these vitamins, these compounds could be used as traceability biomarkers of feeding system, but further studies are necessary to know the possible passage to kid meat.

Analysis of α-Tocopherol Stereoisomers in Fortified Infant Formula by Chiral Chromatography.

Direct measurement of the bioavailable α-tocopherol content presents a significant analytical challenge and requires chiral separation of the α-tocopherol stereoisomers. The objective of the study was to validate an analytical method for the analysis of α-tocopherol stereoisomers in infant formulas and dairy products. Samples were saponified at elevated temperature and lipophilic components were extracted into an organic solvent, with subsequent chromatographic separation of the α-tocopherol stereoisomers achieved by HPLC with a chiral column and fluorescence detection. The method was shown to be accurate, with spike recoveries of 91.9-108.8% for RRR-α-tocopherol and 90.1-104.7% for α-tocopherol, with no statistical bias against NIST 1849a certified reference material (P-value = 0.54) and an HPLC-UV analytical method (P-value = 0.48). Acceptable precision was confirmed, with repeatabilities estimated at 3.5% RSDr (HorRat = 0.6) for RRR-α-tocopherol and 4.6% RSDr (HorRat = 0.4) for α-tocopherol. A straightforward chiral chromatographic method for the analysis of stereoisomeric forms of α-tocopherol is described. In a single analytical run, the method can quantify: (i) the total α-tocopherol content; (ii) the nutritionally important RRR-α-tocopherol and/or 2 R, 4'-ambo, 8'-ambo-α-tocopherol contents; (iii) the amount of all-rac-α-tocopherol, all-rac-α-tocopheryl acetate, or all-rac-α-tocopheryl succinate fortified into the product. An accurate and precise chiral chromatographic method for the analysis of isomeric forms of α-tocopherol is described. The method is able to distinguish between natural and synthetic tocopherol sources. The method is accurate and precise and is suitable either for routine product compliance testing during product manufacture or as a possible reference method.

Vitamin E catabolism in women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase, nonrandomized crossover study

Human vitamin E (α-tocopherol) catabolism is a mechanism for regulating whole-body α-tocopherol. To determine the roles of the intestine and liver on α-tocopherol catabolism as affected by fat or fasting, 2 deuterium-labeled (intravenous d6- and oral d3-) forms of α-tocopherol were used. Healthy women received intravenous d6-α-tocopherol and consumed d3-α-tocopherol with a 600-kcal defined liquid meal (DLM; 40% or 0% fat, n=10) followed by controlled meals; or the 0% fat DLM (n=7) followed by a 12-h fast (0% fat-fast), then controlled meals ≤72 h. The order of the 3-phase crossover design was not randomized and there was no blinding. Samples were analyzed by LC/MS to determine the α-tocopherol catabolites and α-carboxyethyl hydroxychromanol (α-CEHC) in urine, feces, and plasma that were catabolized from administered oral d3- and intravenous d6-α-tocopherols. Urinary and plasma d3- and d6-α-CEHC concentrations varied differently with the interventions. Mean±SEM cumulative urinary d6-α-CEHC derived from the intravenous dose excreted over 72 h during the 40% fat (2.50±0.37 μmol/g creatinine) and 0% fat (2.37±0.37 μmol/g creatinine) interventions were similar, but a ∼50% decrease was observed during the 0% fat-fast (1.05±0.39 μmol/g creatinine) intervention (compared with 0% fat, P=0.0005). Cumulative urinary d3-α-CEHC excretion was not significantly changed by any intervention. Total urinary and fecal excretion of catabolites accounted for <5% of each of the administered doses. Differential catabolism of the intravenous d6-α-tocopherol and oral d3-α-tocopherol doses shows both liver and intestine have roles in α-tocopherol catabolism. During the 40% fat intervention, >90% of urinary d3-α-CEHC excretion was estimated to be liver-derived, whereas during fasting <50% was from the liver with the remainder from the intestine, suggesting that there was increased intestinal α-tocopherol catabolism while d3-α-tocopherol was retained in the intestine in the absence of adequate fat/food for α-tocopherol absorption.This trial was registered at clinicaltrials.gov as NCT00862433.

The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials

The previous meta-analysis of clinical trials revealed a beneficial effect of vitamin E supplementation on serum C-reactive protein (CRP) concentrations; however, it is unknown whether this vitamin has the same influence on other inflammatory biomarkers. Also, several clinical trials have been published since the release of earlier meta-analysis. Therefore, we aimed to conduct a comprehensive meta-analysis to summarize current evidence on the effects of vitamin E supplementation on inflammatory biomarkers in adults. We searched the online databases using relevant keywords up to November 2019. Randomized clinical trials (RCTs) investigating the effect of vitamin E, compared with the placebo, on serum concentrations of inflammatory cytokines were included. Overall, we included 33 trials with a total sample size of 2102 individuals, aged from 20 to 70 years. Based on 36 effect sizes from 26 RCTs on serum concentrations of CRP, we found a significant reduction following supplementation with vitamin E (− 0.52, 95% CI − 0.80, − 0.23 mg/L, P < 0.001). Although the overall effect of vitamin E supplementation on serum concentrations of interleukin-6 (IL-6) was not significant, a significant reduction in this cytokine was seen in studies that used α-tocopherol and those trials that included patients with disorders related to insulin resistance. Moreover, we found a significant reducing effect of vitamin E supplementation on tumor necrosis factor-α (TNF-α) concentrations at high dosages of vitamin E; such that based on dose–response analysis, serum TNF-α concentrations were reduced significantly at the dosages of ≥ 700 mg/day vitamin E (Pnon-linearity = 0.001). Considering different chemical forms of vitamin E, α-tocopherol, unlike other forms, had a reducing effect on serum levels of CRP and IL-6. In conclusion, our findings revealed a beneficial effect of vitamin E supplementation, particularly in the form of α-tocopherol, on subclinical inflammation in adults. Future high-quality RCTs should be conducted to translate this anti-inflammatory effect of vitamin E to the clinical setting.

Distribution of α-tocopherol stereoisomers in mink (Mustela vison) organs varies with the amount of all-rac-α-tocopheryl acetate in the diet.

Synthetic α-tocopherol has eight isomeric configurations including four 2R (RSS, RRS, RSR, RRR) and four 2S (SRR, SSR, SRS, SSS). Only the RRR stereoisomer is naturally synthesised by plants. A ratio of 1·36:1 in biopotency of RRR-α-tocopheryl acetate to all-rac-α-tocopheryl acetate is generally accepted; however, studies indicate that neither biopotency of α-tocopherol stereoisomers nor bioavailability between them is constant, but depend on dose, time, animal species and organs. A total of forty growing young male mink were, after weaning, assigned one of the following treatments for 90 d: no α-tocopherol in diet (ALFA_0), 40 mg/kg RRR-α-tocopheryl acetate (NAT_40), 40 mg/kg all-rac-α-tocopheryl acetate (SYN_40) and 80 mg/kg feed all-rac-α-tocopheryl acetate (SYN_80). Mink were euthanised in CO2 and blood was collected by heart puncture. Mink were pelted and liver, heart, lungs, brain and abdominal fat were collected for α-tocopherol stereoisomer analysis. The proportion of RRR-α-tocopherol decreased in all organs and plasma with increasing amount of synthetic α-tocopherol stereoisomers in the diet (P≤0·05), whereas the proportion of all synthetic α-tocopherol stereoisomers increased with increasing amount of synthetic α-tocopherol stereoisomers in the diet (P≤0·05). The proportion of α-tocopherol stereoisomers in plasma, brain, heart, lungs and abdominal fat showed the following order: RRR>RRS, RSR, RSS>Σ2S, regardless of α-tocopherol supplement. The liver had the highest proportion of Σ2S stereoisomers, and lowest proportion of RRR-α-tocopherol. In conclusion, distribution of α-tocopherol stereoisomers differs with dose and form of α-tocopherol supplementation. The results did also reveal the liver's role as the major organ for accumulation of Σ2S α-tocopherol stereoisomers.

Composition of organic compounds in bottom sediments of lakes in the taiga and steppe zones in Siberia

The paper presents chromatographic–mass spectrometric data on the individual composition of organic compounds in sapropel-like deposits of lakes in the steppe, forest–steppe, and three taiga natural climatic zones (NCZ) in Khakassia and western Siberia. Data on the individual composition of n-alkanes, carboxylic acids and their esters, thiophenes, phytol, phytone, steroids, and di- and triterpenoids and on their distribution in the sediments show systematic variations in the composition of the organic matter (OM) with increasing ambient temperature and the aridity of the climate. The concentrations of all groups of the compounds in lacustrine sediments decrease southward, and simultaneously esters with long (up to С20) alkyl substituents appear. The concentrations of oxygen-bearing compounds increase among the acyclic structures and triterpenoids, as also do the concentrations of structures ketonic substituents among the steroids. The dominance of the carboxylic acids and their esters by high molecular weight homologues gives way to the dominance of palmic acid and its derivatives. Among n-alkanes, the dominance of С27 and С29 hydrocarbons typical of terrestrial plants gives way to a higher percentage of homologues С21–С25 (macrophytes) and С31 (herbaceous plants). Among the tocopheroles, the concentration of the oxidized form of α-tocopherol (acetate) increases.

Vitamin E Nicotinate.

Vitamin E refers to a family of compounds that function as lipid-soluble antioxidants capable of preventing lipid peroxidation. Naturally occurring forms of vitamin E include tocopherols and tocotrienols. Vitamin E in dietary supplements and fortified foods is often an esterified form of α-tocopherol, the most common esters being acetate and succinate. The vitamin E esters are hydrolyzed and converted into free α-tocopherol prior to absorption in the intestinal tract. Because its functions are relevant to many chronic diseases, vitamin E has been extensively studied in respect to a variety of diseases as well as cosmetic applications. The forms of vitamin E most studied are natural α-tocopherol and the esters α-tocopheryl acetate and α-tocopheryl succinate. A small number of studies include or focus on another ester form, α-tocopheryl nicotinate, an ester of vitamin E and niacin. Some of these studies raise the possibility of differences in metabolism and in efficacy between vitamin E nicotinate and other forms of vitamin E. Recently, through metabolomics studies, we identified that α-tocopheryl nicotinate occurs endogenously in the heart and that its level is dramatically decreased in heart failure, indicating the possible biological importance of this vitamin E ester. Since knowledge about vitamin E nicotinate is not readily available in the literature, the purpose of this review is to summarize and evaluate published reports, specifically with respect to α-tocopheryl nicotinate with an emphasis on the differences from natural α-tocopherol or α-tocopheryl acetate.

Microencapsulation of α-tocopherol with zein and β-cyclodextrin using spray drying for colour stability and shelf-life improvement of fruit beverages

Encapsulated forms of α-tocopherol into β-cyclodextrin and zein carriers for colour stability and shelf-life improvement of beverages.

Modulation of Brain Glutathione Reductase and Peroxiredoxin 2 by α-Tocopheryl Phosphate.

α-Tocopheryl phosphate (αTP) is a phosphorylated form of α-tocopherol. Since it is phosphorylated in the hydroxyl group that is essential for the antioxidant property of α-tocopherol, we hypothesized that αTP would modulate the antioxidant system, rather than being an antioxidant agent per se. α-TP demonstrated antioxidant activity in vitro against iron-induced oxidative stress in a mitochondria-enriched fraction preparation treated with 30 or 100µM α-TP. However, this effect was not observed ex vivo with mitochondrial-enriched fraction from mice treated with an intracerebroventricular injection of 0.1 or 1nmol/site of αTP. Two days after treatment (1nmol/site αTP), peroxiredoxin 2 (Prx2) and glutathione reductase (GR) expression and GR activity were decreased in cerebral cortex and hippocampus. Glutathione content, glutathione peroxidase, and thioredoxin reductase activities were not affected by αTP. In conclusion, the persistent decrease in GR and Prx2 protein content is the first report of an in vivo effect of αTP on protein expression in the mouse brain, potentially associated to a novel and biologically relevant function of this naturally occurring compound.

Induction of VEGF expression by alpha-tocopherol and alpha-tocopheryl phosphate via PI3Kγ/PKB and hTAP1/SEC14L2-mediated lipid exchange.

In several studies, vitamin E has been observed to influence angiogenesis and vasculogenesis. We recently showed that the phosphorylated form of α-tocopherol (αT), α-tocopheryl phosphate (αTP), increases the expression of the vascular endothelial growth factor (VEGF). Thus, αTP may act as an active lipid mediator increasing VEGF expression, angiogenesis, and vasculogenesis. Here, we investigated the molecular signaling mechanisms by which αTP induces VEGF expression using cultured HEK293 cells as model system. αT and more so αTP increased VEGF-promoter activity in a phosphatidylinositol-3-kinase gamma (PI3Kγ)-dependent manner. In contrast, after overexpression of PI3Kγ and/or protein kinase B (PKB), VEGF promoter activity was inhibited by αT and more so by αTP. Inhibition by αT and αTP was dependent on the lipid kinase activity of PI3Kγ, whereas an induction was seen with the protein kinase activity, consistent with a model in which PKB inhibition by αT or αTP occurs only when activated at the plasma membrane and possibly involves a phosphatase such as PHLPP1. PI3Kγ-induced VEGF expression was reduced when the human tocopherol-associated protein 1 (hTAP1/SEC14L2) was overexpressed suggesting formation of an inactive PI3Kγ/hTAP1 heterodimer, that could be reactivated by αT and more so by αTP. We suggest a novel signaling mechanism by which αTP stimulates PI3Kγ activity by stimulating hTAP-mediated phosphatidylinositol exchange and presentation to the enzyme and/or dissociation of an inactive heterodimer. At cellular level, hTAP may act as sensor for intracellular lipid information (location, type, and amount of lipid) and translate it into responses of PI3K-mediated signaling and gene expression.

Double-balloon jejunal perfusion to compare absorption of vitamin E and vitamin E acetate in healthy volunteers under maldigestion conditions

The vitamin E derivative, α-tocopheryl acetate, is often included in formulations used in enteral nutrition. In this respect, we compared α-tocopherol and α-tocopheryl acetate absorption under 'maldigestion' conditions, such as occurring during enteral tube feeding, using differentially labeled RRR-[5,7-methyl-((2)H(6))]-α-tocopherol and RRR-[5-methyl-(2)H(3)]-α-tocopheryl acetate allowing direct comparison between free and esterified forms. The two derivatives were given together in a single dose to six volunteers directly into the jejunum using a double-balloon perfusion system. Perfusion lasted for 1 h, and the collected blood and effluent samples were analyzed by liquid chromatography-mass spectrometry. In the isolated 20-cm length of exposed jejunum, on average ~ 6% of the two vitamin E forms were absorbed >1 h based on subtraction of effluent from influent. There was substantial difference in the absolute absorbed quantity between individuals, but no significant differences were observed in the absorption between the two labeled forms as assessed in the plasma. (2)H(3)-α-tocopherol was not present in the influent, but appeared in the effluent, indicating that the acetylated form of vitamin E is cleaved by brush border enzymes in the small intestine. This study shows that even in the absence of digestive enzymes and bile salts, the appropriately solubilized acetylated form of α-tocopherol exhibits the same bioavailability as free α-tocopherol. This suggests that both forms can be absorbed equally under maldigestion conditions such as present clinically during enteral tube feeding.

Stability in the rumen and effect on plasma status of single oral doses of vitamin D and vitamin E in high-yielding dairy cows

The ruminal fate of the fat-soluble vitamins D and E was studied in dairy cows. Ten to 15kg of ruminal contents was taken from each cow through a ruminal fistula. A sample was taken out (0-h sample) and the rest of the contents were mixed with 4,360mg of all-rac-α-tocopheryl acetate (vitamin E; study 1) or 4,360mg of all-rac-α-tocopheryl acetate, 250mg of ergocalciferol (vitamin D2), and 250mg of cholecalciferol (vitamin D3; study 2). After mixing, the ruminal contents were returned to the respective cows. Blood was collected 0, 6, 24, and 30h after introducing the vitamins into the rumen. Samples of ruminal contents were collected at 0, 1, 2, 4, 6, 24, and 30h (in vivo). From the 1-h sample, 6 subsamples from each cow were incubated at 37°C and taken out at 2, 4, 6, 12, 24, and 30h (in vitro). In vivo concentrations of added α-tocopherol, ergocalciferol, and cholecalciferol in the rumen first increased and subsequently declined due to dilution effects of eating and passage out of the rumen. The level of the free-alcohol form of α-tocopherol from the natural content in feed was constant throughout the in vivo study, in contrast to the content of total α-tocopherol, which indicated that no hydrolysis of the acetate form into alcohol form happened in the rumen. In vitro, all added vitamins were found at constant levels; hence, none of the added vitamins were degraded in ruminal contents. The concentration of α-tocopherol in plasma increased at a rate per milligram of ruminally introduced α-tocopherol below the rate of the increase in plasma ergocalciferol or cholecalciferol metabolites per milligram of introduced ergocalciferol or cholecalciferol, respectively, over 24h. In conclusion, ergocalciferol, cholecalciferol, and α-tocopheryl acetate proved to be stable in the rumen and in ruminal contents from high-yielding dairy cows. Changes in plasma concentrations of the vitamins relative to the amount of vitamin introduced to the rumen indicated a lower effect on plasma status of ergocalciferol than of cholecalciferol, and an even lower effect of α-tocopherol. The limited plasma response after a single dose of α-tocopheryl acetate led to the conclusion that oral single dose therapy with all-rac-α-tocopheryl acetate is of limited physiological value.

Oxidized vitamin E and glutathione as markers of clinical status in asthma

Antioxidant status is disturbed in asthma. Measurement of both oxidized and reduced forms of antioxidants provides important information regarding the oxidant/antioxidant balance. The aim of this study was to investigate the clinical relevance of key antioxidants (alpha-tocopherol and glutathione) in asthma, by measuring the oxidized and reduced forms, in the airways (induced sputum) and systemically (peripheral blood). This cross-sectional study examines stable asthmatics (n=44) and healthy controls (n=31) recruited through John Hunter Hospital, NSW, Australia. We collected peripheral blood and induced sputum during hypertonic saline challenge. Alpha-tocopherol and alpha-tocopherol quinone were measured by HPLC. Total glutathione and glutathione disulfide were determined by a colorimetric assay. Plasma alpha-tocopherol was low in asthma versus controls. Subjects with asthma had higher levels of whole blood alpha-tocopherol quinone and %alpha-tocopherol quinone than controls and %alpha-tocopherol quinone correlated with asthma control (p=0.009). Sputum supernatant levels of total, reduced and oxidized glutathione were elevated in asthma versus controls. Oxidized glutathione in sputum supernatant negatively correlated with FEV(1)/FVC% (p=0.029). In asthma, both systemic and airway antioxidant defences are disturbed. Oxidized forms of alpha-tocopherol and glutathione are associated with clinical asthma outcomes, and should be further investigated as a tool for monitoring asthma.

Effect of vitamin E succinate (VES) on hepatic lipids in BALB/c mice injected with LNCaP cells

Cancer cells undergo rapid proliferation and are resistant to apoptosis. Vitamin E succinate (VES), the ester form of α-tocopherol, inhibits the growth of several cancer cell lines. In vitro studies show that VES induces apoptosis and inhibits cell proliferation. We have shown that VES injected intraperitonally inhibits the growth of tumors in nude BALB/c mice, injected with LNCaP cells and fed diets containing 7% soybean oil (SO; group 1), 7% SO with VES (group 2), 20% SO (group 3), or 20% SO with VES (group 4). The present in vivo study was done to determine the effect of VES and dietary fat on liver lipid [triglycerides (TG) and total cholesterol (TC)] levels. At the termination of the study, liver lipids were extracted with hexane:isopropanol (3:2, v/v) and TG and TC were assayed by standard protocols. Mean hepatic TG concentrations were 7.5±1.6, 8.1±1.2, 8.1±2.3 and 9.0± 2.2 mg/g liver in groups 1–4, respectively. Hepatic TC concentrations were 2.2±1.0, 2.8±0.9, 2.9±1.9 and 4.5±2.4 mg/g liver in groups 1–4, respectively. Thus VES increased liver total cholesterol concentrations in both high and low-fat groups but not triglycerides. This study was supported by Human Nutrition Fund, TWU.

5-Trideuteromethyl-α-tocotrienol and 5-14CH3-α-tocotrienol as biological tracers of tocotrienols

The tocotrienols have attracted increased attention recently as evidence has accrued that their biological activities are significantly different from tocopherols. The biokinetics and metabolic fate of tocopherols have long been studied using deuteromethylated forms of α-tocopherol prepared by a stannous chloride catalysed paraformaldehyde methylation of γ- and δ-tocopherols. We show here that his methodology is not an efficient route to deuterated α-tocotrienol because of low yields and extensive exchange of allylic hydrogens under the prolonged acidic conditions of the deuteromethylation. Instead, we have prepared deuteromethylated and 14C-radiolabelled α-tocotrienol by aminomethylation at C-5 of γ-tocotrienol (available from palm oil), followed by reduction with NaCNBD3 in refluxing iso-butanol. The deuteromethylation procedure is amenable to multi-gram scale reactions. Copyright © 2006 John Wiley & Sons, Ltd.