Mixed Tocopherols Research Articles

Inhibition of lung cancer growth in mice by dietary mixed tocopherols

Tocopherols are lipophilic antioxidants found in vegetable oils. Here, we examined the growth inhibitory effect of a gamma-tocopherol-enriched tocopherol mixture (gammaTmT) against CL13 murine lung cancer cells grown in culture and as subcutaneous tumors in A/J mice. We found gammaTmT had no effect after 2 days and weakly inhibited the growth of CL13 in culture after 5 days (28% growth inhibition at 80 microM). Dietary treatment with 0.1 and 0.3% gammaTmT for 50 days inhibited the growth of CL13 tumors in A/J mice by 53.9 and 80.5%, respectively. Histopathological analysis revealed an increase in tumor necrosis compared to control tumors (80 and 240% increase by 0.1 and 0.3% gammaTmT, respectively). Dietary treatment with gammaTmT dose-dependently increased gamma- (10.0-37.6-fold) and delta-tocopherol (8.9-26.7-fold) in the tumors of treated mice compared to controls. Dietary treatment with gammaTmT also increased plasma gamma- (5.4-6.7-fold) and delta-tocopherol (5.5-7-fold). Whereas others have demonstrated the cancer preventive activity of gammaTmT against mammary and colon cancer, this is the first report of growth inhibitory activity against lung cancer. Further studies are needed to determine the underlying mechanisms for this anticancer activity, and to determine if such activity occurs in other models of cancer.

Mixed Tocopherols Prevent Mammary Tumorigenesis by Inhibiting Estrogen Action and Activating PPAR-γ

Tocopherols are lipophilic antioxidants present in vegetable oils. Although the antioxidant and anticancer activities of alpha-tocopherol (vitamin E) have been studied for decades, recent intervention studies with alpha-tocopherol have been negative for protection from cancer in humans. The tocopherols consist of four isoforms, which are the alpha, beta, gamma, and delta variants, and recent attention is being given to other isoforms. In the present study, we investigated the inhibitory effect of a tocopherol mixture rich in gamma- and delta-tocopherols against mammary tumorigenesis. Female Sprague Dawley rats were treated with N-methyl-N-nitrosourea (NMU), and then fed diets containing 0.1%, 0.3%, or 0.5% mixed tocopherols rich in gamma- and delta-tocopherols for 9 weeks. Tumor burden and multiplicity were determined, and the levels of markers of inflammation, proliferation, and apoptosis were evaluated in the serum and in mammary tumors. The regulation of nuclear receptor signaling by tocopherols was studied in mammary tumors and in breast cancer cells. Dietary administration of 0.1%, 0.3%, or 0.5% mixed tocopherols suppressed mammary tumor growth by 38%, 50%, or 80%, respectively. Tumor multiplicity was also significantly reduced in all three mixed tocopherol groups. Mixed tocopherols increased the expression of p21, p27, caspase-3, and peroxisome proliferator activated receptor-gamma, and inhibited AKT and estrogen signaling in mammary tumors. Our mechanistic study found that gamma- and delta-tocopherols, but not alpha-tocopherol, activated peroxisome proliferator activated receptor-gamma and antagonized estrogen action in breast cancer. The results suggest that gamma- and delta-tocopherols may be effective agents for the prevention of breast cancer.

γ‐Tocopherol‐enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice

Gamma-tocopherol (gamma-T) alone or in combination with alpha-tocopherol has been shown to suppress biomarkers of oxidative stress in asthamatics and human subjects with metabolic syndrome. Oxidative stress has been implicated as a key event in prostate carcinogenesis. Hence, the purpose of this study was to examine the effects of gamma-tocopherol-enriched mixed tocopherol diet on prostate carcinogenesis in a murine prostate cancer model (TRAMP). 8 week old TRAMP males were fed 0.1% gamma-T-enriched mixed tocopherol diet that contained 20-fold higher levels of gamma-tocopherol, and roughly 3-fold higher levels of alpha-tocopherol. The effect of such diet on tumor and PIN development was observed. The expression of phase II detoxifying, antioxidant enzymes and Nrf2 mRNA and protein were determined by RT-PCR, immunohistochemistry and western blotting techniques. Treatment with gamma-T-enriched mixed tocopherols significantly suppressed the incidence of palpable tumor and Prostate Intraepithelial Neoplasia (PIN) development without affecting the expression of the transgene (SV-40). Tumor progression occurred with a significant suppression of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, heme-oxygenase-1 and phase II detoxifying enzymes. Treatment with gamma-T-enriched mixed tocopherol diet upregulated the expression of most detoxifying and antioxidant enzymes. Nrf2-a redox sensitive transcription factor known to mediate the expression of phase II detoxifying enzymes, was also significantly upregulated following treatment with gamma-T-enriched mixed tocopherol diet. Gamma-T-enriched mixed tocopherols significantly up-regulated the expression of Nrf2 and its related detoxifying and antioxidant enzymes thereby suppressing PIN and tumor development.

Effects of dietary oxidized oil and vitamin E on the growth, blood parameters and body composition of juvenile Atlantic codGadus morhua(Linnaeus 1758)

The effects of oxidized dietary lipid and the role of vitamin E on the growth performance, blood parameters and body composition of juvenile Atlantic cod (Gadus morhua) were evaluated over a 9-week feeding period. Four isonitrogenous experimental diets containing fresh or oxidized fish oil with or without added vitamin E (α-tocopherol or mixed tocopherols) were fed to juvenile cod. The oxidized lipid used had a peroxide value of 94 mEq kg−1 oil. No significant (P>0.05) differences in growth performance (weight gain and specific growth rate) or feed utilization (feed consumption and feed efficiency ratio) were observed when oxidized dietary lipid was used. The hepatosomatic index (HSI), viscerosomatic index (VSI) and haematocrit did not show any significant (P>0.05) differences among the treatments. However, erythrocyte osmotic fragility (EOF), referred to as susceptibility to haemolysis, of fish fed oxidized oil without added vitamin E was high in comparison with those fed unoxidized oil. Supplementation with α-tocopherol appeared to decrease haemolysis, but mixed tocopherols had no significant (P>0.05) effect on EOF. The proximate composition of fish whole body was also affected by diet treatment. Fatty acid composition of liver total lipid reflected that of dietary lipid. Variations in tissue (liver and muscle) fatty acid composition among the treatments followed the same trend as those of the dietary fatty acids. Fish fed fresh oil had a higher proportion of polyunsaturated fatty acids (PUFA) in muscle and liver lipid than those fed oxidized oil. The results suggest that oxidized dietary oil affected juvenile Atlantic cod in certain tissues and that these effects could be alleviated by supplementation of sufficient amounts of vitamin E in the diet.

Oxidative Stability of Conventional and High‐Oleic Vegetable Oils with Added Antioxidants

AbstractThe oxidative stability of conventional and high‐oleic varieties of commercial vegetable oils, with and without added antioxidants, was evaluated using the oil stability index (OSI). Oil varieties studied were soybean (SOY), partially‐hydrogenated soybean (PHSOY), corn (CORN), sunflower (SUN), canola (CAN), high‐oleic canola (HOCAN), very high‐oleic canola (VHOCAN), oleic safflower (SAF) and high‐oleic sunflower (HOSUN). One or more commercial antioxidants were added to the four most stable oils at supplier‐recommended levels: rosemary extract (RM; 1,000 ppm), ascorbyl palmitate (AP; 1,000 ppm), tert‐butylhydroquinone (TBHQ; 200 ppm), and mixed tocopherols (TOC; 200 ppm). OSI in hours (h) at 110 °C of the conventional oils were 5.2, 7.6, 8.4, 9.8, 10.9 and 14.3 h for SUN, SOY, CAN, CORN, PHSOY and SAF, respectively. OSI of high‐oleic variants were 12.9, 16.5 and 18.5 h for HOCAN, HOSUN and VHOCAN, respectively. Maximum OSI values for the four most stable oils when treated with antioxidants, were 40.9, 48.5, 48.8 and 55.7 h for HOCAN, VHOCAN, SAF and HOSUN, respectively. Addition of TBHQ, alone and in combination with other antioxidants, resulted in the greatest increase in oxidative stability of SAF and other high‐oleic oils evaluated. AP had a positive synergistic effect when used with TBHQ, while RM decreased TBHQ effectiveness.

Opinion on mixed tocopherols, tocotrienol tocopherol and tocotrienols as sources for vitamin E added as a nutritional substance in food supplements ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing aids and Materials in Contact with food (AFC)

Opinion on mixed tocopherols, tocotrienol tocopherol and tocotrienols as sources for vitamin E added as a nutritional substance in food supplements ‐ Scientific Opinion of the Panel on Food Additives, Flavourings, Processing aids and Materials in Contact with food (AFC)

Forms of Vitamin E have Opposing Effects on Experimental Asthma

We previously reported that the endothelial cell adhesion molecule VCAM‐1 signals through reactive oxygen species generated by NOX2 and that this regulates leukocyte trafficking in vitro and in vivo. Therefore, we determined whether leukocyte migration is modulated by two major dietary forms of the antioxidant vitamin E, (d)‐α‐tocopherol (aT) and (d)‐γ‐tocopherol (gT). Mice were treated daily with physiological levels of aT or gT after sensitization and before challenge with the antigen ovalbumin, a model of experimental asthma. aT significantly inhibited inflammation in the lung and inhibited airway hyperresponsiveness (AHR). Surprisingly, gT exacerbated inflammation and AHR in the lung. Most interestingly, when gT and aT were co‐administered, gT ablated the benefit of aT. In addition, gT antagonized aT inhibition of leukocyte transendothelial migration in vitro. In summary, aT and gT have opposing effects on inflammation. These data have implications on the design and interpretation of clinical studies with mixed tocopherols in supplements and diets. Reported studies indicate that aT is beneficial for experimental asthma in mice and for asthma in Europeans who consume diets low gT but not for Americans who consume diets high in gT, suggesting that differences in the outcomes in these reports on vitamin E may, in part, reflect the opposing effects of α‐tocopoherol and γ‐tocopherol.(NIH R01 HL069428 to JC‐M)

Chemoprevention and vitamin E

To the Editor: As a dermatologist and certified nutrition specialist, I am delighted to see chemoprevention making its way into mainstream medical literature. The CME review by Wright et al1Wright T.I. Spencer J.M. Flowers F.P. Chemoprevention of nonmelanoma skin cancer.J Am Acad Dermatol. 2006; 54: 933-946Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar (J Am Acad Dermatol 2006;54:933-46) gives us a good introduction to the subject, but I urge the authors to reserve judgment on vitamin E. The science of vitamin E has progressed in the past 12 years since Wernighaus2Werninghaus K. Meydani M. Bhawan J. Margolis R. Blumberg J.B. Gilchrest B.A. Evaluation of the photoprotective effect of oral vitamin E supplementation.Arch Dermatol. 1994; 130: 1257-1261Crossref PubMed Scopus (129) Google Scholar published the work on which they base their rejection of its benefit. Although our limited clinical data may not support its use at this time, ongoing research suggests that our rejection may be premature. Vitamin E consists of 8 different molecules: 4 tocotrienols and 4 tocopherols. Assays based on rat fetal resorption in the 1940s identified d-alpha-tocopherol as the most biologically active form. Large doses of alpha-tocopherol can reduce red blood cell levels of D-gamma-tocopherol, the form most prevalent in our food supply.3Clarke M.W. Ward N.C. Wu J.H. Hodgson J.M. Puddey I.B. Croft K.D. Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.Am J Clin Nutr. 2006; 83: 95-102PubMed Google Scholar Recent work suggests that for some human health effects, gamma is more beneficial than alpha.4Yoshida E. Watanabe T. Takata J. Yamazaki A. Karube Y. Kobayashi S. Topical application of a novel, hydrophilic gamma-tocopherol derivative reduces photo-inflammation in mice skin.J Invest Dermatol. 2006; 126: 1633-1640Crossref PubMed Scopus (42) Google Scholar The vitamin E molecules all have right-handed stereochemistry. Synthetic alpha-tocopherol contains a racemic mixture of one active and 7 inactive molecules and, in some settings, the latter may interfere with proper function of the biologically active RRR isomer.5Blatt D.H. Pryor W.A. Mata J.E. Rodriguez-Proteau R. Re-evaluation of the relative potency of synthetic and natural alpha-tocopherol: experimental and clinical observations.J Nutr Biochem. 2004; 15: 380-395Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Mouse studies suggest that nonesterified forms of vitamin E are more effective than esterified forms.6McVean M. Liebler D.C. Prevention of DNA photodamage by vitamin E compounds and sunscreens: roles of ultraviolet absorbance and cellular uptake.Mol Carcinog. 1999; 24: 169-176Crossref PubMed Scopus (93) Google Scholar Knowing a bit about the different forms of vitamin E and how their effects differ, we can understand why we see so much variability in results from clinical trials of this nutrient. When it protects against oxidation, vitamin E itself becomes oxidized and can act as a pro-oxidant unless it is reduced, a task often performed by vitamin C.7Fuchs J. Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation.Free Radic Biol Med. 1998; 25: 1006-1012Crossref PubMed Scopus (162) Google Scholar Nutrients tend to operate as part of a system and are more effective given in combination. When designing a vitamin E study, researchers should provide vitamin C as part of the experimental protocol. Completing the cascade by also including glutathione to reconstitute vitamin C may be optimal. Our single-intervention, single-outcome research model does not readily accommodate this systems approach. The CME review authors point out that animal studies support the biochemistry of vitamin E as a chemopreventive and epidemiologic studies provide evidence that vitamin E, especially as part of a nutrient-dense diet, protects against cancer, including skin cancer. It is part of the system that evolved over the millennia to protect us against cancer. In moderate doses, in a natural mixed form, in combination with other nutrients, vitamin E has an excellent safety profile. It certainly carries far less gastrointestinal risk than another chemoprotective agent, nonsteroidal anti-inflammatory drugs. In light of an evolving understanding of vitamin E and its action, I do not think we can state that is has “been disproved” as an agent of chemoprevention.

Mixed Tocopherols Inhibit N-methyl-N-Nitrosourea-Induced Mammary Tumor Growth in Rats

Tocopherols are present in significant amounts in vegetable oils used in human foods. The most prevalent tocopherols in foods are the α, β, γ, and δ variants with (RRR) stereochemistry. Tocopherols are lipophilic phenolic antioxidants, produced by plants. In the United States, γ -tocopherol is the most prominent dietary tocopherol due to its high amount in the dominant commercially produced vegetable oils such as soybean, corn, and cottonseed. In this report, experiments were designed to study the inhibitory effect of mixed tocopherols against N-methyl-N-nitrosourea-induced mammary tumor growth in female Sprague-Dawley rats. Beginning at 21 days of age, rats were treated with a single intraperitoneal injection of 50 mg/kg body weight of N-methyl-N-nitrosourea. One wk later, the rats were fed experimental diets containing 0 or 0.1% mixed tocopherols containing over 50% γ -tocopherol. At 9 wk after N-methyl-N-nitrosourea treatment, all rats were evaluated for inhibition of mammary tumor growth and proliferating cell nuclear antigen. Dietary administration of mixed tocopherols significantly suppressed mammary tumor growth (P < 0.05) and proliferating cell nuclear antigen (P < 0.01) and also moderately suppressed tumor multiplicity. The treatment increased the serum levels of γ - and δ -tocopherols without affecting the body weight. The results of this study suggest that mixed tocopherols may be safe and effective agents for the prevention of breast cancer.

Effects of Oxidized Dietary Oil and Vitamin E Supplementation on Lipid Profile and Oxidation of Muscle and Liver of Juvenile Atlantic Cod (Gadus morhua)

The effects of oxidized dietary lipid and the role of vitamin E on lipid profile, retained tocopherol levels, and lipid oxidation of juvenile Atlantic cod (Gadus morhua) were evaluated following a 9-week feeding trial. Four isonitrogenous experimental diets containing fresh or oxidized (peroxide value of 94 mequiv/kg) fish oil with or without added vitamin E (alpha-tocopherol or mixed tocopherols) were fed to juvenile cod in duplicate tanks. There was no significant (P > 0.05) influence on major lipid classes of cod liver and muscle by diet with the exception of sterols. Sterols content was increased in liver but decreased in muscle by oxidized dietary oil in the absence of vitamin E. Dietary vitamin E supplementation decreased the sterols level in cod liver but with no significant (P > 0.05) effect on their level in the muscle. Fatty acid composition varied between lipid fractions in muscle tissue and was affected by the diet. Oxidized oil significantly (P < 0.05) decreased the deposition of alpha-tocopherol in liver but not in muscle. gamma- and delta-Tocopherols from dietary tocopherol mixtures were retained at very low levels in liver, but higher retention was observed in muscle tissue. The oxidative state of both liver and muscle, as measured by the 2-thiobarbituric acid reactive substances (TBARS) and headspace propanal, negatively correlated with tissue vitamin E levels. It is suggested that oxidized oil affected juvenile Atlantic cod by causing vitamin E deficiency in certain tissues and that these effects could be alleviated by supplementation of a sufficient amount of dietary vitamin E. The results also indicate that mixed tocopherols were good antioxidants for Atlantic cod, although less effective than alpha-tocopherol alone in many tissues with the exception of muscle, where gamma- and delta-tocopherols were deposited at relatively high levels.

Formation of 5-nitro-gamma-tocopherol in smokers and non-smokers after mixed tocopherol supplementation

Formation of 5-nitro-gamma-tocopherol in smokers and non-smokers after mixed tocopherol supplementation

Effects of mixed tocopherol versus alpha-tocopherol supplementation on tocopherol concentrations in plasma and buccal mucosal cells

Effects of mixed tocopherol versus alpha-tocopherol supplementation on tocopherol concentrations in plasma and buccal mucosal cells

Opinion of the Panel on dietetic products, nutrition and allergies [NDA] related to a notification from Cognis, ADM and Cargill on natural mixed tocopherols (E306), natural D‐alpha tocopherol, natural D‐alpha tocopherol acetate and natural D‐alpha tocopherol succinate from soybean sources pursuant to Article 6, paragraph 11 of Directive 2000/13/EC

EFSA JournalVolume 5, Issue 6 485 OpinionOpen Access Opinion of the Panel on dietetic products, nutrition and allergies [NDA] related to a notification from Cognis, ADM and Cargill on natural mixed tocopherols (E306), natural D-alpha tocopherol, natural D-alpha tocopherol acetate and natural D-alpha tocopherol succinate from soybean sources pursuant to Article 6, paragraph 11 of Directive 2000/13/EC European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 06 June 2007 https://doi.org/10.2903/j.efsa.2007.485 Panel members: Jean-Louis Bresson, Albert Flynn, Marina Heinonen, Karin Hulshof, Hannu Korhonen, Pagona Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Andreu Palou, Hildegard Przyrembel, Seppo Salminen, John (Sean) J Strain, Stephan Strobel, Inge Tetens, Henk van den Berg, Hendrik van Loveren and Hans Verhagen. Acknowledgement: The Scientific Panel on Dietetic Products, Nutrition and Allergies wishes to thank Taraneh Dean, Martin Stern and Jean-Michel Wal for their contributions to the draft opinion. Adoption date: 3 May 2007 Published date: 6 June 2007 Question number: EFSA-Q-2006-151 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume5, Issue6June 2007485 ReferencesRelatedInformation

An effort to improve the shelf life of breakfast cereals using natural mixed tocopherols

An experimental investigation was carried out with the aim of appraising the effects of natural tocopherols on lipid oxidation in extruded breakfast cereals. Corn flakes produced on an industrial scale, with and without added tocopherols and stored in commercial packing under shelf conditions, were compared using sensory evaluation and analyses of volatile compounds and triacylglycerol polymerization products. The sensory evaluation showed the effectiveness of tocopherols in limiting the development of off-flavour during storage. The analysis of the volatile compounds, focused on the secondary products of the lipid oxidation, showed that the antioxidant activity of tocopherols limited the evolution of the headspace towards a more intense oxidation, notably the further oxidation of hexanal into hexanoic acid (that reached 32% and 15% in the flakes, respectively, without and with added tocopherols, after 360 days). The percentage of hexanoic acid in the headspace positively correlated with almost all the descriptors of the defect considered for the sensory evaluation. The analysis of the triacylglycerol polymerization products confirmed the inhibiting action of tocopherols on lipid oxidative degradation.

Effects of α-Tocopherol and Mixed Tocopherol Supplementation on Markers of Oxidative Stress and Inflammation in Type 2 Diabetes

Vitamin E isomers may protect against atherosclerosis. The aim of this study was to compare the effects of supplementation with either alpha-tocopherol (alphaT) or mixed tocopherols rich in gamma-tocopherol (gammaT) on markers of oxidative stress and inflammation in patients with type 2 diabetes. In a double-blind, placebo-controlled trial, 55 patients with type 2 diabetes were randomly assigned to receive (500 mg/day) (a) alphaT, (b) mixed tocopherols, or (c) placebo for 6 weeks. Cellular tocopherols, plasma and urine F(2)-isoprostanes, erythrocyte antioxidant enzyme activities, plasma inflammatory markers, and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation. Neutrophil alphaT and gammaT increased (both P <0.001) with mixed tocopherol supplementation, whereas alphaT (P <0.001) increased and gammaT decreased (P <0.005) after alphaT supplementation. Both alphaT and mixed tocopherol supplementation resulted in reduced plasma F(2)-isoprostanes (P <0.001 and P = 0.001, respectively) but did not affect 24-h urinary F(2)-isoprostanes or erythrocyte antioxidant enzyme activities. Neither alphaT nor mixed tocopherol supplementation affected plasma C-reactive protein, interleukin 6, tumor necrosis factor-alpha, or monocyte chemoattractant protein-1. Stimulated neutrophil leukotriene B(4) production decreased significantly in the mixed tocopherol group (P = 0.02) but not in the alphaT group (P = 0.15). The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes. In populations with well-controlled type 2 diabetes, supplementation with either alphaT or mixed tocopherols rich in gammaT is unlikely to confer further benefits in reducing inflammation.

The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial

Oxidative stress has been suggested to play a role in the development of diabetes, hypertension and vascular dysfunction. Vitamin E, a major lipid-soluble dietary antioxidant, has two major dietary forms, alpha-tocopherol and gamma-tocopherol. The potential importance of gamma-tocopherol has largely been overlooked. Our aim was to investigate the effect of alpha-tocopherol and gamma-tocopherol supplementation on 24-h ambulatory blood pressure (BP) and heart rate, vascular function and oxidative stress in individuals with type 2 diabetes. Fifty-eight individuals with type 2 diabetes were randomized in a double-blind, placebo-controlled trial. Participants were randomized to a daily dose of 500 mg/day RRR-alpha-tocopherol, 500 mg/day mixed tocopherols (60% gamma-tocopherol) or placebo for 6 weeks. Primary endpoints were 24-h ambulatory BP and heart rate, endothelium-dependent and independent vasodilation and plasma and urinary F2-isoprostanes. Treatment with alpha-tocopherol significantly increased systolic BP [7.0 (5.2, 8.8) mmHg, P < 0.0001], diastolic BP [5.3 (4.0, 6.5) mmHg, P < 0.0001], pulse pressure [1.8 (0.6, 3.0) mmHg, P < 0.005] and heart rate [2.0 (0.6, 3.3) bpm, P < 0.005] versus placebo. Treatment with mixed tocopherols significantly increased systolic BP [6.8 (4.9, 8.6) mmHg, P < 0.0001], diastolic BP [3.6 (2.3, 4.9) mmHg, P < 0.0001], pulse pressure [3.2 (2.0, 4.4) mmHg, P < 0.0001] and heart rate [1.8 (0.5, 3.2) bpm, P < 0.01] versus placebo. Treatment with alpha-tocopherol or mixed tocopherols significantly reduced plasma F2-isoprostanes versus placebo, but had no effect on urinary F2-isoprostanes. Endothelium-dependent and independent vasodilation was not affected by either treatment. In contrast to our initial hypothesis, treatment with either alpha- or mixed tocopherols significantly increased BP, pulse pressure and heart rate in individuals with type 2 diabetes.

Mixed Tocopherols Inhibit Azoxymethane-Induced Aberrant Crypt Foci in Rats

: Gamma (γ) tocopherol, but not alpha (α) tocopherol (vitamin E), has previously been reported as an effective inhibitor of cyclooxygenase (COX) enzyme activity. In a pilot study of 17 rats, mixed tocopherols containing more than 50% γ-tocopherol, added at 0.1% to an AIN-76A diet, produced a significant inhibition (about 55%) of azoxymethane-induced aberrant crypt foci in the colon of rats. Mixed tocopherols also reduced tetradecanoyl phorbol acetate–induced ear inflammation in mice when topically applied.

Performance of tocopherols as antioxidants in ABS

AbstractMixed tocopherols, γ‐tocopherol, and δ‐tocopherol were evaluated for antioxidant performance in acrylonitrile–butadiene–styrene by using oxidative induction time as the response. Three commonly used phenolic antioxidants and vitamin E (α‐tocopherol) were used as controls. Mixed tocopherols were found to have a greater antioxidant effect than the hindered phenolic antioxidants or vitamin E in acrylonitrile–butadiene–styrene. γ‐tocopherol was found to be primarily responsible for the improved performance of mixed tocopherols. J. VINYL. ADDIT. TECHNOL. 12:66–72, 2006. © 2006 Society of Plastics Engineers

Supplementation with mixed tocopherols increases serum and blood cell γ-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes

Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P < 0.001) in the mixed tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum alpha-tocopherol and serum and cellular gamma-tocopherol. Changes in serum tocopherol closely reflect changes in cellular concentrations of tocopherols after supplementation.

Stability of Spray-Dried Tuna Oil Emulsions Encapsulated with Two-Layered Interfacial Membranes

omega-3 Fatty acids have numerous health benefits, but their addition to foods is limited by oxidative rancidity. Spray-drying tuna oil-in-water emulsion droplets with a coating of lecithin and chitosan multilayer system could produce emulsion droplet interfacial membranes that are cationic and thick, both factors that can help control lipid oxidation. Physicochemical and oxidative stability of the spray-dried emulsions were determined as a function of storage temperature and relative humidity (RH). The combination of ethylenediaminetetraacetic acid (EDTA) and mixed tocopherols was able to increase the oxidative stability of dried emulsions. Lipid oxidation was more rapid during storage at low relative humidity (11% and 33% compared to 52% RH). At high moisture, physical modifications in the sample were observed, including reduced dispersibility and formation of brown pigments. Sugar crystallization or Maillard products produced at the higher humidities may have inhibited oxidation. Overall, spray-dried tuna oil-in-water emulsions stabilized by lecithin-chitosan membranes were more oxidatively stable than bulk oils and thus have excellent potential as an omega-3 fatty acid ingredient for functional foods.