Abstract
This article is a review of the fundamental chemistry of the tocopherols and tocotrienols relevant to their antioxidant action. Despite the general agreement that α-tocopherol is the most efficient antioxidant and vitamin E homologuein vivo, there was always a considerable discrepancy in its “absolute” and “relative” antioxidant effectivenessin vitro, especially when compared to γ-tocopherol. Many chemical, physical, biochemical, physicochemical, and other factors seem responsible for the observed discrepancy between the relative antioxidant potencies of the tocopherolsin vivo andin vitro. This paper aims at highlighting some possible reasons for the observed differences between the tocopherols (α-, β-, γ-, and δ-) in relation to their interactions with the important chemical species involved in lipid peroxidation, specifically trace metal ions, singlet oxygen, nitrogen oxides, and antioxidant synergists. Although literature reports related to the chemistry of the tocotrienols are quite meager, they also were included in the discussion in virtue of their structural and functional resemblance to the tocopherols.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- ESR:
-
electron spin resonance
- LDL:
-
low density lipoprotein
- NO:
-
nitric oxide
- PUFA:
-
polyunsaturated fatty acids
References
Schultz, H.W., Day, E.A., and Sinnhuber, R.D. (eds.) (1962)Symposium on Foods: Lipids and Their Oxidation, AVI Publishing Co., Westport.
Korycha-Dahl, M., and Richardson, T. (1978) Activated Oxygen Species and Oxidation of Food Constituents,CRC Crit. Rev. Food Sci. Nut. 10, 209–241.
Simic, M.G. (1981) Free Radical Mechanisms in Autoxidation Processes,J. Chem. Educ. 58, 125–131.
Allen, J.C., and Hamilton, R.J. (1983)Rancidity in Foods, Applied Science Publishers, Barking.
Frankel, E.N. (1984) Chemistry of Free Radical and Singlet Oxidation of Lipids,Prog. Lipid Res. 23, 197–321.
Min, D.B. and Smouse, T.H. (1985)Flavor Chemistry of Fats and Oils, American Oil Chemists' Society, Champaign.
Aruoma, O.I. (1991) Prooxidant Properties: An Important Consideration for Food Additives and/or Nutrient Components?, inFree Radicals and Food Additives (O.I. Aruoma, and B. Halliwell, eds.), pp. 173–194, Taylor & Francis, London.
Freeman, B.A., and Crapo, J.D. (1982). Biology of Disease, Free Radicals and Tissue Injury,Laboratory Investigation 47, 412–426.
Cross, C.E. (1987) Oxygen Radicals and Human Disease,Ann. Internal Med. 107, 526–545.
Halliwell, B., and Gutteridge, J.M.C. (1989)Free Radicals in Biology and Medicine, Oxford University Press, Oxford.
Ingold, K.U. (1962) Metal Catalysis, inSymposium on Foods: Lipids and Their Oxidation (Schultz, H.W., Day, E.A., and Sinnhuber, R.O., eds.), pp. 93–121, AVI Publishing Company, Westport.
Karel, M. (1980) Lipid Oxidation: Secondary Reactions and Water Activity of Foods, inAutoxidation in Food and Biological Systems (Simic, E.M., and Karel, M., eds.), pp. 191–206, Plenum Press, New York.
Simic, M.G., and Karel, M. (1980)Autoxidation in Food and Biological Systems, Plenum Press, New York.
Kanner, J., German J.B., and Kinsella, J.E. (1987) Initiation of Lipid Peroxidation in Biological Systems,CRC Crit. Rev. Food Sci. Nutr. 25, 317–364.
Chan, H.W.-S. (1987) The Mechanism of Autoxidation, inAutoxidation of Unsaturated Lipids (Chan, H.W.S., ed.), pp. 1–16, Academic Press, London.
McCay, P.B., Fong, K.L., Lai, E.K., and King, M.M. (1978) Possible Role of Vitamin E as a Free Radical Scavenger and Singlet Oxygen Quencher in Biological Systems Which Initiate Radical-Mediated Reactions, inTocopherol, Oxygen and Biomembranes (deSuve, C., and Hayaishi, O., eds.), Elsevier/North Holland Biochemical Press, Amesterdam.
Oski, F.A. (1980) Vitamin E—A Radical Defense,New Engl. J. Med. 303, 454–455.
Machlin, L.J. (1980)Vitamin E: A Comprehensive Treastise, Marcel Dekker, New York.
Machlin, L.J. (1984) Vitamin E, inHandbook of Vitamins: Nutritional Biochemical & Clinical Aspects (Machlin, L.J., ed.), 99–145, Marcel Dekker, New York and Basel.
Burton, G.W., Joyce, A., and Ingold, K.U. (1982) First Proof That Vitamin E Is Major Lipid-Soluble, Chain-Breaking Antioxidant in Human Blood Plasma,Lancet 2, 327.
Burton, G.W., Joyce, A., and Ingold, K.U. (1983) Is Vitamin E the Only Lipid-Soluble, Chain-Breaking Antioxidant in Human Blood Plasma and Erythrocyte Membranes,Arch. Biochem. Biophys. 221, 281–290.
Burton, G.W., Cheesman, K.H., Doba, D., Ingold, K.U., and Slater, T.F. (1983) Vitamin E as an Antioxidantin vitro andin vivo, inBiology of Vitamin E, (Porter, R., and Whelan, J., eds.), pp. 4–18, Ciba Foundation Symposium No. 101, Pitman, London.
Fritsma, G.A. (1983) Vitamin E and Autoxidation,Am. J. Med. Technol. 49, 453–456.
Parker, R.S. (1989) Dietary and Biochemical Aspects of Vitamin E, inAdvances in Food and Nutrition Research, Vol. 33 (Kinsella, J.E., ed.), pp. 157–232, Academic Press Inc., New York.
Burton, G.W., and Traber, M.G. (1990) Vitamin E: Antioxidant Activity, Biokinetics and Bioavailability,Ann. Rev. Nutr. 10, 357–382.
Sies, H. (1986) Biochemistry of Oxidative Stress,Angew Chem. 98, 1061–1076.
Sies, H., and Murphy, M.E. (1991) Role of Tocopherols in the Protection of Biological Systems Against Oxidative Damage,J. Photochem. Photobiol.: B. Biol. 8, 211–224.
Sies, H., Stahl, W., and Sundqvist, A.R. (1992) Antioxidant Functions of Vitamins: Vitamins E and C, Beta-Carotene and Other Carotenoid, inBeyond Difficiency (Sauberlich, E., and Machlin, L.J., eds.) New York Acta,Ann. N.Y. Acad. Sci. 669, 7–20.
van Acker, S.A.B.E., Koymans, L.M.H., and Bast, A. (1993) Molecular Pharmacology of Vitamin E: Structural Aspects of Antioxidant Activity,Free Rad. Biol. Med. 15, 311–328.
Labuza, T.P. (1971) Kinetics of Lipid Oxidation in Foods,CRC Crit. Rev. Food Technol. 2, 355–405.
Hess, J.L. (1993) Vitamin E: α-Tocopherol, inAntioxidants in Higher Plants (Alscher, R.G., and Hess, J.L., eds.) pp. 111–134, CRC Press, Boca Raton.
Combs, G.F., Jr. (1992) Vitamin E, inThe Vitamins: Fundamental Aspects in Nutrition & Health, pp. 179–203, Academic Press Inc., San Diego.
Bauernfeind, J.C., and Desai, I.D. (1977) The Tocopherol Content of Food and Influencing Factors,CRC Crit. Rev. Food Sci. Nutr. 8, 337–382.
Bauernfeind, J.C. (1980) Tocopherols in Foods, inVitamin E: A Comprehensive Treastise (Machlin, L.J., ed.) Marcel Dekker, New York.
McLaughlin, P.J., and Weihrauch, J.L. (1979) Vitamin E Content of Foods,J. Am. Dietitic Assoc. 75, 647–665.
Burton, G.W., and Ingold, K.U. (1981) Autooxidation of Biological Molecules. 1. The Antioxidant Activity of Vitamin E and Related Chain-Breaking Phenolic Antioxidantsin vitro, J. Am. Chem. Soc. 103, 6472–6477.
Burton, G.W., and Ingold, K.U. (1986) Vitamin E: Applications of the Principles of Physical Organic Chemistry to the Exploration of Its Structure and Function,Acc. Chem. Res. 19, 194–201.
Burton, G.W., and Ingold, K.U. (1988) Mechanisms of Antioxidant Action: Preventive and Chain-Breaking Antioxidants, inHandbook of Free Radicals and Antioxidants in Biomedicine, Vol. 2 (Miquel, J., ed.) pp. 29–43, CRC Press, Boca Raton.
Burton, G.W., and Ingold, K.U. (1989) Vitamin E asin vitro andin vivo Antioxidant,Ann. N.Y. Acad. Sci. 570, 7–22.
Pokorny, J. (1987) Major Factors Affecting the Autoxidation of Lipids, inAutoxidation of Unsaturated Lipids (Chan, H.W.S., ed.) pp. 141–206, Academic Press, London.
Dillard, C.J., Gavino, V.C., and Tappel, A.L. (1983) Relative Antioxidant Effectiveness of α-Tocopherol and γ-Tocopherol in Iron-Loaded Rats,J. Nutr. 113, 2266–2273.
VERIS (Vitamin E Research and Information Service) (1993)1993 Vitamin E Abstracts (Horwitt, M.K., ed.) LaGrange, Illinois.
Lea, C.H., and Ward, R.J. (1959) Relative Antioxidant Activity of the Seven Tocopherols,J. Sci. Food Agric. 10, 537–548.
Olcott, H.S., and Van Der Ven, J. (1968) Comparison of Antioxidant Activities of Tocol and Its Methyl Derivatives,Lipids 3, 331–334.
Parkhurst, R.M., Skinner, W.A., and Strum, P.A. (1968) The Effect of Various Concentrations of Tocopherols and Tocopherol Mixtures on the Oxidative Stabilities of a Sample of Lard,J. Am. Oil Chem. Soc. 45, 641–642.
Chow, C.K., and Draper, H.H. (1974) Oxidative Stability and Activity of the Tocopherols in Corn and Soybean Oils,Int. J. Vit. Nutr. Res. 44, 396–403.
Koskas, J.P., Cillard, J., and Cillard, P. (1984) Autooxidation of Linoleic Acid and Behavior of Its Hydroperoxides with and without Tocopherols,J. Am. Oil Chem. Soc. 61, 1466–1469.
Esterbauer, H., Striegl, G., Puhl, H., Oberreither, S., Rothender, M., El-Saadani, M., and Jurgens, G. (1989) The Role of Vitamin E and Carotenoids in Preventing the Oxidation of Low-Density Lipoproteins,Ann. N. Y. Acad. Sci. 570, 254–267.
Gottstein, T., and Grosch, W. (1990) Model Study of Different Antioxidant Properties of α-and γ-Tocopherol in Fats,Fat Sci. Technol. 92, 139–144.
Timmermann, von F. (1990) Tocopherole-Antioxidative Wirkung bei Fetten und Ölen,Fat Sci. & Technol. 92, 201–206.
Moore, R.N., and Bickford, W.G. (1952) A Comparative Evaluation of Several Antioxidants in Edible Fats,J. Am. Oil Chem. Soc. 29, 1–4.
Jung, M.Y., and Min, D.B. (1990) Effects of α-, γ- and δ-Tocopherols on Oxidative Stability of Soybean Oil,J. Food Sci. 55, 1464–1465.
Jung, M.Y., and Min, D.B. (1990) Effects of Oxidized α-, γ-and δ-Tocopherols on the Oxidative Stability of Purified Soybean Oil,Food Chem. 45, 183–187.
Lea, C.H. (1960) On the Antioxidant Activities of the Tocopherols. II. Influence of Substrate, Temperature and Level of Oxidation,J. Sci. Food Agric. 11, 212–218.
Nawar, W.W. (1985) Lipid, inFood Chemistry, 2nd edn. (Fennema, O.R., ed.), pp. 139–244, Marcel Dekker, New York.
Lea, C.H. (1960) Antioxidation in Dry Fat Systems. I. Influence of the Fatty Acid Composition of the Substrate,J. Sci. Food Agric. 11, 143–150.
Frankel, E.N. (1989) The Antioxidant and Nutritional Effects of Tocopherols, Ascorbic Acid and β-Carotene in Relation to Processing of Edible Oils, inNutritional Impacts of Food Processing, No. 43 (Somogyi, J.C., and Muller, H.R. eds.), pp. 297–312, Bibliotheca ‘Nutritio et dieta, Basel, Karger.
Cillard, J., Cillard, P., Cormier, M., and Girre, L. (1980) α-Tocopherol Prooxidant Effect in Aqueous Media: Increased Autooxidation Rate of Linoleic Acid,J. Am. Oil Chem. Soc. 57, 252–255.
Cillard, J., Cillard, P., and Cormier, M. (1980) Effect of Experimental Factors on the Prooxidant Behavior of α-Tocopherol,J. Am. Oil Chem. Soc. 57, 255–261.
Tasuta, T. (1971) Relationship Between Chemical Structure and Biological Activity of Vitamin E,Vitamins 44, 185–190.
Lehmann, J., and Slover, H.T. (1976) Relative Antioxidative and Photolytic Stabilities of Tocols and Tocotrienols,Lipids 11, 853–857.
Nakano, M., Sugioka, K., Nakamura, T., and Oki, T. (1980) Interaction Between an Organic Hydroperoxide and an Unsaturated Phospholipid and α-Tocopherol in Model Membranes,Biochim. Biophys. Acta 619, 274–286.
Komiyama, K., Iizuka, K., Yamaoka, M., Watanabe, H., Tsuchiya, N., and Umezawa, I. (1989) Studies on the Biological Activity of Tocotrienol,Chem. Pharm. Bull. 37, 1369–1371.
Goh, S.H., Hew, N.F., Ong, A.S.H., Choo, Y.M., and Brumby, S. (1990) Tocotrienols from Palm Oil: Electron Spin Resonance Spectra of Tocotrienoxyl Radicals,J. Am. Oil Chem. Soc. 67, 250–254.
Yamaoka, M., and Komiyama, K. (1989) Antioxidative Activities of α-Tocotrienol and Its Derivative in the Oxidation of Dilinoleolylphosphatidylcholine Liposomes,J. Jpn. Oil Chem. Soc. 38, 478.
Yamaoka, M., Carrillo, M.J.H., Nakahara, T., and Komiyama, K. (1991) Antioxidative Activities of Tocotrienols on Phospholipid Liposomes,J. Am. Oil Chem. Soc. 68, 114–118.
Serbinova, E., Kagan, V., Han, D., and Packer, L. (1991) Free Radical Recycling and Intermembrane Mobility in the Antioxidation Properties of alpha-Tocopherol and alpha-Tocotrienol,Free Radic. Biol. Med. 10, 263–275.
Suarna, C, Hood, R.L., Dean, R.T., and Stocker, R. (1993) Comparative Antioxidant Activity of Tocotrienols and Other Lipid-Soluble Antioxidants in a Homogeneous System and in Rat and Human Lipoproteins,Biochem. Biophys. Acta 1166, 163–170.
Suzuki, Y.J., Tsuchiya, M., Wassall, S.R., Choo, Y.M., Govil, G., Kagan, V.E., and Packer, L. (1993) Structural and Dynamic Membrane Properties of α-Tocopherol and α-Tocotrienol: Implications to the Molecular Mechanism of Their Antioxidant Potency,Biochemistry 32, 10692–10699.
Evans, H.M., and Bishop, K.S. (1922) On the Existence of a Hitherto Unrecognized Dietary Factor Essential for Reproduction,Science 56, 650–651.
IUNS (International Union of Nutritional Sciences) Committee on Nomenclature (1978)Nutr. Abst. Rev. 48A, 831–835.
IUPAC-IUB Joint Commission on Biochemical Nomenclature (1982) Nomenclature of Tocopherols and Related Compounds: Recommendations 1981,Eur. J. Biochem. 123, 473–475.
Nelan, D.R., and Robeson, C.D. (1962) The Oxidation Product from α-Tocopherol and Potassium Ferricyanide and Its Reaction with Ascorbic and Hydrochloric Acids,J. Am. Chem. Soc. 84, 2963–2968.
Frampton, V.L., Skinner, W.A., Cambour, P., and Bailey, P.S. (1969) α-Tocopurple: An Oxidation Product of α-Tocopherol,J. Am. Chem. Soc. 82, 4632–4634.
Hjarde, W., Leerbeck, E., and Leth, T. (1973) The Chemistry of Vitamin E (including its chemical determination),Acta Agric Scand. (Suppl.)19, 87–96.
Kasparek, S. (1980) Chemistry of Tocopherols and Tocotrienols, inVitamin E, A Comprehensive Treatise (Machlin, L.J., ed.), pp. 7–65, Marcel Dekker, Inc, New York and Basel.
Simic, M.G. (1981) Vitamin E Radicals, inOxygen and Oxyradicals in Chemistry and Biology (Rodgers, M.A.J., and Powers, E.L., eds.) Academic Press, New York, p. 109.
Doba, T., Burton, G.W., and Ingold, K.U. (1983) EPR Spectra of Some α-Tocopherol Model Compounds. Polar and Conformational Effects and Their Relation to Antioxidant Activities,J. Am. Chem. Soc. 105, 6505–6506.
Matsuo, M., Matsumoto, S., and Ozawa, T. (1983) Electron Spin Resonance Spectra and Hyperfine Coupling Constants of the Tocopheroxyl and 2,2,5,7,8-Pentamethylchroman-6-Oxyl Radicals Derived from Vitamin E and Its Model and Deuterated Model Compounds,Org. Mag. Res. 21, 261–264.
Burton, G.W., Doba, T., Gabe, E.J., Hughes, L., Lee, F.L., Prasad, L., and Ingold, K.U. (1985) Autooxidation of Biological Molecules. 4. Maximizing the Antioxidant Activity of Phenols,J. Am. Chem. Soc. 107, 7053–7065.
Boguth, W., and Niemann, H. (1971) Electron Spin Resonance of Chromanoxy Free Radicals from Tocopherol and Tocol,Biochim. Biophys. Acta 248, 121–130.
Mukai, K., Tsuzuki, N., Ishizu, K, Ouchi, S., and Fukuzawa, K. (1981) Electron Nuclear Double Resonance Studies on Radicals Produced by the Lead (II) Oxide Oxidation of α-Tocopherol and Its Model Compound in Solution,Chem. Phys. Lipids 29, 129–135.
Mukai, K., Tsuzuki, N., Ouchi, S., and Fukuzawa, K. (1982) Electron Spin Resonance Studies of Chromanoxyl Radicals Derived from Tocopherols,Chem. Phys. Lipids 30, 337–345.
Matsuo, M., and Matsumoto, S. (1983) Electron Spin Resonance Spectra of the Chromanoxyl Radicals Derived from Tocopherols (vitamin E) and Their Related Compounds,Lipids 18, 81–86.
Tsuchiya, J., Niki, E., and Kamiya, Y. (1983) Oxidation of Lipids. IV. Formation and Reaction of Chromanoxyl Radicals as Studies by Electron Spin Resonance,Bull. Chem. Soc. Jpn 56, 229–231.
Kagan, V.E., Sebinova, E.A., and Packer, L. (1990) Recylcing and Antioxidant Activity of Tocopherol Homologs of Differing Hydrocarbon Chain Lengths in Liver Microsomes,Arch. Biochem. Biophys. 282, 221–225.
Sumarno, M., Atkinson, E., Suarna, C., Saunders, J.K., Cole, E.R., and Southwell-Keely, P. T. (1987) Solvent Influence on Model Oxidations of α-Tocopherol,Biochim. Biophys. Acta 920, 247–250.
Suarna, C., and Southwell-Keely, P.T. (1988) New Oxidation Products of α-Tocopherol,Lipids 23, 137–139.
Suarna, C., and Southwell-Keely, P.T. (1989) Effect of Alcohols on the Oxidation of Vitamin E Model Compound 2,2,5,7,8-Pentamethyl-6-Chromanol,Lipids 24, 56–60.
Suarna, C., Sumarno, D. N., and Southwell-Keely, P.T. (1988) New Oxidation Products of 2,2,5,7,8-Pentamethyl-6-Chromanol,Lipids 23, 1129–1131.
Suarna, C., Baca, M., and Southwell-Keely, P.T. (1992) Oxidation of the α-Tocopherol Model Compound 2,2,5,7,8-Pentamethyl-6-Chromanol in the Presence of Alcohols,Lipids 27, 447–453.
Suarna, C., Craig, D.C., Cross, K.G., and Southwell-Keely, P.T. (1988) Oxidation of Vitamin E (α-tocopherol) and Its Model Compound 2,2,5,7,8-Pentamethyl-6-Hydroxychroman: A New Dimer,J. Org. Chem. 53, 1281–1284.
Suarna, C., and Southwell-Keely, P.T. (1991) Antioxidant Activity of Oxidation Products of α-Tocopherol and of Its Model Compound 2,2,5,7,8-Pentamethyl-6-Chromanol,Lipids 26, 187–190.
Nillson, J.L.G., Doyle Daves, G., and Folkers, K. (1968) New Tocopherol Dimers,Acta Chem. Scand. 22, 200–206.
Nillson, J.L.G., Doyle Daves, G., and Folkers, K. (1968) The Oxidative Dimerization of α-, β-, ψ-, and Δ-Tocopherols,Acta Chem. Scand. 22, 207–218.
Gross, A.J., and Sizer, I.W. (1959) The Oxidation of Tyramine, Tyrosine and Related Compounds by Peroxidase,J. Biol. Chem. 234, 1611–1614.
Nakamura, T., and Kijima, S. (1972) Studies on Tocopherol Derivatives. III. Oxidation of Δ-Tocopherol and 6-Hydroxy-2,2,8-Trimethylchroman,Chem. Pharm. Bull. 20, 1297–1304.
Lambelet, P., and Löliger, J. (1984) The Fate of Antioxidant Radicals During Lipid Autoxidation. 1. The Tocopheroxyl Radical,Chem. Phys. Lipids 35, 185–198.
Denisov, E.T., and Khudyakov, I.V. (1987) Mechanisms of Action and Reactivities of the Free Radicals of Inhibitors,Chem. Revs. 87, 1313–1357.
Rousseau-Richard, C., Richard, C., and Martin, R. (1988) Kinetics of Bimolecular Decay of α-Tocopheroxyl Free Radicals Studied by ESR,FEBS Lett. 233, 307–310.
Skinner, W.A., and Parkhurst, R.M. (1966) Oxidation Products of Vitamin E and Its Model, 6-Hydroxyl-2,2,5,7,8-Pentamethylchroman. VIII. Oxidation with Benzoyl Peroxide,J. Org. Chem. 31, 1248–1251.
Draper, H.H., Csallany, A.S., and Chiu,M. (1976) Isolation of a Trimer of α-Tocopherol from Mammalian Liver,Lipids 2, 47–54.
Yamauchi, R, Kato, K., and Ueno, K. (1988) Formation of Trimers of α-Tocopherol and Its Model Compound, 2,2,5,7,8-Pentamethylchroman-6-ol in Autoxidizing Methyl Linoleate,Lipids 23, 779–783.
Yamauchi, R, Matsui, T., Kato, K., and Ueno, K. (1989) Reaction Products of α-Tocopherol with a Free Radical Initiator, 2,2′-Azobis(2,4-dimethylvaleronitrile),Lipids 24, 204–209.
Yamauchi, R, Matsui, T., Kato, K, and Ueno, K. (1989) Reaction of α-Tocopherol with 2,2′-Azobis(2,4-dimethyl-valeronitrile) in Benzene,Agric. Biol. Chem. 53, 3257–3262.
Igarashi, O., Hagino, M., and Inagaki, C. (1973) Decomposition of α-Tocopheryl Spirodimer by Alkaline Saponification,J. Nutr. Sci. Vitaminol. 19, 469–474.
Matsuo, M., Matsumoto, S., Iitaka, Y., and Niki, E. (1989) Radical Scavenging Reactions of Vitamin E and Its Model Compound, 2,2,5,7,8-Pentamethylchroman-6-ol, in aterl-Butylperoxy Radical Generating System,J. Am. Chem. Soc. 111, 7179–7185.
Liebler, D.C., Baker, P.F., and Kaysen, K.L. (1990) Oxidation of Vitamin E: Evidence for Competing Autoxidation and Peroxy Radical Trapping Reactions of the Tocopheroxyl Radical,J. Am. Chem. Soc. 112, 6995–7000.
Winterle, J.S., Dulin, D., and Mill, T. (1984) Products and Stoichiometry of Reaction of Vitamin E with Alkyl Peroxy Radicals,J. Org. Chem. 49, 491–495.
Csallany, A.S., Draper, H.H., and Shah, S.N. (1962). Conversion of α-Tocopherol-C14 to Tocopheryl-p-Quinonein vivo, Arch. Biochem. Biophys 98, 142–145.
Komoda, M., and Harada, I. (1969). A Dimeric Oxidation Product of γ-Tocopherol in Soybean Oil,J. Am. Chem. Soc. 46, 18–22.
Yamauchi, R., Matsui, T., Kato, K., and Ueno, K. (1990) Reaction Products of γ-Tocopherol with an Alkyl Peroxy Radical in Benzene,Agric. Biol. Chem. 54, 2703–2709.
McHale, D., and Green, J. (1963). A Dimeric Oxidation Product of γ-Tocopherol,Chem. & Ind. (London), 982–983.
Ishikawa, Y. (1974) Yellow Reaction Products from Tocopherol and Trimethylamine Oxide,Agric. Biol. Chem. 38, 2545–2547.
Ishikawa, Y., and Yuki, E. (1975) Reaction Products from Various Tocopherols with Trimethylamine Oxide and Their Antioxidative Activities,Agric. Biol. Chem. 39, 851–857.
Fujitani, T., and Ando, H. (1981) Oxidation Dimerization of Tocopherols During the Course of Autoxidation of Methyl Esters of Saturated and Unsaturated Fatty Acids. I. Oxidative Dimerization of γ-Tocopherol Under A.O.M. Condition,J. Japan Oil Chem. Soc. 30, 145–150.
Fujitani, T., and Ando, H. (1984) Oxidation Dimerization of Tocopherols During the Course of Autoxidation of Methyl Esters of Saturated and Unsaturated Fatty Acids. II. Oxidative Dimerization of α- and Δ-Tocopherols Under A.O.M. Conditions,J. Japan. Oil Chem. Soc. 33, 356–360.
Kwi-Hyun, H., and Igarashi, O. (1990) The Oxidation Products from Two Kinds of Tocopherols Co-Existing in Autoxidation System of Methyl Linoleate,J. Nutr. Sci. Vitaminol 36, 411–421.
Yamauchi, R., Miyake, N., Kato, K., and Ueno, K. (1993) Reaction of α-Tocopherol with Alkyl and Alkyl Peroxy Radicals of Methyl Linoleate,Lipids 28, 201–206.
Wasson, J.J., and Smith, W.M. (1953) Effect of Alkyl Substitution on Antioxidant Properties of Phenols,Ind. & Ing. Chem. 45, 197.
Cort, W.M. (1974) Hemoglobin Peroxidation Test Screens Antioxidants,Food Technol. 10, 60–66.
Wacks, W. (1949) Elektrometrische Redoxmessungen an Natürlichen Fett-Antioxydantien,Biochem. Z. 319, 561–570.
Niki, E., Tsuchiya, J., Yoshikawa, Y., Yamamoto, Y., and Kamiya, Y. (1986) Antioxidant Activities of α-, β-, ψ- and Δ-Tocopherols,Bull. Chem. Soc. Jpn 59, 497–501.
Burton, G.W., LaPage, Y., Fabe, E.J., and Ingold, K.U. (1980) Antioxidant Activity of Vitamin E and Related Phenols: Importance of Stereoelectronic Factors,J. Am. Chem. Soc. 102, 7791–7792.
Mukai, K., Uemoto, Y., Fukuhara, M., Nagaoka, S., and Ishizu, K. (1992) ENDOR Study of the Cation Radicals of Vitamin E Derivatives: Relation Between Antioxidant Activity and Molecular Structure,Bull. Chem. Soc. Jpn. 65, 2016–2020.
Nagaoka, S., Sawada, K., Fukumoto, Y., Nagashima, U., Katasumata, S., and Mukai, K. (1992) Mechanism of Antioxidant Reaction of Vitamin E: Kinetic, Spectroscopic andab initio Study of Proton-Transfer Reactions,J. Phys. Chem. 96, 6663–6668.
Nagaoka, S., Mukai, K., Itoh, T., and Katsumata, S. (1992) Mechanism of Antioxidant Reaction of Vitamin E: Photoelectron Spectroscopy andab initio Calculation,J. Phys. Chem. 96, 8184–8187.
Nagaoka, S., Kuranaka, A., Tsuboi, H., Nagashima, U., and Mukai, K. (1992) Mechanism of Antioxidant Reaction of Vitamin E: Charge Transfer and Tunneling Effect in Proton-Transfer Reactions,J. Phys. Chem. 86, 2754–2761.
Sliwiok, von J., and Kocjan, B (1992) Chromatographische Untersuchungen der Hydrophoben Eigenschaften von Tocopherolen,Fat Sci. Technol. 94, 157–159.
Ingold, K.U., and Howard, J.A. (1962) Reactions of Phenols with Peroxy Radicals,Nature 195, 280–281.
Howard, J.A., and Ingold, K.U. (1962) The Inhibited Autoxidation of Styrene. III. The Relative Inhibiting Effeciencies ofmeta- andpara-Substituted Phenols,Can. J. Chem. 41, 1744–1751.
Howard, J.A., and Ingold, K.U. (1963) The Inhibited Autoxidation of Styrene. III. The Relative Inhibiting Efficiencies oforth-Alkyl Phenols,Can. J. Chem. 41, 2800–2806.
Massey, J.B. (1984) Kinetics of Transfer of α-Tocopherol Between Model and Native Plasma Lipoproteins,Biochim. Biophys. Acta 793, 387–392.
Ingold, K.U., Burton, G.W., Foster, D.O., Zuker, M., Hughes, L., Lacelle, S., Lusztyk, E., and Slaby, M. (1986) A New Vitamin E Analogue More Active Than α-Tocopherol in the Rat Curative Myopathy Bioassay,FEBS Lett. 205, 117–120.
Ingold, K.U., Webb, A., Witter, D., Burton, G.W., Metacalfe, T.A., and Muller, D.P. (1987) Vitamin E Remains the Major Lipid-Soluble, Chain-Breaking Antioxidant in Human Plasma Even in Individuals Suffering Severe Vitamin E Deficiency,Arch. Biochem. Biophys. 259, 224–225.
Ingold, K.U., Burton, G.W., Foster, D.O., and Hughes, L. (1990) Further Studies of a New Vitamin E Analogue More Active Than α-Tocopherol in the Rat Curative Myopathy Bioassay,FEBS Lett. 267, 63–67.
Ingold, K.U., Burton, G.W., Foster, D.O., and Hughes, L. (1990) Is Methyl-Branching in α-Tocopherol's “Tail” Important for Itsin vivo Activity? Rat Curative Bioassay Measurements of the Vitamin E Activity of three 2RS-n-alkyl-2,5,7,8-Tetramethyl-6-Hydroxychromans,Free Radic. Biol. Med. 9, 205–210.
Burton, G.W., Hughes, L., and Ingold, K.U. (1983) Antioxidant Activity of Phenols Related to Vitamin E: Are There Chain-Breaking Antioxidants Better Than α-Tocopherol?,J. Am. Chem. Soc. 105, 5950–5951.
Hughes, L., Burton, G.W., Ingold, K.U., Slaby, M., and Foster, D.O. (1992) Custom Design of Betterin vivo Antioxidants Structurally Related to Vitamin E, inPhenolic Compounds in Food and Their Effects on Health, vol. 2: Antioxidants and Cancer Prevention, Chapter 14 (Ho, C.-T., Lee, C.Y., and Huang, M.-T., eds.) pp. 350–366, ACS Series 507, Washington D.C.
Ames, S.R. (1971) Isomers of α-Tocopheryl Acetate and Their Bioligical Activity,Lipids 6, 281–290.
Ames, S.R. (1979) Biopotencies in Rat of Several Forms of α-Tocopherol,J. Nutr. 109, 2198–2204.
Weiser, H, and Vecchi, M. (1981) Stereoisomers of α-Tocopheryl Acetate: Characterization of the Samples by Physicochemical Methods and Determination of Biological Activities in the Rat Resorption Gestation Test,Int. J. Vit. Nutr. Res. 51, 100–113.
Weiser, H, and Vecchi, M. (1982) Stereoisomers of α-Tocopheryl Acetates. II. Biopotencies of Eight Stereoisomers, Individually or in Mixtures as Determined by Rat Resorption-Gestation Tests,Int. J. Vit. Nutr. Res. 52, 351–370.
Machlin, L.J., Gabriel, E., and Brin, M. (1982) Biopotency of α-Tocopherol as Determined by Curative Myopathy Bioassay in the Rat,J. Nutr. 112, 1437–1440.
Ingold, K.U., Burton, G.W., Foster, D.O., Hughes, L., Lindsay, D.A., and Webb, A. (1987) Biokinetics and Discrimination Between DietaryRRR- andSRR-α-Tocopherol in the Male Rat,Lipids 22, 163–172.
Niki, E., Tsuchiya, J., Kawakimi, A., Saito, M., Yamamoto, Y., and Kamiya, Y. (1985) Effects of Phytyl Side Chain of Vitamin E on Its Antioxidant Activity,J. Biol. Chem. 260, 2191–2196.
Diplock, A.T., and Lucy, J. (1973) The Biochemical Modes of Action of Vitamin E and Selenium: A Hypothesis,FEBS Lett. 29, 205–210.
Perly, B., Smith, L.C.P., Hughes, L.H., Burton, G.W., and Ingold, K.U. (1985) Estimation of the Location of Natural α-Tocopherol in Lipid Bilayers,Biochim. Biophys. Acta 819, 131–135.
Wefers, H., and Sies, H. (1988) The Protection by Ascorbate and Glutathione Against Microsomal Lipid Peroxidation Is Dependent on Vitamin E,Eur. J. Biochem. 174, 353–357.
Wefers, H., and Sies, H. (1988) Antioxidant Defense: Vitamins E and C and Beta-Carotene, inOxy-Radicals in Molecular Biology and Pathology (Cerutti, P.A., Fridovich, I., and McCord, J.M., eds.) pp. 481–490, Alan R. Liss, Inc., New York.
Diplock, A.T. (1985) Vitamin E, inFat-Soluble Vitamins (Diplock, A.T., ed.) pp. 154–224, Technomic Publisher, Lancaster.
Bunyan, J., McHale, D., Green, J., and Marcinkiewicz, S. (1961) Biological Potencies of ε and ζ1-Tocopherol and 5-Methyltocol,Br. J. Nutr. 15, 253–257.
Traber, M.G., Burton, G.W., Hughes, L., Ingold, K.U., Hidaka, H., Malloy, M., Kane, J., Hyams, J., and Kayden, H.J. (1992) Discrimination Between Forms of Vitamin E by Humans with and without Genetic Abnormalities of Lipoprotein Metabolism,J. Lipid Res. 33, 1171–1182.
Kayden, H.J., and Traber, M.G. (1993) Absorption, Lipoprotein Transport and Regulation of Plasma Concentrations of Vitamin E in Humans,J. Lipid Res. 34, 343–358.
Clément, M., Dinh, L., and Bourre, J.-M. (1995) Uptake of DietaryRRR-α- andRRR-γ-Tocopherol by Nervous Tissues, Liver and Muscle in Vitamin E-Deficient Rats,Biochim. Biophys. Acta 1256, 175–180.
Traber, M.G., Burton, G.W., Ingold, K.U., and Kayden, H.J. (1990)RRR- andSRR-Tocopherols Are Secreted Without Discrimination in Human Chylomicrons, ButRRR-α-Tocopherol Is Preferentially Secreted in Very Low Density Lipiproteins,J. Lipid Res. 31, 675–685.
Kiyose, C., Hayashi, K., Ueda, T., and Igarashi, O (1994) Distribution of α-Tocopherol Stereoisomers in Rats,Biosci. Biotech. Biochem. 58, 2000–2003.
Kiyose, C., Muramatsu, R., Ueda, T, and Igarashi, O. (1995) Change in Distribution of α-Tocopherol Stereoisomers in Rats After Intravenous Administration,Biosci. Biotech. Biochem. 59, 791–795.
Kiyose, C., Muramatsu, R., Fujiama-Fujiwara, Y., Ueda, T., and Igarashi, O. (1995) Biodiscrimination of α-Tocopherol Stereoisomers During Intestinal Absorption,Lipids 30, 1015–1018.
Catignani, G.L., and Bieri, J.G. (1975) Rat Liver α-Tocopherol Binding Protein,Biochem. Biophys. Acta 497, 349–357.
Kaplowitz, N., Yoshida, H., Kuhlenkamp, J., Slitsky, B., Ren, I., and Stolz, A. (1989) Tocopherol-Binding Protein of Hepatic Cytosol,Ann. N.Y. Acad. Sci. 570, 85–94.
Sato, Y., Hagiwara, K., Arai, H., and Inoue, K. (1991) Purification and Characterization of the α-Tocopherol Transfer Protein from Rat Liver,FEBS Lett. 288, 41–45.
Yoshida, H., Yusin, M., Ren, I., Kuklenkamp, J., Hirano, T., Stolz, A., and Kaplowitz, N. (1992) Identification, Purification and Immunochemical Characterization of a Tocopherol-Binding Protein in Rat Liver Cytosol,J. Lipid Res. 33, 343–350.
Gotoda, T., Arita, M., Arai, H., Inoue, K., Yokota, T., Fukuo, Y., Yazaki, Y., and Yamada, N. (1995) Adult-Onset Spinocerebellar Dysfunction Caused by Mutation in the Gene for the α-Tocopherol-Transfer Protein,N. Eng. J. Med. 333, 1313–1318.
Leth, T., and Sondergaad, H. (1977) Biological Activity of Vitamin E Compounds and Natural Materials by the Resorption-Gestation Test and Chemical Determination of Vitamin E Activity in Foods and Feeds,J. Nutr. 107, 2236–2243.
Cadenas, E. (1989) Biochemistry of Oxygen Toxicity, A Review,Biochemistry 58, 79–110.
Hennig, B., and Chow, C.K. (1988) Lipid Peroxidation and Endothelial Cell Injury: Implications in Athersclerosis,Free Radic. Biol. Med. 4, 99–106.
Packer, J.E., Mahood, J.S., Mora-Arellano, V.O., Slater, T.F., Wilson, R.L., and Wolfenden, B.S. (1981) Free Radicals and Singlet Oxygen-Scavengers: Reactions of a Peroxy Radical with β-Carotene, Diphenyl Furan and 1,4-Diazobicyclo-(2,2,2)-Octane,Biochem. Biophys. Res. Commun. 98, 901–906.
Maillard, B., Ingold, K.U., and Scaniano, J.C. (1983) Rate Constants for the Reactions of Free Radicals with Oxygen in Solution,J. Am. Chem. Soc. 105, 5095–5099.
Ingold, K.U. (1961) Inhibition of the Autoxidation of Organic Substances in the Liquid Phase,Chem. Rev. 61, 563–589.
Schaich, K.M. (1992) Metals and Lipid Peroxidation: Contemporary Issues,Lipids 27, 209–218.
Campbell, T.W., and Coppinger, G.M. (1952) The Reaction oftert-Butyl Hydroperoxide with Some Phenols,J. Am. Chem. Soc. 74, 1467–1469.
Gardner, H.W., Eskins, K., Grams, G.W., and Inglett, G.E. (1972) Radical Addition of Linoleic Hydroperoxides to α-Tocopherol or the Analogous Hydroxychroman,Lipids 7, 324–334.
Yamauchi, R., Kato, K., and Ueno, Y. (1995) Free Radical Scavenging Reactions of α-Tocopherol During the Autoxidation of Methyl Linoleate in Bulk Phase,J. Agric. Food. Chem. 43, 1455–1461.
Yamauchi, R., Yamamoto, N., and Koji, K. (1995) Iron-Catalyzed Reaction Products of α-Tocopherol with Methyl-13(S)-Hydroperoxy-9(Z),11(E)-Octadecadienoate,Lipids 30, 395–404.
Liebler, D.C., and Burr, J.A. (1995) Antioxidant Stoichiometry and the Oxidative Fate of Vitamin E in Peroxy Radical Scavening Reactions,Lipids 30, 789–793.
Winterle, J.S., and Mill, T. (1981) Reactions of Vitamin E with Alkyl Peroxy Radicals in Homoggeneous Solution and Liposome, inOxygen and Oxy-Radicals in Chemistry and Biology (Rodgers, M.A.J., and Powers, E.L., eds.) pp. 779–780, Academic Press, New York.
Pryor, W.A., Cornicelli, J.A., Devall, L.J., Tait, D., Trevedi, B.K., Witiak, D.T., and Wu, M. (1993) A Rapid Screening Test to Determine the Antioxidant Potencies of Natural and Synthetic Antioxidants,J. Org. Chem. 58, 3521–3532.
Kharitonova, A.A., Kozlova, Z.G., Tsepalov, V.F., and Gladyshev, G. (1979) Kinetic Analysis of the Properties of Antioxidants in Complex Compositions Using a Model Chain-Reaction,Kinet. Katal. 20, 593–599.
Packer, J.E., Slater, T.F., and Willison, R.L. (1979) Direct Observation of a Free Radical Interaction Between Vitamin E and Vitamin C,Nature 278, 737–738.
Patterson, L.K. (1981) Studies of Radiation-Induced Peroxidation in Fatty Acid Micelles, inOxygen and Oxy-Radicals in Chemistry and Biology (Rodgers, M.A.J., and Powers, E.L., eds.) pp. 89–95, Academic Press, New York.
Chance, B., Sies, H., and Boveris, A. (1979) Hydroperoxide Metabolism in Mamalian Organs,Physiol. Rev. 59, 527–605.
Fukuzawa, K., and Gebicki, J.M. (1983) Oxidation of α-Tocopherol in Micelles and Liposomes by the Hydroxyl, Perhydroxyl and Superoxide Free Radicals,Arch. Biochem. Biophys. 226, 242–251.
Csallany, A.S., and Ha, Y.L. (1992) α-Tocopherol Oxidation Mediated by Superoxide Anion (O −2 . I. Reactions in Aprotic and Protic Conditions,Lipids 27, 195–200.
Ha, Y.L., and Csallany, A.S. (1992) α-Tocopherol Oxidation Mediated by Superoxide Anion (O −2 ). II. Identification of the Stable α-Tocopherol Oxidation Products,Lipids 27, 201–205.
Nishikimi, M., Yamada, H., and Yagi, K. (1980) Oxidation by Superoxide of Tocopherols Dispersed in Aqueous Media with Deoxycholate,Biochim. Biophys. Acta 627, 101–108.
Durckheimer, W., and Cohen, L.A. (1964) The Chemistry of 9-Hydroxy-α-Tocopherone: A Quinone Hemiacetal,J. Am. Chem. Soc. 86, 4388–4393.
Grams, G.W., and Eskins, K. (1972) Dye-Sensitized Photoxidation of Tocopherols: Correlation Between Singlet Oxygen Reactivity and Vitamin E Activity,Biochemistry 11, 606–608.
Fahrenholtz, S.R., Doleiden, F.H., Trozzolo, A.M., and Lamola, A.A. (1974) On the Quenching of Singlet Oxygen by α-Tocopherol,Photochem. Photobiol. 20, 505–509.
Foote, C.S., Ching, T.Y., and Geller, G.G. (1974) Chemistry of Singlet Oxygen. VIII. Rates of Reaction and Quenching of α-Tocopherol and Singlet Oxygen,Photochem. Photobiol. 20, 511–513.
Foote, C.S. (1979) Quenching of Singlet Oxygen, inSinglet Oxygen (Wasserman, H.H., and Murray, R.W., eds.) pp. 139–171, Academic Press, New York.
Stevens, B., Small, R.D., and Perez, S.R. (1974) The Photoperoxidation of Unsaturated Organic Molecules. XIII. O2 1Δg Quenching by α-Tocopherol,Photochem. Photobiol. 20, 515–517.
Yamauchi, R., and Matsushita, S. (1977) Quenching Effect of Tocopherols on the Methyl Linoleate Photooxidation and Their Oxidation Products,Agric. Biol. Chem. 41, 1425–1430.
Yamauchi, R., and Matsushita, S. (1979) Products Formed by Photosensitized Oxidation of Tocopherols,Agric. Biol. Chem. 43, 2151–2156.
Clough, R.L., and Yee, B.G. (1978) Photoxidation of Tocopherols, inTocopherol, Oxygen and Biomembranes (deDuve, C., and Hayaishi, O., eds.) Elsevier, Amesterdam.
Clough, R.L., Yee, B.G., and Foote, C.S. (1979) Chemistry of Singlet Oxygen. XXX. The Unstable Primary products of Tocopherol Photoxidation,J. Am. Chem. Soc. 101, 683–686.
Gorman, A.A., Gould, I.R., Hamblett, I., and Standen, M.C. (1984) Reversible Exciplex Formation Between Singlet Oxygen (1Δg) and Vitamin E: Solvent and Temperature Effects,J. Am. Chem. Soc. 106, 6956–6959.
Neely, W.C., Martin, J.M., and Barker, S.A. (1988) Products and Relative Reaction Rates of the Oxidation of Tocopherols with Singlet Molecular Oxygen,Photochem. Photobiol. 48, 423–428.
Kaiser, S., DiMascio, P., Murphy, M.E., and Sies, H. (1990) Physical and Chemical Scavening of Singlet Molecular Oxygen by the Tocopherols,Arch. Biochem. Biophys. 277, 101–108.
Kough, K., and Min, D.B. (1993) Reaction Rates of α-, γ- and δ-Tocopherols with Singlet Oxygen,INFORM 4, 528.
Jung, M.Y., Lee, E., and Min, D.B. (1991) α-, γ- and δ-Tocopherols Effects on Chlorophyll Photosensitized Oxidation of Soybean Oil,J. Food Sci. 56, 807–810.
D'Ischia, M., Costantini, C., and Aprota, G. (1991) Dye-Sensetized Photoxidation of Vitamin E Revisitized: New 7-Oxaspiro[4.5]-dec-1-ene-3,6-Dione Products by Oxygenation and Ring Contraction of α-Tocopherol,J. Am. Chem. Soc. 113, 8353–8356.
Thomas, M., and Foote, C.S. (1974) Chemistry of Oxygen. XXVI. Photooxygenation of Phenols,Photochem. Photobiol. 27, 683–693.
Foote, C.S. (1976) Photosensitized Oxidations and Singlet Oxygen: Consequences in Biological Systems, inFree Radicals in Biology—Vol. 2 (Pryor, W.A., ed.) pp. 85, Academic Press, New York.
Fragata, M., and Bellemare, F. (1980) Model of Singlet Oxygen Scavenging by α-Tocopherol in Biomembranes,Chem. Phys. Lipids 27, 93–99.
Krinsky, N.I. (1992) Mechanism of Action of Biological Antioxidants,Proc. Soc. Expt. Biol. Med. 200, 248–254.
Di Mascio, P., Kaiser, S., and Sies, H. (1989) Lycopene as the Most Efficient Biological Carotenoid Singlet Oxygen Quencer,Arch. Biochem. Biophys. 274, 532–538.
Zweig, A., and Hunderson, Jr., W.A. (1975) Singlet Oxygen and Polymer Photoxidation. I. Sensitizers, Quenchers and Reactants,J. Polymer Sci. Polym. Chem. Ed. Pt. A, 1, 717–736.
Grams, G.W. (1971) Oxidation of α-Tocopherol by Singlet Oxygen,Tetrahedron Lett. 4823–4825.
Grams, G.W., Eskins, K., and Inglett, G.E. (1972) Dye-Sensitized Photo-Oxidation of α-Tocopherol,J. Am. Chem. Soc. 94, 866–868.
Terao, J., and Matsushita, S. (1980) The Isomeric Composition of Monohydroperoxides Produced by Oxidation of Unsaturated Fatty Acid Esters with Singlet Oxygen,J. Food Process Preserv. 3, 329–337.
Carlson, D.J., Suprunchuk, T., and Willes, D.M. (1976) Photoxidation of Unsaturated Oils: Effect of Singlet Oxygen Quenchers,J. Am. Oil. Chem. Soc. 53, 656–660.
Mukai, K., and Okauchi, Y. (1989) Kinetic Study of the Reaction Between Tocopheroxyl Radical and Unsaturated Fatty Acid Esters in Benzene,Lipids 24, 936–939.
Mukai, K., Kohno, Y., and Ishizu, K. (1988) Kinetic Study of the Reaction Between Vitamin E Radical and Alkyl Hydroperoxides in Solution,Biochem. Biophys. Res. Commun. 155, 1046–1050.
Mukai, K., Morimoto, H., Okauchi, Y., and Nagaoka, S. (1993) Kinetic Study of Reactions Between Tocopheroxyl Radicals and Fatty Acids,Lipids 28, 753–756.
Mukai, K., Sawada, K., Kohno, Y., and Terao, J. (1993) Kinetic Study of the Prooxidant Effect of Tocopherol. Hydrogen Abstraction from Lipid Hydroperoxides by Tocopheroxyls in Solution,Lipids 28, 747–752.
Bowry, V.W., Ingold, K.U., and Stocker, R. (1992) Vitamin E in Human Low-Density Lipoprotein,Biochem. J. 288, 341–344.
Bowry, V.W., and Stocker, R. (1993) Tocopherol-Mediated Peroxidation: The Prooxidant Effect of Vitamin E on the Radical-Initiated Oxidation of Human Low-Density Lipoprotein,J. Am. Chem. Soc. 115, 6029–6044.
Ingold, K.U., Bowry, V.W., Stocker, R., and Walling, C. (1993) Autoxidation of Lipids and Antioxidation by α-Tocopherol and Ubiquinol in Homogeneous Solution and in Aqueous Dispersions of Lipids: Unrecognized Consequences of Lipid Particle Size as Examined by Oxidation of Human Low Density Lipoprotein,Proc. Natl Acad. Sci. USA 90, 45–49.
Hicks, M., and Gebicki, J.M. (1981) Inhibition of Peroxidation in Linoleic Acid Membranes by Nitroxide Radicals, Butylated Hydroxy Toluene and α-Tocopherol,Arch. Biochem. Biophys. 210, 56–63.
Martemianov, V.S., Denisov, E.T., and Samoilova, L.A. (1972)Izv. Akad. Nauk SSSR, Ser. Khim, 1039.
Grunger, E.H., and Tappel, A.L. (1970) Reactions of Biological Antioxidants. I. Fe(III)-Catalyzed Reactions of Lipid Hydroperoxides with alpha-Tocopherol,Lipids 5, 326–331.
Igarashi, O., Matsukawa, H., and Ingaki, C. (1976) Reactivity of alpha-Tocopherol with Hydroperoxide of Methyl Linoleate,J. Nutr. Sci. Vitaminol. 22, 267–270.
Fukuzawa, K., and Fujii, T. (1992) Peroxide Dependent and Independent Lipid Peroxidation: Site-Specific Mechanisms of Initation by Chelated Iron and Inhibition by α-Tocopherol,Lipids 27, 227–233.
Minoti, G., and Aust, S.D. (1992) Redox Cycling of Iron and Lipid Peroxidation,Lipids 27, 219–226.
Cort, W.M., Mergens, W., and Greene, A. (1978) Stability of α- and γ-Tocopherol: Fe3+ and Cu2+ Interactions,J. Food Sci. 43, 797–798.
Willson, R.L. (1979) Hydroxyl Radicals and Biological Damagein vitro: What Relevancein vivo?, inOxygen Free Radicals and Tissue Damage (Ciba Foundation Symposium 65), pp. 19–42, Excerpta Medica, Amesterdam.
Doba, T., Burton, G.W., Ingold, K.U., and Matsu, M. (1984) α-Tocopherol Decay: Lack of Effect of Oxygen,J. Chem. Soc. Chem. Commun. 461–462.
Kornhurst, O.J., and Mavis, R.D. (1979) Microsomal Lipid Peroxidation: Characterization of the Role of Iron and NADPH,Mol. Pharmacol. 17, 400–407.
Peers, K.E., and Coxon, D.T. (1983) Controlled Synthesis of Monohydroperoxides by α-Tocopherol Inhibited Autoxidation of Polyunsaturated Lipids,Chem. Phys. Lipids 32, 49–56.
Peers, K.E., Coxon, D.T., and Chan, H.-W.-S. (1981) Autoxidation of Methyl Linolenate and Methyl Linoleate: The Effect of α-Tocopherol,J. Sci. Food. Agric. 32, 898–904.
Loury, M., Bloch, R., and Francois, R. (1966) Use of Tocopherol as an Antioxidant in Fats,Rev. Fr. Corp. Gras 13, 747–752.
Terao, J., and Matsushita, S. (1986) The Peroxidizing Effect of α-Tocopherol on Autoxidation of Methyl Linoleate in Bulk Phase,Lipids 21, 255–260.
Buettner, G.R. (1993) The Pecking Order of Free Radicals and Antioxidants: Lipid Peroxidation, α-Tocopherol and Ascorbate,Arch. Biochem. Biophys. 300, 535–543.
Kanner, J., and Mendel, H. (1979) Pro-Oxidant and Antioxidant Effects of Ascorbic Acid and Metal Salts in a β-Carotene-Linoleate Model System,J. Food. Sci. 42, 60–64.
Nishina, A., Sakurai, Y., Hashimoto, K.-I., Isoda, Y., and Inatomi, H. (1992) Effect of Tocopherols on the Peroxidative Kinetics of Ethyl Eicosapentaenoate and Methyl Linoleate,Biosci. Biotech. Biochem. 56, 2060–2061.
Toth, B., and Patil, K. (1983) Enhancing Effect of Vitamin E on Murine Intestinal Tumerogenesis by 1,2-Dimethylhydrazine Dihydrochloride,J. Natl. Cancer. Inst. 70, 1107–1111.
Ikeda, N., and Fukuzumi, K. (1977) Synergistic Antioxidant Effect of Nucleic Acids and Tocopherols,J. Am. Oil. Chem. Soc. 54, 360–366.
Budowski, P., and Sklan, D. (1989) Vitamin E and A, inThe Role of Fats in Human Nutrition (Vergroesen, A.J., and Grawford, M., ess.) pp. 363–406, Academic Press Ltd., London.
Govind Rao, M.K., and Achaya, K.T. (1967) Role of Tocopherol as an Antioxidant in Safflower Oil,Fette Seifen Anstrichm. 69, 711–714.
Kovats, T.K., and Berndorfer-Kraszner, E. (1968) On the Antioxidative Mechanisms of alpha-, beta-, gamma-, and delta-Tocopherols in Lard,Nahrung 12, 407–414.
Marinova, E.M., and Yanishlieva, N.V. (1992) Effect of Temperature on the Antioxidative Action of Inhibitors in Lipid Autoxidation,J. Sci. Food Agric. 60, 313–318.
Saucy, F., Ducret, F., Lambelet, P., and Löliger, J. (1990) The Fate of Antioxidant Radicals During Lipid Autoxidation. II. The Influence of Oxygen Supply on Lipid Autooxidation,Chem. Phys. Lipids 55, 215–221.
Warner, K. (1993) Effects of Adding Various Tocopherol Ratios on the Stability of Purified Vegetable Oils,INFORM 4, 529.
Cort, W.M. (1974) Antioxidant Activity of Tocopherols, Ascorbyl Palmitate, and Ascorbic Acid and Their Mode of Action,J. Am. Oil Chem. Soc. 51, 321–325.
Yuki, E., and Ishikawa, Y. (1976) Tocopherol Content of Nine Vegetable Frying Oils and Their Changes Under Stimulated Deep-Fat Frying Conditions,J. Am. Oil Chem. Soc. 53, 673–376.
Dugan, L.R., and Kraybill, H.R. (1956) Tocopherols as Carry-through Antioxidants,J. Am. Oil Chem. Soc. 33, 527–528.
Porter, W.L., Black, E.D., and Drolet, A.M. (1989) Use of Polyamide Oxidative Fluorescence Test on Lipid Emulsions: Contrast in Relative Effectiveness of Antioxidants in Bulk Versus Dispersed Systems,J. Agric. Food Chem. 37, 615–624.
Porter, W.L. (1993) Paradoxial Behaviour of Antioxidants in Food and Biological Systems,Toxicol. Ind. Health 9, 93–122.
Takahashi, M., Tsuchiya, J., and Niki, E. (1989) Scavenging of Radicals by Vitamin E in the Membranes as Studied by Spin Labelling,J. Am. Chem. Soc. 111, 6350–6353.
Frankel, E.N., Huang, S.-W., Kanner, J., and German, J.B. (1994) Interfacial Phenomena in the Evaluation of Antioxidants: Bulk Oils Versus Emulsions,J. Agric. Food Chem. 42, 1054–1059.
Pryor, W.A., Strickland, T., and Church, D.F. (1988) Comparison of the Efficiencies of Several Natural and Synthetic Antioxidants in Aqueous Sodium Dodecyl Sulfate Micelle Solutions,J. Am. Chem. Soc. 110, 2224–2229.
Castle, L., and Perkins, M.J. (1986) Inhibition Kinetics of Chain-Breaking Phenolic Antioxidants in SDS Micelles. Evidence That Intermicellar Diffusion Rates May Be Rate-Limiting for Hydrophobic Inhibitors Such as α-Tocopherol,J. Am. Chem. Soc. 108, 6381–6382.
Cillard, J., and Cillard, P. (1980) Behavior of alpha, gamma, and delta Tocopherols with Linoleic Acid in Aqueous Media,J. Am. Oil Chem. Soc. 57, 39–42.
Iwatsuki, M., Tsuchiya, J., Komuro, E., Yamamoto, Y., and Niki, E. (1994) Effects of Solvents and Media on the Antioxidant Activity of α-Tocopherol,Biochim. Biophys. Acta 1200, 19–26.
O'Brien, P.J. (1969) Intracellular Mechanisms for the Decomposition of a Lipid Peroxide. I. Decomposition of a Lipid Peroxide by Metal Ions, Heme Compounds and Nucleophiles,Can. J. Biochem. 47, 485–492.
Chen, H., Lee, D.J., and Schanus, E.G. (1992) The Inhibitory Effect of Water on the Co2+ and Cu2+-Catalyzed Decomposition of Methyl Linoleate Hydroperoxides,Lipids 27, 234–239.
Simic, M.G. (1980) Kinetic and Mechanistic Studies of Peroxy, Vitamin E and Antioxidant Free Radicals by Pulse Radiolysis, inAutoxidation in Food and Biological Systems (Simic, M.G., and Karel, M., eds.), pp. 17–26, Plenum Press, New York.
Lambelet, P., Saucy, F., and Löliger, J. (1984) Radical Exchange Reactions Between Vitamin E, Vitamin C and Phosphatides in Autoxidizing Polyunsaturated Lipids,Free Radic. Res. 20, 1–10.
Gardner, H.W., Kleiman, R., Weisleder, D., and Inglett, G.E. (1977) Cysteine Adds to Lipid Hydroperoxides,Lipids 12, 655–660.
Sims, R.J., and Fioriti, J.A. (1977) Methional as an Antioxidant for Vegetable Oils,J. Am. Oil Chem. Soc., 54, 4–7.
Terao, J., Yamauchi, R., Murkami, H., and Matsushita, S. (1980) Inhibitory Effects of Tocopherols and β-Carotene on Singlet Oxygen-Initiated Photooxidation of Methyl Linoleate and Soybean Oil,J. Food Process Preserv. 4, 79–93.
Burton, G.W., and Ingold, K.U. (1984) β-Carotene: An Unsual Type of Antioxidant,Science 224, 569–573.
Kennedy, T.A., and Leibler, D.C. (1992) Peroxy Radical Scavenging by β-Carotene in Lipid Bilayers: Effect of Oxygen Partial Pressure,J. Biol. Chem. 267, 4658–4663.
Golumbic, C., and Matill, H.A. (1941) Antioxidants and the Autoxidation of Fats. XIII. The Antioxygenic Action of Ascorbic Acid in Association with Tocopherols, Hydroquinones and Related Compounds,J. Am. Chem. Soc. 63, 1279–1280.
Niki, F. (1980) Synergistic Inhibition of Oxidations by Vitamins E and C, inCellular Antioxidant Defence Mechanisms (Chow, C.K. ed.) pp. 111–122, CRC, Boca Raton.
Niki, E., Tsuchiya, J., Tanimura, R., and Kamiya, Y. (1982). Regeneration of Vitamin E from α-Chromanoxyl Radical by Glutathione and Vitamin C,Chem. Lett. 789–792.
Niki, E., Saito, M., Kawakami, A., and Kamiya, Y. (1984) Inhibition of Oxidation of Methyl Linoleate by Vitamin E and Vitamin C,J. Biol. Chem. 259, 4177–4182.
Niki, E., Kawakimi, A., Yamamoto, Y., and Kamiya, Y. (1985) Synergistic Inhibition of Oxidation of Soybean Phosphatidyl Choline Liposomes in Aqueous Dispersion by Vitamin E and Vitamin C,Bull. Chem. Soc. Japan 58, 1971–1975.
Leung, H.W., Vang, M.J., and Mavis, R.D. (1981) The Cooperative Interaction Between Vitamin E and Vitamin C in Suppression of Peroxidation of Membrane Phospholipids,Biochim. Biophys. Acta 664, 266–272.
Barclay, L.R.C., Locke, S.J., and MacNeil, J.M. (1983) The Autoxidation of Unsaturated Lipids in Micelles, Synergism of Inhibitors: Vitamins C and E,Can. J. Chem. 61, 1288–1290.
Barclay, L.R.C., Locke, S.J., and MacNeil, J.M. (1985) The Autoxidation of Unsaturated Lipids in Micelles, Synergism of Vitamin C with Lipid-Soluble Vitamin E and Water-Soluble Trolox,Can. J. Chem. 63, 366–374.
Bascetta, E., Gunstone, F.D., and Watton, J.C. (1983) Electron Spin Resonance Study of the Role of Vitamin E and Vitamin C in the Inhibition of Fatty Acid Oxidation in a Model Membrane,Chem. Phys. Lipids 33, 207–210.
Doba, T., Burton, G.W., and Ingold, K.U. (1985) Antioxidant and Co-Antioxidant Effect of Vitamin C. The Effect of Vitamin C Either Alone Or in the Presence of Vitamin E or a Water-Soluble Vitamin E Analogue, upon the Peroxidation of Aqueous Multi-Lamellar Phospholipid Liposomes,Biochim. Biophys. Acta 835, 298–303.
Lambelet, P., Saucy, F., and Löliger, J. (1985) Chemical Evidence for Interaction Between Vitamins E and C,Experientia 41, 1384–1388.
McCay, P.B. (1985) Vitamin E: Interactions with Free Radicals and Ascorbate,Ann. Rev. Nutr. 5, 323–340.
Löliger, J., Lambelet, P., Savoy, M.-C., and Ducret, F. (1986) Radical Exchange Between Autoxidizing Lipids, Vitamin E and Vitamin C in Binary Lipid/Water Systems,Fette Seifen Anstrichm. 88, 584–588.
Niki, E. (1987) Interaction of Ascorbate and α-Tocopherol,Ann. N.Y. Acad. Sci. 498, 186–199.
Nijus, D., and Kelley, P.M. (1991) Vitamins C and E Donate Single Hydrogen Atomsin vivo, FEBS Lett. 284, 147–151.
Scarpa, M., Rigo, A., Maisorino, M., Ursini, F., and Gregolinn, C. (1984) Formation of α-Tocopherol Radical and Recycling of α-Tocopherol by Ascorbic Acid During Peroxidation of Phosphatidyl Choline Liposomes: An Electron Paramagnetic Resonance Study,Biochim. Biophys. Acta 801, 215–219.
Sharma, M., and Buettner, G.R. (1993) Interaction of Vitamin C and Vitamin E During the Free Radical Stress in Plasma: An ESR Study,Free Radic. Biol. Med. 14, 649–653.
Yi, O.-S., Han, D., and Shin, H.-K. (1991) Synergistic Antioxidative Effects of Tocopherol and Ascorbic Acid in Fish Oil/Lecithin/Water system,J. Am. Oil Chem. Soc. 68, 881–883.
Wayner, D.D.M., Burton, G.W., Ingold, K.U., Barklay, L.R.C., and Locke, S.J. (1987) The Relative Contributions of Vitamin E, Urate, Ascorbate and Proteins to the Total Peroxy Radical Trapping Antioxidant Activity of Human Blood Plasma,Biochim. Biophys. Acta 924, 408–419.
Ha, K.H., and Igarashi, O. (1988). Disappearance and Interrelationship of Tocopherol Analogues During Autoxidation of Corn Oil and Synergistic Effect ofl-Ascorbyl Palmitate with α-Tocopherol,Japan J. Food Sci. Technol. 35, 464–470.
Han, D., Yi, O.-S., and Shin, H.K. (1991) Solubilization of Vitamin C in Fish Oil and Synergistic Effect with Vitamin E in Retarding Oxidation,J. Am. Oil Chem. Soc. 68, 740–743.
Wang, X.C., and Grodon, M.H. (1993) Antioxidant Synergy Between Phosphatidylethanolamine and α-Tocopherylquinone,Food Chem. 48, 165–168.
Buettner, G.R. (1993b) Ascorbate Autoxidation in the Presence of Iron and Copper Chelates,Free Radic. Res. Commun. 1, 349–353.
Evans, C.D., Cooney, P.M., Scholfield, C.R., and Dutton, H.J. (1954) Soybean “Lecithin” and Its Fractions as Metal-Inactivating Agents,J. Am. Oil Chem. Soc. 31, 295–297.
Hildebrand, D.H., Jerao, J., and Kito, M. (1984) Phospholipids Plus Tocopherols Increase Soybean Oil Stability,J. Am. Oil Chem. Soc. 61, 552–555.
Hudson, B.J.F., and Mahgoub, S.E.O. (1981) Synergism Between Phospholipids and Naturally Occuring Antioxidants in Leaf Lipids,J. Sci. Food Agric. 32, 208–210.
Hudson, B.J.F., and Ghavami, M. (1984) Phospholipids as Antioxidant Synergists for Tocopherols in the Autoxidation of Edible Oils,Lebensm.-Wiss. u.-Technol. 17, 191–194.
Dziedzic, S.Z., and Hudson, B.J.F. (1984) Phosphatidyl Ethanolamine As a Synergist for Primary Antioxidants in Edible Oils,J. Am. Oil Chem. Soc. 61, 1042–1045.
Bazin, B., Cillard, J., Koskas, J.-P., and Cillard, P. (1984) Arachidonic Acid Autoxidation in an Aqueous Media: Effect of α-Tocopherol, Cysteine and Nucleic Acids,J. Am. Oil Chem. Soc. 61, 1212–1215.
Hamzawi, L.F. (1990) Role of Phospholipids and α-Tocopherol as Natural Antioxidants in Buffalo Butter Fat,Michwissenschaft 45, 95–97.
Szuhaj, B.F., and Sipos, E.F. (1989) Flavor Chemistry of Phospholipids, inFlavor Chemistry of Lipid Foods (Min, D.B., and Smouse, T.H., eds.) pp. 265–288, American Oil Chemists' Society, Champaign.
Linow, F., and Mieth, G. (1976) The Fat-Stabilizing Properties of Phosphatides. III. The Synergistic Action of Selected Phosphatides,Nahrung 20, 19–24.
Yee, J.J., and Shipe, W.F. (1981) Using Enzymatic Proteolysis to Reduce Copper-Protein Catalysis of Lipid Oxidation,J. Food Sci. 46, 966–967.
Riisom, T., Sims, R.J., and Fioriti, J.A. (1980) Effect of Amino Acids on the Autoxidation of Safflower Oil in Emulsions,J. Am. Oil Chem. Soc. 57, 354–359.
Bishov, S.J., and Henick, A.S. (1972) Antioxidant Effect of Protein Hydrolyzates in a Freeze-Dried Model System,J. Food Sci. 37, 873–875.
Yuki, E., Ishikawa, Y., and Yoshiwa, T. (1974) Antioxidative Activities of Amino Acids and Their Esters Under Various Conditions,J. Japan Oil Chem. Soc. 23, 497–500.
Yamagushi, N., and Fujimaki, M. (1974) Browning Reaction Products from Reducing Sugars and Amino Acids. XV. Comparison of Antioxidative Activity of Melanoidin with That of Tocopherol Homologues and the Synergistic Effect of Melanoidin with Tocopherols,Japan J. Food Sci. Technol. 21, 13–18.
El-Zeany, B.A., Janicek, G., and Pokorny, J. (1973) inProc. 3rd Symp. on Metal-Catalyzed Lipid Oxidation, pp. 177–183, Sept. 27–30, 1973, Institut des Corps Gras, Paris.
Kago, T., and Terao, J. (1995) Phospholipids Increase Radical Scavenging Activity of Vitamin E in a Bulk Oil Model System,J. Agric. Food Chem. 43, 1450–1454.
Frankel, E.N., and Gardner, H.W. (1989) Effect of α-Tocopherol on the Volatile Thermal Decomposition Products of Methyl Linoleate Hydroperoxides,Lipids 24, 603–608.
Chan, H.W.S., and Levett, G. (1977) Autoxidation of Methyl Linolenate: Analysis of Methyl Hydrolinolenate Isomers by High-Performance Liquid Chromatography,Lipids 12, 837–840.
Chan, H.W.-S., Levett, G., and Matthew, J.A. (1979) The Mechanism of the Rearrangement of Linoleate Hydroperoxides,Chem. Phys. Lipids 24, 245–256.
Porter, N.A., Weber, B.A., Weenen, H., and Khan, J.A. (1980) Autoxidation of Polyunsaturated Lipids: Factors Controlling the Stereochemistry of Product Hydroperoxides,J. Am. Chem. Soc. 102, 5597–5601.
Neff, W.E., Frankel, E.N., and Weisleder, D. (1981) High-Pressure Liquid Chromatography of Autoxidized Lipids. II. Hydroperoxy Cyclic Peroxides and Other Secondary Products from Methyl Linolenate,Lipids 16, 439–448.
Coxon, D.T., Price, K.R., and Chan, H.W.-S. (1981) Formation, Isolation and Structural Determination of Methyl Linolenate Hydroperoxides,Chem. Phys. Lipids 28, 365–378.
Coxon, D.T., Peers, K.E., and Rigby, N.M. (1984) Selective Formation of Dihydroperoxidesin the α-Tocopherol Inhibited Autoxidation of Methyl Linolenate,J. Chem. Soc. Chem. Commun: 67–68.
Yamagata, S., Murakami, H., Terao, J., and Matsushita, S. (1983) Non-Enzymatic Oxidation Products of Methyl Arachidonate,Agric. Biol. Chem. 47, 2791–2799.
Mergens, W.J. (1992) Tocopherol: Natural Phenolic Inhibitor of Nitrosation, inPhenolic Compounds in Food and Their Effects on Health, Vol. 2: Antioxidants and Cancer Prevention (Ho, C.-T., Lee, C.Y. and Huang, M.-T., eds.) pp. 350–366, ACS Ser 507, Washington D.C.
Pignatelli, B., Friesen, M., and Walker, E.A. (1980) The Role of Phenols in Catalysis of Nitrosamine Formation,IARC Sci. Pub. (Lyon)31, 95–105.
Kurechi, T., Kikugawa, K., and Kato, T. (1979) C-Nitrosation of Sesamol and Its Effects onN-Nitrosamine Formationin vitro, Chem. Pharm. Bull. 27, 2442–2449.
Kamm, J.J., Dashman, T., Newmark, H., and Mergens, W.J. (1977) Inhibition of Amine-Nitrite Hepatotoxicity by α-Tocopherol,Toxicol. Appl. Pharm. 41, 575–583.
Lathia, D., and Blum, A. (1989) Role of Vitamin E as Nitrite Scavenger andN-Nitrosamine Inhibitor: A Review,Int. J. Vit. Nutr. Res. 59, 430–438.
Davies, R., and McWeeny, D.J. (1977) Catalytic Effect of Nitrosophenols onN-Nitrosamine Formation,Nature 266, 657–658.
Davies, R., Dennis, M.J., Massey, R.C., and McWeeny, D.J. (1978) Some Effects of Phenol- and Thiol-Nitrosation Reactions onN-Nitrosamine Formation, inEnvironmental Aspects of N-Nitrosocompounds (Walker, E.A., Castegnaro, M., Griciute, L. and Lyle, R.E., eds.) Vol. 19, pp. 183–199, IARC Scientific Publications, Lyon.
Davies, R., Massey, R.C., and McWeeny, D.J. (1980) The Catalysis of TheN-Nitrosation of Secondary Amines by Nitrosophenols.Food Chem. 6, 115–122.
Tannenbaum, S.R., and Mergens, W. (1980) Reaction of Nitrite with Vitamins C and E,Ann. N.Y. Acad. Sci. 355, 267–277.
Janzen, E.G., Wilcox, A.L., and Monoharan, V. (1993) Reactions of Nitric Oxide with Phenolic Antioxidants and Phenoxyl Radicals,J. Org. Chem. 58, 3597–3599.
Cooney, R.V., and Ross, P.D. (1987)N-Nitosation andN-Nitration of Morpholine by Nitrogen Dioxide in Aqueous Solution: Effects of Vanillin and Related Phenols,J. Agric. Food Chem. 35, 789–793.
Cooney, R.V., Franke, A.A., Harwood, P.J., Hatch-Pigott, V., Custer, L.J., and Mordan, L.J. (1993) γ-Tocopherol Detoxification of Nitrogen Dioxide: Superiority to α-Tocopherol,Proc. Natl. Acad. Sci. USA 90, 1771–1775.
Author information
Authors and Affiliations
About this article
Cite this article
Kamal-Eldin, A., Appelqvist, LÅ. The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids 31, 671–701 (1996). https://doi.org/10.1007/BF02522884
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02522884