1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Nutrition
  4. Volume 41, 2021
  5. Article

Annual Review of Nutrition

Volume 41, 2021

Vitamin A and Vitamin E: Will the Real Antioxidant Please Stand Up?

Abstract

Vitamin A, acting through its metabolite, all--retinoic acid, is a potent transcriptional regulator affecting expression levels of hundreds of genes through retinoic acid response elements present within these genes. However, the literature is replete with claims that consider vitamin A to be an antioxidant vitamin, like vitamins C and E. This apparent contradiction in the understanding of how vitamin A acts mechanistically within the body is a major focus of this review. Vitamin E, which is generally understood to act as a lipophilic antioxidant protecting polyunsaturated fatty acids present in membranes, is often proposed to be a transcriptional regulator. The evaluation of this claim is another focus of the review. We conclude that vitamin A is an indirect antioxidant, whose indirect function is to transcriptionally regulate a number of genes involved in mediating the body's canonical antioxidant responses. Vitamin E, in addition to being a direct antioxidant, prevents the increase of peroxidized lipids that alter both metabolic pathways and gene expression profiles within tissues and cells. However, there is little compelling evidence that vitamin E has a direct transcriptional mechanism like that of vitamin A. Thus, we propose that the term antioxidant not be applied to vitamin A, and we discourage the use of the term transcriptional mediator when discussing vitamin E.

Keyword(s): all-trans-retinoic acid, ATRA, gene expression, oxidative stress, reactive oxygen species, retinoid, ROS, transcription factor, α-tocopherol
Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-082018-124228
2021-10-11
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/nutr/41/1/annurev-nutr-082018-124228.html?itemId=/content/journals/10.1146/annurev-nutr-082018-124228&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Ahmed SM, Luo L, Namani A, Wang XJ, Tang X. 2017. Nrf2 signaling pathway: pivotal roles in inflammation. Biochim. Biophys. Acta Mol. Basis Dis. 1863:585–97
     [Google Scholar]
  2. 2. 
    Al Tanoury Z, Piskunov A, Rochette-Egly C 2013. Vitamin A and retinoid signaling: genomic and nongenomic effects. J. Lipid Res. 54:1761–75
     [Google Scholar]
  3. 3. 
    Ames BN. 2018. Prolonging healthy aging: longevity vitamins and proteins. PNAS 115:10836–44
     [Google Scholar]
  4. 4. 
    Ammon Avalos L, Galindo C, Li DK 2012. A systematic review to calculate background miscarriage rates using life table analysis. Birth Defects Res. A Clin. Mol. Teratol. 94:417–23
     [Google Scholar]
  5. 5. 
    Azzi A. 2018. Many tocopherols, one vitamin E. Mol. Aspects Med. 61:92–103
     [Google Scholar]
  6. 6. 
    Bailey P. 1963. Cerebellar encephalomalacia produced by diets deficient in tocopherol. Am. J. Clin. Nutr. 12:275–77
     [Google Scholar]
  7. 7. 
    Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH et al. 2016. Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort. Am. J. Clin. Nutr. 103:454–64
     [Google Scholar]
  8. 8. 
    Balmer JE, Blomhoff R. 2002. Gene expression regulation by retinoic acid. J. Lipid Res. 43:1773–808
     [Google Scholar]
  9. 9. 
    Barella L, Muller PY, Schlachter M, Hunziker W, Stöcklin E et al. 2004. Identification of hepatic molecular mechanisms of action of α-tocopherol using global gene expression profile analysis in rats. Biochim. Biophys. Acta Mol. Basis Dis. 1689:66–74
     [Google Scholar]
  10. 10. 
    Barella L, Rota C, Stöcklin E, Rimbach G. 2004. α-Tocopherol affects androgen metabolism in male rat. Ann. N. Y. Acad. Sci. 1031:334–36
     [Google Scholar]
  11. 11. 
    Bartolini D, Marinelli R, Giusepponi D, Galarini R, Barola C et al. 2021. α-Tocopherol metabolites (the vitamin E metabolome) and their interindividual variability during supplementation. Antioxidants 10:173
     [Google Scholar]
  12. 12. 
    Blaner WS. 2019. Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders. Pharmacol. Ther. 197:153–78
     [Google Scholar]
  13. 13. 
    Blaner WS. 2020. Vitamin A. Present Knowledge in Nutrition, Vol. 1 B Marriott, DF Birt, V Stalling, A Yates 73–92 San Diego, CA: Academic. , 11th ed..
     [Google Scholar]
  14. 14. 
    Blaner WS, O'Byrne SM, Wongsiriroj N, Kluwe J, D'Ambrosio DM et al. 2009. Hepatic stellate cell lipid droplets: a specialized lipid droplet for retinoid storage. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1791:467–73
     [Google Scholar]
  15. 15. 
    Bohm F, Edge R, Truscott G. 2012. Interactions of dietary carotenoids with activated (singlet) oxygen and free radicals: potential effects for human health. Mol. Nutr. Food Res. 56:205–16
     [Google Scholar]
  16. 16. 
    Bruno RS, Leonard SW, Li J, Bray TM, Traber MG. 2005. Lower plasma α-carboxyethyl-hydroxychroman after deuterium-labeled α-tocopherol supplementation suggests decreased vitamin E metabolism in smokers. Am. J. Clin. Nutr. 81:1052–59
     [Google Scholar]
  17. 17. 
    Bruno RS, Ramakrishnan R, Montine TJ, Bray TM, Traber MG. 2005. α-Tocopherol disappearance is faster in cigarette smokers and is inversely related to their ascorbic acid status. Am. J. Clin. Nutr. 81:95–103
     [Google Scholar]
  18. 18. 
    Buettner GR. 1993. The pecking order of free radicals and antioxidants: lipid peroxidation, α-tocopherol, and ascorbate. Arch. Biochem. Biophys. 300:535–43
     [Google Scholar]
  19. 19. 
    Burk RF, Hill KE, Nakayama A, Mostert V, Levander XA et al. 2008. Selenium deficiency activates mouse liver Nrf2-ARE but vitamin E deficiency does not. Free Radic. . Biol. Med. 44:1617–23
     [Google Scholar]
  20. 20. 
    Burton GW, Ingold KU. 1984. β-Carotene: an unusual type of lipid antioxidant. Science 224:569–73
     [Google Scholar]
  21. 21. 
    Burton GW, Joyce A, Ingold KU 1982. First proof that vitamin E is major lipid-soluble, chain-breaking antioxidant in human blood plasma. Lancet 2:327
     [Google Scholar]
  22. 22. 
    Cadenas E, Packer L, Traber MG. 2016. Antioxidants, oxidants, and redox impacts on cell function—a tribute to Helmut Sies. Arch. Biochem. Biophys. 595:94–99
     [Google Scholar]
  23. 23. 
    Carlson BA, Tobe R, Yefremova E, Tsuji PA, Hoffmann VJ et al. 2016. Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. Redox Biol 9:22–31
     [Google Scholar]
  24. 24. 
    Chambon P. 1996. A decade of molecular biology of retinoic acid receptors. FASEB J 10:940–54
     [Google Scholar]
  25. 25. 
    Chan MY, Lee BJ, Chang PS, Hsiao HY, Hsu LP et al. 2020. The risks of ubiquinone and β-carotene deficiency and metabolic disorders in patients with oral cancer. BMC Cancer 20:310
     [Google Scholar]
  26. 26. 
    Chang WH, Reddy SP, Di YP, Yoneda K, Harper R, Wu R. 2002. Regulation of thioredoxin gene expression by vitamin A in human airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 26:627–35
     [Google Scholar]
  27. 27. 
    Cheng DW, Chang LF, Bairnson TA. 1957. Gross observations on developing abnormal embryos induced by maternal vitamin E deficiency. Anat. Rec. 129:167–85
     [Google Scholar]
  28. 28. 
    Choi J, Leonard SW, Kasper K, McDougall M, Stevens JF et al. 2015. Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics. J. Lipid Res. 56:1182–90
     [Google Scholar]
  29. 29. 
    Ciaccio M, Valenza M, Tesoriere L, Bongiorno A, Albiero R, Livrea MA. 1993. Vitamin A inhibits doxorubicin-induced membrane lipid peroxidation in rat tissues in vivo. Arch. Biochem. Biophys. 302:103–8
     [Google Scholar]
  30. 30. 
    Clugston RD. 2020. Carotenoids and fatty liver disease: current knowledge and research gaps. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1865:158597
     [Google Scholar]
  31. 31. 
    Conte da Frota ML Jr, Gomes da Silva E, Behr GA, de Oliveira MR, Dal-Pizzol F et al. 2006. All-trans retinoic acid induces free radical generation and modulate antioxidant enzyme activities in rat sertoli cells. Mol. Cell Biochem. 285:173–79
     [Google Scholar]
  32. 32. 
    Copp AJ, Greene ND. 2010. Genetics and development of neural tube defects. J. Pathol. 220:217–30
     [Google Scholar]
  33. 33. 
    Dao DQ, Ngo TC, Thong NM, Nam PC. 2017. Is vitamin A an antioxidant or a pro-oxidant?. J. Phys. Chem. B 121:9348–57
     [Google Scholar]
  34. 34. 
    de Miranda Ramos V, Gasparotto J, Figueiro F, de Fraga Dias A, Rostirolla DC et al. 2019. Retinoic acid downregulates thiol antioxidant defences and homologous recombination while promotes A549 cells sensitization to cisplatin. Cell Signal 62:109356
     [Google Scholar]
  35. 35. 
    de Miranda Ramos V, Zanotto-Filho A, de Bittencourt Pasquali MA, Klafke K, Gasparotto J et al. 2016. NRF2 mediates neuroblastoma proliferation and resistance to retinoic acid cytotoxicity in a model of in vitro neuronal differentiation. Mol. Neurobiol. 53:6124–35
     [Google Scholar]
  36. 36. 
    de Wilde MC, Vellas B, Girault E, Yavuz AC, Sijben JW. 2017. Lower brain and blood nutrient status in Alzheimer's disease: results from meta-analyses. Alzheimer's Dement 3:416–31
     [Google Scholar]
  37. 37. 
    DellaPenna D, Pogson BJ. 2006. Vitamin synthesis in plants: tocopherols and carotenoids. Annu. Rev. Plant Biol. 57:711–38
     [Google Scholar]
  38. 38. 
    Di Domenico F, Tramutola A, Foppoli C, Head E, Perluigi M, Butterfield DA. 2018. mTOR in Down syndrome: role in Aβ and tau neuropathology and transition to Alzheimer disease–like dementia. Free Radic. . Biol. Med. 114:94–101
     [Google Scholar]
  39. 39. 
    Di Donato I, Bianchi S, Federico A. 2010. Ataxia with vitamin E deficiency: update of molecular diagnosis. Neurol. Sci. 31:511–15
     [Google Scholar]
  40. 40. 
    Dibble CC, Manning BD. 2013. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat. Cell Biol. 15:555–64
     [Google Scholar]
  41. 41. 
    Dinkova-Kostova AT, Talalay P 2008. Direct and indirect antioxidant properties of inducers of cytoprotective proteins. Mol. Nutr. Food Res. 52:Suppl. 1S128–128
     [Google Scholar]
  42. 42. 
    Dysken MW, Sano M, Asthana S, Vertrees JE, Pallaki M et al. 2014. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA 311:33–44
     [Google Scholar]
  43. 43. 
    Egawa J, Pearn ML, Lemkuil BP, Patel PM, Head BP. 2016. Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function. J. Physiol. 594:4565–79
     [Google Scholar]
  44. 44. 
    Evans HM, Bishop KS. 1922. On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science 56:650–51
     [Google Scholar]
  45. 45. 
    Farina N, Isaac MG, Clark AR, Rusted J, Tabet N. 2012. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst. Rev. 11:CD002854
     [Google Scholar]
  46. 46. 
    Farina N, Llewellyn D, Isaac MG, Tabet N. 2017. Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database Syst. Rev. 1:CD002854
     [Google Scholar]
  47. 47. 
    Finno CJ, Bordbari MH, Valberg SJ, Lee D, Herron J et al. 2016. Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes. Free Radic. Biol. Med. 101:261–71
     [Google Scholar]
  48. 48. 
    Food Drug Adm. Food labeling; nutrient content claims; definition for “high potency” and definition of “antioxidant” for use in nutrient content claims for dietary supplements and conventional foods. 62 Fed. Reg. 49868 Sept. 23, 1997.)
  49. 49. 
    Food Nutr. Board, Inst. Med 2000. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids Washington, DC: Natl. Acad.
  50. 50. 
    Francisqueti-Ferron FV, Togneri Ferron AJ, Garcia JL, de Almeida Silva CCV, Róvero Costa M et al. 2019. Basic concepts on the role of nuclear factor erythroid-derived 2–like 2 (Nrf2) in age-related diseases. Int. J. Mol. Sci. 20:3208
     [Google Scholar]
  51. 51. 
    Galano JM, Lee YY, Durand T, Lee JC 2015. Special issue on “Analytical Methods for Oxidized Biomolecules and Antioxidants”: the use of isoprostanoids as biomarkers of oxidative damage, and their role in human dietary intervention studies. Free Radic Res 49:583–98
     [Google Scholar]
  52. 52. 
    Ghyselinck NB, Duester G. 2019. Retinoic acid signaling pathways. Development 146:dev167502
     [Google Scholar]
  53. 53. 
    Gohil K, Schock BC, Chakraborty AA, Terasawa Y, Raber J et al. 2003. Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in α-tocopherol transfer protein. Free Radic. Biol. Med. 35:1343–54
     [Google Scholar]
  54. 54. 
    Gu X, Orozco JM, Saxton RA, Condon KJ, Liu GY et al. 2017. SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Science 358:813–18
     [Google Scholar]
  55. 55. 
    Harrison EH, Quadro L. 2018. Apocarotenoids: emerging roles in mammals. Annu. Rev. Nutr. 38:153–72
     [Google Scholar]
  56. 56. 
    Hawkes HJ, Karlenius TC, Tonissen KF. 2014. Regulation of the human thioredoxin gene promoter and its key substrates: a study of functional and putative regulatory elements. Biochim. Biophys. Acta Gen. Subj. 1840:303–14
     [Google Scholar]
  57. 57. 
    Head B, La Du J, Tanguay RL, Kioussi C, Traber MG 2020. Vitamin E is necessary for zebrafish nervous system development. Sci. Rep. 10:15028
     [Google Scholar]
  58. 58. 
    Head B, Ramsey SA, Kioussi C, Tanguay RL, Traber MG. 2021. Vitamin E deficiency disrupts gene expression networks during zebrafish development. Nutrients 13:468
     [Google Scholar]
  59. 59. 
    Hyland S, Muller D, Hayton S, Stoecklin E, Barella L. 2006. Cortical gene expression in the vitamin E–deficient rat: possible mechanisms for the electrophysiological abnormalities of visual and neural function. Ann. Nutr. Metab. 50:433–41
     [Google Scholar]
  60. 60. 
    Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G et al. 2018. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell 172:409–22.e21
     [Google Scholar]
  61. 61. 
    Jiang X, Stockwell BR, Conrad M 2021. Ferroptosis: mechanisms, biology and role in disease. Nat. Rev. Mol. Cell Biol. 22:266–82
     [Google Scholar]
  62. 62. 
    Johnson CH, Bonzo JA, Cheng J, Krausz KW, Kang DW et al. 2013. Cytochrome P450 regulation by α-tocopherol in Pxr-null and PXR-humanized mice. Drug Metab. Dispos. 41:406–13
     [Google Scholar]
  63. 63. 
    Jones DP, Sies H. 2015. The redox code. Antioxid. Redox Signal. 23:734–46
     [Google Scholar]
  64. 64. 
    Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB et al. 2005. Biomarkers of oxidative stress study. II: Are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic. . Biol. Med. 38:698–710
     [Google Scholar]
  65. 65. 
    Kamal-Eldin A, Appelqvist LA. 1996. The chemistry and antioxidant properties of tocopherols and tocotrienols. Lipids 31:671–701
     [Google Scholar]
  66. 66. 
    Kane MA, Chen N, Sparks S, Napoli JL. 2005. Quantification of endogenous retinoic acid in limited biological samples by LC/MS/MS. Biochem. J. 388:363–69
     [Google Scholar]
  67. 67. 
    Kim HK, Han SN. 2019. Vitamin E: regulatory role on gene and protein expression and metabolomics profiles. IUBMB Life 71:442–55
     [Google Scholar]
  68. 68. 
    Koh M, Takitani K, Miyazaki H, Yamaoka S, Tamai H. 2013. Liver X receptor up-regulates α-tocopherol transfer protein expression and α-tocopherol status. J. Nutr. Biochem. 24:2158–67
     [Google Scholar]
  69. 69. 
    Kohlschütter A, Finckh B, Nickel M, Bley A, Hübner C. 2020. First recognized patient with genetic vitamin E deficiency stable after 36 years of controlled supplement therapy. Neurodegener. Dis. 20:35–38
     [Google Scholar]
  70. 70. 
    Landes N, Pfluger P, Kluth D, Birringer M, Rühl R et al. 2003. Vitamin E activates gene expression via the pregnane X receptor. Biochem. Pharmacol. 65:269–73
     [Google Scholar]
  71. 71. 
    Lebold KM, Kirkwood JS, Taylor AW, Choi J, Barton CL et al. 2013. Novel liquid chromatography–mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio) embryos. Redox Biol 2:105–13
     [Google Scholar]
  72. 72. 
    Leist M, Raab B, Maurer S, Rosick U, Brigelius-Flohe R. 1996. Conventional cell culture media do not adequately supply cells with antioxidants and thus facilitate peroxide-induced genotoxicity. Free Radic. Biol. Med. 21:297–306
     [Google Scholar]
  73. 73. 
    Li G, Lee MJ, Liu AB, Yang Z, Lin Y et al. 2012. The antioxidant and anti-inflammatory activities of tocopherols are independent of Nrf2 in mice. Free Radic. Biol. Med. 52:1151–58
     [Google Scholar]
  74. 74. 
    Lim JY, Wang XD. 2020. Mechanistic understanding of β-cryptoxanthin and lycopene in cancer prevention in animal models. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1865:158652
     [Google Scholar]
  75. 75. 
    Liu D, Xue J, Liu Y, Gu H, Wei X et al. 2018. Inhibition of NRF2 signaling and increased reactive oxygen species during embryogenesis in a rat model of retinoic acid–induced neural tube defects. Neurotoxicology 69:84–92
     [Google Scholar]
  76. 76. 
    Maras JE, Bermudez OI, Qiao N, Bakun PJ, Boody-Alter EL, Tucker KL 2004. Intake of α-tocopherol is limited among US adults. J. Am. Diet. Assoc. 104:567–75
     [Google Scholar]
  77. 77. 
    Marcos P, González-Fuentes J, Castro-Vázquez L, Lozano MV, Santander-Ortega MJ et al. 2018. Vitamin transporters in mice brain with aging. J. Anat. 232:699–715
     [Google Scholar]
  78. 78. 
    McBean GJ. 2012. The transsulfuration pathway: a source of cysteine for glutathione in astrocytes. Amino Acids 42:199–205
     [Google Scholar]
  79. 79. 
    McDougall M, Choi J, Kim HK, Bobe G, Stevens JF et al. 2017. Lethal dysregulation of energy metabolism during embryonic vitamin E deficiency. Free Radic. Biol. Med. 104:324–32
     [Google Scholar]
  80. 80. 
    McDougall M, Choi J, Kim HK, Bobe G, Stevens JF et al. 2017. Lipid quantitation and metabolomics data from vitamin E–deficient and –sufficient zebrafish embryos from 0 to 120 hours-post-fertilization. Data Brief 11:432–41
     [Google Scholar]
  81. 81. 
    McDougall M, Choi J, Magnusson K, Truong L, Tanguay R, Traber MG. 2017. Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism. Free Radic. . Biol. Med. 112:308–17
     [Google Scholar]
  82. 82. 
    McDougall M, Choi J, Truong L, Tanguay R, Traber MG. 2017. Vitamin E deficiency during embryogenesis in zebrafish causes lasting metabolic and cognitive impairments despite refeeding adequate diets. Free Radic. Biol. Med. 110:250–60
     [Google Scholar]
  83. 83. 
    McDougall MQ, Choi J, Stevens JF, Truong L, Tanguay RL, Traber MG. 2016. Lipidomics and H218O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (Danio rerio) embryos. Redox Biol 8:165–74
     [Google Scholar]
  84. 84. 
    Miller GW, Labut EM, Lebold KM, Floeter A, Tanguay RL, Traber MG. 2012. Zebrafish (Danio rerio) fed vitamin E–deficient diets produce embryos with increased morphologic abnormalities and mortality. J. Nutr. Biochem. 23:478–86
     [Google Scholar]
  85. 85. 
    Miller GW, Ulatowski L, Labut EM, Lebold KM, Manor D et al. 2012. The α-tocopherol transfer protein is essential for vertebrate embryogenesis. PLOS ONE 7:e47402
     [Google Scholar]
  86. 86. 
    Molina-Jijón E, Rodríguez-Muñoz R, Namorado MC, Bautista-García P, Medina-Campos ON et al. 2015. All-trans retinoic acid prevents oxidative stress–induced loss of renal tight junction proteins in type-1 diabetic model. J. Nutr. Biochem. 26:441–54
     [Google Scholar]
  87. 87. 
    Monaghan BR, Schmitt FO. 1932. The effects of carotene and of vitamin A on the oxidation of linoleic acid. J. Biol. Chem. 96:387–95
     [Google Scholar]
  88. 88. 
    Moran NE, Mohn ES, Hason N, Erdman JW Jr., Johnson EJ. 2018. Intrinsic and extrinsic factors impacting absorption, metabolism, and health effects of dietary carotenoids. Adv. Nutr. 9:465–92
     [Google Scholar]
  89. 89. 
    Muller DPR. 2010. Vitamin E and neurological function. Mol. Nutr. Food Res. 54:710–18
     [Google Scholar]
  90. 90. 
    Murata M, Kawanishi S. 2000. Oxidative DNA damage by vitamin A and its derivative via superoxide generation. J. Biol. Chem. 275:2003–8
     [Google Scholar]
  91. 91. 
    Mustacich DJ, Gohil K, Bruno RS, Yan M, Leonard SW et al. 2009. α-Tocopherol modulates genes involved in hepatic xenobiotic pathways in mice. J. Nutr. Biochem. 20:469–76
     [Google Scholar]
  92. 92. 
    Napoli JL. 2017. Cellular retinoid binding proteins, CRBP, CRABP, FABP5: effects on retinoid metabolism, function and related diseases. Pharmacol. Ther. 173:19–33
     [Google Scholar]
  93. 93. 
    Nier B, Weinberg PD, Rimbach G, Stöcklin E, Barella L. 2006. Differential gene expression in skeletal muscle of rats with vitamin E deficiency. IUBMB Life 58:540–48
     [Google Scholar]
  94. 94. 
    Niture SK, Khatri R, Jaiswal AK. 2014. Regulation of Nrf2—an update. Free Radic. Biol. Med. 66:36–44
     [Google Scholar]
  95. 95. 
    Noguchi N, Yamashita H, Hamahara J, Nakamura A, Kuhn H, Niki E 2002. The specificity of lipoxygenase-catalyzed lipid peroxidation and the effects of radical-scavenging antioxidants. Biol. Chem. 383:619–26
     [Google Scholar]
  96. 96. 
    Olthof MR, Brink EJ, Katan MB, Verhoef P. 2005. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am. J. Clin. Nutr. 82:111–17
     [Google Scholar]
  97. 97. 
    Ong DE, Newcomer ME, Chytil F 1994. Cellular retinoid-binding proteins. The Retinoids: Biology, Chemistry and Medicine MB Sporn, AB Roberts, DS Goodman 283–318 New York: Raven
     [Google Scholar]
  98. 98. 
    Oommen S, Vasu VT, Leonard SW, Traber MG, Cross CE, Gohil K. 2007. Genome wide responses of murine lungs to dietary α-tocopherol. Free Radic Res 41:98–109
     [Google Scholar]
  99. 99. 
    Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M et al. 1995. Ataxia with isolated vitamin E deficiency is caused by mutations in the α-tocopherol transfer protein. Nat. Genet. 9:141–45
     [Google Scholar]
  100. 100. 
    Pascual I, Larrayoz IM, Rodriguez IR. 2009. Retinoic acid regulates the human methionine sulfoxide reductase A (MSRA) gene via two distinct promoters. Genomics 93:62–71
     [Google Scholar]
  101. 101. 
    Peeri NC, Chai W, Cooney RV, Tao MH. 2020. Association of serum levels of antioxidant micronutrients with mortality in US adults: National Health and Nutrition Examination Survey 1999–2002. Public Health Nutr https://doi.org/10.1017/S1368980020004619
    [Crossref] [Google Scholar]
  102. 102. 
    Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R et al. 2005. Vitamin E and donepezil for the treatment of mild cognitive impairment. N. Engl. J. Med. 352:2379–88
     [Google Scholar]
  103. 103. 
    Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M. 2016. World Alzheimer Report 2016: improving healthcare for people living with dementia Rep., Int. Fed. Alzheimer's Dis. Relat. Disord. Soc London:
  104. 104. 
    Rota C, Barella L, Minihane AM, Stöcklin E, Rimbach G. 2004. Dietary α-tocopherol affects differential gene expression in rat testes. IUBMB Life 56:277–80
     [Google Scholar]
  105. 105. 
    Sabatini DM. 2017. Twenty-five years of mTOR: uncovering the link from nutrients to growth. PNAS 114:11818–25
     [Google Scholar]
  106. 106. 
    Saito Y, Yoshida Y, Akazawa T, Takahashi K, Niki E 2003. Cell death caused by selenium deficiency and protective effect of antioxidants. J. Biol. Chem. 278:39428–34
     [Google Scholar]
  107. 107. 
    Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K et al. 1997. A controlled trial of selegiline, α-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N. Engl. J. Med. 336:1216–22
     [Google Scholar]
  108. 108. 
    Saxton RA, Sabatini DM. 2017. mTOR signaling in growth, metabolism, and disease. Cell 168:960–76
     [Google Scholar]
  109. 109. 
    Schuelke M 2016. 1993. Ataxia with vitamin E deficiency. GeneReviews®, ed. RA Pagon, MP Adam, HH Ardinger, SE Wallace, A Amemiya et al. Seattle: Univ. Wash.
     [Google Scholar]
  110. 110. 
    Shamim AA, Schulze K, Merrill RD, Kabir A, Christian P et al. 2015. First-trimester plasma tocopherols are associated with risk of miscarriage in rural Bangladesh. Am. J. Clin. Nutr. 101:294–301
     [Google Scholar]
  111. 111. 
    Shindou H, Hishikawa D, Harayama T, Eto M, Shimizu T. 2013. Generation of membrane diversity by lysophospholipid acyltransferases. J. Biochem. 154:21–28
     [Google Scholar]
  112. 112. 
    Shmarakov IO, Yuen JJ, Blaner WS 2013. Carotenoid metabolism and enzymology. Carotenoids and Human Health SA Tanumihardjo 29–56 Totowa, NJ: Humana
     [Google Scholar]
  113. 113. 
    Sies H, Berndt C, Jones DP. 2017. Oxidative stress. Annu. Rev. Biochem. 86:715–48
     [Google Scholar]
  114. 114. 
    Sies H, Jones DP. 2020. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat. Rev. Mol. Cell Biol. 21:363–83
     [Google Scholar]
  115. 115. 
    Sies H, Stahl W, Sundquist AR. 1992. Antioxidant functions of vitamins. Vitamins E and C, β-carotene, and other carotenoids. Ann. N. Y. Acad. Sci. 669:7–20
     [Google Scholar]
  116. 116. 
    Song BL, DeBose-Boyd RA. 2006. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase stimulated by δ- and γ-tocotrienols. J. Biol. Chem. 281:25054–61
     [Google Scholar]
  117. 117. 
    Sporn MB, Dunlop NM, Newton DL, Smith JM. 1976. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed. Proc. 35:1332–38
     [Google Scholar]
  118. 118. 
    Tan KP, Kosuge K, Yang M, Ito S 2008. NRF2 as a determinant of cellular resistance in retinoic acid cytotoxicity. Free Radic. Biol. Med. 45:1663–73
     [Google Scholar]
  119. 119. 
    Tesoriere L, Ciaccio M, Bongiorno A, Riccio A, Pintaudi AM, Livrea MA. 1993. Antioxidant activity of all-trans-retinol in homogeneous solution and in phosphatidylcholine liposomes. Arch. Biochem. Biophys. 307:217–23
     [Google Scholar]
  120. 120. 
    Traber MG, Atkinson J. 2007. Vitamin E, antioxidant and nothing more. Free Radic. Biol. Med. 43:4–15
     [Google Scholar]
  121. 121. 
    Traber MG, Sokol RJ, Burton GW, Ingold KU, Papas AM et al. 1990. Impaired ability of patients with familial isolated vitamin E deficiency to incorporate α-tocopherol into lipoproteins secreted by the liver. J. Clin. Investig. 85:397–407
     [Google Scholar]
  122. 122. 
    Tramutola A, Triplett JC, Di Domenico F, Niedowicz DM, Murphy MP et al. 2015. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD. J. Neurochem. 133:739–49
     [Google Scholar]
  123. 123. 
    Ulatowski L, Dreussi C, Noy N, Barnholtz-Sloan J, Klein E, Manor D. 2012. Expression of the α-tocopherol transfer protein gene is regulated by oxidative stress and common single-nucleotide polymorphisms. Free Radic. Biol. Med. 53:2318–26
     [Google Scholar]
  124. 124. 
    Ulatowski L, Parker R, Warrier G, Sultana R, Butterfield DA, Manor D. 2014. Vitamin E is essential for Purkinje neuron integrity. Neuroscience 260:120–29
     [Google Scholar]
  125. 125. 
    Ursini F, Maiorino M. 2020. Lipid peroxidation and ferroptosis: the role of GSH and GPx4. Free Radic. Biol. Med. 152:175–85
     [Google Scholar]
  126. 126. 
    Ursini F, Maiorino M, Valente M, Ferri L, Gregolin C. 1982. Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochim. Biophys. Acta Lipids Lipid Metab. 710:197–211
     [Google Scholar]
  127. 127. 
    Valastyan S, Thakur V, Johnson A, Kumar K, Manor D. 2008. Novel transcriptional activities of vitamin E: inhibition of cholesterol biosynthesis. Biochemistry 47:744–52
     [Google Scholar]
  128. 128. 
    Vasu VT, Oommen S, Lim Y, Valacchi G, Hobson B et al. 2010. Modulation of ozone-sensitive genes in α-tocopherol transfer protein null mice. Inhal. Toxicol. 22:1–16
     [Google Scholar]
  129. 129. 
    Verma K, Wei King D 1967. Disorders of the developing nervous system of vitamin E–deficient rats. Acta Anat. 67:623–35
     [Google Scholar]
  130. 130. 
    von Lintig J, Moon J, Lee J, Ramkumar S. 2020. Carotenoid metabolism at the intestinal barrier. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1865:158580
     [Google Scholar]
  131. 131. 
    Wagner BA, Buettner GR, Burns CP. 1994. Free radical–mediated lipid peroxidation in cells: Oxidizability is a function of cell lipid bis-allylic hydrogen content. Biochemistry 33:4449–53
     [Google Scholar]
  132. 132. 
    Wang XJ, Hayes JD, Henderson CJ, Wolf CR 2007. Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor α. PNAS 104:19589–94
     [Google Scholar]
  133. 133. 
    Yokota T, Igarashi K, Uchihara T, Jishage K, Tomita H et al. 2001. Delayed-onset ataxia in mice lacking α-tocopherol transfer protein: model for neuronal degeneration caused by chronic oxidative stress. PNAS 98:15185–90
     [Google Scholar]
  134. 134. 
    Yoshida Y, Itoh N, Hayakawa M, Habuchi Y, Saito Y et al. 2010. The role of α-tocopherol in motor hypofunction with aging in α-tocopherol transfer protein knockout mice as assessed by oxidative stress biomarkers. J. Nutr. Biochem. 21:66–76
     [Google Scholar]
  135. 135. 
    Zanetti R, Catalá A. 2000. Changes in n-6 and n-3 polyunsaturated fatty acids during lipid-peroxidation of mitochondria obtained from rat liver and several brain regions: effect of α-tocopherol. Prostaglandins Leukot. Essent. Fatty Acids 62:379–85
     [Google Scholar]
  136. 136. 
    Zhang J, Head B, Leonard SW, Choi J, Tanguay RL, Traber MG. 2020. Vitamin E deficiency dysregulates thiols, amino acids and related molecules during zebrafish embryogenesis. Redox Biol 38:101784
     [Google Scholar]
  137. 137. 
    Zhao F, Wu T, Lau A, Jiang T, Huang Z et al. 2009. Nrf2 promotes neuronal cell differentiation. Free Radic. Biol. Med. 47:867–79
     [Google Scholar]
  138. 138. 
    Zingg JM. 2019. Vitamin E: regulatory role on signal transduction. IUBMB Life 71:456–78
     [Google Scholar]
/content/journals/10.1146/annurev-nutr-082018-124228
Loading
Vitamin A and Vitamin E: Will the Real Antioxidant Please Stand Up?
Annual Review of Nutrition 41, 105 (2021); https://doi.org/10.1146/annurev-nutr-082018-124228
/content/journals/10.1146/annurev-nutr-082018-124228
/content/journals/10.1146/annurev-nutr-082018-124228
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error