Vitamin E

Abstract

Vitamin E or RRR‐α‐tocopherol, as all vitamins, is indispensable for human life. Insufficient vitamin E availability results in a neurological condition, ‘ataxia with vitamin E deficiency’ (AVED), and vitamin E administration prevents the progression of the disease. Vitamin E is available especially in nuts, vegetable oils and greens. The reference daily intake for healthy adults is 15 mg and the maximum dose is 1000 mg daily. Many ailments, from cancer to atherosclerosis and neurodegenerative diseases, had been proposed to be prevented or cured by vitamin E; however, recent studies have shown that only low‐grade chronic inflammation, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD) and immune response may benefit from vitamin E. The mechanism of action of this vitamin is still an object of debate, scientists being either in favour of an antioxidant mechanism or of an action of vitamin E on signal transduction and gene expression modulation.

Key Concepts

  • Low intake of vitamin E results in ataxia with vitamin E deficiency (AVED).
  • Administration of α‐tocopherol protects against the progression of AVED.
  • Vitamin E does not prevent or cure cancer, cardiovascular and neurodegenerative diseases.
  • Low‐grade inflammation and nonalcoholic fatty liver disease (NASH, NAFLD) are diminished by vitamin E.
  • Vitamin E improves the immune response, especially in the elderly.
  • A better knowledge of the mechanism of action of vitamin E would be useful to better use its potentials, established its correct dosage and the possible relation between genetic background of humans taking vitamin E and their response to this vitamin.

Keywords: tocopherol; RRR‐α‐tocopherol; vitamin E; avitaminosis E; AVED; antioxidant; cell signalling; gene expression

Figure 1. Molecular structures of tocopherols.
Figure 2. Intestinal absorption of vitamin E.
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References

Albanes D, Heinonen OP, Huttunen JK, et al. (1995) Effects of alpha‐tocopherol and beta‐carotene supplements on cancer incidence in the Alpha‐Tocopherol Beta‐Carotene Cancer Prevention Study. American Journal of Clinical Nutrition 62 (6 Suppl): 1427S–1430S.

Arita M, Sato Y, Miyata A, et al. (1995) Human alpha‐tocopherol transfer protein: cDNA cloning, expression and chromosomal localization. Biochemical Journal 306 (Pt 2): 437–443.

Azzi A (2007) Molecular mechanism of alpha‐tocopherol action. Free Radical Biology & Medicine 43 (1): 16–21.

Barella L, Muller PY, Schlachter M, et al. (2004) Identification of hepatic molecular mechanisms of action of alpha‐tocopherol using global gene expression profile analysis in rats. Biochimica et Biophysica Acta 1689 (1): 66–74.

Bjorneboe A, Bjorneboe GE, Drevon CA (1990) Absorption, transport and distribution of vitamin E. Journal of Nutrition 120 (3): 233–242.

Bjornson LK, Kayden HJ, Miller E, et al. (1976) The transport of alpha‐tocopherol and beta‐carotene in human blood. Journal of Lipid Research 17 (4): 343–352.

Chan AC (1989) Normal plasma vitamin E concentration. Biochemical Journal 260 (2): 623.

Christen WG, Glynn RJ, Chew EY, et al. (2010) Vitamin E and age‐related macular degeneration in a randomized trial of women. Ophthalmology 117 (6): 1163–1168.

Christen WG, Glynn RJ, Gaziano JM, et al. (2015) Age‐related cataract in men in the selenium and vitamin e cancer prevention trial eye endpoints study: a randomized clinical trial. JAMA Ophthalmology 133 (1): 17–24.

Craft NE, Haitema TB, Garnett KM, et al. (2004) Carotenoid, tocopherol, and retinol concentrations in elderly human brain. Journal of Nutrition, Health & Aging 8 (3): 156–162.

Esterbauer H, Puhl H, Waeg G, et al. (1992) Vitamin E and atherosclerosis: an overview. Journal of Nutritional Science and Vitaminology Spec No: 177–182.

Evans HM and Bishop KS (1922) On the existence of a hitherto unrecognized dietary factor essential for reproduction. Science 56 (1458): 650–651.

Farina N, Llewellyn D, Isaac MG, et al. (2017) Vitamin E for Alzheimer's dementia and mild cognitive impairment. Cochrane Database of Systematic Reviews 4: CD002854.

Galli F, Azzi A, Birringer M, et al. (2017) Vitamin E: emerging aspects and new directions. Free Radical Biology & Medicine 102: 16–36.

Gianello R, Libinaki R, Azzi A, et al. (2005) Alpha‐tocopheryl phosphate: a novel, natural form of vitamin E. Free Radical Biology & Medicine 39 (7): 970–976.

Gohil K, Schock BC, Chakraborty AA, et al. (2003) Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in alpha‐tocopherol transfer protein. Free Radical Biology & Medicine 35 (11): 1343–1354.

Goldenstein H, Levy NS, Lipener YT, et al. (2013) Patient selection and vitamin E treatment in diabetes mellitus. Expert Review of Cardiovascular Therapy 11 (3): 319–326.

Grebenstein N, Schumacher M, Graeve L, et al. (2014) alpha‐Tocopherol transfer protein is not required for the discrimination against gamma‐tocopherol in vivo but protects it from side‐chain degradation in vitro. Molecular Nutrition & Food Research 58 (5): 1052–1060.

Ji HF, Sun Y and Shen L (2014) Effect of vitamin E supplementation on aminotransferase levels in patients with NAFLD, NASH, and CHC: results from a meta‐analysis. Nutrition 30 (9): 986–991.

Klein EA, Thompson IM Jr, Tangen CM, et al. (2011) Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306 (14): 1549–1556.

Krinsky NI, Beecher GR, Burk RF, et al. (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academic Press.

Kushi LH (1999) Vitamin E and heart disease: a case study. American Journal of Clinical Nutrition 69 (6): 1322S–1329S.

Machlin LJ (1991) Vitamin E. In: Machlin LJ (ed) Handbook of Vitamins, 2nd edn, pp. 99–144. New York: Marcel Dekker.

Marchioli R (1999) Results of GISSI Prevenzione: diet, drugs, and cardiovascular risk. Researchers of GISSI Prevenzione. Cardiologia 44 (Suppl 1 Pt 2): 745–746.

Marko MG, Ahmed T, Bunnell SC, et al. (2007) Age‐associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation. Journal of Immunology 178 (3): 1443–1449.

Mattill HA (1947) Antioxidants. Annual Review of Biochemistry 16: 177–192.

Meydani SN, Barklund MP, Liu S, et al. (1990) Vitamin E supplementation enhances cell‐mediated immunity in healthy elderly subjects. The American Journal of Clinical Nutrition 52 (3): 557–563.

Negis Y, Zingg JM, Ogru E, et al. (2005) On the existence of cellular tocopheryl phosphate, its synthesis, degradation and cellular roles: a hypothesis. IUBMB Life 57 (1): 23–25.

Olcott HS and Mattill HA (1931) The unsaponifiable lipids of lettuce: III. Antioxidant. Journal of Biological Chemistry 91: 65–70.

Ouahchi K, Arita M, Kayden H, et al. (1995) Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha‐tocopherol transfer protein. Nature Genetics 9 (2): 141–145.

Packer L (1992) Interactions among antioxidants in health and disease: vitamin E and its redox cycle. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 200 (2): 271–276.

Pazdro R and Burgess JR (2010) The role of vitamin E and oxidative stress in diabetes complications. Mechanisms of Ageing and Development 131 (4): 276–286.

Porter TD (2003) Supernatant protein factor and tocopherol‐associated protein: an unexpected link between cholesterol synthesis and vitamin E (review). The Journal of Nutritional Biochemistry 14 (1): 3–6.

Rimm EB, Stampfer MJ, Ascherio A, et al. (1993) Vitamin E consumption and the risk of coronary heart disease in men. The New England Journal of Medicine 328 (20): 1450–1456.

Salonen RM, Nyyssonen K, Kaikkonen J, et al. (2003) Six‐year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Circulation 107 (7): 947–953.

Sanyal AJ, Chalasani N, Kowdley KV, et al. (2010) Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. The New England Journal of Medicine 362 (18): 1675–1685.

Schuelke M (1993) Ataxia with vitamin E deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al. (eds) GeneReviews®. Seattle, WA: University of Washington.

Stampfer MJ and Rimm EB (1995) Epidemiologic evidence for vitamin E in prevention of cardiovascular disease. The American Journal of Clinical Nutrition 62 (6 Suppl): 1365S–1369S.

Steinberg D (2000) Is there a potential therapeutic role for vitamin E or other antioxidants in atherosclerosis? Current Opinion in Lipidology 11 (6): 603–607.

Stephens NG, Parsons A, Schofield PM, et al. (1996) Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347 (9004): 781–786.

Stocker A and Azzi A (2000) Tocopherol‐binding proteins: their function and physiological significance. Antioxidants & Redox Signaling 2 (3): 397–404.

Takahashi Y, Uruno K and Kimura S (1977) Vitamin E binding proteins in human serum. Journal of Nutritional Science and Vitaminology 23 (3): 201–209.

The ATBC Cancer Prevention Study Group (1994) The alpha‐tocopherol, beta‐carotene lung cancer prevention study: design, methods, participant characteristics, and compliance. Annals of Epidemiology 4 (1): 1–10.

The HOPE Study Investigators (1996) The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin‐converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. Canadian Journal of Cardiology 12 (2): 127–137.

Traber MG and Atkinson J (2007) Vitamin E, antioxidant and nothing more. Free Radical Biology & Medicine 43 (1): 4–15.

Tutuncu NB, Bayraktar M, Varli K, et al. (1998) Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study. Diabetes Care 21 (11): 1915–1918.

Wang X, Ring BZ, Seitz RS, et al. (2015) Expression of α‐Tocopherol‐Associated protein (TAP) is associated with clinical outcome in breast cancer patients. BMC Clinical Pathology 15: 21.

Wilson RB, Middleton CC and Sun GY (1978) Vitamin E, antioxidants and lipid peroxidation in experimental atherosclerosis of rabbits. The Journal of Nutrition 108 (11): 1858–1867.

Wu D and Meydani SN (2014) Age‐associated changes in immune function: impact of vitamin E intervention and the underlying mechanisms. Endocrine, Metabolic & Immune Disorders: Drug Targets 14 (4): 283–289.

Zimmer S, Stocker A, Sarbolouki MN, et al. (2000) A novel human tocopherol‐associated protein: cloning, in vitro expression, and characterization. The Journal of Biological Chemistry 275 (33): 25672–25680.

Zingg JM and Azzi A (2004) Non‐antioxidant activities of vitamin E. Current Medicinal Chemistry 11 (9): 1113–1133.

Zingg JM, Libinaki R, Meydani M (2010) Modulation of gene expression by alpha‐tocopherol and alpha‐tocopheryl phosphate in THP‐1 monocytes. Free Radical Biology & Medicine 49 (12): 1989–2000.

Zingg JM (2015) Vitamin E: a role in signal transduction. Annual Review of Nutrition 35: 135–173.

Zingg JM, Azzi A, Lai CQ, et al. (2015) Induction of VEGF expression by alpha‐tocopherol and alpha‐tocopheryl phosphate via PI3Kgamma/PKB and hTAP1/SEC14L2‐mediated lipid exchange. Journal of Cellular Biochemistry 116 (3): 398–407.

Further Reading

Azzi A (2018) Many tocopherols, one vitamin E. Molecular Aspects of Medicine 58: 1–20.

Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds (2000) Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academies Press. Available from: https://www.ncbi.nlm.nih.gov/books/NBK225483/.

Schuelke M (2005) Ataxia with vitamin E deficiency (updated 13 Oct 2016). In: Adam MP, Ardinger HH, Pagon RA, et al. (eds) GeneReviews®. Seattle, WA: University of Washington; 1993–2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1241/.

Zingg JM and Azzi A (2004) Non‐antioxidant activities of vitamin E. Current Medicinal Chemistry 11: 1113–1133.

Zingg JM (2015) Vitamin E: a role in signal transduction. Annual Review of Nutrition 35: 135–173.

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Azzi, Angelo(Feb 2018) Vitamin E. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027652]