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Vitamin E
2D structure for Vitamin E
Chemical Name	(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]chroman-6-ol
Chemical Formula	C29H50O2
CAS Number	59-02-9
Chemical Information	HMDB01893
Biochemical Taxonomy	Steroids and Steroid Derivatives
Functional Taxonomy	Not Available
Nutritional Taxonomy	Not Available
Metabolic Pathways	Not Available
Biofluid Location	Blood Breast Milk Cerebrospinal Fluid (CSF)
Tissue Location	Bladder Epidermis Erythrocyte Eye Lens Fibroblasts Intestine Liver Lymphocyte Muscle Nerves Nervous Tissues Neurons Pancreas Placenta Platelet Prostate Skeletal Muscle Skin Spleen Stratum Corneum Testes Testis Adipose Tissue
Normal Biofluid Concentrations	Blood: 21.0 (7.0-35.0) uM Blood: 24.1 +/- 6.3 uM Blood: 24.6 +/- 5.8 uM Blood: 29.0 (18.0-43.7) umol/L Breast Milk: 1.5685229 +/- 0.8530929 uM
Normal Tissue Concentrations	Not Available
Diseases / Conditions Related to Nutrition	Parkinson's Disease
Other (Monogenic Disorders)	Abetalipoproteinemia OMIM: 200100 Vitamin e, familial isolated deficiency of OMIM: 277460
Abnormal Biofluid Concentrations	Cerebrospinal Fluid (CSF) (Parkinson's Disease): 0.11 uM
Abnormal Tissue Concentrations	Not Available
Physiological Processes	Not Available

Authors:
Affiliations:

Contents 1 Introduction 2 Biological Function 3 Catabolism 4 Other (Monogenic) Disorders 5 Nutritional Information 6 Drivers for biological variation 6.1 ADME 6.2 Indicator of adequacy 6.3 Status marker(s) 6.4 Requirement (EAR) based on 6.5 Underlying studies 6.6 Factors affecting requirement (relation intake - status) 6.7 Factors affecting requirement (relation status - health) 6.8 (potential) indicators of health 6.9 Factors reported with increased levels 7 Vulnerable groups 8 Markers of homeostasis and / or health 9 Determinants of requirements 10 Other resources 11 Links

Introduction

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Alpha-tocopherol is traditionally recognized as the most active form of vitamin E in humans, and is a powerful biological antioxidant. The measurement of "vitamin E" activity in international units (IU) was based on fertility enhancement by the prevention of spontaneous abortions in pregnant rats relative to alpha tocopherol. Natural vitamin E exists in eight different forms or isomers, four tocopherols and four tocotrienols. In foods, the most abundant sources of vitamin E are vegetable oils such as palm oil, sunflower, corn, soybean and olive oil. Nuts, sunflower seeds, and wheat germ are also good sources. --Wikipedia

Biological Function

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To protect PUFAs and other components of cell membranes and LDL from oxidation by free radicals. Located primarily within the phospholipid bilayer of cell membranes.

Catabolism

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Other (Monogenic) Disorders

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• Apolipoprotein b; APOB; Apob100, included; Apob48, included; Apolipoprotein b allotypes, included; Ag lipoprotein types, included; Hypobetalipoproteinemia, familial, included; FHBL, included; Hypobetalipoproteinemia, familial, 1, included; FHBL1, included; Acanthocytosis with hypobetalipoproteinemia, included; Hypobetalipoproteinemia, normotriglyceridemic, included OMIM: 107730

• Abetalipoproteinemia; ABL; Acanthocytosis; Bassen-kornzweig syndrome; Apolipoprotein b deficiency; Microsomal triglyceride transfer protein deficiency; MTP deficiency OMIM: 200100

• Vitamin e, familial isolated deficiency of; VED; Ataxia, friedreich-like, with selective vitamin e deficiency; AVED; Friedreich-like ataxia OMIM: 277460

• OMIM: 606721

• OMIM: 607692

Nutritional Information

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Drivers for biological variation

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ADME

Absorption in small intestine (51-86%). Depends on:

• biliary and pancreatic secretions
• micelle formation
• uptake into enterocytes
• chylomicron secretion

Secretion from liver in VLDL (alpha-TTP). Transport via lipoproteins and erythrocytes, no specific plasma transport proteins. Uptake in tissues via

• lipoprotein lipase mediated TG-rich lipoprotein catabolism
• LDL uptake via LDL receptor
• HDL-mediated delivery systems
• Non-specific transfer between lipoproteins and tissues (plasma phospholipid transfer protein)

Oxidation to tocopheryl radical and tocopheryl quinine. Excretion in urine as CECH. Mostly fecal excretion.

Indicator of adequacy

No consistent evidence that supplementing the diet with vitamin E protects against chronic disease Hydrogen peroxide-induced erythrocyte lysis (as observed in induced vitamin E deficiency)

Status marker(s)

Plasma alpha-tocopherol concentration (low correlation with intake) (IOM) Lipid-standardized vitamin E concentration greater than 2.25 (umol/mmol)

Requirement (EAR) based on

Intake sufficient to prevent hydrogen peroxide-induced hemolysis: 12 mg/day for adults (IOM) No data on which to base EAR on for infants and children: extrapolation from adult data CV 10% assumed, no data on SD

Underlying studies

• Horwitt 1960, 1962, 1956
• Horwitt 1960: repletion study, 7 subjects. One dose per individual. Correlation between intake and plasma concentration –linear between 0-17 mg. 12 mg correlates with plasma conc at which hemolysis is prevented.

Factors affecting requirement (relation intake - status)

• Bioavailability – fat in diet
• Nutrient-nutrient interactions: antioxidants (vitamin C) and dietary PUFA: “suggested that when the main PUFA in the diet is * linoleic acid, a d-alpha-tocopherol-PUFA ratio of 0.4 (expressed as mh tocopherol per g PUFA) is adequate for adult humans”
• No data on individual variation in physiological factors affecting requirement
• Plasma vitamin E concentrations vary little over wide range of dietary intakes

Factors affecting requirement (relation status - health)

• No data on the variation in plasma concentration that is associated with prevention of hemolysis
• Exercise – unknown
• Body size or composition – unknown
• Smoking – unknown
• No effect assumed:
• Aging
• gender
• pregnancy

Effect assumed:

• Infancy
• Lactation: average vitamin E secreted in human milk (4 mg) is added to EAR (IOM; not by other advisory bodies)

(potential) indicators of health

Not selected for estimating requirement: Lipid peroxidation markers, F2 isoprostanes suggested to be the best Inhibition of LDL-oxidation Inhibition of smooth muscle cell proliferation through inhibition of protein kinase C Inhibition of platelet adhesion, aggregation, platelet release reaction Inhibition of plasma generation of thrombin

Factors reported with increased levels

• Acute Alcoholism
• Alcohol Withdrawal
• Anticonvulsants
• Diabetes Mellitus
• Groundnut Oil
• Guillain-Barre Syndrome
• Hypercholesterolemia
• Hyperlipidemia
• Pre-eclampsia
• Pregnancy
• Sesame Oil
• Vitamin E

Vulnerable groups

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Markers of homeostasis and / or health

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Category	Markers	sign yes/no/?	I/D	S/I	ref	score
inflammation, immune response	CRP / hsCRP	Yes	I	I	3	3
	fibrinogen
	Albumin
	White blood cell count
	TNF-alpha	Yes & No	I	I	3, 23, 38	3
	Il-6	Yes & No	I	I	3, 9, 38	3
	Il1-beta	No		I	3, 23, 38	3
	Il-10
	Prostaglandin F2alpha
	Prostaglandin E1 (PGE1)
	Prostaglandin E2 (PGE2)	Yes	I	S	39	2
	Thromboxane B2	No		S	11	2
	Nitric Oxide (NO)	Yes & No	D	I	15	2
	Serum Amyloid A (SAA)
	NfkB
	alpha1-antichymotrypsin
oxidative stress	8(OH)-DG	No		I	21	2
	F2-isoprostanes
	8-iso-prostaglandin F2alpha
	oxidized LDL	Yes & No	I	I	7, 12, 16, 18, 20, 22, 28, 30	4
	SOD	Yes & No	D & I	I	8, 15, 19, 27	4
	TBARS	Yes & No	I	I	14, 22, 36	3
	myeloperoxidase
	nitrotyrosine
Metabolic stress	diastolic BP	No		I	26
	systolic BP	No		I	26
	total cholesterol	Yes & No	D & I	S & I	1, 2, 6, 10, 13, 25	5
	LDL	Yes & No	D & I	S & I	1, 5, 6, 8, 10, 22, 23, 24, 29, 31-33, 35-37	5
	HDL	Yes & No	D & I	S & I	1, 8, 10, 17, 19, 22, 24, 33	5
	HDL/TC
	triglycerides	Yes	I	S	29	3
	homocysteine
	tPA/PAI-1
	Fibrin fragment D-dimer
	Factor VIIa
	sICAM
	Monocyte chemotactic protein 1 (MCP1)
	fasting glucose
	fasting insulin
	OGTT
	insulin tolerance test	Yes	D	I	34	3
	HbA1c	Yes	I	I	4	3
	fructosamine

References

1. Olmedilla-Alonso B, Granado-Lorencio F, Herrero-Barbudo C,et al. Consumption of restructured meat products with added walnuts has a cholesterol-lowering effect in subjects at high cardiovascular risk: a randomised, crossover, placebo-controlled study. Am Coll Nutr. 2008;27(2):342-8.
2. Ravaglia G, Forti P, Lucicesare A, Pisacane N, et al. Plasma tocopherols and risk of cognitive impairment in an elderly Italian cohort. Am J Clin Nutr. 2008;87(5):1306-13.
3. Devaraj S, Leonard S, Traber MG, Jialal I. Gamma-tocopherol supplementation alone and in combination with alpha-tocopherol alters biomarkers of oxidative stress and inflammation in subjects with metabolic syndrome. Free Radic Biol Med. 2008 Mar 15;44(6):1203-8. Epub 2007 Dec 23.
4. Ble-Castillo JL, Cleva-Villanueva G, Díaz-Zagoya JC, Medina-Santillán R, et al. Effects of alpha-tocopherol on oxidative status and metabolic profile in overweight women. Int J Environ Res Public Health. 2007 ;4(4):260-7.
5. Singh I, Turner AH, Sinclair AJ, Li D, Hawley JA. Effects of gamma-tocopherol supplementation on thrombotic risk factors.Asia Pac J Clin Nutr. 2007;16(3):422-8.
6. Rasool AH, Yuen KH, Yusoff K, Wong AR, et al. Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E. J Nutr Sci Vitaminol (Tokyo). 2006 Dec;52(6):473-8.
7. Magliano D, McNeil J, Branley P, Shiel L, et al. The Melbourne Atherosclerosis Vitamin E Trial (MAVET): a study of high dose vitamin E in smokers. Eur J Cardiovasc Prev Rehabil. 2006 Jun;13(3):341-7.
8. Sutken E, Inal M, Ozdemir F. Effects of vitamin E and gemfibrozil on lipid profiles, lipid peroxidation and antioxidant status in the elderly and young hyperlipidemic subjects. Saudi Med J. 2006 Apr;27(4):453-9.
9. Sacheck JM, Cannon JG, Hamada K, Vannier E, et al. Age-related loss of associations between acute exercise-induced IL-6 and oxidative stress. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E340-9. Epub 2006 Feb 28.
10. Viroonudomphol D, Mahaisiriyodom A, Mingkhawn R, Sadomthian P, et al. Relationship between serum antioxidant vitamins A, E, and C and lipid profiles in priest subjects at the Priest Hospital. Southeast Asian J Trop Med Public Health. 2005;36 Suppl 4:246-53.
11. Clarke MW, Ward NC, Wu JH, Hodgson JM, et al. Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes. Am J Clin Nutr. 2006 Jan;83(1):95-102.
12. Seppo L, Lähteenmäki T, Tikkanen MJ, Vanhanen H, et al. Effects of vitamin E on the toxicity of oxidized LDL on endothelial cells in vitro in smokers vs nonsmokers on diets rich in fish. Eur J Clin Nutr. 2005 Nov;59(11):1282-90.
13. Waldmann A, Koschizke JW, Leitzmann C, Hahn A. Dietary intakes and blood concentrations of antioxidant vitamins in German vegans. Int J Vitam Nutr Res. 2005 Jan;75(1):28-36.
14. Park OJ, Kim HY, Kim WK, Kim YJ, et al. Effect of vitamin E supplementation on antioxidant defense systems and humoral immune responses in young, middle-aged and elderly Korean women. J Nutr Sci Vitaminol (Tokyo). 2003 Apr;49(2):94-9.
15. Liu M, Wallmon A, Olsson-Mortlock C, Wallin R, et al. Mixed tocopherols inhibit platelet aggregation in humans: potential mechanisms. Am J Clin Nutr. 2003 Mar;77(3):700-6.
16. Hodis HN, Mack WJ, LaBree L, Mahrer PR, et al. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation. 2002 Sep 17;106(12):1453-9.
17. Schnell JW, Anderson RA, Stegner JE, Schindler SP, et al. Effects of a high polyunsaturated fat diet and vitamin E supplementation on high-density lipoprotein oxidation in humans. Atherosclerosis. 2001 Dec;159(2):459-66.
18. Sampson MJ, Astley S, Richardson T, Willis G, et al. Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of alpha-tocopherol supplementation. Clin Sci (Lond). 2001 Sep;101(3):235-41.
19. Akova B, Sürmen-Gür E, Gür H, Dirican M, et al. Exercise-induced oxidative stress and muscle performance in healthy women: role of vitamin E supplementation and endogenous oestradiol. Eur J Appl Physiol. 2001 Jan-Feb;84(1-2):141-7.
20. van Tits LJ, de Waart F, Hak-Lemmers HL, van Heijst P, et al. Effects of alpha-tocopherol on superoxide production and plasma intercellular adhesion molecule-1 and antibodies to oxidized LDL in chronic smokers. Free Radic Biol Med. 2001 May 15;30(10):1122-9.
21. Porkkala-Sarataho E, Salonen JT, Nyyssönen K, Kaikkonen J, et al. Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men. Arterioscler Thromb Vasc Biol. 2000 Sep;20(9):2087-93.
22. Arrol S, Mackness MI, Durrington PN. Vitamin E supplementation increases the resistance of both LDL and HDL to oxidation and increases cholesteryl ester transfer activity. Atherosclerosis. 2000 May;150(1):129-34.
23. van Tits LJ, Demacker PN, de Graaf J, Hak-Lemmers HL, et al. alpha-tocopherol supplementation decreases production of superoxide and cytokines by leukocytes ex vivo in both normolipidemic and hypertriglyceridemic individuals. Am J Clin Nutr. 2000 Feb;71(2):458-64.
24. Perugini C, Bagnati M, Cau C, Bordone R, Paffoni P, et al. Distribution of lipid-soluble antioxidants in lipoproteins from healthy subjects. II. Effects of in vivo supplementation with alpha-tocopherol. Pharmacol Res. 2000 Jan;41(1):67-74.
25. Ford ES, Sowell A. Serum alpha-tocopherol status in the United States population: findings from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 1999 Aug 1;150(3):290-300.
26. Simons LA, von Konigsmark M, Simons J, Stocker R, et al. Vitamin E ingestion does not improve arterial endothelial dysfunction in older adults. Atherosclerosis. 1999 Mar;143(1):193-9.
27. Collins AR, Gedik CM, Olmedilla B, Southon S, et al. Oxidative DNA damage measured in human lymphocytes: large differences between sexes and between countries, and correlations with heart disease mortality rates. FASEB J. 1998 Oct;12(13):1397-400.
28. Devaraj S, Adams-Huet B, Fuller CJ, Jialal I. Dose-response comparison of RRR-alpha-tocopherol and all-racemic alpha-tocopherol on LDL oxidation. Arterioscler Thromb Vasc Biol. 1997 Oct;17(10):2273-9.
29. Salonen JT, Nyyssönen K, Tuomainen TP, Mäenpää PH, et al. Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men. BMJ. 1995 Oct 28;311(7013):1124-7.
30. Reaven PD, Herold DA, Barnett J, Edelman S. Effects of Vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM. Diabetes Care. 1995 Jun;18(6):807-16.
31. Princen HM, van Duyvenvoorde W, Buytenhek R, van der Laarse A, et al. Supplementation with low doses of vitamin E protects LDL from lipid peroxidation in men and women. Arterioscler Thromb Vasc Biol. 1995 Mar;15(3):325-33.
32. Jialal I, Fuller CJ, Huet BA. The effect of alpha-tocopherol supplementation on LDL oxidation. A dose-response study.Arterioscler Thromb Vasc Biol. 1995 Feb;15(2):190-8.
33. Suzukawa M, Ishikawa T, Yoshida H, Nakamura H. Effect of in-vivo supplementation with low-dose vitamin E on susceptibility of low-density lipoprotein and high-density lipoprotein to oxidative modification. J Am Coll Nutr. 1995 Feb;14(1):46-52.
34. Paolisso G, Di Maro G, Galzerano D, Cacciapuoti F, et al. Pharmacological doses of vitamin E and insulin action in elderly subjects. Am J Clin Nutr. 1994 Jun;59(6):1291-6.
35. Reaven PD, Witztum JL. Comparison of supplementation of RRR-alpha-tocopherol and racemic alpha-tocopherol in humans. Effects on lipid levels and lipoprotein susceptibility to oxidation. Arterioscler Thromb. 1993 Apr;13(4):601-8.
36. Jialal I, Grundy SM. Effect of dietary supplementation with alpha-tocopherol on the oxidative modification of low density lipoprotein. J Lipid Res. 1992 Jun;33(6):899-906.
37. Dieber-Rotheneder M, Puhl H, Waeg G, Striegl G, et al. Effect of oral supplementation with D-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. J Lipid Res. 1991 Aug;32(8):1325-32.
38. Cannon JG, Meydani SN, Fielding RA, Fiatarone MA, et al. Acute phase response in exercise. II. Associations between vitamin E, cytokines, and muscle proteolysis. Am J Physiol. 1991 Jun;260(6 Pt 2):R1235-40.
39. Meydani SN, Barklund MP, Liu S, Meydani M, et al. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr. 1990 Sep;52(3):557-63.

Determinants of requirements

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Category	Determinants of status	sign yes/no/? help	independent of intake yes/no/?
general	gender
	age (adults)	Yes & No	Yes
	age (children)	Yes	Yes
	ethnicity	No	Yes
physiological status	polymorphisms	No	Yes
	pregnancy	Yes	Yes
	lactation	Yes	No
	menopause
	physical fitness	Yes	Yes
	gut flora
anthropometric variables	body weight	Yes	?
	BMI
	waist circumference
	fat free mass
Lifestyle variables	smoking	No	Yes
	physical activity	Yes	Yes & No
	alcohol use
	medication use (incl. contraceptive pill)
	stress

References

1. Ziegler E.E., Filer L.J. Conocimentos actuales sobre Nutrición.. Vitamina E. 7a ed. OPS,1997.
2. Salas-Salvador J., Bonada A., Trallero R., Saló M.E. Nutrición y Dietética Clínica Masson 2000.

Other resources

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IOM FAO/WHO report 2004

Links

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