Vitamin E Oxygen Society Education Program Traber 1 Regulation of Vitamin E, a Nutritional Antioxidant Maret G. Traber, Ph.D. Department of Nutrition & Food Management Department of Nutrition & Food Management Linus Pauling Institute Linus Pauling Institute 571 Weniger Hall 571 Weniger Hall Oregon State University Oregon State University Corvallis, Oregon Corvallis, Oregon 541-737-7977 541-737-7977 Fax: 541-737-5077 Fax: 541-737-5077 Email: [email protected]Email: [email protected]The Virtual Free Radical School
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Vitamin E Oxygen Society Education Program Traber 1 Regulation of Vitamin E, a Nutritional Antioxidant Maret G. Traber, Ph.D. Department of Nutrition &
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Vitamin E Oxygen Society Education Program Traber 1
Regulation of Vitamin E, a Nutritional Antioxidant
Maret G. Traber, Ph.D.Department of Nutrition & Food ManagementDepartment of Nutrition & Food Management
Vitamin E Oxygen Society Education Program Traber 5
Vitamin E Oxygen Society Education Program Traber 6
Vitamin E FunctionsVitamin E Functions
Specific role in a required metabolic Specific role in a required metabolic function has not been foundfunction has not been found
Major function appears to be as a fat-Major function appears to be as a fat-soluble, “chain-breaking” antioxidantsoluble, “chain-breaking” antioxidant Peroxyl radical scavenger Protects polyunsaturated fatty acids
Vitamin E Oxygen Society Education Program Traber 10
Vitamin E Biologic Activity Vitamin E Biologic Activity in Humansin Humans
Absorption & Chylomicron CatabolismAbsorption & Chylomicron Catabolism All forms absorbed and transported to liver
Lipoprotein TransportLipoprotein Transport All lipoproteins transport vitamin E
Liver TraffickingLiver Trafficking -Tocopherol specifically secreted into plasma
MetabolismMetabolism Vitamin E metabolites are NOT oxidation products
Brigelius-Flohe, R. and M.G. Traber. Faseb J. 13: 1145-1155, 1999.
Vitamin E Vitamin E Delivery to Delivery to Tissues & Tissues &
Lipoproteins Lipoproteins During During
Chylomicron Chylomicron CatabolismCatabolism
Traber, M.G. 1999. Vitamin E. In Modern Nutrition in Health and Disease. M. E. Shils, J. A. Olson, M. Shike, and A. C. Ross, eds. Williams & Wilkins. Baltimore. 347-362.
LPL
Fatty acids & vitamin Eto tissues
Vitamin
E
Vit.E
CIRCULATING LIPOPROTEINS
Vitamin E
CHYLOMICRONREMNANTS
Liver Uptake
Vitamin E
Vit.E
HDL
Tissue Vitamin E
Uptake
CHYLOMICRONS
Vitamin E Oxygen Society Education Program Traber 11
Intestine
Circulation
Preferential Secretion of Preferential Secretion of Tocopherol in Tocopherol in VLDL and Its Delivery to TissuesVLDL and Its Delivery to Tissues
LIVER
CHYLOMICRONREMNANTS
Vitamin E
VLDL
LDL HDL
TT
PreferentialSecretion
Lipolysis
Tissue Uptake
RRR-T
Vitamin E
BILE
Traber, M.G. 1999. Vitamin E. In Modern Nutrition in Health and Disease. M. E. Shils, J. A. Olson, M. Shike, and A. C. Ross, eds. Williams & Wilkins. Baltimore. 347-362.
Vitamin E Oxygen Society Education Program Traber 12
Vitamin E Oxygen Society Education Program Traber 13
Regulation of Liver Vitamin ERegulation of Liver Vitamin E
Kayden, H.J. and M.G. Traber. J. Lipid Res. 34: 343-358, 1993.
ChylomicronRemnants
lipoproteins
tocopherolother vitamin E
Plasmatocopherol
{
Bile
Vit E Vit E
tocopherol transfer protein
Vitamin E Oxygen Society Education Program Traber 14
Traber, M.G. 1999. Vitamin E. In Modern Nutrition in Health and Disease. M. E. Shils, J. A. Olson, M. Shike, and A. C. Ross, eds. Williams & Wilkins. Baltimore. p347-362.
Vitamin E Deficiency in HumansVitamin E Deficiency in Humans Malabsorption Syndromes Malabsorption Syndromes
Abetalipoproteinemia Cholestatic Liver Disease Cystic Fibrosis Short Bowel Syndrome Total Parenteral Nutrition
Genetic Abnormalities in Genetic Abnormalities in -Tocopherol Transfer -Tocopherol Transfer ProteinProtein Familial Isolated Vitamin E Deficiency (FIVE) Friedreich's Ataxia Variants (AVED)
Vitamin E Oxygen Society Education Program Traber 15
Traber, M.G. 1999. Vitamin E. In Modern Nutrition in Health and Disease. M. E. Shils, J. A. Olson, M. Shike, and A. C. Ross, eds. Williams & Wilkins. Baltimore. p347-362.
Clinical Features and Associated Clinical Features and Associated Neuromuscular Lesions Neuromuscular Lesions
in Human Vitamin E Deficiencyin Human Vitamin E Deficiency
Loss of Position and Vibratory SensationLoss of Position and Vibratory Sensation Peripheral Nerve Posterior Columns
AtaxiaAtaxia Cerebellum Spinocerebellar tracts
WeaknessWeakness Skeletal Muscle
Vitamin E Oxygen Society Education Program Traber 16
Plasma deuterated Plasma deuterated -tocopherol -tocopherol concentrations in controls and subject withconcentrations in controls and subject with
ataxia with vitamin E deficiency (AVED)ataxia with vitamin E deficiency (AVED)
Time (hours)
0.01
0.1
1
10
0 12 24 36 48 60 72
[d3-SRR]
[d6-RRR]
AVED SUBJECT
0.01
0.1
1
10
0 12 24 36 48 60 72
CONTROLS
nmol/ml
Traber, M.G. et al. J Clin Invest. 85: 397-407, 1990.
Vitamin E Oxygen Society Education Program Traber 17
Vitamin E DefinitionVitamin E Definition
Recommended intakes limited to the 2Recommended intakes limited to the 2RR––stereoisomer forms of stereoisomer forms of tocopheroltocopherol RRR--tocopherol Half of the stereoisomers in all rac--tocopherol No other forms such as –tocopherol or tocotrienols
meet vitamin E requirement
All forms of supplemental All forms of supplemental tocopherol used to tocopherol used to establish the UL(upper limit)establish the UL(upper limit)
Food and Nutrition Board and Institute of Medicine. 2000. Dietary Reference Intakes for
Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press. Washington, DC.
Vitamin E Oxygen Society Education Program Traber 18
Estimated Average Requirement (EAR) and Estimated Average Requirement (EAR) and Recommended Daily Allowance (RDAs) for Recommended Daily Allowance (RDAs) for
-Tocopherol (mg/day)-Tocopherol (mg/day)
Life Stage EAR RDA
19+ yrs, M19+ yrs, F
PregnancyLactation
1212
1216
1515
1519
Food and Nutrition Board and Institute of Medicine. 2000. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press. Washington, DC.
Vitamin E Oxygen Society Education Program Traber 19
Plasma Plasma -Tocopherol in Response -Tocopherol in Response to Vitamin E Supplementsto Vitamin E Supplements
0
20
40
60
80
100
0 200 400 600 800
Plasma -tocopherol
µM
-tocopherol (mg/day)
all rac-
RRR-
-tocopherol ( -T) and -tocopheryl acetate ( -TAC) from supplements:1 IU RRR--TAC divided by 1.36 equals mg RRR- -TAC 1 IU all rac -TAc divided by 2 equals mg 2R--TAC
400 IU Vitamin E = 294 mg RRR--TAc or 268 mg RRR- -T
200 mg 2R- - TAc Or 182 mg 2R- -T Devaraj et al. Arterio Thromb Vasc Biol 17:2273, 1997