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Vitamin E: What It Is And What It Does

What is vitamin E?

Is there a difference between natural and synthetic vitamin E?

How does vitamin E work?

How does vitamin E function as an antioxidant?

Is vitamin E a "typical" vitamin?

Clinical conditions in which free radicals are thought to be involved

What is vitamin E?

Vitamin E is an essential nutrient that functions as an antioxidant in the human body. It is essential, by definition, because the body cannot manufacture its own vitamin E and thus it must be provided by foods and supplements.

Vitamin E is a generic term that includes all entities that exhibit the biological activity of alpha-tocopherol.



In nature, eight substances have been found to have vitamin E activity: alpha-, beta-, gamma- and delta-tocopherol; and alpha-, beta-, gamma- and delta-tocotrienol. The acetate and succinate derivatives of the natural tocopherols have vitamin E activity, as do synthetic tocopherols and their acetate and succinate derivatives.

Of these, d-alpha-tocopherol (RRR-alpha-tocopherol) has the highest bioavailability and is the standard against which all the others must be compared.



Is there a difference between natural and synthetic vitamin E?

Natural and synthetic vitamin E are not equivalent in composition, structure or bioavailability. Natural vitamin E (RRR-alpha-tocopherol or d-alpha-tocopherol) is a single entity.


Synthetic vitamin E (all-rac-alpha-tocopherol or dl-alpha-tocopherol) is a mixture of eight stereoisomers in equal amounts. The other seven stereoisomers have different molecular configurations and lower biological activities that range from 21-90% of the activity of natural vitamin E based on rat assays.

Natural vitamin E is officially recognized as having 36% greater potency than its synthetic counterpart as determined by studies in animals. However, recent human studies using deuterium-labeled vitamin E indicate that the bioavailability of natural vitamin E is approximately twice that of synthetic vitamin E, as natural vitamin E is retained longer in body tissues.

In a recent study of six healthy volunteers, the ratio of labeled natural vitamin E in blood plasma was 2.1 times higher than that of synthetic vitamin E after 24 hours. In contrast, the level of a breakdown product of vitamin E in urine was about 2.7 times higher from synthetic vitamin E.1

In another study of six healthy subjects, supplementation with natural vitamin E resulted in two-fold higher blood plasma vitamin E levels than synthetic vitamin E.2 The bioavailability of natural vitamin E administered at 100 mg per day was similar to that of synthetic vitamin E acetate administered at 300 mg per day in a study of seven healthy women.3

Results of a study of 15 pregnant women supplemented with natural and synthetic vitamin E acetate showed that the average ratio of natural to synthetic vitamin E was 1.86 in maternal blood and 3.42 in cord blood.4 In healthy volunteers, the ratio of natural to synthetic vitamin E in blood plasma ranged from 1.5 to 1.8 during supplementation, with equal doses of both vitamin E compounds, and increased to 2.0 after supplementation ended. For elective surgery patients, the ratio of natural to synthetic vitamin E was about 1.7 in blood plasma and 1.5 in all tissues except the liver. The ratio of natural to synthetic vitamin E was 2.0-2.1 in blood plasma and 1.7-2.0 in tissues of two terminally ill patients supplemented with vitamin E for 1-2 years.5

Lower retention of synthetic vitamin E should be anticipated as there are specific protein receptors for d-alpha-tocopherol that make its transport and retention more efficient.6 The alpha-tocopherol transfer protein, which is present in the liver, binds vitamin E and enhances transport of the vitamin between membranes. This transfer protein binds alpha-tocopherol in preference to other homologs (beta-, gamma- and delta-), and the naturally occurring stereoisomer (RRR-alpha-tocopherol or d-alpha-tocopherol) in preference to the other stereoisomers present in synthetic vitamin E.7

1. Traber, M.G., Elsner, A. and Brigelius-Flohe, R. Synthetic as Compared with Natural Vitamin E Is Preferentially Excreted as Alpha-CEHC in Human Urine: Studies Using Deuterated Alpha-Tocopheryl Acetates. FEBS Letters 437:145-148, 1998.

2. Acuff, R.V., Thedford, S.S., Hidiroglou, N.N., Papas, A.M. and Odom, T.A. Relative Bioavailability of RRR- and All-Rac-Alpha-Tocopheryl Acetate in Humans: Studies Using Deuterated Compounds. Am. J. Clin. Nutr. 60:397-402, 1994.

3. Kiyose, C., Muramatsu, R., Kameyama, Y., Ueda, T. and Igarashi, O. Biodiscrimination of Alpha-Tocopherol Stereoisomers in Humans after Oral Administration. Am. J. Clin. Nutr. 65:785-789, 1997.

4. Acuff, R.V., Dunworth, R.G., Webb, L.W. and Lane, J.R. Transport of Deuterium-Labeled Tocopherols during Pregnancy. Am. J. Clin. Nutr. 67:459-464, 1998.

5. Burton, G.W., Traber, M.G., Acuff, R.V., Walters, D.N., Kayden, H., Hughes, L., and Ingold, K.U. Humana Plasma and Tissue Alpha-Tocopherol Concentrations in Response to Supplementation with Deuterated Natural and Synthetic Vitamin E. Am. J. Clin. Nutr. 67:669-684, 1998.

6. Kitabchi, A.E., Wimalasena, J. and Barker, J. Specific Receptor Sites for Alpha-Tocopherol in Purified Isolated Adrenocortical Cell Membrane. Biochem. Biophys. Res. Comm. 96:1739-1746, 1980.

7. Hosomi, A., Arita, M., Sato, Y., Kiyose, C., Ueda, T., Igarashi, O., Arai, H., and Inoue, K. Affinity for Alpha-Tocopherol Transfer Protein as a Determinant of the Biological Activities of Vitamin E Analogs. FEBS Letters. 409:105-108, 1997.



How does vitamin E work?

Vitamin E functions in several ways:

The first, and most important, is as an antioxidant that protects cells and other body components from free radical attack. Oxidative damage resulting from free radical attack has been linked to the onset of premature aging, cancer, coronary heart disease, cataracts and an array of degenerative diseases.

Vitamin E stimulates the immune response. Some studies have shown lower incidence of infections when vitamin E levels are high, and vitamin E may inhibit cancer initiation through enhanced immunocompetence.

Vitamin E appears to lessen the severity of prostaglandin-mediated disorders such as inflammation, premenstrual syndrome and circulatory irregularities (nocturnal leg cramps and blood platelet adhesion).

Vitamin E also has a direct chemical function. It inhibits the conversion of nitrites in smoked, pickled and cured foods to nitrosamines in the stomach. Nitrosamines are strong tumor promoters.

Vitamin E has a regulatory effect on gene expression. It has been shown to control proliferation of smooth muscle cells, which are involved in the development of atherosclerosis.



How does vitamin E function as an antioxidant?

Vitamin E, which is fat soluble, is present in lipids, most significantly in the lipids of cell membranes and in circulating low-density lipoproteins. Free radicals produced as byproducts of metabolic processes and those originating from environmental pollutants (such as nitrogen dioxide and ozone of polluted air, heavy metals, halogenated hydrocarbons, ionizing radiation and cigarette smoke) are scavenged by available vitamin E.

Unchecked by an antioxidant, the highly unstable free radicals attack cell constituents, including DNA and other opportune targets, particularly those containing polyunsaturated fatty acids (PUFAs). When free radicals react with PUFAs, chain reactions generate free radicals in profusion. Free radicals can damage both the structure and function of cell membranes; nucleic acids and electron-dense regions of proteins also come under attack. This can result in:

  • Cell death or alteration of the cell's response to hormones and neurotransmitters
  • Mutations that may be carcinogenic
  • Inactivation of enzymes and other proteins
Vitamin E is recognized to be the major antioxidant in lipid body tissues and the primary defense against lipid peroxidation–neutralizing free radicals, terminating chain reactions and limiting free radical/oxidative damage. Vitamin E is particularly important in tissues that contain relatively high levels of polyunsaturated fatty acids (brain and central nervous system) and in those that are in contact with oxygen (lung), providing protection for microsomes and mitochondria.



Is vitamin E a "typical" vitamin?

Vitamin E is more appropriately described as an antioxidant than a vitamin.

Most vitamins function as cofactors for enzymatic reactions. Vitamin E does not function as a cofactor. Requirements for and utilization of vitamin E vary according to an individual's oxidative stress status. Concentrations of free radicals, other oxidants and the polyunsaturated fatty acid content of body tissues are major determinants of oxidative stress status.

Also, deficiency of vitamin E does not produce a disease with rapidly developing symptoms such as scurvy, beriberi, pellagra, rickets or xerophthalmia. In humans, vitamin E produces overt deficiency symptoms in cases involving fat malabsorption syndromes, premature infants and patients on total parenteral nutrition. The effects of inadequate vitamin E intake usually develop over a long time, typically decades, and have been linked to degenerative diseases such as cancer, atherosclerosis and other forms of heart disease.



Clinical conditions in which free radicals are thought to be involved

Following is a listing of scores of conditions to which free radicals have been linked.1 Most likely, free radicals will be the sole cause of only a few. However, free radicals may predispose the human body to a disease that is directly caused by other factors–that is, they may make some conditions worse–and may be an antagonist to the body's natural healing processes. In these cases, vitamin E would be useful as an adjunct therapy.



Free radical-related conditions:

Primary single organ involvement

Heart and cardiovascular system

Alcohol cardiomyopathy
Keshan disease (selenium deficiency)
Doxorubicin toxicity
Peripheral circulation problems


Hyperbaric oxygen
Alzheimer's disease
Senile dementia
Parkinson's disease-MPTP
Hypertensive cerebrovascular injury; cerebral trauma
Neuronal ceroid lipofuscinoses
Allergic encephalomyelitis and other demyelinating diseases
Ataxia-telangiectasia syndrome
Potentiation of traumatic injury
Aluminum overload


Cigarette-smoke effects
Bronchopulmonary dysplasia
Oxidant pollutants
Acute respiratory distress syndrome
Mineral dust pneumoconiosis
Bleomycin toxicity
Paraquat toxicity


Solar radiation
Thermal injury
Contact dermatitis
Photosensitive dyes
Bloom syndrome


Age-related macular degeneration
Ocular hemorrhage
Degenerative retinal damage
Retinopathy of prematurity
Photic retinopathy

Joint abnormalities

Rheumatoid arthritis

Gastrointestinal tract

Endotoxin liver injury
Carbon tetrachloride liver injury
Diabetogenic action of alloxan
Free fatty acid-induced pancreatitis
Nonsteroidal antiinflammatory drug-induced lesions


Nephrotic antiglomerular basement membrane disease
Aminoglycoside nephrotoxicity
Heavy metal nephrotoxicity
Renal graft rejection


Lead poisoning
Protoporphyrin photooxidation
Sickle-cell anemia
Fanconi anemia

Multiorgan involvement



Disorders of "premature aging"
Immune deficiency of aging

Inflammatory-immune injury

Glomerulonephritis (idiopathic, membranous)
Vasculitis (hepatitis B virus, drugs)
Autoimmune diseases

Ischemia-reflow states

Drug and toxin-induced reactions

Iron overload

Idiopathic hemochromatosis
Dietary iron overload
Thalassemia and other chronic anemias

Nutritional deficiencies

Vitamin E deficiency

Alcohol damage

Radiation injury

Amyloid diseases


1. Cross, C.E. Oxygen Radicals and Human Disease. Ann. Intern. Med. 107:526-545, 1987.

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