Tocopherol
Overview
 
Tocopherols are a class of chemical compounds of which many have vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 activity. It is a series of organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...

s consisting of various methylated phenol
Phenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...

s. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rats, it was given the name "tocopherol" from the Greek words “τόκος” [birth], and “φέρειν”, [to bear or carry] meaning in sum "to carry a pregnancy," with the ending "-ol" signifying its status as a chemical alcohol.

alpha-Tocopherol is the main source found in supplements and in the European diet, while gamma-tocopherol is the most common form in the American diet.
Encyclopedia
Tocopherols are a class of chemical compounds of which many have vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 activity. It is a series of organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...

s consisting of various methylated phenol
Phenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...

s. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rats, it was given the name "tocopherol" from the Greek words “τόκος” [birth], and “φέρειν”, [to bear or carry] meaning in sum "to carry a pregnancy," with the ending "-ol" signifying its status as a chemical alcohol.

alpha-Tocopherol is the main source found in supplements and in the European diet, while gamma-tocopherol is the most common form in the American diet. The compound α-tocopherol
Alpha-tocopherol
α-Tocopherol is a type of tocopherol with formula C29H50O2. It has E number "E307".α-Tocopherol is a form of vitamin E that is preferentially absorbed and accumulated in humans...

, a common form of tocopherol added to food products, is denoted by the E number
E number
E numbers are number codes for food additives that have been assessed for use within the European Union . They are commonly found on food labels throughout the European Union. Safety assessment and approval are the responsibility of the European Food Safety Authority...

 E307.

Tocotrienol
Tocotrienol
Tocotrienols are members of the vitamin E family. An essential nutrient for the body, vitamin E is made up of four tocopherols and four tocotrienols . The slight difference between tocotrienols and tocopherols lie in the unsaturated side chain having three double bonds in its farnesyl isoprenoid...

s, which are related compounds, also have vitamin E activity. All of these various derivatives with vitamin activity may correctly be referred to as "vitamin E." Tocopherols and tocotrienols are fat-soluble antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...

s but also seem to have many other functions in the body.

Forms

Vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...

 exists in eight different forms, four tocopherols and four tocotrienol
Tocotrienol
Tocotrienols are members of the vitamin E family. An essential nutrient for the body, vitamin E is made up of four tocopherols and four tocotrienols . The slight difference between tocotrienols and tocopherols lie in the unsaturated side chain having three double bonds in its farnesyl isoprenoid...

s. All feature a chromanol ring, with a hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

 group that can donate a hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...

 atom to reduce
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....

 free radicals and a hydrophobic side chain
Side chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...

 which allows for penetration into biological membrane
Biological membrane
A biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...

s.

Both the tocopherols and tocotrienols occur in alpha, beta, gamma and delta forms, determined by the number and position of methyl groups on the chromanol ring.

The tocotrienols have the same methyl structure at the ring and the same Greek letter-methyl-notation, but differ from the analogous tocopherols by the presence of three double bond
Double bond
A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...

s in the hydrophobic side chain. The unsaturation of the tails gives tocotrienols only a single stereoisomeric carbon (and thus two possible isomers per structural formula, one of which occurs naturally), whereas tocopherols have 3 centers (and eight possible stereoisomers per structural formula, again, only one of which occurs naturally).
Each form has slightly different biological activity
Biological activity
In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or pharmacophore but can be modified by the other...

.
In general, the unnatural l-isomers of tocotrienols lack almost all vitamin activity, and half of the possible 8 isomers of the tocopherols (those with 2S chirality at the ring-tail junction) also lack vitamin activity. Of the stereoisomers which retain activity, increasing methylation, especially full methylation to the alpha-form, increases vitamin activity. In tocopherols, this is due to the preference of the tocophrol binding protein for the alpha-tocopherol form of the vitamin.

As a food additive
Food additive
Food additives are substances added to food to preserve flavor or enhance its taste and appearance.Some additives have been used for centuries; for example, preserving food by pickling , salting, as with bacon, preserving sweets or using sulfur dioxide as in some wines...

, tocopherol is labeled with these E number
E number
E numbers are number codes for food additives that have been assessed for use within the European Union . They are commonly found on food labels throughout the European Union. Safety assessment and approval are the responsibility of the European Food Safety Authority...

s:E306 (tocopherol), E307 (α-tocopherol/alpha-tocopherol), E308 (γ-tocopherol/gamma-tocopherol), and E309 (δ-tocopherol/delta-tocopherol). These are all approved in the USA, EU and Australia and New Zealand for use as antioxidants.

Alpha-tocopherol

Alpha-tocopherol is the form of vitamin E that is preferentially absorbed and accumulated in humans. The measurement of "vitamin E" activity in international unit
International unit
In pharmacology, the International Unit is a unit of measurement for the amount of a substance, based on biological activity or effect. It is abbreviated as IU, as UI , or as IE...

s (IU) was based on fertility enhancement by the prevention of miscarriages in pregnant rats relative to alpha-tocopherol.

Although the mono-methylated form ddd-gamma-tocopherol is the most prevalent form of vitamin E in oils, there is evidence that rats can methylate this form to the preferred alpha-tocopherol, since several generations of rats retained alpha-tocopherol tissue levels, even when fed only gamma-tocopherol through their lives.

There are three stereocenter
Stereocenter
A stereocenter or stereogenic center is an atom, bearing groups such that an interchanging of any two groups leads to a stereoisomer.A chirality center is a stereocenter consisting of an atom holding a set of ligands in a spatial arrangement which is not superposable on its mirror image...

s in alpha-tocopherol, so this is a chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....

 molecule. The eight stereoisomers
Stereoisomerism
Stereoisomers are isomeric molecules that have the same molecular formula and sequence of bonded atoms , but that differ only in the three-dimensional orientations of their atoms in space. This contrasts with structural isomers, which share the same molecular formula, but the bond connections...

 of alpha-tocopherol differ in the arrangement of groups around these stereocenters. In the image of RRR-alpha-tocopherol below, all three stereocenters are in the R form. However, if the middle of the three stereocenters were changed (so the hydrogen was now pointing down and the methyl group
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...

 pointing up), this would become the structure of RSR-alpha-tocopherol. These stereoisomers can also be named in an alternative older nomenclature, where the stereocenters are either in the d or l form.

1 IU of tocopherol is defined as ⅔ milligrams of RRR-alpha-tocopherol (formerly named d-alpha-tocopherol or sometimes ddd-alpha-tocopherol). 1 IU is also defined as 1 milligram of an equal mix of the eight stereoisomers, which is a racemic mixture called all-rac-alpha-tocopheryl acetate
Tocopheryl acetate
Tocopheryl acetate, also known as vitamin E acetate, is a common vitamin supplement with the molecular formula C31H52O3 . It is the ester of acetic acid and tocopherol . It is often used in dermatological products such as skin creams...

. This mix of stereoisomers is often called dl-alpha-tocopheryl acetate, even though it is more precisely dl,dl,dl-alpha-tocopheryl acetate). However, 1 IU of this racemic mixture is not now considered equivalent to 1 IU of natural (RRR) α-tocopherol, and the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

 and the USDA now convert IU's of the racemic mixture to milligrams of equivalent RRR using 1 IU racemic mixture = 0.45 "milligrams α-tocopherol".

Tocotrienols

Tocotrienol
Tocotrienol
Tocotrienols are members of the vitamin E family. An essential nutrient for the body, vitamin E is made up of four tocopherols and four tocotrienols . The slight difference between tocotrienols and tocopherols lie in the unsaturated side chain having three double bonds in its farnesyl isoprenoid...

s, although less commonly known, also belong to the vitamin E family. Tocotrienols have four natural 2' d-isomers (they have a stereoisomeric carbon only at the 2' ring-tail position). The four tocotrienols (in order of decreasing methylation: d-alpha, d-beta, d-gamma, and d-delta-tocotrienol) have structures corresponding to the four tocopherols, except with an unsaturated bond in each of the three isoprene
Isoprene
Isoprene , or 2-methyl-1,3-butadiene, is a common organic compound with the formula CH2=CCH=CH2. Under standard conditions it is a colorless liquid...

 units that form the hydrocarbon tail, whereas tocopherols have a saturated phytyl tail (the phytyl tail of tocopherols gives the possibility for 2 more stereoisomeric sites in these molecules that tocotrienols do not have). Tocotrienol has been subject to fewer clinical studies and seen less research as compared to tocopherol. However, there is growing interest in the health effects of these compounds.

History

During feeding experiments with rats Herbert McLean Evans
Herbert McLean Evans
Herbert McLean Evans was a U.S. anatomist and embryologist.He was born in Modesto, California. In 1908, he obtained his medical degree from Johns Hopkins University, eventually becoming its associate professor of anatomy...

 concluded in 1922 that besides vitamins B and C, an unknown vitamin existed. Although every other nutrition was present, the rats were not fertile. This condition could be changed by additional feeding with wheat germ. It took several years until 1936 when the substance was isolated from wheat germ and the formula C29H50O2 was determined. Evans also found that the compound reacted like an alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

 and concluded that one of the oxygen atoms was part of an OH (hydroxyl) group. As noted in the introduction, the vitamin was given its name by Evans from Greek words meaning "to bear young" with the addition of the -ol as an alcohol.
The structure was determined shortly thereafter in 1938.

Recommended amounts

The U.S. Dietary Reference Intake
Dietary Reference Intake
The Dietary Reference Intake is a system of nutrition recommendations from the Institute of Medicine of the U.S. National Academy of Sciences. The DRI system is used by both the United States and Canada and is intended for the general public and health professionals...

 (DRI) Recommended Daily Amount (RDA) for a 25-year old male for Vitamin E is 15 mg/day. The DRI for vitamin E is based on the alpha-tocopherol form because it is the most active form as originally tested. Results of two national surveys, the National Health and Nutrition Examination Survey (NHANES III 1988-91) and the Continuing Survey of Food Intakes of Individuals (1994 CSFII) indicated that the dietary intakes of most Americans do not provide the recommended amounts of vitamin E. However, a 2000 Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

 (IOM) report on vitamin E states that intake estimates of vitamin E may be low because energy and fat intake is often underreported in national surveys and because the kind and amount of fat added during cooking is often not known. The IOM states that most North American adults get enough vitamin E from their normal diets to meet current recommendations. However, they do caution individuals who consume low fat diets because vegetable oils are such a good dietary source of vitamin E. "Low-fat diets can substantially decrease vitamin E intakes if food choices are not carefully made to enhance alpha-tocopherol intakes". Vitamin E supplements are absorbed best when taken with meals.

Because vitamin E can act as an anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...

 and may increase the risk of bleeding problems, many agencies have set an upper tolerable intake level (UL) for vitamin E at 1,000 mg (1,500 IU) per day.

Sources

In general, food sources with the highest concentrations of vitamin E are vegetable oils, followed by nuts
Nut (fruit)
A nut is a hard-shelled fruit of some plants having an indehiscent seed. While a wide variety of dried seeds and fruits are called nuts in English, only a certain number of them are considered by biologists to be true nuts...

 and seed
Seed
A seed is a small embryonic plant enclosed in a covering called the seed coat, usually with some stored food. It is the product of the ripened ovule of gymnosperm and angiosperm plants which occurs after fertilization and some growth within the mother plant...

s including whole grain
Whole grain
Whole grains are cereal grains that contain cereal germ, endosperm, and bran, in contrast to refined grains, which retain only the endosperm. Whole grains can generally be sprouted while refined grains generally will not sprout. Whole-meal products are made by grinding whole grains in order to make...

s. Adjusting for typical portion sizes, however, for many people in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 the most important sources of vitamin E include commercial breakfast cereal
Breakfast cereal
A breakfast cereal is a food made from processed grains that is often, but not always, eaten with the first meal of the day. It is often eaten cold, usually mixed with milk , water, or yogurt, and sometimes fruit but sometimes eaten dry. Some cereals, such as oatmeal, may be served hot as porridge...

 and tomato
Tomato
The word "tomato" may refer to the plant or the edible, typically red, fruit which it bears. Originating in South America, the tomato was spread around the world following the Spanish colonization of the Americas, and its many varieties are now widely grown, often in greenhouses in cooler...

 sauce. Although originally extracted from wheat germ oil, most natural vitamin E supplements are now derived from vegetable oils, usually soybean oil.

Vitamin E content per 100 g of source include:
A 100 g serving of certain fortified breakfast cereals may contain 24 mg (or more) vitamin E.

The proportion of vitamin E to other tocopherols in a nutrient source varies greatly. For example, the tocopherol content is 96% vitamin E in almond
Almond
The almond , is a species of tree native to the Middle East and South Asia. Almond is also the name of the edible and widely cultivated seed of this tree...

s and 9% vitamin E in poppy seeds.

Deficiency

Vitamin E deficiency causes neurological problems due to poor nerve conduction. These include neuromuscular problems such as spinocerebellar ataxia
Spinocerebellar ataxia
Spinocerebellar ataxia is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right.-Classification:...

 and myopathies
Myopathy
In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...

. Deficiency can also cause anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

, due to oxidative damage to red blood cells.

Supplements

Commercial vitamin E supplements can be classified into several distinct categories:
  • Fully synthetic vitamin E, "dl-alpha-tocopherol", the most inexpensive, most commonly sold supplement form usually as the acetate ester;
  • Semi-synthetic "natural source" vitamin E esters, the "natural source" forms used in tablets and multiple vitamins. These are highly fractionated d-alpha tocopherol or its esters, often made by synthetic methylation of gamma and beta d,d,d tocopherol vitamers extracted from plant oils.
  • Less fractionated "natural mixed tocopherols" and high d-gamma-tocopherol fraction supplements

Synthetic all-racemic

Synthetic vitamin E derived from petroleum products is manufactured as all-racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...

 alpha tocopheryl acetate with a mixture of eight stereoisomers. In this mixture, one alpha-tocopherol molecule in eight molecules are in the form of RRR-alpha-tocopherol (12.5% of the total).

The 8-isomer all-rac vitamin E is always marked on labels simply as dl-tocopherol or dl-tocopheryl acetate, even though it is (if fully written out) actually dl,dl,dl-tocopherol. The present largest manufacturers of this type are DSM
DSM (company)
DSM is a multinational life sciences and materials sciences-based company. DSM's global end markets include food and dietary supplements, personal care, feed, pharmaceuticals, medical devices, automotive, paints, electrical and electronics, life protection, alternative energy and bio-based materials...

 and BASF
BASF
BASF SE is the largest chemical company in the world and is headquartered in Germany. BASF originally stood for Badische Anilin- und Soda-Fabrik . Today, the four letters are a registered trademark and the company is listed on the Frankfurt Stock Exchange, London Stock Exchange, and Zurich Stock...

.

(An earlier semisynthetic vitamin E actually contained 50% d,d,d-alpha tocopherol moiety and 50% l,d,d-alpha-tocopherol moiety, as synthesized by an earlier process which started with a plant sterol intermediate with the correct chirality in the tail, and thus resulted in a racemic mixture at only one chiral center. This form, known as 2-ambo tocopherol, is no longer made.)

Natural alpha-tocopherol is the RRR-alpha (or ddd-alpha) form. The synthetic dl,dl,dl-alpha ("dl-alpha") form is not as active as the natural ddd-alpha ("d-alpha") tocopherol form. This is mainly due to reduced vitamin activity of the 4 possible stereoisomers which are represented by the l or S enantiomer at the first stereocenter (an S or l configuration between the chromanol ring and the tail, i.e., the SRR, SRS, SSR, and SSS stereoisomers). The 3 unnatural "2R" stereoisomers with natural R configuration at this 2' stereocenter, but S at one of the other centers in the tail (i.e., RSR, RRS, RSS), appear to retain substantial RRR vitamin activity, because they are recognized by the alpha-tocopherol transport protein, and thus maintained in the plasma, where the other four stereoisomers (SRR, SRS, SSR, and SSS) are not. Thus, the synthetic all-rac-α-tocopherol in theory would have approximately about half the vitamin activity of RRR-alpha-tocopherol in humans. Experimentally, the ratio of activities of the 8 stereoisomer racemic mixture to the natural vitamin, is 1 to 1.36 in the rat pregnancy model (suggesting a measured activity ratio of 1/1.36 = 74% of natural, for the 8-isomer racemic mix).

Although it is clear that mixtures of stereoisomers are not as active as the natural RRR-alpha-tocopherol form, in the ratios discussed above, specific information on any side effects of the seven synthetic vitamin E stereoisomers is not readily available.

Esters

Manufacturers also commonly convert the phenol form of the vitamins (with a free hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...

 group) to ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

s, using acetic or succinic acid. These tocopheryl esters are more stable and are easy to use in vitamin supplements. Alpha tocopheryl esters are de-esterified in the gut and then absorbed as the free tocopherol. Tocopheryl nicotinate and tocopheryl linolate esters are also used in cosmetics and some pharmaceuticals.
An initial study in humans saw large variability between different people's absorption of all these forms of vitamin E, with no statistically-significant differences seen between tocopheryl esters and the free tocopherol. Later studies saw no difference between the rate of absorption of these forms of vitamin E and found that tocopheryl esters and free tocopherol had the same bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

. The esterase
Esterase
An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis.A wide range of different esterases exist that differ in their substrate specificity, their protein structure, and their biological function.- EC classification/list...

 activity responsible for releasing the free tocopherol may be reduced in children with cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

.

Mixed tocopherols

“Mixed tocopherols” in the US contain at least 20% w/w other natural R, R,R- tocopherols, i.e. R, R,R-alpha-tocopherol content plus at least 25% R, R,R-beta-, R, R,R-gamma-, R, R,R-delta-tocopherols.

Some brands may contain 200% w/w or more of the other tocopherols and measurable tocotrienols. Some mixed tocopherols with higher gamma-tocopherol content are marketed as "High Gamma-Tocopherol." The label should report each component in milligrams, except R, R,R-alpha-tocopherol may still be reported in IU. Mixed tocopherols can also be found in other nutritional supplements.

Age-related macular degeneration (AMD)

Age-related macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...

 (AMD) is the leading cause of visual impairment and blindness in the United States and the developed world among people 65 years and older. It has been shown that vitamin E alone does not attenuate the development or progression of AMD.

However, studies focusing on efficacy of Vitamin E combined with other antioxidants, like zinc and vitamin C, indicate a protective effect against the onset and progression of AMD.

Alternative medicine

A variety of schools of alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....

 advocate high intake of dietary or supplementary vitamin E. A review of a number of randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...

s in the scientific literature by the Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...

 published in JAMA
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...

 in 2007 also found an increase in mortality, of 4% (Relative Risk 1.04, 95% confidence interval 1.01-1.07). Excessive intake of vitamin E may increase risk of bleeding. A 2005 meta-analysis found that high-dosage vitamin E supplements may increase all-cause mortality. "High dose" vitamin E esters (>400 units/day) were also associated with an increased risk in all-cause mortality of 39 per 10,000 persons, and a statistically significant relation existed between dose and mortality, with increased risk at doses exceeding 150 units per day. The Miller study was criticised in the Journal of the American Nutraceutical Association.

Proponents of megavitamin
Megavitamin therapy
Megavitamin therapy is the use of large doses of vitamins, often many times greater than the recommended dietary allowance in the attempt to prevent or treat diseases...

, orthomolecular
Orthomolecular medicine
Orthomolecular medicine is a form of complementary and alternative medicine that seeks to maintain health and prevent or treat diseases by optimizing nutritional intake and/or prescribing supplements...

, and naturally based therapies have for the last two thirds of a century advocated and used the natural tocopherols, often mixed tocopherols with an additional 25% - 200% w/w d-beta-, d-gamma-, and d-delta-tocopherol. Studies on vitamin E have largely concentrated on use of either a synthetic all-racemic ("d, l-") alpha tocopheryl ester (acetate or succinate) or a semi-synthetic d-alpha tocopheryl ester (acetate or succinate).

Alzheimer's disease

Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

 is a wasting disease of the brain. As oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...

 may be involved in the pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

 of Alzheimer's, tocopherols have been tested as both a means of prevention and treatment. The results of these studies have been mixed, with some research suggesting that high levels of vitamin E in the diet may reduce the risk of Alzheimer's, while other studies found no such link. Studies on progression have also been contradictory, with the Alzheimer’s Disease Cooperative Study suggesting that vitamin E supplementation might be beneficial, but a later trial finding no clinical benefit. Due to this contradictory and confusing evidence, vitamin E or tocopherol supplements are not currently recommended for treating or preventing Alzheimer's disease.

Cancer

, human trials and surveys that have investigated potential association of vitamin E intake with incidence of cancer remain generally inconclusive. Antioxidants such as vitamin E help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. Vitamin E also may block the formation of nitrosamine
Nitrosamine
Nitrosamines are chemical compounds of the chemical structure R1N-N=O, some of which are carcinogenic.-Usages:Nitrosamines are used in manufacture of some cosmetics, pesticides, and in most rubber products. -Occurrences:...

s, which are carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...

s formed in the stomach from nitrite
Nitrite
The nitrite ion has the chemical formula NO2−. The anion is symmetric with equal N-O bond lengths and a O-N-O bond angle of ca. 120°. On protonation the unstable weak acid nitrous acid is produced. Nitrite can be oxidised or reduced, with product somewhat dependent on the oxidizing/reducing agent...

s consumed in the diet. It also may protect against the development of cancers by enhancing immune function.

Some evidence associates higher intake of vitamin E with a decreased incidence of prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...

 (see ATBC study) and breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

. Some studies correlate additional cofactors, such as specific vitamin E isomers, e.g. gamma-tocopherol, and other nutrients, e.g. selenium
Selenium
Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...

, with dramatic risk reductions in prostate cancer. However, an examination of the effect of dietary factors, including vitamin E, on incidence of postmenopausal breast cancer in over 18,000 women from New York State did not associate a greater vitamin E intake with a reduced risk of developing breast cancer. A study of the effect on lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

 in smokers also showed no benefit.

Recent studies have found that increased intake of vitamin E, especially among smokers may be responsible for an increase in the incidence of lung cancer, with one study finding an increase in the incidence of lung cancer by 7% for each 100 IU of vitamin E taken daily.

A potential confounding factor is the form of Vitamin E used in these studies. As explained earlier, synthetic, racemic mixtures of Vitamin E isomers are not bioequivalent to natural, non-racemic mixtures, yet are widely used academically and commercially. The SELECT study for prostate cancer used racemic alpha-tocopherol, for instance, and has shown no benefit. The study, cited above, showing a modest increase in cancer risk with Vitamin E supplementation, reported that over 90% of its respondents used a racemic form of Vitamin E (d,l-alpha-tocopherol). A meta-analysis of studies using Vitamin E, sorting results by the form (racemic vs non-racemic) used, is necessary.

Cataracts

Antioxidants are being studied to determine whether they can help prevent or delay age-related growth of cataracts, a clouding of the tissue of the lens of the eye. A controlled trial of high doses of vitamins C and E and beta carotene found no effect on the risk of developing cataracts. Similarly, a trial using vitamin E alone found that vitamin E supplementation produced no change in the risk of developing cataracts or the rate of progression of existing cataracts.

Glaucoma

A 2007 study published in the European Journal of Ophthalmology found that, along with other treatments for glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

, adding alpha-tocopherol appeared to help protect the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

 from glaucomatous damage. Groups receiving 300 mg and 600 mg per day of alpha-tocopherol, delivered orally, showed statistically significant decreases in the resistivity index in the posterior ciliary arteries and in the pulsatility index in the ophthalmic arteries, after six and twelve months of therapy. Alpha-tocopherol-treated patients also had significantly lower differences in mean visual field deviations."

Heart disease

Preliminary research has led to a widely held belief that vitamin E may help prevent or delay coronary heart disease
Coronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...

, but larger controlled studies have not shown any benefit. Many researchers advance the belief that oxidative modification of LDL-cholesterol (sometimes called "bad" cholesterol) promotes blockages in coronary arteries that may lead to atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...

 and heart attacks
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...

. Vitamin E may help prevent or delay coronary heart disease by limiting the oxidation of LDL-cholesterol. Vitamin E also may help prevent the formation of blood clots, which could lead to a heart attack. Observational studies have associated lower rates of heart disease with higher vitamin E intake. A study of approximately 90,000 nurses suggested that the incidence of heart disease was 30% to 40% lower among nurses with the highest intake of vitamin E from diet and supplements. The range of intakes from both diet and supplements in this group was 21.6 to 1,000 IU (32 to 1,500 mg), with the median intake being 208 IU (139 mg). A 1994 review of 5,133 Finnish men and women aged 30 – 69 years suggested that increased dietary intake of vitamin E was associated with decreased mortality (death) from heart disease.

Despite these promising observations, randomized clinical trials have consistently shown lack of benefit to the role of vitamin E supplements in heart disease. The Heart Outcomes Prevention Evaluation (HOPE) Study followed almost 10,000 patients for 4.5 years who were at high risk for heart attack or stroke. In this intervention study the subjects who received 265 mg (400) IU of vitamin E daily did not experience significantly fewer cardiovascular events or hospitalizations for heart failure or chest pain when compared to those who received a sugar pill. The researchers suggested that it is unlikely that the vitamin E supplement provided any protection against cardiovascular disease in the HOPE study. This study is continuing, to determine whether a longer duration of intervention with vitamin E supplements will provide any protection against cardiovascular disease.

Furthermore, meta analysis of several trials of antioxidants, including vitamin E, have not shown any benefit to vitamin E supplementation for preventing coronary heart disease. One study suggested that Vitamin E (as alpha-tocopherol only) supplementation may increase the risk for heart failure. Supplementing alpha-tocopherol without gamma-tocopherol is known to lead to reduced serum gamma- and delta-tocopherol concentrations.

A large-scale 10-year study published in 2007 examined the rates of venous thromboembolism (VTE) and pulmonary embolism in women taking 600 IU of vitamin E on alternate days. The study found a significant reduction in VTE especially in women who had a history of thrombtic events or a genetic predispostion.

Parkinson's disease

In May 2005, The Lancet
The Lancet
The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

 Neurology
published a study suggesting that vitamin E may help protect against Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

. Individuals with moderate to high intakes of dietary vitamin E were found to have a lower risk of Parkinson's. No conclusion could be made whether supplemental vitamin E has the same effect. Other trials have tested whether giving vitamin E supplements reduces the risk of Parkinson's disease, or if they can slow the progression of the disease. In a 1998 study, vitamin E supplements had no effect on the rate of progression.

Pregnancy

Recent studies into the use of both vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

 and the single isomer vitamin E esters as possible aids in preventing oxidative stress leading to pre-eclampsia
Pre-eclampsia
Pre-eclampsia or preeclampsia is a medical condition in which hypertension arises in pregnancy in association with significant amounts of protein in the urine....

 has failed to show significant benefits, but did increase the rate of babies born with a low birthweight
Birth weight
Birth weight is the body weight of a baby at its birth.There have been numerous studies that have attempted, with varying degrees of success, to show links between birth weight and later-life conditions, including diabetes, obesity, tobacco smoking and intelligence.-Determinants:There are...

 in one study.

Preservative

Tocopherols are sometimes used as a food preservative
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....

 to prevent oils from going rancid.

Topical use

Vitamin E is widely used as an inexpensive antioxidant in cosmetics and foods. Vitamin E containing products are commonly used in the belief that vitamin E is good for the skin; many cosmetics include it, often labeled as tocopherol acetate, tocopheryl linoleate or tocopheryl nicotinate. Some individuals experience allergic reactions to some tocopheryl esters or develop a rash and hives that may spread over the entire body from the use of topical products with alpha tocopheryl esters.

Vitamin E is often claimed by manufacturers of skin creams and lotions to play a role in encouraging skin healing and reducing scarring after injuries such as burns on the basis of limited research, but the weak evidence of a benefit of silicon gel sheeting with or without added Vitamin E is limited by the poor quality of the research. One study found that it did not improve or worsen the cosmetic appearance in 90% of patients, with a third developing contact dermatitis
Contact dermatitis
Contact dermatitis is a term for a skin reaction resulting from exposure to allergens or irritants . Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight....

.

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK