2.5-3.5 °C
200-220 °C at 0.1 mmHg
Tocopherol, known as vitamin E, describes a series of organic compounds consisting of a methylated phenols. The various derivatives are also vitamin E. Vitamin E is a fat-soluble antioxidant.

Forms
Alpha-tocopherol is traditionally recognized as the most biological antioxidant in humans. 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. It increases naturally to about 150% of normal in the maternal circulation during human pregnancies.
1 IU of vitamin E is defined as the biological equivalent of 0.667 milligrams of RRR-alpha-tocopherol (formerly named d-alpha-tocopherol, or of 1 milligram of all-rac-alpha-tocopheryl acetate (commercially called dl-alpha-tocopheryl acetate, the original d, l- synthetic molecular mix, properly named 2-ambo-alpha-tocopherol, is no longer manufactured).

Alpha-tocopherol
The other R, R, R tocopherol vitamers are slowly being recognized as research begins to elucidate their additional roles in the human body. Many naturopathic and orthomolecular medicine advocates suggest that vitamin E supplements contain at least 20% by weight of the other natural vitamin E isomers.

Other R, R, R tocopherol
Tocotrienols, with four d- isomers, also belong to the vitamin E family. The four tocotrienols have structures corresponding to the four tocopherols, except with an unsaturated bond in each of the three isoprene units that form the hydrocarbon tail. Tocopherols have a saturated phytyl tail.

Tocotrienols
During feeding experiments with rats Herbert McLean Evans concluded in 1922 that besides vitamins B and C, an unknown vitamin existed.

History
The U.S. Dietary Reference Intake (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 (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.

Sources
There are three specific situations when a vitamin E deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3.5 pounds), and is seen in individuals with rare disorders of fat metabolism. A vitamin E deficiency is usually characterized by neurological problems due to poor nerve conduction.
Individuals who cannot absorb fat may require a vitamin E supplement because some dietary fat is needed for the absorption of vitamin E from the gastrointestinal tract. Anyone diagnosed with cystic fibrosis, individuals who have had part or all of their stomach removed, and individuals with malabsorptive problems such as Crohn's disease, liver disease or pancreatic insufficiency may not absorb fat and should discuss the need for supplemental vitamin E with their physician (3). People who cannot absorb fat often pass greasy stools or have chronic diarrhea.
Very low birth weight infants may be deficient in vitamin E. A neonatologist, a pediatrician specializing in the care of newborns, typically evaluates the nutritional needs of premature infants.
Abetalipoproteinemia is a rare inherited disorder of fat metabolism that results in poor absorption of dietary fat and vitamin E. The vitamin E deficiency associated with this disease causes problems such as poor transmission of nerve impulses, muscle weakness, and degeneration of the retina that can cause blindness. Individuals with abetalipoproteinemia may be prescribed special vitamin E supplements by a physician to treat this disorder. In addition, there is a rare genetic condition termed isolated vitamin E deficiency or ataxia with isolated with vitamin E deficiency, caused by mutations in the tocopherol transfer protein gene. These individuals have an extremly poor capacity to absorb vitamin E and develop neurological complications that are reversible by supplementation with high doses of vitamin E.
Also, in adults, erythrocyte membrane fragility results as the erythrocytes are oxidized.

Deficiency
Commercial vitamin E supplements can be classified into several distinct categories:
"Megadoses" of Vitamin E are not recommended by many government agencies, due to a possible increased risk of bleeding. Two meta-analyses have concluded that synthetic and semisynthetic vitamin E supplements increase mortality, although these meta-analyses have been challenged by the nutrition literature.
A 2005 meta-analysis by Miller found that high-dosage vitamin E supplements may increase all-cause mortality.

Fully synthetic vitamin E, "d, l-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; highly fractionated natural d-alpha tocopherol
Less fractionated "natural mixed tocopherols" and high gamma-tocopherol fraction supplements Supplements
Due to its wide use as a preservative and the commonly belief that vitamin E is good for the skin, many cosmetics (and inexpensive foods) include it as a preservative (usually labeled tocopherol acetate in cosmetics). Despite this, individuals can still experience allergic reactions to tocopherol.

Allergic Reactions
Synthetic vitamin E is now manufactured as all-racemic alpha tocopheryl acetate with three chiral centers, with only one alpha tocopherol molecule (moiety) in 8 molecules as actual R, R,R-alpha tocopherol.
Synthetic all-rac vitamin E is usually marked as d, l-tocopherol or d, l-tocopheryl acetate, with 50% d-alpha tocopherol moiety and 50% l-alpha-tocopherol moiety, as synthesized by an earlier process with only one chiral center.
The synthetic form is not as active as the natural alpha tocopherol form. Information on any side effects of the synthetic vitamin E epimers is not readily available. Naturopathic and orthomolecular medicine advocates have long considered the synthetic vitamin E forms to be with little or no merit for cancer, circulatory and heart diseases.

Synthetic
Semisynthetic "natural source" vitamin E, manufacturers convert the common natural beta, gamma and delta tocopherol isomers into esters using acetic or succinic acid and add methyl groups to yield d-alpha tocopheryl esters such as d-alpha tocopheryl acetate or d-alpha tocopheryl succinate. These tocopheryl esters are more stable and are easy to use in tablets and multiple vitamin pills.
Because only alpha tocopherols were officially counted as "vitamin E" in supplements, refiners and manufacturers faced enormous economic pressure to esterify and methylate the other natural tocopherol isomers, d-beta-, d-gamma- and d-delta-tocopherol into d-alpha tocopheryl acetate or succinate. However these alpha tocopheryl esters have been shown to be variably and less efficiently absorbed in humans than in the original normative tests using rats. In the healthy human body, the semisynthetic forms are easily de-esterified over several days, primarily in the liver, but not for common problems in premature babies, aged or ill patients.
Tocopheryl nicotinate and tocopheryl linolate esters are used in cosmetics and some pharmaceuticals.

Semi-synthetic
"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 premium 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 various nutritional supplements manufactured by high end supplement companies.

Mixed tocopherols
Conventional medical studies on vitamin E, as of 2006 and as below, use either a synthetic all-racemic ("d, l-") alpha tocopheryl ester (acetate or succinate) or a semi-synthetic d-alpha tocopheryl ester (acetate or succinate). Proponents of megavitamin, orthomolecular and naturally based therapies have advocated, for the last two thirds of a century, and have used the natural tocopherols, often mixed tocopherols with an additional 25% - 200% w/w d-beta-, d-gamma-,

Other uses
Vitamin E is widely used in industry as an inexpensive preservative (namely for cosmetics and foods).

As a Preservative
Topical use of 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,

Reduce scarring
Recent studies into the use of both vitamin C and the single isomer vitamin E esters as possible help in preventing oxidative stress leading to pre-eclampsia has failed to show significant benefits,

During pregnancy
Preliminary research has led to a widely held belief that vitamin E may help prevent or delay coronary heart disease, but larger controlled studies have not shown any benefit. Researchers are fairly certain that oxidative modification of LDL-cholesterol (sometimes called "bad" cholesterol) promotes blockages in coronary arteries that may lead to atherosclerosis and heart attacks

Heart disease
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 nitrosamines, which are carcinogens formed in the stomach from nitrites consumed in the diet. It also may protect against the development of cancers by enhancing immune function. To date, human trials and surveys that have tried to associate vitamin E with incidence of cancer remain generally inconclusive.
Some evidence associates higher intake of vitamin E with a decreased incidence of prostate cancer (see ATBC study) and breast cancer. Some studies correlate additional cofactors, such as specific vitamin E isomers, e.g. gamma-tocopherol, and other nutrients, e.g. selenium, with dramatic risk reductions in prostate cancer. At this time there is limited evidence to recommend vitamin E supplements for the prevention of cancer.

Cancer
A cataract is a condition of clouding of the tissue of the lens of the eye. They increase the risk of disability and blindness in aging adults. Antioxidants are being studied to determine whether they can help prevent or delay cataract growth. Observational studies have found that lens clarity, which is used to diagnose cataracts, was better in regular users of vitamin E supplements and in persons with higher blood levels of vitamin E. A study of middle aged male smokers, however, did not demonstrate any effect from vitamin E supplements on the incidence of cataract formation. The effects of smoking, a major risk factor for developing cataracts, may have overridden any potential benefit from the vitamin E, but the conflicting results also indicate a need for further studies before researchers can confidently recommend extra vitamin E for the prevention of cataracts.
It is important to note that the term "cataract" may be used in common parlance for an opacity involving any tissue of the eye, for example a corneal scar. Thus a character in theater or on television who is blind from cataracts might have white instead of clear corneas, covering over the iris and pupil. Since the lens is behind the pupil, real cataracts are difficult to see without special instrumentation, so people with cataracts have rather normally appearing eyes.

Cataracts
Age-related macular degeneration (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.

Age-related macular degeneration (AMD)
A 2007 study published in the European Journal of Ophthalmology found that, along with other treatments for glaucoma, adding alpha-tocopherol appeared to help protect the retina 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."

Glaucoma
Alzheimer's disease is a wasting disease of the brain. An observational trial conducted by The Johns Hopkins University Bloomberg School of Public Health found that when vitamin E is taken daily in large doses (400-1000IU) in combination with vitamin C (500-1000mg) the onset of Alzheimer's was reduced between 64 and 78%.

Parkinson's disease

Alkylresorcinols