Tocopherol, or Vitamin E, is a fat-soluble vitamin in eight forms that is an important antioxidant. Vitamin E is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns.
Natural vitamin E exists in eight different forms or isomers, four tocopherols and tocotrienols. All isomers have a chromanol ring, with a hydroxyl group which can donate
a hydrogen atom to reduce free radicals and a hydrophobic side chain which allows for penetration into biological membranes. There is an alpha, beta, gamma and delta form of both the tocopherols and tocotrienols, determined by the number of methyl groups on the chromanol ring. Each form has its own biological activity, the measure of potency or functional use in the body.
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. The other isomers 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. Commercially available blends of natural vitamin E include "mixed tocopherols" and "high gamma tocopherol" formulas. Also selenium, Coenzyme Q10, and ample vitamin C have been shown to be essential cofactors of natural tocopherols.
Antioxidants such as vitamin E act to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Free radicals can cause cell damage that may contribute to the development of cardiovascular disease and cancer. Vitamin C and other anti-oxidants recycle vitamin E end-products back into effective suppressors of free radicals. Studies are underway to determine whether vitamin E might help prevent or delay the development of those chronic diseases.
Vegetable oils, nuts, wheat germ and green leafy vegetables are the main dietary sources of vitamin E. Fortified breakfast cereals are also an important source of vitamin E in the United States. Although originally extracted from wheat germ oil, most natural vitamin E supplements are now derived from vegetable oils, usually soybean oil.
Commercial vitamin E supplements can be classified into several distinct categories: fully synthetic vitamin E, "d,l-alpha-tocopherol", the most inexpensive, most commonly sold supplement form usually as the acetate ester; semisynthetic "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"; high gamma-tocopherol fraction supplements; and tocotrienol supplements.
Synthetic vitamin E, usually marked as d,l-tocopherol or d,l tocopheryl acetate, with 50% d-alpha tocopherol moiety and 50% l-alpha-tocopherol moeity, as synthesized by an earlier process is now actually manufactured as all-racemic alpha tocopherol, with only about one alpha tocopherol molecule in 8 molecules as actual d-alpha tocpherol. The synthetic form is not as active as the natural alpha tocopherol form. The 1950's thalidomide disaster with numerous severe birth defects is a common example of d- vs l- epimer forms type problem with synthesized racemic mixtures. 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.
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. 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 aged or ill patients.
The Recommended Daily Allowance for vitamin E is based on the alpha-tocopherol form because it is the most active, or usable, 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 intake of most Americans does not provide the recommended intake for 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".
When can vitamin E deficiency occur?
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 1/2 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.
Who may need extra vitamin E to prevent a deficiency?
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 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. These infants are usually under the care of a neonatologist, a pediatrician specializing in the care of newborns, who evaluates and treats the exact 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.
What are some current issues and controversies about vitamin E?
Vitamin E and heart disease
Preliminary research has led to a widely held belief that vitamin E may help prevent or delay coronary heart disease. 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. 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.
But even though these observations are promising, randomized clinical trials raise questions about 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.
Vitamin E and cancer
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. Unfortunately, human trials and surveys that tried to associate vitamin E with incidence of cancer have been generally inconclusive.
Some evidence associates higher intake of vitamin E with a decreased incidence of prostate cancer 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 . 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 women in Iowa provided evidence that an increased dietary intake of vitamin E may decrease the risk of colon cancer, especially in women under 65 years of age. On the other hand, vitamin E intake was not statistically associated with risk of colon cancer in almost 2,000 adults with cancer who were compared to controls without cancer. At this time there is limited evidence to recommend vitamin E supplements for the prevention of cancer.
Vitamin E and cataracts
Cataracts are growths on the lens of the eye that cloud vision. 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.
Vitamin E and alzheimer's disease
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%.
External Link - Johns Hopkins press release
What is the health risk of too much vitamin E?
The health risk of too much vitamin E is low. A recent review of the safety of vitamin E in the elderly indicated that taking vitamin E supplements for up to four months at doses of 530 mg or 800 IU (35 times the current RDA) had no significant adverse effect on general health, body weight, levels of body proteins, lipid levels, liver or kidney function, thyroid hormones, amount or kinds of blood cells, and bleeding time. Even though this study provides evidence that taking a vitamin E supplement containing 530 mg or 800 IU for four months is safe, the long term safety of vitamin E supplementation has not been authoritatively tested. However, "toxicity symptoms have not been reported even at intakes of 800 IU per kilogram of body weight daily for 5 months" according to the Food and Nutrition Board (Rosenberg, et al), an amount that corresponds to 60,000 IU per day for a 75 kg adult.
The Institute of Medicine has set an upper tolerable intake level for vitamin E at 1,000 mg (1,500 IU) for any form of supplementary alpha-tocopherol per day because the nutrient can act as an anticoagulant and increase the risk of bleeding problems. Upper tolerable intake levels "represent the maximum intake of a nutrient that is likely to pose no risk of adverse health effects in almost all individuals in the general population".
A recent metastudy at Johns Hopkins, however, suggests that "Vitamin E supplements, which millions take in the hope of longer, healthier lives, may do more harm than good." Others  have suggested that several selection and inclusion criteria introduced significant bias with a resultant inaccurate and overbroad statement. Of the 19 studies utilized, only one study clearly used the natural isomer, d-alpha tocopherol (more correctly: R,R,R-alpha tocopherol since 1981) instead of the commonly used synthetic (all-racemic) alpha tocopherol composed of all 8 alpha tocopherol epimers. The Shute brothers  , Canadian doctors, and others frequently prescribed d-alpha tocopherol for tens of thousands of cardiac patients, in many cases for decades, in the range of 450-3200 IU/day. The Shute brothers did carefully limit the amount administered to 90-150 IU/day for chronic rheumatic heart disease, and used lower starting dosages first. No information in the metastudy addressed natural vitamin E blends, mixed tocopherols, in use since before 1940.
- Institute of Medicine, Food and Nutrition board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academy Press, Washington, DC, 2000.
- U.S. Department of Agriculture, Agricultural Research Service, 1999. USDA Nutrient Database for Standard Reference, Release 13. Nutrient Data Laboratory Home Page, http://www.nal.usda.gov/fnic/foodcomp
- Dietary Guidelines Advisory Committee, Agricultural Research Service, United States Department of Agriculture (USDA). Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans, 2000. http://www.ars.usda.gov/dgac
- Rosenberg H and Feldzamen AN. The book of vitamin therapy. New York: Berkley Publishing Corp, 1974.