Vitamin E was discovered in the 1920s when rats fed a vitamin E- deficient diet became unable to reproduce; but it was not officially considered essential for humans until 1966. It is the name given to a group of fat soluble compounds which are also called tocopherols and tocotrienols. The term "tocopherol" comes from the Greek words meaning "to bear offspring". The most abundant and active form of vitamin E is alpha tocopherol.

Function of vitamin E in the body

Antioxidant properties
Unlike the other vitamins which take part in metabolic reactions or function as hormones, the main role of vitamin E appears to be to act as an antioxidant. Vitamin E is incorporated into the lipid portion of cell membranes and carrier molecules and protects these structures from toxic compounds, heavy metals, drugs, radiation and free radicals. Vitamin E also protects cholesterol from oxidative damage. Because of its antioxidant effects, a diet high in vitamin E appears to be protective against common health conditions such as heart disease, cancer and strokes (See page 417 for more information.)

Immune system
Vitamin E is essential for the maintenance of a healthy immune system as it protects the thymus gland and circulating white blood cells from damage. Vitamin E is particularly important in protecting the immune system from damage during times of oxidative stress and chronic viral illness.

Eyes
Vitamin E is vital for healthy eyes. It is essential for the development of the retina and protects the eyes against free radical damage associated with cataract formation and macular degeneration. It also protects vitamin A in the eyes from damage.

Aging
As an antioxidant, vitamin E may protect against the effects of aging by destroying free radicals which cause degeneration in tissues such as the skin and blood vessels. Studies in mice have shown that high doses of vitamin E may help prevent aging-related damage to proteins involved in immune and central nervous system function. Vitamin E may also protect against the mental effects of aging, such as memory loss.

Absorption and metabolism
Vitamin E requires the presence of fats and bile in the gut to be absorbed. Approximately 20 to 60 per cent of dietary vitamin E is absorbed and it is stored in the liver, heart, fatty tissues, heart, muscles, testes, uterus, blood, adrenal and pituitary glands. Absorption and transport are likely to be reduced in elderly people.

Deficiency
The symptoms of vitamin E deficiency in infants are irritability, fluid retention, hemolytic anemia (the breaking down of red blood cells) and eye disorders. In adults, vitamin E deficiency can lead to nerve damage and symptoms of lethargy, apathy, inability to concentrate, staggering gait, low thyroid hormone levels, decreased immune response, loss of balance and anemia.

Severe vitamin E deficiency is very rare. Those at risk include people with chronic liver disease and fat malabsorption syndromes, such as celiac disease and cystic fibrosis. Hemodialysis patients, those with inherited red blood cell disorders, premature and low birthweight infants, and elderly people may also be at risk of vitamin E deficiency and are often given supplements.

As vitamin E is stored in the body, it can take some time before deficiency symptoms become apparent in someone consuming a diet low in vitamin E. Marginal vitamin E deficiency may be relatively common and several studies have shown an increased risk of heart disease, cancer and other disorders in those with low vitamin E levels.

Cardiovascular disease
Low dietary intake of vitamin E seems to increase the risk of heart disease. This is illustrated by results from the Iowa Women's Health Study published in 1996 in the New England Journal of Medicine. Researchers studied 34 486 postmenopausal women with no cardiovascular disease who in early 1986 completed a questionnaire that assessed, among other factors, their intake of vitamins A, E, and C from food sources and supplements. During seven years of follow-up, 242 women died of coronary heart disease. The results showed that high vitamin E consumption reduced the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21 809 women who did not consume vitamin supplements.

Similar results have been seen in men. Harvard School of Public Health researchers have assessed the links between diet and heart disease in 39 910 US male health professionals aged between 40 to 75 years of age. Participants responded to a questionnaire in 1986 and were then followed up for four years, during which time there were 667 cases of coronary disease. The results showed a lower risk of disease among men with higher intakes of vitamin E. Men consuming more than 40 mg (60 IU) per day had a 36 per cent lower risk than those consuming less than 5 mg (7.5 IU) per day. Men who took at least 67 mg (100 IU) per day for at least two years had a 37 per cent lower risk than those who did not take supplements.

The results of a 1996 study done in Japan suggest that low vitamin E levels increase the risk of a type of angina caused by coronary artery spasm. Animal studies suggest that brain damage after stroke may be greater in those who are vitamin E-deficient

Cancer
There is some evidence that vitamin E can protect against cancer, although studies have shown conflicting results. Some population studies suggest that low vitamin E levels increase the risk of certain cancers, particularly those of the gastrointestinal tract, cervix and lungs.

Cancers of the gastrointestinal tract
Results from the Iowa Women's Health Study suggest that high intakes of vitamin E reduce the risk of colon cancer. Researchers analyzed the links between vitamin E and colon cancer in 35 215 Iowa women aged 55 to 69 years without a history of cancer. During the follow-up period, there were 212 cases of colon cancer. The results showed that low vitamin E intake increased the risk of colon cancer and those in the high intake group had 30 per cent of the risk of those in the low intake group. The protective factor was stronger in the younger women.

Other results from the Iowa Women's Health Study show that higher intakes of antioxidants, including vitamin E, are linked to lower risks of both oral, pharyngeal, esophageal and gastric cancers.

Breast cancer
Researchers at the University of Southern California investigated the relationship between blood levels of various nutrients, including vitamin E, and the risks of breast cancer and proliferative benign breast disease (BBD) in postmenopausal women in the Boston area. Women whose intake of vitamin E from food sources only was high had around 60 per cent less risk of breast cancer compared to those in the low intake group. However, not all studies have shown protective effects.

Cervical cancer
Utah University researchers investigating the relationship between cervical cancer and dietary intake of antioxidant vitamins and selenium in 266 women with cervical cancer and 408 women without the disorder found that women with high vitamin E intakes had a 40 per cent lower risk of cervical cancer. Blood levels of vitamin E have also been found to be low in women with cervical cancer.

Lung cancer
Several epidemiological studies suggest that low vitamin E intakes increase the risk of lung cancer. In 1974 and 1975, researchers at Johns Hopkins School of Hygiene and Public Health, Baltimore, collected blood samples from 25 802 volunteers. They assessed vitamin E levels in samples from 436 cancer cases and 765 matched control subjects. The results showed that high vitamin E levels protected against lung cancer.

Cataracts
Low vitamin E levels may increase the risk of cataract formation. A 1996 Finnish study of over 400 men found an increased risk of cataracts in those with low vitamin E levels. The researchers evaluated the link between vitamin E levels and progression of eye lens opacities in 410 men with high cholesterol. The results showed that those with low vitamin E levels had almost four times the risk of lens opacities when compared with those in the highest intake group.

Parkinson's disease
The results of several studies suggest that high levels of vitamin E can protect against Parkinson's disease. In a 1997 study, researchers at Erasmus University Medical School in Holland examined the relationship between dietary intake of antioxidants and Parkinson's Disease and found a reduction in risk associated with high vitamin E intake. The study involved over 5300 men and women living independently and without dementia. It included 31 people with Parkinson's Disease.

Sources
The best natural sources of vitamin E are wheatgerm oil, hazelnut oil, sunflower oil, almond oil, wheatgerm, whole grain cereals and eggs. Peaches, avocados, broccoli and leafy greens are also good sources. Different foods have varying amounts of the different forms of vitamin E. For example, soybean oil is composed of about 10 per cent alpha tocopherol with the rest made up of other tocopherols. The specific benefits of the different forms of vitamin E remain to be discovered.

The results of a 1997 study suggest that the mixed forms of vitamin E found in food may be more beneficial than the alpha tocopherol form which is the main ingredient in supplements. Scientists at the University of California compared the abilities of alpha tocopherol and gamma tocopherol to protect against lipid peroxidation by compounds known as peroxynitrites which are formed in response to cigarette smoke, pollution and inflammation. Results showed that the gamma tocopherol form may be better at inhibiting these damaging reactions. About 75 per cent of the vitamin E found in food is the gamma tocopherol form while supplements may not contain any gamma tocopherol and it is possible that taking very high doses of alpha tocopherol may displace gamma tocopherol.

Cooking and processing reduces the vitamin E content of foods such as flours and oils. Cold-pressed oils therefore have a higher vitamin E content than refined vegetable oils. Exposure to light and oxygen also destroys vitamin E.

Recommended dietary allowances
The amount of vitamin E required depends on the amount of polyunsaturated fats in the diet. The greater the amount of these fats in the diet, the greater the risk that they will be damaged by free radicals and exert harmful effects. As vitamin E prevents this damage, recommended intake is roughly proportional to the amount of polyunsaturated fats in the diet. The US RDA is based on an intake of 0.4 mg per g of polyunsaturated fats. Vitamin E is measured in International Units (IU) and more commonly nowadays, mg alpha TE. 1 IU equals 0.67 mg alpha TE.

USA

Men 10 mg alpha TE (15 IU)

Women 8 mg alpha TE (12 IU)

Pregnancy 10 mg alpha TE (15 IU)

Lactation 12 mg alpha TE (18 IU)

No RNI has been given in the UK. A 1991 Department of Health report concluded that a fixed amount is impossible to recommend as required vitamin E needs depend on the intake of polyunsaturated fats, which varies considerably from person to person.

Supplements
Vitamin E supplements are available in natural and synthetic forms. Natural forms of vitamin E are derived from soybean or wheatgerm oil and are indicated by a 'd' prefix. These include d-alpha-tocopherol, d-alpha-tocopheryl acetate and d-alpha-tocopheryl succinate. The synthetic forms are manufactured from purified petroleum oil and are indicated by a 'dl' prefix. These include dl-alpha-tocopherol, dl-alpha-tocopheryl acetate and dl-alpha-tocopheryl succinate. Natural vitamin E supplements containing mixed tocopherols appear to offer the most beneficial effects. Water soluble vitamin E supplements are also available and, although more expensive, may not necessarily be more beneficial. As they require fat for absorption, vitamin E supplements should be taken with food.

In studies where benefits of vitamin E supplementation have been shown, the doses used have usually well exceeded the RDAs. In many studies, daily doses of up to 536 mg (800 IU) or even 804 mg (1200 IU) have been used. It is not possible to get such large amounts of vitamin E from food without consuming a high fat diet. Therefore many experts believe that supplements are necessary.

Toxic effects of excess intake
Vitamin E is considered safe even in large doses. Doses over 536 mg (800 IU) may lead to an increased risk of bleeding, diarrhea, abdominal pain, fatigue, reduced resistance to bacterial infection and transiently raised blood pressure.

Some research suggests that vitamin E may actually be pro-oxidant at high doses; that is, may actually increase free radical damage. The results of a 1997 study done in Scotland showed that red cells of nonsmokers receiving 1050 mg of vitamin E had an increased susceptibility to peroxidation. Also, prolonged supplementation with vitamin E led to a decline in vitamin C concentrations in the blood.

Therapeutic uses of supplements
Vitamin E supplements are used to treat deficiency and to prevent it in those at risk. Supplements are also used in a wide range of disorders where there is an increased need for immune support and protection against free radical damage.

A study published in 1996 by researchers from the National Institute on Aging examined the effects of vitamin E and vitamin C supplement on mortality risk in 11 178 persons aged from 67 to 105 who were taking part in the Established Populations for Epidemiologic Studies of the Elderly Study. From 1984 through 1993 there were 3490 deaths. The results showed that those using the vitamin E supplements had a 34 per cent lower risk of death when compared to those not using vitamin E supplements, and around half the risk of death from coronary disease.

Cardiovascular disease
Several studies have shown that high vitamin E intake can reduce the risk of developing heart disease and improve the symptoms in those who do have the disease. Results from the Nurses Health Study provide evidence for the protective effects of vitamin E. Results published in 1993 assessed the links between vitamin E and heart disease in 87 245 female nurses aged from 34 to 59 who were free of diagnosed cardiovascular disease and cancer in 1980. During the follow-up period of eight years, there were 552 cases of major coronary disease (437 nonfatal heart attacks and 115 deaths due to coronary disease). The results showed that women with the highest vitamin E intakes had 34 per cent less risk of major coronary disease compared to those with the lowest intakes. Most of the reduction in risk was attributable to vitamin E consumed as supplements, a finding which conflicts with some other studies which only show benefit from high dietary intakes. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had an even lower risk of disease.

Results from a British study known as the Cambridge Heart Antioxidant Study (CHAOS) which were published in The Lancet in 1996 provide further evidence of a link between vitamin E supplements and reduction in heart disease risk. In this double-blind, placebo-controlled study, 2002 patients with coronary atherosclerosis were enrolled and followed up for 510 days. 546 patients were given 536 mg (800 IU) daily; 589 were given 268 mg (400 IU) per day and 967 received identical placebo capsules. The results showed that those who received vitamin E supplements had a 75 per cent reduction in the risk of fatal heart attacks. However, when nonfatal events were included there did not appear to be any benefit from the vitamin E supplements.

As part of the Finnish Alpha-Tocopherol, Beta carotene Cancer (ATBC) Prevention Study, researchers studied the preventive effect of vitamin E and beta carotene supplements on major coronary events. A total of 27 271 Finnish male smokers aged 50 to 69 years with no history of heart attack were randomly assigned to receive 50 mg (75 IU) and a 20 mg dose of beta carotene, both supplements, or placebo daily for five to eight years. During this period there were 1204 nonfatal heart attacks and 907 fatal ones. The results showed that major coronary events decreased 4 per cent among those taking vitamin E. Supplementation with vitamin E also decreased the incidence of fatal coronary heart disease by 8 per cent although did not appear to affect the incidence of nonfatal heart attacks. The dose of vitamin E used in this study is smaller than that commonly used.

Vitamin E may help prevent heart disease in a number of ways. It lowers total blood cholesterol levels, and as it is easily incorporated into the harmful LDL cholesterol molecule, it can protect it from oxidation by free radicals. Oxidized LDL cholesterol is more likely to block arteries and contribute to the atherosclerotic process than unoxidised LDL cholesterol. Vitamin E may be able to prevent the free radical damage that occurs when blood is cut off then re-supplied, for example during surgery or in the case of a blood vessel spasm. Vitamin E also has important direct effects on vascular endothelial and smooth muscle cells and also inhibits the clumping together of platelets which helps to reduce atherosclerotic plaque formation. It also seems to inhibit the attachment of white blood cells to artery linings which is caused by LDL cholesterol.

A study published in 1996 suggests that the minimum dose of supplementary vitamin E which will significantly reduce the susceptibility of LDL to oxidation is 335 mg (500 IU) per day.

Angina
Vitamin E appears to play a part in decreasing the risk of angina. Results of the Finnish ATBC Prevention Study found a slightly reduced risk in those taking vitamin E supplements.

Cancer
Vitamin E supplements, especially when combined with selenium, have shown beneficial effects in the prevention of certain types of cancer, including breast cancer. Results from the US National Institute on Aging study mentioned above showed a 22 per cent decrease in the risk of death from cancer in those taking vitamin E supplements.

Vitamin E may protect against cell membrane and chromosome damage that would otherwise lead to cancerous changes in cells. Vitamin E also inhibits the growth of abnormal cells and plays a role in their conversion back to normal cells. Vitamin E can also prevent the formation of certain carcinogens by combining with substances in the intestine. For example, the formation of cancer-causing nitrosamines from dietary nitrites in the stomach may be inhibited by vitamin E.

Prostate cancer
According to more results from the ATBC study published in 1998 in the Journal of the National Cancer Institute, vitamin E reduces the risk of prostate cancer among smokers. Researchers studied the effects of 50 mg (75 IU) in Finnish men and the results showed a 32 per cent decrease in the incidence of prostate cancer and a 41 per cent decrease in prostate cancer deaths among the men taking vitamin E, compared with those who took no vitamin E.

Immunity
High doses of vitamin E boost the immune system in elderly people. In a 1997 study of 88 healthy people, aged 65 or older, those who took 200 mg (300 IU) each day for about four months showed an improvement in immune response. Researchers assessed the effects of either 60 mg (90 IU), 200 mg (300 IU) or 800 mg (1333) on a measure of immune system strength known as delayed hypersensitivity skin response. The results showed that those who took 200 mg a day had a 65 per cent increase in immune function. Those taking 60 mg or 800 mg of vitamin E also showed some improvements in immune function but the ideal response was seen in those taking 200 mg. In other tests, those who took the supplements produced six times more antibodies to hepatitis B after being given the vaccine than those who took placebo. They also produced more antibodies against tetanus infection. The study, which was reported in the Journal of the American Medical Association provides more support for vitamin E supplementation in older people.

HIV/AIDS
Vitamin E may also help to slow disease progression in HIV-positive people. The results of a nine year study involving 311 HIV-positive men showed that those patients with the highest vitamin E intakes had a 35 per cent decrease in risk of progression to AIDS when compared to those in the lowest intake group.

Diabetes
Vitamin E may improve insulin action in some diabetics. Those with the disorder are particularly susceptible to oxidative damage and vitamin E may play a role in preventing the long-term complications of diabetes. Studies show that vitamin E can protect diabetics against LDL cholesterol oxidation and other adverse effects of the disease.

In a study published in 1996, Louisiana researchers examined whether 67 mg (100 IU) per day had any effect on blood lipid oxidation products and blood lipid profiles of 35 diabetic patients over a three month period. The results showed that vitamin E supplementation significantly lowered lipid peroxidation products and lipid levels in diabetic patients.

Type I diabetes
The results of a 1997 study done in Italy show that vitamin E can protect against damage to beta cells which produce insulin in Type I diabetes patients. The one year study involved 84 patients between 5 and 35 years of age. One group was treated with vitamin E supplements and the other group received nicotinic acid which has been shown to protect pancreatic beta cell function (See page 80 for more information.) All patients were under intensive insulin therapy with three to four injections a day. The results showed that vitamin E was as effective as nicotinic acid in protecting the beta cells.

Cataract
Vitamin E supplements may help to prevent cataract progression, according to a 1998 study published in the journal Ophthalmology. Researchers found that among a group of around 750 elderly people, those who took vitamin E supplements had half the risk that their cataracts would progress over a four-and-a-half-year period. Taking a multivitamin pill lowered the risk by one-third.

Fertility
Animal studies suggest that moderate doses of vitamin E may enhance the ability of sperm to fertilize eggs. Recent studies suggest that vitamin E supplements may be useful in treating male infertility by improving sperm function.

Arthritis
Vitamin E has anti-inflammatory and analgesic activity which may be useful in rheumatoid arthritis patients. In a study published in 1997, UK researchers treated 42 patients with 600 mg (895 IU) twice a day or with placebo for 12 weeks. The patients were already receiving anti-rheumatic drug treatment. Laboratory and clinical measures of inflammation were not influenced by the treatment. However, the pain measures; including pain in the morning, pain in the evening, and pain after chosen activity; were significantly decreased after vitamin E treatment when compared with placebo.

Asthma
Antioxidants may help asthmatics. According to researchers at the University of Washington, antioxidant vitamin supplements may help relieve the symptoms of asthma. The researchers measured the amount of breath expelled by the lungs in 17 asthma sufferers. The subjects took peak flow lung function tests while running on a treadmill and breathing in high levels of polluted air. In those asthmatics whose diets were supplemented with daily doses of 268 mg (400 IU) and 500 mg of vitamin C, an 18 per cent increase in peak flow capacity was seen.

Alzheimer's disease
Vitamin E may slow the progression of Alzheimer's disease. Researchers at Columbia University have found that treatment with vitamin E slows the progression of Alzheimer's disease symptoms. In a study reported in 1997 in the New England Journal of Medicine, patients were treated with 1340 mg (2000 IU) daily, 10 mg of selegiline daily, a combination of the two, or a placebo for two years. The patients were monitored every three months by the researchers who looked for signs such as the loss of ability to perform basic activities, institutionalization or severe dementia. Researchers found that all the treatment groups had delayed rate of loss of function when compared with the placebo group.

Liver disorders
Vitamin E levels have been found to be low in patients with liver damage and supplements have been shown to protect against liver damage induced by oxidative stress in animal experiments. In a 1997 German study, researchers treated 23 hepatitis C patients with two 268 mg (400 IU) doses per day for 12 weeks. In 11 of 23 patients, the measurements in clinical tests to assess liver damage showed improvement during vitamin E treatment.

Hot flashes
In a study published in 1998, researchers at the Mayo Clinic in Minnesota looked at the effect of vitamin E on hot flashes in 104 women who had survived breast cancer. The women were experiencing at least two hot flashes per day. The study took nine weeks. In weeks two to five, the women took either vitamin E or a placebo and in weeks six to nine, they took the alternative pill. The results showed that in general, women taking vitamin E experienced approximately one less hot flash per day than women taking the placebo.

Skin protection
Vitamins E may help to protect against sunburn. In a study reported in 1998, dermatologists at Ludwig Maximilians University in Germany found that people who take the antioxidant vitamins C and E have a higher threshold for sunburn reaction. The researchers tested ultraviolet sensitivity in two groups of ten Caucasian people by exposing a section of skin to UV light. Subjects in one of the groups then took 2 g of vitamin C and 670 mg (1000 IU) for 8 days. The UV test was then re-done. Those taking the vitamins showed increased tolerance, particularly at higher UV doses. The researchers speculate that combined intake of both vitamins is necessary for protection. However, the researchers stress that in comparison with the protection afforded by topical sunscreens, this level of protection is small.

Exercise
A growing amount of evidence indicates that free radicals play an important role in causing skeletal muscle damage and inflammation after strenuous exercise. The generation of oxygen-free radicals may be increased during exercise as a result of increases in oxygen metabolism in the energy producing organelles of the cell - the mitochondria. These changes may lead to damage to cholesterol and DNA. Increased antioxidant activity can help to prevent this damage and some research suggests that antioxidant vitamin supplementation can be protective in people who regularly exercise heavily.

In a study published in 1998, Pennsylvania State University researchers investigated the effects of high intensity resistance exercise on free radical production and also whether vitamin E supplementation could affect free radical formation or muscle membrane disruption. They divided 12 weight-trained males into two groups. The supplement group received 804 mg (1200 IU) once a day for a period of two weeks and the other group received a placebo. The results showed that high intensity resistance exercise increased free radical production and that vitamin E supplementation decreased muscle membrane disruption.

Interactions with other nutrients
Vitamin E exerts antioxidant effects in combination with other antioxidants including beta carotene, vitamin C and selenium. Vitamin C can restore oxidized vitamin E to its natural antioxidant form. Megadoses of vitamin C may increase vitamin E requirements. Vitamin E can also protect against some of the effects of excessive vitamin A and regulates levels of that vitamin. Vitamin E is necessary for the action of vitamin A and high intake of vitamin A may decrease vitamin E absorption

Vitamin E may be necessary for the conversion of vitamin B12 to its active form and may reduce some of the symptoms of zinc deficiency. Large doses of vitamin E may interfere with the anticoagulant action of vitamin K and may reduce intestinal absorption of vitamin K. Inorganic iron destroys vitamin E, so the two supplements should not be taken together.

Interactions with drugs
Cholestyramine, mineral oil and alcohol may reduce the absorption of vitamin E from the intestine. Vitamin E can enhance the action of anticoagulant drugs on blood clotting and should not be taken in large doses. However, the results of a 1996 study in which 21 people taking chronic warfarin therapy received either vitamin E or placebo suggest that vitamin E can safely be given to patients who require chronic warfarin therapy.

Anticonvulsants such as phenobarbital, phenytoin and carbamazepine may lower plasma vitamin E levels by altering absorption, distribution and metabolism. Isoniazid also decreases vitamin E absorption. Neomycin impairs utilization of vitamin E.

Cautions
Vitamin E should be used cautiously by anyone with an overactive thyroid or rheumatic heart disease. Vitamin E in large doses may aggravate iron deficiency anemia. Vitamin E supplements can cause a transient rise in blood pressure and should be used with caution by anyone suffering from hypertension.