Vitamin E Overview

Vitamin E is an antioxidant that fights damaging natural substances known as free radicals. It works in lipids (fats and oils), which makes it complementary to vitamin C, which fights free radicals dissolved in water. As an antioxidant, vitamin E has been widely advocated for preventing heart disease and cancer. However, the results of large, well-designed trials have generally not been encouraging. Many other proposed benefits of vitamin E have also failed to stand up in studies. There are nomedicinal uses for vitamin E with solid scientific support.

Vitamin E dosage recommendations are a bit complex because the vitamin exists in many forms.

New vitamin E recommendations are in milligrams of alpha-tocopherol. Alpha-tocopherol can come from either natural vitamin E (called, somewhat incorrectly, d-alpha-tocopherol) or synthetic vitamin E (called, also somewhat incorrectly, dl-alpha-tocopherol). However, much of the alpha-tocopherol in synthetic vitamin E is inactive. For this reason, you have to take about twice as much of it to get the same effect. ^{1 2} There are other forms of vitamin E as well, such as beta-, delta-, and gamma-tocopherols, all of which occur in food. These other forms may be important; for example, preliminary evidence hints that gamma-tocopherol may be the most important (or, perhaps, the only) form of vitamin E for preventing prostate cancer. ³ On this basis, it has been suggested that the best vitamin E supplement would be a mixture of all these. ^{4 5} To make matters even more confusing, vitamin E dosages are commonly listed on labels as international units (IU). Here's how you make the conversion. One IU natural vitamin E equals 0.67 mg alpha-tocopherol; one IU synthetic vitamin E equals 0.45 mg alpha-tocopherol. Therefore, to meet the new dietary recommendations for vitamin E (15 mg per day), you need to get either 22 IU natural vitamin E (22 IU x 0.67 = 15 mg) or 33 IU synthetic vitamin E (33 IU x 0.45 = 15 mg). The official US and Canadian recommendations for daily intake of vitamin E are as follows:

• Infants

• 0-6 months: 4 mg

• 7-12 months: 5 mg

• Children

• 1-3 years: 6 mg

• 4-8 years: 7 mg

• 9-13 years: 11 mg

• Males and Females

• 14 years and older: 15 mg

• Pregnant Women: 15 mg

• Nursing Women: 19 mg

In developed countries, mild dietary deficiency of vitamin E is relatively common. ^{6 7} The best food sources of vitamin E are polyunsaturated vegetable oils, seeds, nuts, and whole grains. To get a therapeutic dosage, though, you need to take a supplement.

The optimal therapeutic dosage of vitamin E has not been established. Most studies have used between 50 IU and 800 IU daily, and some have used even higher doses. This would correspond to about 50 mg to 800 mg of synthetic vitamin E (dl-alpha-tocopherol), or 25 mg to 400 mg of natural vitamin E (d-alpha- or mixed tocopherols).

If you wish to purchase natural vitamin E, look for a label that says "mixed tocopherols." However, some manufacturers use this term to mean the synthetic dl-alpha-tocopherol, so you need to read the contents closely. Natural tocopherols come as d-alpha-, d-gamma-, d-delta-, and d-beta-tocopherol.

Cancer Prevention

The results of observational trials have been mixed, but on balance, they suggest that high intake of vitamin E and other antioxidants is associated with reduced risk of lung cancer and many other forms of cancer, including bladder, stomach, mouth, throat, laryngeal, liver, and prostate. ⁸ Based on these and other results, researchers developed the hypothesis that antioxidants can help prevent cancer and set in motion very large, long-term, double-blind, placebo-controlled studies to verify it. Unfortunately, these studies generally failed to find vitamin E helpful for the prevention of cancer in people at high risk for it. ⁹ The one positive note came in a double-blind trial of 29,133 smokers. ¹⁰ In this study, 50 mg of synthetic vitamin E (dl-alpha-tocopherol) daily for 5 to 8 years caused a 32% reduction in the incidence of prostate cancer and a 41% drop in prostate cancer deaths. ¹¹ Surprisingly, results were seen soon after the beginning of supplementation. This was unexpected because prostate cancer grows very slowly. A cancer that shows up today actually started to develop many years ago. The fact that vitamin E almost immediately lowered the incidence of prostate cancer suggests that it somehow blocks the step at which a hidden prostate cancer makes the leap to being detectable.

Nonetheless, the negative results regarding most other types of cancer have made scientists hesitant to place too much hope in these findings. It has been suggested that alpha-tocopherol alone is less effective than the multiple forms of tocopherol that occur in nature; in particular, it has been suggested that gamma-tocopherol rather than alpha-tocopherol might be the most relevant form of vitamin E for cancer prevention. ¹² Interestingly, use of alpha-tocopherol supplements may deplete both gamma- and delta-tocopherol levels, potentially producing a negative effect. ¹³ However, gamma-tocopherol has not yet been tested in meaningful controlled trials, and it is quite possible that were one to be performed, the results would prove as disappointing as those for other forms of vitamin E.

In addition, under certain circumstances, vitamin E may have a pro-oxidant effect—the reverse of what is desired. ¹⁴

Cardiovascular Disease

Most but not all observational studies have found associations between high intake of vitamin E and reduced risk of cardiovascular disease ( heart disease and strokes ). ¹⁵ However, as we’ve explained, observational studies by themselves cannot be relied upon to identify useful treatments. Double-blind studies, which provide much more convincing evidence of effectiveness, have generally failed to find vitamin E supplements effective.

The Heart Outcomes Prevention Evaluation (HOPE) trial found that natural vitamin E (d-alpha-tocopherol) at a dose of 400 IU daily did not reduce the number of heart attacks, strokes, or deaths from heart disease any more than placebo. ¹⁶ The trial followed more than 9,000 men and women who had existing heart disease or were at high risk for it.

Negative results were seen in numerous other large trials, as well. ¹⁷ When the results of these studies began to come in, some antioxidant proponents suggested that the people enrolled in these trials already had disease too advanced for vitamin E to help. However, a subsequent large trial found vitamin E ineffective for slowing the progression of heart disease in healthy people as well. ¹⁸ Moreover, in an extremely large placebo-controlled trial involving over 14,000 US male physicians at low risk for heart disease, 400 IU of vitamin E every other day failed to lower the risk of major cardiovascular events or mortality over a period of 8 years. ¹⁹ On the contrary, vitamin E was associated with a slightly increased risk of stroke.

As with preventing cancer, critics have suggested that the form of vitamin E used in these studies (alpha-tocopherol) was not the best choice, and that gamma-tocopherol might be more helpful. ²⁰ Gamma-tocopherol is present in the diet much more abundantly than alpha-tocopherol, and it could be that the studies showing benefits with dietary vitamin E actually tracked the influence of gamma-tocopherol. However, an observational study specifically looking to see if gamma-tocopherol levels were associated with risk of heart attack found no relationship between the two. ²¹ Nonetheless, intervention trials of gamma-tocopherol are currently underway.

In addition, as noted above, under certain circumstances, vitamin E may have a pro-oxidant effect, and this could explain the negative outcomes. ²² Interestingly, one study found that vitamin E might help prevent serious cardiovascular events in patients with diabetes who also have a particular genetic marker known as “Hp 2.” ²³ It has been hypothesized that people with the Hp 2 gene have an inadequate endogenous (“built-in”) antioxidant defense system, and for this reason, they might be particularly benefited by taking antioxidant supplements such as vitamin E. However, this concept still remains highly preliminary.

Preeclampsia Prevention

Preeclampsia is a dangerous complication of pregnancy that involves high blood pressure, swelling of the whole body, and improper kidney function. A double-blind, placebo-controlled study of 283 women at increased risk for preeclampsia found that supplementation with vitamin E (400 IU daily of natural vitamin E) and vitamin C (1,000 mg daily) significantly reduced the chances of developing this disease. ²⁴ While this research is promising, larger studies are necessary to confirm whether vitamins E and C will actually work. The authors of this study point out that studies of similar size found benefits with other treatments, such as aspirin, that later proved to be ineffective when large-scale studies were performed. Furthermore, keep in mind that we don't know whether such high dosages of these vitamins are absolutely safe for pregnant women.

Tardive Dyskinesia

Between 1987 and 1998, at least five double-blind studies were published that indicated vitamin E was beneficial in treating tardive dyskinesia (TD). ²⁵ Although most of these studies were small and lasted only 4 to 12 weeks, one 36-week study enrolled 40 individuals. ²⁶ Three small double-blind studies reported that vitamin E was not helpful. ²⁷ Nonetheless, a statistical analysis of the double-blind studies done before 1999 found good evidence that vitamin E was more effective than placebo. ²⁸ Most studies found that vitamin E worked best for TD of more recent onset. ²⁹ However, in 1999, the picture on vitamin E changed with the publication of one more study—the largest and longest to date. ³⁰ This double-blind study included 107 participants from nine different research sites who took 1,600 IU of vitamin E or placebo daily for at least 1 year. In contrast to most of the previous studies, this trial did not find vitamin E effective in decreasing TD symptoms.

Why the discrepancy between this study and the earlier ones? The researchers, some of whom had worked on the earlier, positive studies of vitamin E, were at pains to develop an answer. ³¹ They proposed a number of possible explanations. One was that the earlier studies were too small or too short to be accurate, and that vitamin E really didn't help at all. Another was the most complicated: that vitamin E might help only a subgroup of people who have TD—those with milder TD symptoms of more recent onset—and that fewer of these people had participated in the latest study. They also pointed to changes in schizophrenia treatment since the last study was done, including the growing use of antipsychotic medications that do not cause TD.

The bottom line:The effectiveness of vitamin E for a given individual is simply not known. Given the lack of other good treatments for TD and the general safety of the vitamin, it may be worth discussing with your physician.

Immune Support

Seniors often do not respond adequately to vaccinations. One double-blind study suggests that vitamin E may be able to strengthen the immune response to vaccines. In this trial, 88 people over the age of 65 were given either placebo or vitamin E at 60 IU, 200 IU, or 800 IU dl-alpha-tocopherol daily. ³² The researchers then gave all participants immunizations against hepatitis B, tetanus, diphtheria, and pneumonia, and looked at subjects' immune response to these vaccinations. The researchers also used a skin test that evaluates the overall strength of the immune response.

The results were promising. Vitamin E at 200 mg per day and, to a lesser extent, at 800 mg per day significantly increased the strength of the immune response.

However, it is not clear whether vitamin E has a general “immune support” effect. One study in seniors found that use of vitamin E did not help prevent colds and other respiratory infections, and, in fact, seemed to slightly increase the severity of infections that did occur. ³³ In a similar-sized double-blind study of long-term care residents, use of vitamin E at 200 IU daily failed to reduce incidence or number of days of respiratory infection or antibiotic use. ³⁴ The researchers managed to find some evidence of benefit by breaking down the respiratory infections by type, but such after-the-fact analysis is questionable from a statistical perspective. Subsequently, the same researchers repeated the study with a larger group and did find a reduction in frequency of colds. ³⁵ Another researcher found evidence that vitamin E can have either a harmful or a helpful effect depending on who takes it (the exact differences being as yet undefined). ³⁶

Alzheimer's Disease

Evidence is conflicting regarding whether high-dose vitamin E can slow the progression of Alzheimer's disease . ³⁷ In a double-blind, placebo-controlled study, 341 people with Alzheimer's disease received either 2,000 IU daily of vitamin E (dl-alpha-tocopherol), the antioxidant drug selegiline, or placebo. Those given vitamin E took nearly 200 days longer to reach a severe state of the disease than the placebo group. (Selegiline was even more effective.)

However, negative results were seen in a study of 769 people at high risk of developing Alzheimer's disease based on early symptoms. ³⁸ Participants were given either 2,000 IU of vitamin E, the drug donepezil, or placebo for 3 years. Neither treatment reduced the percentage of people who went on to develop Alzheimer's disease.

Warning:Such high dosages of vitamin E should not be taken except under a doctor's supervision. (See Safety Issues .)

Dysmenorrhea (Menstrual Pain)

In a double-blind, placebo-controlled trial, 100 young women complaining of significant menstrual pain were given either 500 IU of vitamin E or placebo for 5 days. ³⁹ Treatment began 2 days before and continued for 3 days after the expected onset of menstruation. While both groups showed significant improvement in pain over the 2 months of the study (presumably due to the power of placebo), pain reduction was greater in the treatment group as compared to the placebo group.

Benefits were also seen in an Iranian, 4-month, double-blind, placebo-controlled study of 278 adolescent girls. ⁴⁰ The dose used in this study was 200 IU twice daily.

Low Sperm Count/Infertility

In a double-blind, placebo-controlled study of 110 men whose sperm showed subnormal activity, treatment with 100 IU of vitamin E daily resulted in improved sperm activity and higher actual fertility (measured in pregnancies). ⁴¹ However, a smaller double-blind trial found no benefit. ⁴²

Cardiac Autonomic Neuropathy

People with diabetes sometimes develop irregularities of their heart-beat called cardiac autonomic neuropathy . A 4-month, double-blind, placebo-controlled trial found that vitamin E at a dose of 600 mg daily might improve these symptoms. ⁴³

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