Health Information

Vitamin E

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Principal Proposed UsesOther Proposed UsesProbably Not Effective Uses


Supplement Forms/Alternate Names

  • Alpha Tocopherol
  • D-Tocopherol
  • DL-Tocopherol
  • DL-Alpha-Tocopherol
  • Tocopheryl Succinate
  • Tocopheryl Acetate
  • D-Alpha-Tocopherol
  • D-Delta-Tocopherol
  • D-Beta-Tocopherol
  • D-Gamma-Tocopherol
  • Mixed Tocopherols
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 no medicinal uses for vitamin E with solid scientific support.

Requirements/Sources

Requirements

Vitamin E dosage recommendations are a bit complex because the vitamin exists in many forms.
Newer 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. 1-3
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. 4,211 On this basis, it has been suggested that the best vitamin E supplement would be a mixture of all these. 5-7
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

Sources

The best food sources of vitamin E are polyunsaturated vegetable oils, seeds, and nuts. To get a therapeutic dosage, though, you need to take a supplement. The National Institutes of Health's Office of Dietary Supplements offers this list of foods that are high in vitamin E:239
Food Serving size Vitamin E content
(milligrams [mg]) 		% Daily Value
Wheat germ 1 tablespoon 20.3 100
Sunflower seeds, dry roasted 1 ounce 7.4 37
Almonds, dry roasted 1 ounce 6.8 34
Sunflower oil 1 tablespoon 5.6 28
Safflower oil 1 tablespoon 4.6 25
Hazelnuts, dry roasted 1 ounce 4.3 22
Peanut butter 2 tablespoons 2.9 15
Peanuts, dry roasted 1 ounce 2.2 11
Corn oil 1 tablespoon 1.9 10
Olive oil 1 tablespoon 1.9 10
Spinach, boiled ½ cup 1.9 10
Broccoli, boiled ½ cup 1.2 6
Soybean oil ½ cup 1.1 6
Kiwifruit 1 medium 1.1 6
Mango ½ cup 0.7 4
Tomato, raw 1 medium 0.7 4
Spinach, raw 1 cup 0.6 3

Vitamin E Deficiency

In developed countries, mild dietary deficiency of vitamin E is relatively common. 8-10

Therapeutic Dosages

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.

Therapeutic Uses

Observational studies raised hopes that vitamin E supplements could help prevent various forms of cancer as well as heart disease . 82-84,86,104-107,144,145 However, observational studies are notoriously unreliable for determining the effectiveness of treatments. Only double-blind trials can do that (for information why, see Why Does This Database Rely on Double-blind Studies? ), and such studies have, on balance, found vitamin E ineffective for preventing heart disease or any common form of cancer other than, possibly, prostate cancer. 75-78,81,96-102,146,155,157-159,180-182,201,225,226,229,230,232-235 . In fact, use of high-dose vitamin E for a long period might slightly increase death rate. 177,210,235
Other potential uses of vitamin E have limited supporting evidence. Intriguing but far from definitive studies suggest that vitamin E might improve immune response to vaccinations, 42 control symptoms of restless legs syndrome , 59 help prevent deep venous thrombosis (DVTs) , 213 reduce symptoms of premenstrual syndrome (PMS) , 61,62 and decrease symptoms of menstrual pain . 139,183 Vitamin E, combined with evening primrose , has also been studied as a way to alleviate premenstrual breast pain (mastalgia 222 But, more research needs to be done in this area.
While there is weak evidence that vitamin E supplements can reduce discomfort in rheumatoid arthritis, 44,45,147-149 there is strong evidence that it does not prevent it. 219
Although preliminary studies hinted that use of vitamin E might prevent or slow the progression of cataracts , 51-54 in a 10-year study of almost 40,000 female healthcare professionals, use of natural vitamin E at a dose of 600 mg every other day failed to have any effect on cataract development. 216 And another large, 8-year trial involving 11,545 physicians aged 50 years and older concluded that vitamins C (500 mg daily) and E (400 IU every other day), alone or in combination, did not lower the risk of developing cataracts. 224
Evidence regarding whether vitamin E can slow the progression of Alzheimer's disease is inconsistent. 43,184,236 A very large study failed to find vitamin E helpful for preventing mental decline (resulting from any cause) in women over 65. 209
Studies of vitamin E in combination with vitamin C for prevention of preeclampsia (high blood pressure during pregnancy) have yielded inconsistent results. 41,185-186 Also, a combination of vitamins E and C does not seem to reduce the risk of preterm birth. 228
Vitamin E has also shown equivocal promise in diabetes. One double-blind trial found benefits for cardiac autonomic neuropathy , 40 a complication of diabetes. Weaker evidence hints at possible benefits for diabetic peripheral neuropathy . 46,47 However, the best-designed study of all, a long-term trial involving 3,654 people with diabetes, found that use of vitamin E did not protect against diabetes-induced kidney or heart damage. 157 Similarly, while a few studies performed by one research group suggested that vitamin E might be helpful for improving glucose control in people with diabetes, 55-57 subsequent evidence found that the benefits, if they exist at all, are limited to the short-term. 169,187 In addition, in an extremely large double-blind study, use of vitamin E at a dose of 600 IU every other day failed to reduce risk of participants developing type 2 diabetes. 202 Finally, a study unexpectedly found that when people with diabetes took 500 mg of vitamin E daily (either as natural alpha tocopherol or a mixture of alpha and gamma tocopherol), their blood pressure increased . 208
Similarly, studies on whether vitamin E is helpful for allergic rhinitis (hay fever) have produced conflicting results. 168,193
A small double-blind study conducted in Iran reported that vitamin E (400 IU daily) was more effective than placebo for treating menopausal hot flashes . 212 However, a larger US study failed to find vitamin E significantly helpful for hot flashes associated with breast cancer treatment. 74
Vitamin E might help reduce the lung-related side effects caused by the drug amiodarone (used to prevent abnormal heart rhythms). 66
A trial of 108 patients undergoing chemotherapy cisplatin found that vitamin E supplementation (extended 3 months past chemotherapy) reduced cisplatin-related neurotoxicity (damage to nerves not uncommonly occurring with cisplatin). 221
Studies have yielded mixed results on whether vitamin E is helpful for controlling seizures in people with epilepsy , 160-163 reducing symptoms of tardive dyskinesia , 29-33 aiding recovery during heavy exercise , 63,64,65,170 and treating male infertility . 49,50
When combined with vitamin C , vitamin E may protect against sunburn to a small extent. 34-38 The same combination has also shown promise for acute anterior uveitis . 39 A separate study failed to find vitamin E alone (at the high dose of 1,600 mg daily) helpful for macular edema (swelling of the center of the retina) associated with uveitis. 188
Vitamin E has been tried for amyotrophic lateral sclerosis (Lou Gehrig's disease), but the results in the first reported double-blind study showed questionable benefits if any. 137 Some vitamin E proponents felt that the dose of vitamin E used in this study might have been too low. Accordingly, they conducted another study using 10 times the dose, this one lasting 18 months and enrolling 160 people. 171 Once again, vitamin E failed to prove significantly more effective than placebo.
In one observational study, high intake of vitamin E was linked to decreased risk of progression to AIDS in people with HIV infection. 67 However, a double-blind study of 49 people with HIV who took combined vitamins C and E or placebo for 3 months did not show any significant effects on the amount of HIV virus detected or the number of opportunistic infections. 68 It has been suggested that vitamin E may enhance the antiviral effects of AZT, but evidence for this is minimal. 69
Vitamin E has been suggested for preventing the cardiac toxicity caused by the drug doxorubicin . However, while it has shown promise in animal studies, when studied in people vitamin E has persistently failed to prove effective for this purpose. 204-207
Vitamin E is sometimes recommended for osteoarthritis . However, a 2-year, double-blind, placebo-controlled study of 136 people with osteoarthritis of the knee failed to find any benefit in terms of symptom control or slowing disease progression. 164 A previous 6-month, double-blind, placebo-controlled trial of 77 individuals with osteoarthritis also failed to find benefit. 138
A 4-year, double-blind, placebo-controlled trial of 1,193 people with macular degeneration failed to find vitamin E alone helpful for preventing or treating macular degeneration. 165 In addition, a review of 3 randomized, placebo-controlled trials, which included 23,099 people, did not find evidence to support the use of vitamin E and beta carotene to delay the onset of this common condition. 237
Vitamin E has also so far failed to prove helpful for preventing or treating alcoholic hepatitis , 173asthma , 172congestive heart failure , 80fibrocystic breast disease , 70 or Parkinson's disease . 71-73
In a very large study involving over 29,000 male smokers, researchers failed to find benefit of alpha-tocopherol (50 IU/day), beta-carotene (20 mg/day), or the two taken together for the prevention of type 2 diabetes over 5-8 year period. 214 As part of another large study, researchers focused on whether supplementation with vitamin E (in the form of alpha-tocopherol) or beta-carotene could reduce diabetes complications (coronary artery disease) in 1,700 male smokers. 227 At the 19-year follow-up, neither of the supplements offered any protective benefits.

What Is the Scientific Evidence for Vitamin E?

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. 83-95,144,145,166,218 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. 14,146,158,159,189-190,225,226,229,230,232-235
An analysis that included 9 carefully designed clinical trials found that antioxidant supplementation ( beta carotene , selenium , and vitamin E) was not effective in reducing the incidence of cancer or cancer deaths. 225 Another analysis focused on whether vitamin E could reduce the risk of developing colorectal cancer. 226 The Women’s Antioxidant Cardiovascular Study, a double-blind, placebo-controlled trial involving 8,171 women, also did not find evidence to support the use of antioxidants (vitamin C, vitamin E, and beta carotene) to reduce the risk of cancer. 232
Researchers analyzed 4 trials involving 94,069 people aged 40 and older who were randomized to receive vitamin E or placebo. At the 7-10 year follow-up period, it did not appear that vitamin E had an effect on the incidence of colorectal cancer. And, in an analysis of 20 randomized trials, researchers concluded that antioxidants (beta-carotene, selenium, and vitamins A, C, and E) do not prevent gastrointestinal cancer. 235 In some studies, the antioxidants appeared to increase overall mortality rates.
On the brighter side, a double-blind trial of 29,133 smokers does offer some positive news. 25 In this study, 50 mg of synthetic vitamin E daily for 5-8 years caused a 32% reduction in the incidence of prostate cancer and a 41% drop in prostate cancer deaths. 81 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.
Other studies, however, have not been so supportive. For example, researchers reviewed data from the Prostate Cancer Prevention Trial, which included 9,559 men, to find out if certain nutritional supplements had any effect on cancer occurrence. 229 They concluded that none of the supplements (vitamin E, vitamin D , lycopene , omega-3 fatty acids) reduced the risk of prostate cancer.
Similarly, an analysis of 9 randomized controlled trials involving 165,056 subjects found that the supplements beta-carotene, vitamin C , vitamin E, and selenium did not reduce the number of men who developed prostate cancer or who died from the condition. 230 Along the same line, a trial that included 35,533 men found that neither selenium nor vitamin E (either alone or in combination) prevented prostate cancer. 233 And, as part of the Physician's Health Study, researchers examined what effect vitamin E (400 IU every other day) and vitamin C (500 mg daily) may have on the development of cancer. 234 Again, the results showed that neither of these vitamins reduced the risk of cancer (including prostate cancer) in the 14,641 male physicians (aged 50 years and older) who participated in the study.
If vitamin E does have any effect on preventing certain forms of cancer, it has been suggested that gamma-tocopherol rather than alpha-tocopherol might be the most relevant form for this purpose. 211 Interestingly, use of alpha-tocopherol supplements may deplete both gamma- and delta-tocopherol levels, potentially producing a negative effect. 174 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. 203

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 ). 104-107,150,151 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. 96 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. 99-102,129,152,153,157,175,194-195,223
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. 155 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. 220 On the contrary, vitamin E was associated with a slightly increased risk of stroke.
Along the same line, a large systematic review that included 9 randomized trials and 118,765 people found that vitamin E may increase the risk of a type of stroke called hemorrhagic 223 . This stroke occurs when a blood vessel breaks and bleeds into or around the brain. The review also found that vitamin E may reduce the risk of ischemic stroke (when blood flow to the brain is blocked). Since hemorrhagic stroke can lead to more serious complications, the researchers recommended against widespread use of this vitamin.
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. 140-142,154 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. 143 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. 203
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.” 215 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.

Prevention of Complications During Pregnancy

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. 112 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.
Vitamins E and C have also been studied for their potential benefits in reducing the risk of preterm birth. 228 In a review of data from a trial involving 9,968 pregnant women, those that took vitamin E (400 IU daily) and vitamin C (1,000 mg daily) from 9-16 weeks gestation to their delivery day did not experience a reduction of preterm births compared to the women in the placebo group.

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). 113,114 Although most of these studies were small and lasted only 4 to 12 weeks, one 36-week study enrolled 40 individuals. 115 Three small double-blind studies reported that vitamin E was not helpful. 116,117 Nonetheless, a statistical analysis of the double-blind studies done before 1999 found good evidence that vitamin E was more effective than placebo. 118 Most studies found that vitamin E worked best for TD of more recent onset. 119
However, in 1999, the picture on vitamin E changed with the publication of one more study—the largest and longest to date. 120 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. 121,122 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. 123 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. 156 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. 176 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. 191 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). 200

Alzheimer's Disease

Evidence is conflicting regarding whether high-dose vitamin E can slow the progression of Alzheimer's disease . 124,236
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.)
In another promising trial, researchers studied the potential cognitive benefits of taking vitamins E and C along with nonsteroidal anti-inflammatory drugs (NSAIDs). 236 Over a period of 8 years, 3,376 elderly people participated in the trial by filling out mental status questionnaires. Those that took the vitamins and NSAIDs dropped fewer points on their mental status scores compared to the control group during that period. The researchers also found that the people with a particular gene variant that has been linked to Alzheimer’s disease seemed to benefit the most from the treatment, suggesting that the vitamin supplements and the NSAIDs may be especially helpful in slowing the rate of cognitive decline in this group.
Negative results were seen, though, in a study of 769 people at high risk of developing Alzheimer's disease based on early symptoms. 192 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. 139 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. 196 The dose used in this study was 200 IU twice daily.

Mastalgia (Breast Pain)

Eight-five women with premenstrual mastalgia were randomized to receive 1 of 4 treatments for 6 months: vitamin E (1,200 IU) and placebo, evening primrose (3,000 mg) and placebo, vitamin E and evening primrose, or placebo alone. In this small study, none of the treatment groups experienced better results than the placebo group. 222

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). 125 However, a smaller double-blind trial found no benefit. 126 

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. 127

Safety Issues

The adult safe upper intake level (UL) for vitamin E is set at 1,000 mg daily. 128 The equivalent amounts are 1,500 IU of natural vitamin E and 1,100 IU of synthetic vitamin E. (For technical reasons, the conversion factor is a bit different than in the daily intake recommendations above.) For pregnant women under 19 years of age, the upper limit is 800 mg.

Blood-thinning Effect

Vitamin E has a blood-thinning effect that could lead to problems in certain situations. In one study of 28,519 men, vitamin E supplementation at the low dose of about 50 IU synthetic vitamin E per day caused an increase in fatal hemorrhagic strokes, the kind of stroke caused by bleeding. 129 (However, it reduced the risk of a more common type of stroke, 130 and the two effects essentially canceled out.)
Based on its blood-thinning effects, there are concerns that vitamin E could cause problems if it is combined with medications that also thin the blood, such as warfarin (Coumadin), heparin, clopidogrel (Plavix), ticlopidine (Ticlid), pentoxifylline (Trental), and aspirin. Theoretically, the net result could be to thin the blood too much, causing bleeding problems. A study that evaluated vitamin E plus aspirin did in fact find an additive effect. 131 In contrast, the results of a study on vitamin E and Coumadin found no evidence of interaction, but it would still not be advisable to combine these treatments except under a physician's supervision. 132
There is also at least a remote possibility that vitamin E could also interact with supplements that possess a mild blood-thinning effect, such as garlic , policosanol , and ginkgo . Individuals with bleeding disorders, such as hemophilia, and those about to undergo surgery or labor and delivery should also approach vitamin E with caution.

Diabetes

In addition, vitamin E might at least temporarily enhance the body's sensitivity to its own insulin in individuals with adult-onset diabetes. 133,134 This could lead to a risk of blood sugar levels falling too low. In addition, one study found that use of vitamin E can raise blood pressure in people with diabetes. 197
The bottom line: If you have diabetes, do not take high-dose vitamin E without first consulting your physician.

Smoking

The results of one large study involving 29,000 males indicate that vitamin E supplementation may increase risk of tuberculosis in heavy smokers. Curiously, however, this was only true in those participants who also consumed high levels of vitamin C (at least 90 mg/d) in their diet. Consuming high levels of vitamin C without supplemental vitamin E actually led to a reduction in tuberculosis risk. 217

Cancer Treatment

Considerable controversy exists regarding whether it is safe or appropriate to combine vitamin E with standard chemotherapy drugs. 135,178 The reasoning behind this concern is that some chemotherapy drugs may work in part by creating free radicals that destroy cancer cells. Antioxidants like vitamin E might interfere with this beneficial effect. However, there is no good evidence that antioxidants actually interfere with chemotherapy drugs, growing evidence that they do not, and some evidence of potential benefit under certain circumstances. 136,167,179,198 Nonetheless, in view of the high stakes involved, we strongly recommend that you do not take any supplements while undergoing cancer chemotherapy, except on the advice of a physician.
One study appeared to find evidence that use of vitamin E plus beta-carotene may impair the effectiveness of radiation therapy for head and neck cancers. 199

Congential Heart Defects

One trial compared 276 mothers with children who were born with congenital heart defects (CHD) with 324 mothers whose children did not have defects. 231 Based on food frequency questionnaires, mothers who had a high intake of vitamin E were more likely to have children with CHD. However, since studies of this design are notoriously misleading, it is not possible to draw any reliable conclusions about the risk of consuming foods rich in vitamin E during pregnancy.

Mortality

When all major vitamin E studies are statistically combined through a process called “meta-analysis,” some evidence appears suggesting that long-term usage of vitamin E at high doses might increase overall death rate for reasons that are unclear. 177,210

Interactions You Should Know About

  • Seek medical advice before taking vitamin E if you are taking blood thinning drugs, such as:
  • Vitamin E may help protect you from lung-related side effects if you are taking amiodarone .
  • Vitamin E may help reduce side effects if you are taking phenothiazine drugs .
  • Seek medical advice before taking vitamin E if you are taking chemotherapy drugs.
  • High-dose vitamin E might cause your blood sugar levels to fall too low, requiring an adjustment in medication dosage, if you are taking oral hypoglycemic medications .

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17 Macready N. Vitamins associated with lower colon-cancer risk. Lancet. 1997;350:9089.

18 Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996;64:190-196.

19 Bostick RM, Potter JD, McKenzie DR, et al. Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. Cancer Res. 1993;53:4230-4237.

20 Ocke MC, Bueno-de-Mesquita H, Feskens EJ, et al. Repeated measurements of vegetables, fruits, beta-carotene, and vitamins C and E in relation to lung cancer. The Zutphen Study. Am J Epidemiol. 1997;145:358-365.

21 Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. 1998;129:517-524.

22 Malila N, Virtamo J, Virtanen M, et al. The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Cancer Epidemiol Biomarkers Prev. 1999;8:489-493.

23 Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996;334:1145-1149.

24 Greenberg ER, Baron JA, Tosteson TD, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med. 1994;331:141-147.

25 Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998;90:440-446.

26 Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta-carotene on the incidence of angina pectoris. JAMA. 1996;275:693-698.

27 Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:154-160.

28 Collaborative Group of the Primary Prevention Project (PPP). Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet. 2001;357:89-95.

29 Adler LA, Edson R, Lavori P, et al. Long-term treatment effects of vitamin E for tardive dyskinesia. Biol Psychiatry. 1998;43:868-872.

30 Lohr JB, Caligiuri MP. A double-blind placebo-controlled study of vitamin E treatment of tardive dyskinesia. J Clin Psychiatry. 1996;57:167-173.

31 Rotrosen J, Adler L, Lohr J, et al. Antioxidant treatment of tardive dyskinesia. Prostaglandins Leukot Essent Fatty Acids. 1996;55:77-81.

32 Adler LA, Peselow E, Rotrosen J, et al. Vitamin E treatment of tardive dyskinesia. Am J Psychiatry. 1993;150:1405-1407.

33 Sajjad SH. Vitamin E in the treatment of tardive dyskinesia: a preliminary study over 7 months at different doses. Int Clin Psychopharmacol. 1998;13:147-155.

34 Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by d-alpha-tocopherol and l-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med. 1998;25:1006-1012.

35 Eberlein-Konig B, Placzek M, and Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E). J Am Acad Dermatol. 1998;38:45-48.

36 Darr D, Dunston S, Faust H, et al. Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants. Acta Derm Venereol. 1996;76:264-268.

37 Trevithick JR, Shum DT, Redae S, et al. Reduction of sunburn damage to skin by topical application of vitamin E acetate following exposure to ultraviolet B radiation: effect of delaying application or of reducing concentration of vitamin E acetate applied. Scanning Microsc. 1993;7:1269-1281.

38 Trevithick JR, Xiong H, Lee S, et al. Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice. Arch Biochem Biophys. 1992;296:575-582.

39 van Rooij J, Schwartzenberg SGWS, Mulder PGH, et al. Oral vitamins C and E as additional treatment in patients with acute anterior uveitis: a randomised double masked study in 145 patients. Br J Ophthalmol. 1999;83:1277-1282.

40 Manzella D, Barbieri M, Ragno E, et al. Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes. Am J Clin Nutr. 2001;73:1052-1057.

41 Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet. 1999;354:810-816.

42 Meydani SN, Meydani M, Blumberg JB, et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997;277:1380-1386.

43 Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med. 1997;336:1216-1222.

44 Edmonds SE, Winyard PG, Guo R, et al. Putative analgesic activity of repeated oral doses of vitamin E in the treatment of rheumatoid arthritis. Results of a prospective placebo controlled double blind trial. Ann Rheum Dis. 1997;56:649-655.

45 Knekt P, Heliovaara M, Aho K, et al. Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis [abstract]. Epidemiology. 2000;11:402-405.

46 Tutuncu NB, Baraktar M, Varli K. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes. Diabetes Care. 1998;21:1915-1918.

47 Kahler W, Kuklinski B, Ruhlmann C, et al. Diabetes mellitus—a free radical-associated disease. Results of adjuvant antioxidant supplementation [in German; English abstract]. Z Gesamte Inn Med. 1993;48:223-232.

48 Bursell SE, Clermont AC, Aiello LP, et al. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care. 1999;22:1245-1251.

49 Suleiman SA, Ali ME, Zaki ZM, et al. Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl. 1996;17:530-537.

50 Rolf C, Cooper TG, Yeung CH, et al. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod. 1999;14:1028-1033.

51 Tavani A, Negri E, La Vecchia C. Food and nutrient intake and risk of cataract. Ann Epidemiol. 1996;6:41-46.

52 Leske MC, Chylack LT Jr, He Q, et al. Antioxidant vitamins and nuclear opacities: the longitudinal study of cataract. Ophthalmology. 1998;105:831-836.

53 Teikari JM, Rautalahti M, Haukka J, et al. Incidence of cataract operations in Finnish male smokers unaffected by alpha tocopherol or beta carotene supplements. J Epidemiol Community Health. 1998;52:468-472.

54 Seddon JM, Christen WG, Manson JE, et al. The use of vitamin supplements and the risk of cataract among US male physicians. Am J Public Health. 1994;84:788-792.

55 Paolisso G, D'Amore A, Galzerano D, et al. Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients. Diabetes Care. 1993;16:1433-1437.

56 Paolisso G, Di Maro G, Galzerano D, et al. Pharmacological doses of vitamin E and insulin action in elderly subjects. Am J Clin Nutr. 1994;59:1291-1296.

57 Paolisso G, D'Amore A, Giugliano D, et al. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr. 1993;57:650-656.

58 McAlindon TE, Jacques P, Zhang Y, et al. Do antioxidant micronutrients protect against the development and progression of knee osteoarthritis? Arthritis Rheum. 1996;39:648-656.

59 Ayres S, Mihan R. Restless legs syndrome: response to vitamin E. J Appl Nutr. 1973;25:8-15.

60 Masaki KH, Losonczy KG, Izmirlian G, et al. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000;54:1265-1272.

61 London RS, Murphy L, Kitlowski KE, et al. Efficacy of alpha-tocopherol in the treatment of the premenstrual syndrome. J Reprod Med. 1987;32:400-404.

62 London RS, Sundaram GS, Murphy L, et al. The effect of alpha-tocopherol on premenstrual symptomatology: a double-blind study. J Am Coll Nutr. 1983;2:115-122.

63 McBride JM, Kraemer WJ, Triplett-McBride T, et al. Effect of resistance exercise on free radical production. Med Sci Sports Exerc. 1998;30:67-72.

64 Craig BW. The effects of vitamin E supplementation on the oxidative and mechanical stresses associated with an acute bout of resistance training. Presented at: The Integrative Biology of Exercise; September 20-23, 2000; Portland, ME.

65 Buchman AL, Killip D, Ou C-N, et al. Short-term vitamin E supplementation before marathon running: a placebo-controlled trial. Nutrition. 1999;15:278-283.

66 Kachel DL, Moyer TP, Martin WJ II. Amiodarone-induced injury of human pulmonary artery endothelial cells: protection by alpha-tocopherol. J Pharmacol Exp Ther. 1990;254:1107-1112.

67 Abrams B, Duncan D, Hertz-Picciotto I. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. J Acquir Immune Defic Syndr. 1993;6:949-958.

68 Allard JP, Aghdassi E, Chau J, et al. Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects. AIDS. 1998;12:1653-1659.

69 Gogu SR, Beckman BS, Rangan SR, et al. Increased therapeutic efficacy of zidovudine in combination with vitamin E. Biochem Biophys Res Commun. 1989;165:401-407.

70 London RS, Sundaram GS, Murphy L, et al. The effect of vitamin E on mammary dysplasia: a double-blind study. Obstet Gynecol. 1985;65:104-106.

71 The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. New Engl J Med. 1993;97:176-183.

72 Kieburtz K, McDermott M, Como P, et al. The effect of deprenyl and tocopherol on cognitive performance in early untreated Parkinson's disease. Parkinson Study Group. Neurology. 1994;44:1756-1759.

73 Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP patients requiring levodopa. Ann Neurol. 1996;39:37-45.

74 Barton DL, Loprinzi CL, Quella SK, et al. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors. J Clin Oncol. 1998;16:495-500.

75 Tornwall ME, Virtamo J, Haukka JK, et al. The effect of alpha-tocopherol and beta-carotene supplementation on symptoms and progression of intermittent claudication in a controlled trial. Atherosclerosis. 1999;147:193-197.

76 Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998;90:440-446.

77 Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 1995;62(suppl):S1427-S1430.

78 Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta carotene on the incidence of angina pectoris. JAMA. 1996;275:693-698.

79 Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998;90:440-446.

80 Keith ME, Jeejeebhoy KN, Langer A, et al. A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure. Am J Clin Nutr. 2001;73:219-224.

81 Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 1998;90:440-446.

82 Helzlsouer KJ, Huang HY, Alberg AJ, et al. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst. 2000;92:2018-2023.

83 Zheng W, Sellers TA, Doyle TJ, et al. Retinol, antioxidant vitamins, and cancers of the upper digestive tract in a prospective cohort study of postmenopausal women. Am J Epidemiol. 1995;142:955-960.

84 Esteve J, Riboli E, Pequignot G, et al. Diet and cancers of the larynx and hypopharynx: the IARC multi-center study in southwestern Europe. Cancer Causes Control. 1996;7:240-252.

85 Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 1995;62(suppl):1427S-1430S.

86 Chen J, Geissler C, Parpia B, et al. Antioxidant status and cancer mortality in China. Int J Epidemiol. 1992;21:625-635.

87 White E, Shannon JS, Patterson RE. Relationship between vitamin and calcium supplement use and colon cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:769-774.

88 Macready N. Vitamins associated with lower colon-cancer risk. Lancet. 1997;350:1452.

89 Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996;64:190-196.

90 Bostick RM, Potter JD, McKenzie DR, et al. Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women's Health Study. Cancer Res. 1993;53:4230-4237.

91 Ocke MC, Bueno-de-Mesquita H, Feskens EJ, et al. Repeated measurements of vegetables, fruits, beta-carotene, and vitamins C and E in relation to lung cancer. The Zutphen Study. Am J Epidemiol. 1997;145:358-365.

92 Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. 1998;129:517-524.

93 Malila N, Virtamo J, Virtanen M, et al. The effect of alpha-tocopherol and beta-carotene supplementation on colorectal adenomas in middle-aged male smokers. Cancer Epidemiol Biomarkers Prev. 1999;8:489-493.

94 Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996;334:1145-1149.

95 Greenberg ER, Baron JA, Tosteson TD, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. Polyp Prevention Study Group. N Engl J Med. 1994;331:141-147.

96 Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:154-160.

97 Lonn EM, Yusuf S, Dzavik V, et al. Effects of Ramipril and vitamin E on atherosclerosis. The study to evaluate carotid ultrasound changes in patients treated with Ramipril and vitamin E (SECURE). Circulation. 2001;103:919-925.

98 Collaborative Group of the Primary Prevention Project (PPP). Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet. 2001;357:89-95.

99 Rapola JM, Virtamo J, Ripatti S, et al. Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infraction. Lancet. 1997;349:1715-1720.

100 Rapola JM, Virtamo J, Haukka JK, et al. Effect of vitamin E and beta carotene on the incidence of angina pectoris. A randomized, double-blind, controlled trial. JAMA. 1996;275:693-698.

101 Albanes D, Heinonen OP, Huttunen JK, et al. Effects of alpha-tocopherol and beta-carotene supplements on cancer incidence in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 1995;62(suppl):1427S-1430S.

102 Tornwall ME, Virtamo J, Haukka JK, et al. Alpha-tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial. Atherosclerosis. 2001;157:167-173.

103 Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study. Lancet. 1996;347:781-786.

104 Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328:1450-1456.

105 Manson JE, Stampfer MJ, Willitt WC, et al. A prospective study of antioxidant vitamins and incidence of coronary heart disease in women [abstract]. J Am Coll Nutr. 1992;11:609.

106 Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328:1444-1449.

107 Bazzano LA, He J, Ogden LG, et al. Dietary vitamin E intake and risk of coronary heart disease in a representative sample of US adults: NHANES I Epidemiologic Follow-up Study [abstract]. Circulation. 2001;103:1366.

108 Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996;64:190-196.

109 Meagher EA, Barry OP, Lawson JA, et al. Effects of vitamin E on lipid peroxidation in healthy persons. JAMA. 2001;285:1178-1182.

110 Christen S, Woodall AA, Shigenaga MK, et al. Gamma-tocopherol traps mutagenic electrophiles such as NO(X) and complements alpha-tocopherol: physiological implications. Proc Natl Acad Sci USA. 1997;94:3217-3222.

111 Rimm EB, Ascherio A, Giovannucci E, et al. A prospective study of vitamin E and coronary heart disease among men: is benefit restricted only to primary prevention [abstract]. Circulation. 2001;103:1347.

112 Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet. 1999;354:810-816.

113 Elkashef AM, Wyatt RJ. Tardive dyskinesia: possible involvement of free radicals and treatment with vitamin E. Schizophr Bull. 1999;25:731-740.

114 Adler LA, Edson R, Lavori P, et al. Long-term treatment effects of vitamin E for tardive dyskinesia. Biol Psychiatry. 1998;43:868-872.

115 Adler LA, Edson R, Lavori P, et al. Long-term treatment effects of vitamin E for tardive dyskinesia. Biol Psychiatry. 1998;43:868-872.

116 Elkashef AM, Wyatt RJ. Tardive dyskinesia: possible involvement of free radicals and treatment with vitamin E. Schizophr Bull. 1999;25:731-740.

117 Shriqui CL, Bradwejn J, Annable L, et al. Vitamin E in the treatment of tardive dyskinesia: a double-blind placebo-controlled study. Am J Psychiatry. 1992;149:391-393.

118 Soares, KV, BcGrath JJ. The treatment of tardive dyskinesia—a systematic review and meta-analysis. Schizophr Res. 1999;39:1-16.

119 Rotrosen, J, Adler L, Lohr J, et al. Antioxidant treatment of tardive dyskinesia. Prostaglandins Leukot Essent Fatty Acids. 1996;55:77-81.

120 Adler LA, Rotrosen J, Edson R, et al. Vitamin E treatment for tardive dyskinesia. Arch Gen Psychiatry. 1999;56:836-841.

121 Adler LA, Rotrosen J, Edson R, et al. Vitamin E treatment for tardive dyskinesia. Arch Gen Psychiatry. 1999;56:836-841.

122 Lohr JB, Lavori P. Whither vitamin E and tardive dyskinesia? [editorial] Biol Psychiatry. 1998;43:861-862.

123 Meydani SN, Meydani M, Blumberg JB, et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997;277:1380-1386.

124 Sano M, Ernesto C, Thomas RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med. 1997;336:1216-1222.

125 Suleiman SA, Ali ME, Zaki ZM, et al. Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl. 1996;17:530-537.

126 Rolf C, Cooper TG, Yeung CH, et al. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod. 1999;14:1028-1033.

127 Manzella D, Barbieri M, Ragno E, et al. Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes. Am J Clin Nutr. 2001;73:1052-1057.

128 Dietary reference intakes (DRIs) for vitamins C and E, selenium and carotenoids. National Academies website. Available at: http://www4.nationalacademies.org/IOM/IOMHome.nsf/Pages/Food+and+Nutrition+Board . Accessed January 16, 2001.

129 Leppala JM, Virtamo J, Fogelholm R, et al. Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers. Arterioscler Thromb Vasc Biol. 2000;20:230-235.

130 Leppala JM, Virtamo J, Fogelholm R, et al. Vitamin E and beta carotene supplementation in high risk for stroke. A subgroup analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Arch Neurol. 2000;57:1503-1509.

131 Liede KE, Haukka JK, Saxen LM, et al. Increased tendency towards gingival bleeding caused by joint effect of alpha-tocopherol supplementation and acetylsalicylic acid. Ann Med. 1998;30:542-546.

132 Kim JM, White RH. Effect of vitamin E on the anticoagulant response to warfarin. Am J Cardiol. 1996;77:545-546.

133 Paolisso G, D'Amore A, Giugliano D, et al. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr. 1993;57:650-656.

134 Paolisso G, D'Amore A, Galzerano D, et al. Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients. Diabetes Care. 1993;16:1433-1437.

135 Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology. 1999;13:1003-1012.

136 Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat Rev. 1997;23:209-240.

137 Desnuelle C, Dib M, Garrel C, et al. A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Amyotroph Lateral Scler Other Motor Neuron Disord. 2001;2:9-18.

138 Brand C, Snaddon J, Bailey M, et al. Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study. Ann Rheum Dis. 2001;60:946-949.

139 Ziaei S, Faghihzadeh S, Sohrabvand F, et al. A randomized, placebo-controlled trial to determine the effect of vitamin E in treatment of primary dysmenorrhoea. BJOG. 2001;108:1181-1183.

140 Ohrvall M, Sundlof G, Vessby B. Gamma- but not alpha-tocopherol levels in serum are reduced in coronary heart disease patients. J Intern Med. 1996;239:111-117.

141 Kristenson M, Zieden B, Kucinskiene Z, et al. Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross-sectional study of men aged 50. BMJ. 1997;314:629-633.

142 Kontush A, Spranger T, Reich A, et al. Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol. Atherosclerosis. 1999;144:117-122.

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144 Woodson K, Tangrea JA, Barrett MJ, et al. Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. J Natl Cancer Inst. 1999;91:1738-1743

145 Omenn GS. Micronutrients (vitamins and minerals) as cancer-preventive agents. IARC Sci Publ. 1996;139:33-45.

146 [No authors listed]. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23-33.

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148 Kolarz G, Scherak O, El Shohoumi M, Blankenhorn G. High dose vitamin E for chronic arthritis. Akt Rheumatol. 1990;15:233-237.

149 Scherak O, Kolarz G. Vitamin E and rheumatoid arthritis. Arthrit Rheum. 1991;34:1205-1206.

150 Muntwyler J, Hennekens CH, Manson JE, et al. Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality. Arch Intern Med. 2002;162:1472-1476.

151 Marchioli R, Schweiger C, Levantesi G, et al. Antioxidant vitamins and prevention of cardiovascular disease: epidemiological and clinical trial data. Lipids. 2001;36:S53-63.

152 MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23-33.

153 Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583-1592.

154 Jiang Q, Christen S, Shigenaga MK, Ames BN. Gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am J Clin Nutr. 2001;74:714-722.

155 Hodis HN, Mack WJ, LaBree L, et al. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Circulation. 2002;106:1453-1459.

156 Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA. 2002;288:715-21.

157 Lonn E, Yusuf S, Hoogwerf B, et al. Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Diabetes Care. 2002;25:1919-1927.

158 Malila N, Taylor PR, Virtanen MJ, et al. Effects of alpha-tocopherol and beta-carotene supplementation on gastric cancer incidence in male smokers (ATBC Study, Finland). Cancer Causes Control. 2002;13:617-623.

159 Virtamo J, Edwards BK, Virtanen M, et al. Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland). Cancer Causes Control. 2000;11:933-939.

160 Ogunmekan AO, Hwang PA. A randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopheryl acetate (vitamin E), as add-on therapy, for epilepsy in children. Epilepsia. 1989;30:84-89.

161 Raju GB, Behari M, Prasad K, et al. Randomized, double-blind, placebo-controlled, clinical trial of D-alpha-tocopherol (vitamin E) as add-on therapy in uncontrolled epilepsy. Epilepsia. 1994;35:368-372.

162 Levy SL, Burnham WM, Bishai A, et al. The anticonvulsant effects of vitamin E: a further evaluation. Can J Neurol Sci. 1992;19:201-203.

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164 Wluka AE, Stuckey S, Brand C, et al. Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. J Rheumatol. 2002;29:2585-2591.

165 Taylor HR, Tikellis G, Robman LD, et al. Vitamin E supplementation and macular degeneration: randomised controlled trial. BMJ. 2002;325:11.

166 Michaud DS, Pietinen P, Taylor PR, et al. Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Br J Cancer. 2002;87:960-965.

167 Drisko JA, Chapman J, Hunter VJ. The use of antioxidant therapies during chemotherapy. Gynecol Oncol. 2003;88:434-439.

168 Shahar E, Hassoun G, Pollack S. Effect of vitamin E supplementation on the regular treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2004;92:654-658.

169 Manning PJ, Sutherland WH, Walker RJ, et al. Effect of high-dose vitamin E on insulin resistance and associated parameters in overweight subjects. Diabetes Care. 2004;27:2166-2171.

170 Avery NG, Kaiser JL, Sharman MJ, et al. Effects of vitamin E supplementation on recovery from repeated bouts of resistance exercise. J Strength Cond Res. 2003;17:801-809.

171 Graf M, Ecker D, Horowski R, et al. High dose vitamin E therapy in amyotrophic lateral sclerosis as add-on therapy to riluzole: results of a placebo-controlled double-blind study. J Neural Transm. 2004 Oct 27. [Epub ahead of print]

172 Pearson PJ, Lewis SA, Britton J, et al. Vitamin E supplements in asthma: a parallel group randomised placebo controlled trial. Thorax. 2004;59:652-656.

173 Mezey E, Potter JJ, Rennie-Tankersley L, et al. A randomized placebo controlled trial of vitamin E for alcoholic hepatitis. J Hepatol. 2004;40:40-46.

174 Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr. 2003;133:3137-3140.

175 Eidelman RS, Hollar D, Hebert PR, et al. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med. 2004;164:1552-1556.

176 Meydani SN, Leka LS, Fine BC, et al. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA. 2004;292:828-836.

177 Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2004 Dec 10. [Epub ahead of print]

178 Seifried HE, McDonald SS, Anderson DE, et al. The antioxidant conundrum in cancer. Cancer Res. 2003;63:4295-4298.

179 Branda RF, Naud SJ, Brooks EM, et al. Effect of vitamin B 12 , folate, and dietary supplements on breast carcinoma chemotherapy-induced mucositis and neutropenia. Cancer. 2004;101:1058-64.

180 Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293:1338-1347.

181 Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294:56-65.

182 Bairati I, Meyer F, Gelinas M, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005;97:481-488.

183 Ziaei S, Zakeri M, Kazemnejad A, et al. A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea. BJOG. 2005;112:466-469.

184 Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379-2388.

185 Rumbold AR, Crowther CA, Haslam RR, et al. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006;354:1796-1806.

186 Beazley D, Ahokas R, Livingston J, et al. Vitamin C and E supplementation in women at high risk for preeclampsia: A double-blind, placebo-controlled trial. Am J Obstet Gynecol. 2005;192:520-521.

187 Boshtam M, Rafiei M, Golshadi ID, et al. Long term effects of oral vitamin E supplement in type II diabetic patients. Int J Vitam Nutr Res. 2006;75:341-346.

188 Nussenblatt RB, Kim J, Thompson DJ, et al. Vitamin E in the treatment of uveitis-associated macular edema. Am J Ophthalmol. 2006;141:193-194.

189 Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294:56-65.

190 Bairati I, Meyer F, Gelinas M, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005;97:481-488.

191 Meydani SN, Han SN, Hamer DH, et al. Vitamin E and respiratory infection in the elderly. Ann N Y Acad Sci. 2005;1031:214-222.

192 Petersen RC, Thomas RG, Grundman M, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352:2379-88.

193 Montano Velazquez BB, Jauregui-Renaud K, Banuelos Arias Adel C, et al. Vitamin E effects on nasal symptoms and serum specific IgE levels in patients with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2006;96:45-50.

194 Lee IM, Cook NR, Gaziano JM, et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005;294:56-65.

195 Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293:1338-1347.

196 Ziaei S, Zakeri M, Kazemnejad A, et al. A randomised controlled trial of vitamin E in the treatment of primary dysmenorrhoea. BJOG. 2005;112:466-469.

197 Ward NC, Hodgson JM, Puddey IB, et al. Vitamin E increases blood pressure in type 2 diabetic subjects, independent of vascular function and oxidative stress. Asia Pac J Clin Nutr. 2005;14(suppl):S41.

198 Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology. 2005;64:26-31.

199 Bairati I, Meyer F, Gelinas M, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005;97:481-488.

200 Hemila H, Virtamo J, Albanes D, et al. The effect of vitamin e on common cold incidence is modified by age, smoking and residential neighborhood. J Am Coll Nutr. 2006;25:332-339.

201 Buring JE. Aspirin prevents stroke but not MI in women; vitamin E has no effect on CV disease or cancer. Cleve Clin J Med. 2006;73:863-870.

202 Liu S, Lee IM, Song Y, et al. Vitamin E and Risk of Type 2 Diabetes in the Women's Health Study Randomized Controlled Trial. Diabetes. 2006;55:2856-62.

203 Pearson P, Lewis SA, Britton J, et al. The pro-oxidant activity of high-dose vitamin e supplements in vivo. BioDrugs. 2006;20:271-3.

204 Puri A, Maulik SK, Ray R, et al. Electrocardiographic and biochemical evidence for the cardioprotective effect of vitamin E in doxorubicin-induced acute cardiotoxicity in rats. Eur J Pediatr Surg. 2006;15:387-391.

205 Berthiaume JM, Oliveira PJ, Fariss MW, et al. Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction. Cardiovasc Toxicol. 2005;5:257-267.

206 Wahab MH, Akoul ES, Abdel-Aziz AA. Modulatory effects of melatonin and vitamin E on doxorubicin-induced cardiotoxicity in Ehrlich ascites carcinoma-bearing mice. Tumor. 2000;86:157-162.

207 Legha SS, Wang YM, Mackay B, et al. Clinical and pharmacologic investigation of the effects of alpha-tocopherol on adriamycin cardiotoxicity. Ann N Y Acad Sci. 1983;393:411-418.

208 Ward NC, Wu JH, Clarke MW, et al. The effect of vitamin E on blood pressure in individuals with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. J Hypertens. 2007;25:227-234.

209 Kang JH, Cook N, Manson J, et al. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med, 2006;166:2462-2468.

210 Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297:842-857.

211 Wright ME, Weinstein SJ, Lawson KA, et al. Supplemental and dietary vitamin E intakes and risk of prostate cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2007;16:1128-1135.

212 Ziaei S, Kazemnejad A, Zareai M. The effect of vitamin E on hot flashes in menopausal women. Gynecol Obstet Invest. 2007 Jul 30. [Epub ahead of print]

213 Glynn RJ, Ridker PM, Goldhaber SZ, et al. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism. Report from the Women's Health Study. Circulation. 2007 Sep 10. [Epub ahead of print]

214 Kataja-Tuomola M, Sundell JR, Mannisto S, et al. Effect of alpha-tocopherol and beta-carotene supplementation on the incidence of type 2 diabetes. Diabetologia. 2007 Nov 10. [Epub ahead of print]

215 Milman U, Blum S, Shapira C, et al. Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype. A prospective double-blinded clinical trial. Arterioscler Thromb Vasc Biol. 2007 Nov 21. [Epub ahead of print]

216 Christen WG, Glynn RJ, Chew EY, et al. Vitamin E and age-related cataract in a randomized trial of women. Ophthalmology. 2007 Dec 5.

217 Hemila H, Kaprio J. Vitamin E supplementation may transiently increase tuberculosis risk in males who smoke heavily and have high dietary vitamin C intake. Br J Nutr. 2008 Feb 18.

218 Peters U, Littman AJ, Kristal AR, Patterson RE, Potter JD, White E. Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort. Cancer Causes Control. 2008;19:75-87.

219 Karlson EW, Shadick NA, Cook NR, et al. Vitamin E in the primary prevention of rheumatoid arthritis: the Women's Health Study. Arthritis Rheum. 2008;59:1589-1595.

220 Sesso HD, Buring JE, Christen WG, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2008;300:2123-2133.

221 Pace A, Giannarelli D, Galiè E, et al. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology. 2010 Mar 2;74(9):762.

222 Pruthi S, Wahner-Roedler DL, Torkelson CJ, et al. Vitamin E and evening primrose oil for management of cyclical mastalgia: a randomized pilot study. Altern Med Rev. 2010;15(1):59-67.

223 Schürks M, Glynn RJ, Rist PM, Tzourio C, Kurth T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ. 2010;341:c5702.

224 Christen WG, Glynn RJ, Sesso HD, et al. Age-related cataract in a randomized trial of vitamins E and C in men. Arch Ophthalmol. 2010;128(11):1397-1405.

225 Bardia A, Tleyjeh IM, Cerhan JR, Sood AK, Limburg PJ, Erwin PJ, Montori VM. Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis. Mayo Clin Proc. 2008 Jan;83(1):23

226 Arain MA, Abdul Qadeer A. Systematic review on "vitamin E and prevention of colorectal cancer." Pak J Pharm Sci. 2010;23(2):125-130.

227 Kataja-Tuomola MK, Kontto JP, Männistö S, Albanes D, Virtamo JR. Effect of alpha-tocopherol and beta-carotene supplementation on macrovascular complications and total mortality from diabetes: results of the ATBC Study. Ann Med. 2010;42(3):178-186.

228 Hauth JC, Clifton RG, Roberts JM, et al. Vitamin C and E supplementation to prevent spontaneous preterm birth: a randomized controlled trial. Obstet Gynecol. 2010;116(3):653-658.

229 Kristal AR, Arnold KB, Neuhouser ML, et al. Diet, supplement use, and prostate cancer risk: results from the prostate cancer prevention trial. Am J Epidemiol. 2010;172(5):566-577.

230 Jiang L, Yang KH, Tian JH, et al. Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials. Nutr Cancer. 2010;62(6):719-727.

231 Smedts HP, de Vries JH, Rakhshandehroo M, et al. High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring. BJOG. 2009;116(3):416-423.

232 Lin J, Cook NR, Albert C, Zaharris E, et al. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J Natl Cancer Inst. 2009;101(1):14-23.

233 Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2009;301(1):39-51.

234 Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2009;301(1):52-62.

235 Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev. 2008;(3):CD004183.

236 Fotuhi M, Zandi PP, Hayden KM, et al. Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study. Alzheimers Dement. 2008;4(3):223-227.

237 Evans JR, Henshaw K. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. Cochrane Database Syst Rev. 2008;(1):CD000253.

238 Sezikli M, Cetinkaya ZA, Sezikli H, et al. Oxidative stress in Helicobacter pylori infection: does supplementation with vitamins C and E increase the eradication rate? Helicobacter. 2009;14(4):280-285.

239 Dietary supplement fact sheet: vitamin E. Office of Dietary Supplements website. Available at: http://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/. Accessed September 10, 2012.

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