studies raised hopes that vitamin E supplements could help prevent various forms of
as well as
However, observational studies are notoriously unreliable for determining the effectiveness of treatments. Only
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.
. In fact, use of high-dose vitamin E for a long period might slightly
Other potential uses of vitamin E have limited supporting evidence.
Intriguing but far from definitive studies suggest that vitamin E might
control symptoms of
restless legs syndrome
deep venous thrombosis (DVTs)
reduce symptoms of
premenstrual syndrome (PMS)
and decrease symptoms of
Vitamin E, combined with
, has also been studied as a way to alleviate premenstrual
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,
there is strong evidence that it does not prevent it.
Although preliminary studies hinted that use of vitamin E might prevent or slow the progression of
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.
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.
Evidence regarding whether vitamin E can slow the progression of
A very large study failed to find vitamin E helpful for preventing mental decline (resulting from any cause) in women over 65.
Studies of vitamin E in combination with vitamin C for prevention of
(high blood pressure during pregnancy)
have yielded inconsistent results.
Also, a combination of vitamins E and C does not seem to reduce the risk of preterm birth.
Vitamin E has also shown equivocal promise in diabetes. One double-blind trial found benefits for
cardiac autonomic neuropathy
a complication of diabetes. Weaker evidence hints at possible benefits for
diabetic peripheral neuropathy
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.
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,
subsequent evidence found that the benefits, if they exist at all, are limited to the short-term.
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.
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
Similarly, studies on whether vitamin E is helpful for
(hay fever) have produced conflicting results.
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
However, a larger US study failed to find vitamin E significantly helpful for hot flashes associated with breast cancer treatment.
Vitamin E might help reduce the lung-related side effects caused by the drug amiodarone (used to prevent abnormal heart rhythms).
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).
Studies have yielded mixed results on whether vitamin E is helpful for controlling seizures in people with
reducing symptoms of
recovery during heavy exercise
When combined with
, vitamin E may protect against sunburn to a small extent.
The same combination has also shown promise for
acute anterior uveitis
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.
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.
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
the dose, this one lasting 18 months and enrolling 160 people.
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
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.
It has been suggested that vitamin E may enhance the antiviral effects of AZT, but evidence for this is minimal.
Vitamin E has been suggested for preventing the cardiac toxicity caused by the drug
. However, while it has shown promise in animal studies, when studied in people vitamin E has persistently failed to prove effective for this purpose.
Vitamin E is sometimes recommended for
. 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.
A previous 6-month, double-blind, placebo-controlled trial of 77 individuals with osteoarthritis also failed to find benefit.
A 4-year, double-blind, placebo-controlled trial of 1,193 people with
failed to find vitamin E alone helpful for preventing or treating macular degeneration.
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.
Vitamin E has also so far failed to prove helpful for preventing or treating
172congestive heart failure
80fibrocystic breast disease
In a very large study involving over 29,000 male smokers, researchers failed to find benefit of alpha-tocopherol (50 IU/day),
(20 mg/day), or the two taken together for the
prevention of type 2 diabetes
over 5-8 year period.
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.
At the 19-year follow-up, neither of the supplements offered any protective benefits.
What Is the Scientific Evidence for Vitamin E?
The results of
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.
Based on these and other results, researchers developed the hypothesis that antioxidants can help
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.
An analysis that included 9 carefully designed clinical trials found that antioxidant supplementation (
, and vitamin E) was not effective in reducing the incidence of cancer or cancer deaths.
Another analysis focused on whether vitamin E could reduce the risk of developing colorectal cancer.
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.
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.
In some studies, the antioxidants appeared to
overall mortality rates.
On the brighter side, a double-blind trial of 29,133 smokers does offer some positive news.
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.
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.
They concluded that none of the supplements (vitamin E,
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 E, and selenium did not reduce the number of men who developed prostate cancer or who died from the condition.
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.
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.
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.
Interestingly, use of alpha-tocopherol supplements may deplete both gamma- and delta-tocopherol levels, potentially producing a negative effect.
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.
Most but not all observational studies have found associations between high intake of vitamin E and reduced risk of cardiovascular disease (
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.
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.
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.
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.
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
. 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.
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.
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.
Interestingly, one study found that vitamin E might help prevent serious cardiovascular events in patients with
who also have a particular genetic marker known as “Hp 2.”
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
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.
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.
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.
Between 1987 and 1998, at least five double-blind studies were published that indicated vitamin E was beneficial in treating
Although most of these studies were small and lasted only 4 to 12 weeks, one 36-week study enrolled 40 individuals.
Three small double-blind studies reported that vitamin E was not helpful.
Nonetheless, a statistical analysis of the double-blind studies done before 1999 found good evidence that vitamin E was more effective than placebo.
Most studies found that vitamin E worked best for TD of more recent onset.
However, in 1999, the picture on vitamin E changed with the publication of one more study—the largest and longest to date.
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.
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.
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.
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
effect. One study in seniors found that use of vitamin E did not help prevent
and other respiratory infections, and, in fact, seemed to slightly increase the severity of infections that did occur.
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.
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.
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).
Evidence is conflicting regarding whether high-dose vitamin E can slow the progression of
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).
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.
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.
Such high dosages of vitamin E should not be taken except under a doctor's supervision. (See
Dysmenorrhea (Menstrual Pain)
In a double-blind, placebo-controlled trial, 100 young women complaining of significant
were given either 500 IU of vitamin E or placebo for 5 days.
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.
The dose used in this study was 200 IU twice daily.
Mastalgia (Breast Pain)
Eight-five women with premenstrual
were randomized to receive 1 of 4 treatments for 6 months: vitamin E (1,200 IU) and placebo,
(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.
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
(measured in pregnancies).
However, a smaller double-blind trial found no benefit.
Cardiac Autonomic Neuropathy
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.
The adult safe upper intake level (UL) for vitamin E is set at 1,000 mg daily.
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.
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.
(However, it reduced the risk of a more common type of stroke,
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
much, causing bleeding problems. A study that evaluated vitamin E plus aspirin did in fact find an additive effect.
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.
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
. Individuals with bleeding disorders, such as hemophilia, and those about to undergo surgery or labor and delivery should also approach vitamin E with caution.
In addition, vitamin E might at least temporarily enhance the body's sensitivity to its own insulin in individuals with adult-onset diabetes.
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.
The bottom line:
If you have diabetes, do not take high-dose vitamin E without first consulting your physician.
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.
Considerable controversy exists regarding whether it is safe or appropriate to combine vitamin E with standard chemotherapy drugs.
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.
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
may impair the effectiveness of radiation therapy for head and neck cancers.
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.
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.
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.