For Patients & Caregivers
Bottom Line: A diet containing adequate amounts of vitamin E is important in maintaining general health, and may prevent against some forms of cancer. The ability of vitamin E to prevent or treat Alzheimer’s disease, rheumatoid arthritis, or heart disease requires further study.
Vitamin E, also known as alpha-tocopherol, is a natural antioxidant that is found in foods such as plant oils, eggs, nuts, green leafy vegetables, and whole grains. The major function of vitamin E is to act as a free-radical scavenger, meaning that it neutralizes free radicals and protects cells from their damaging effects. Therefore, vitamin E is being investigated in conditions such as Alzheimer’s disease and cancer, in which free radical damage is known to play a part. (See the Research Evidence section for more information about this.)
Vitamin E also lessens the blood’s ability to clot by suppressing the number of adhesion molecules on the lining of the blood vessel walls. With fewer adhesion molecules, cells in the blood are less likely to “dock” on the blood vessel wall and start forming a clot. In addition, vitamin E causes the release of prostacyclin, which itself dilates the blood vessels and inhibits blood clotting. This may be helpful in patients with coronary artery disease, in which blood clots can form around atherosclerotic plaques in coronary arteries.
Scientists think that vitamin E also inhibits a molecule called protein kinase C, which is involved in cell proliferation and differentiation in smooth muscle, platelets, and monocytes (a type of immune cell). Although in theory this would be helpful against cancer cells, this effect has not been strongly shown in humans. An animal study shows NAC can speed up the growth of lung cancer cells due to its antioxidant activity.
- To prevent the progression of Alzheimer’s disease
One clinical trial showed that vitamin E helped prevent progression of Alzheimer’s disease. A few population-based studies have suggested that high intake of vitamin E in the diet is associated with a lower risk of developing Alzheimer’s disease.
- To treat arthritis
One clinical trial suggested that vitamin E can relieve pain in patients with rheumatoid arthritis, but has no anti-inflammatory effect. No other clinical trials have tested this use.
- To prevent cancer
Large population-based studies in Finland found that taking vitamin E supplements reduced the risk of prostate and colorectal cancers in male smokers. However, initial data from a large scale SELECT (Selenium and Vitamin E Cancer Prevention) Trial shows vitamin E taken alone or with selenium for five years, did not reduce the risk of prostate cancer. Vitamin E supplementation had no effect on lung, urinary tract, pancreas, mouth or stomach cancer risks.
- To manage heart disease
Data from clinical trials show that vitamin E does not help prevent heart disease.
- To prevent cataracts
Two clinical trials do not support this use
- To prevent the cardiovascular complications of diabetes
Several clinical trials have shown that vitamin E supplements may be helpful in preventing LDL oxidation in patients with diabetes, which may help prevent progression to atherosclerosis.
- To treat liver diseases
- Vitamin E can be used to treat fatty liver disease not caused by alcohol in adults
- To stimulate the immune system
No scientific evidence supports this use.
- To prevent the progression of Parkinson’s disease
Clinical trials do not support this use.
- To improve wound healing
No scientific evidence supports this use.
- To reduce hot flashes
A clinical trial showed that vitamin E reduces hot flashes in breast cancer survivors.
Prevention of age-related macular degeneration:
A randomized controlled trial studied the long-term use of vitamin E for preventing macular degeneration. For four years, 1193 healthy volunteers aged 55-80 took either 500 IU of vitamin E or a placebo pill daily. At the end of the study, people taking vitamin E developed age-related macular degeneration at about the same rate as people taking the placebo (8.6% versus 8.1%). These results indicate that daily supplementation with vitamin E does not prevent the development of macular degeneration, but this study does not address whether it has any effects greater than four years down the line.
In a very large clinical trial, patients with high-risk heart disease were randomly split into two groups: 4761 took 400 IU of vitamin E, while 4780 took a placebo pill. It was found that the patients in both groups had similar rates of heart attacks, strokes, death from coronary heart disease, and death from any cause. This indicates that supplementation with 400 IU of natural vitamin E does not reduce the risk of cardiovascular events in high-risk patients.
A separate analysis of seven large trials covering 81,788 subjects revealed that vitamin E did not lower the death rate or significantly decrease the risk of death from heart disease.
- In a randomized controlled trial, 341 patients with Alzheimer’s disease were randomly assigned to one of four groups: (1) selegiline (an MAOI) alone, (2) 2000 IU of vitamin E alone, (3) both selegiline and vitamin E, or (4) two placebo pills. Patients taking vitamin E alone had a higher average time to progression of Alzheimer’s disease than all other groups.
- In a prospective cohort study, 815 healthy adults older than age 65 were asked about their diets and followed to see whether their dietary intake of antioxidants would affect the risk of developing Alzheimer’s disease. After about four years, it was found that the people who developed Alzheimer’s disease, on average, consumed less vitamin E in their diet (not from supplements) than people who did not develop the disease. However, because this study only followed people for four years, it did not address the long-term effects of dietary antioxidants. Also, a problem with nutrition studies is that they measure dietary intake of foods with a questionnaire at the time of the study, and have no way of assessing what a person’s diet was like throughout his or her life.
- A similar prospective cohort study followed 5393 men and women at least 55 years old for an average of six years. It was found that, after adjusting for many variables that affect the development of Alzheimer’s disease, high intake of vitamin C and vitamin E were correlated with lower risk of this disease. However, one problem with this study is that people who were starting to develop Alzheimer’s disease at the start of the study, but were not yet diagnosed, may have had a poorer diet (lower intake of antioxidants) or may have had a hard time filling out the diet questionnaire, and this may also explain the association.
Prevention of prostate cancer:
Initial data from a large scale Selenium and Vitamin E Cancer Prevention trial (SELECT) shows vitamin E taken alone or with selenium for five years, did not reduce the risk of prostate cancer. A small increase in prostate cancer cases was observed in men taking only vitamin E.
Prevention of prostate and lung cancer in male smokers:
A randomized controlled trial studied the effects of beta-carotene and vitamin E supplements on the risk of prostate cancer. A total of 29,133 male smokers (50-69 years old) were split into four groups: (1) 50 mg of vitamin E, (2) 10 mg of beta-carotene, (3) both supplements, or (4) two placebo pills. Compared to the placebo group, the men taking vitamin E had an average of 36% lower risk of prostate cancer. However, men taking beta-carotene had an increased risk of lung cancer, heart disease, and hemorrhagic stroke. These results may not apply to women.
A recent review of 14 clinical trials shows that supplementation with antioxidants beta-carotene, vitamins A, C, and E does not seem to prevent gastrointestinal cancer and may actually increase overall mortality.
Head and neck cancer:
This study involved 540 patients with head and neck cancers who were given either 400 IU/day of vitamin E or placebo starting on the first day of radiation therapy for three years. Researchers found that patients who received vitamin E had a higher rate of second primary cancer compared to those on placebo. They also suggest that vitamin E may interfere with radiation therapy.
A randomized controlled trial studied the effects of vitamin E and selegiline (an MAOI) on the progression of Parkinson’s disease. Eight hundred patients with Parkinson’s disease were randomly assigned to one of four groups: (1) 2000 IU vitamin E, (2) 10 mg of selegiline, (3) both medications, or (4) two placebo pills. At the end of the study, it was found that patients taking vitamin E progressed just as rapidly as patients who were taking a placebo pill. This indicates that vitamin E is not effective for this use.
In a placebo-controlled, randomized trial involving 120 patients, 800 IU daily of vitamin E has been shown to be more effective than a placebo in reducing hot flashes in breast cancer survivors. However, most patients did not prefer vitamin E over the placebo at the conclusion of the study. The author pointed out the clinical magnitude of the reduction was marginal.
- A recent analysis of seven brands of commercially available vitamin E found their actual content to vary considerably from the labeled dosage, from 41% less than the labeled amount, to 57% more.
- This product is regulated by the F.D.A. as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
- Natural vitamin E supplements that are derived from plant oils contain d-alpha-tocopherol (which is believed to be the active form), while synthetic vitamin E supplements are a mixture of d-alpha-tocopherol and l-alpha-tocopherol (inactive).
- It is controversial whether antioxidants like vitamin E can lessen or negate the effects of chemotherapy and radiation therapy. Because these therapies work by creating free radicals that kill cancer cells, some physicians have suggested that high levels of antioxidants can neutralize these free radicals and thereby protect cancer cells from these therapies. So what protects healthy cells may protect cancer cells as well. This question is still not fully understood and patients who are interested in taking more than the RDA of any antioxidant should consult with their doctor.
For Healthcare Professionals
Vitamin E is a fat-soluble vitamin derived from plant. Natural food sources include plant oils, wheat germ, eggs, green leafy vegetables, and whole grains (3). Vitamin E acts as an antioxidant and is thought to help prevent and treat many diseases. Although available in a variety of formulations, only the d-isomer is considered active (1). Studies evaluating vitamin E supplementation suggest that it may improve immune response in the elderly.
Vitamin E may slow the progression of Alzheimer’s disease (9)(15)(16)(18); however, conflicting data from another study do not support the utility of antioxidants (vitamin E, vitamin C, lipoid acid, and Coenzyme Q)(43).
It was also ineffective in arresting the development or progression of macular degeneration (14) and Early Parkinson’s Disease (21).
Vitamin E did not decrease the incidence of acute respiratory tract infections (12), reduce mortality, or reduce the risk of cardiovascular death or cerebrovascular accident (26). When taken along with vitamin C, vitamin E may increase mortality and nonfatal myocardial infarction in patients with coronary artery disease (13). Further, findings from the recent Physicians’ Health Study II show that neither vitamin E nor C is beneficial in preventing cardiovascular events; vitamin E may actually increase the risk of stroke (36).
The Women’s Health Study also failed to find any benefit of vitamin E supplementation in lowering the risk of heart failure in healthy women (42).
A meta-analysis showed that vitamin E increases the risk for hemorrhagic stroke but reduces the risk of ischemic stroke (38).
Vitamin E can reduce signs and symptoms of nonalcoholic steatohepatitis in adults (45), but not in children and adolescents (46) .
Vitamin E was shown to reduce the risk of some cancers (19)(20). It may help to relieve hot flashes in breast cancer survivors (27), and to reduce the incidence of cisplatin-induced neurotoxicity (22). However, data suggest that supplementation with vitamins C, E, and beta carotene is not beneficial in preventing cancer incidence or affecting cancer mortality (37). Furthermore, vitamin E when used alone or with other supplements did not prevent gastrointestinal cancer (28). A large scale clinical Selenium and Vitamin E Cancer Prevention Trial (SELECT) evaluated the role of vitamin E in prostate cancer prevention. Initial review shows that vitamin E taken alone or with selenium for five years did not reduce the risk of prostate cancer (35); observational data from seven years of participant follow-up indicate a significant increase in the risk of prostate cancer with vitamin E supplementation (41). Vitamin E, when used together with soy and selenium, did not prevent prostate cancer progression (40). Further, findings from other studies indicate vitamin E may actually increase risk of lung cancer (33) and overall mortality (28). But conflicting data suggest an association between dietary tocopherol and a reduction in risk of lung cancer (38)(48). Also, both dietary and supplemental form of vitamin E may reduce the risk of liver cancer (44).
Toxicity may occur with chronic supplementation of vitamin E with doses greater than 800 IU. Daily supplementation over 400 IU may increase all-cause mortality (29). Vitamin E may also enhance the activity of warfarin, but data are inconsistent (7)(8).
Vitamin E is a fat soluble vitamin that acts as an antioxidant. The natural form of vitamin E is comprised of four different tocopherol and four different tocotrienol homologues (alpha, beta, delta and gamma). All eight forms have antioxidant activity but recent data indicate that the different homologues have different activities unrelated to antioxidant effects (34). Gamma-tocopherol is a stronger inhibitor of cyclooxygenase and traps reactive oxygen species more effectively than alpha-tocopherol. Gamma-tocopherol exhibits anti-proliferative and pro-apoptotic effects where alpha-tocopherol does not. But these observations come only from in vitro and in vivo studies (34).
The d-alpha-tocopherol isomer is believed to be the active principle. Natural vitamin E supplements contain d-alpha-tocopherol derived from plant oil sources, whereas synthetic supplements are composed of a racemic mixture of d- and l-alpha-tocopherols. The major function of d-alpha-tocopherol is to prevent the propagation of free radical reactions by acting as a peroxyl radical scavenger and protecting polyunsaturated fatty acids (PUFAs) within membrane phospholipids and in plasma lipoproteins. Alpha tocopherol reportedly causes inhibition of protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes. Vitamin E enrichment of endothelial cells, down regulates the expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby decreasing the adhesion of blood cell components to the endothelium. Vitamin E also up regulates the expression of cytosolic phospholipase A2 and cyclooxegenase-1, which leads to the release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation in humans(3).
In an animal study, vitamin E increased lung cancer cell proliferation due to its antioxidant activity by reducing reactive oxygen species (ROS), DNA damage and p53 expression (47).
Vitamin E absorption is low in humans, although the precise bioavailability is unknown. Absorption from the intestinal lumen is dependent upon biliary and pancreatic secretions, micelle formation, uptake into enterocytes, and chylomicron secretion, which has been suggested as the most important factor for efficient absorption. All forms of vitamin E (solubilized, natural, and synthetic) have similar intestinal absorption of d-alpha-tocopherol.
Vitamin E is fat soluble. It distributes throughout the body and is primarily stored in adipose tissue and various organs.
Alpha tocopherol is oxidized to the tocopheroxyl radical that can be reduced back to the unoxidized form by reducing agents such as vitamin C. Further oxidation of the tocopheroxyl radical forms tocopheryl quinone. The tocopheryl quinone is not converted back to tocopherol in physiologically significant amounts. The major route of excretion of ingested vitamin E is fecal elimination due to its relatively low intestinal absorption, although vitamin E metabolites appear to be primarily eliminated via the kidneys. Excess alpha-tocopherol, as well as forms of vitamin E not used preferentially, are probably excreted unchanged in bile.
Although many research protocols use milligrams of vitamin E, most commercial products are sold in international units (IU). One IU natural vitamin E equals 0.67 mg d-alpha-tocopherol and one IU of synthetic vitamin E equals 0.45 mg d-alpha-tocopherol.
While both alpha- and gamma-tocopherols exhibit anti-inflammatory effects in vitro and in vivo, gamma-enriched mixed tocopherols may be more potent compared to alpha tocopherols. This may help explain the negative outcomes of recent large-scale intervention studies that used only the alpha homologue (34).
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(18):2123-2133.
This long-term study sought to evaluate the role of vitamin C or E supplementation in reducing the risk of cardiovascular disease, and involved over 14,000 men aged 50 or older. The participants were randomized to 400 IU of vitamin E every other day or its placebo and 500 mg of vitamin C daily or its placebo. The primary outcome of the study was onset of major cardiovascular events including, nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular disease.
At the 8-year follow-up, researchers observed the same number of cases in both vitamin and the placebo groups, with increased risk of hemorrhagic stroke in the vitamin E group. These findings suggest no significant effects of vitamins in lowering the risk of cardiovascular disease as widely believed.
It should be noted that both the vitamins used in the study were synthetic and at much higher levels than those achieved via dietary intake, which may have led to the effects observed. More studies at different doses and involving other populations are warranted to fully assess the role of vitamin supplementation for cardiovascular health.
Slatore CG, Littman AJ, Au DH, et al. Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer. Am J Respir Crit Care Med. 2008;177(5):524-30.
The VITAL (Vitamins and Lifestyle) cohort of 77,221 men was used to determine association between vitamin supplementation (multivitamins, vitamin C, vitamin E, and folate) and occurrence of lung cancer. Researchers identified 521 cases of lung cancer and observed that vitamin supplementation did not decrease the risk of lung cancer. They also report that supplemental vitamin E was associated with a small increase in risk of lung cancer.
Peters U, Littman AJ, Kristal AJ, et al. Vitamin E and selenium supplementation and risk of prostate cancer in the Vitamins and lifestyle (VITAL) study cohort. Cancer Causes Control. 2008;19(1):75-87.
In this prospective study of 35,242 men recruited between 2000 and 2002, researchers documented 830 new cases of prostate cancer from baseline through December 2004. They also report that a 10-year average intake of supplemental vitamin E and selenium did not reduce the risk of prostate cancer. However, the risk of advanced prostate cancer was reduced with long-term vitamin E supplementation.
Engelhart MJ, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 2002;287:3223-9.
A population-based, prospective cohort study evaluating antioxidant intake and risk of developing Alzheimer disease. Subjects (n=5393) were at least 55 years old, free of dementia, noninstitutionalized, and had reliable dietary assessment at baseline. Dietary intake was assessed by self-reported checklist and interview with dietitian using the semiquantitative food-frequency questionnaire (SFFQ). After mean follow-up of 6 years, 146 patients developed Alzheimer disease. After adjustments for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of supplements, high intake of vitamin C and vitamin E were correlated with lower risk of Alzheimer disease. However, as has been pointed out, the apparent association may be caused by the influence of a preclinical illness on diet or diet recall/reporting, since the SFFQ itself may indirectly assess cognitive functioning. Furthermore, the multiple comparisons suggest that some associations may be due to chance and that the critical P value should be set lower than .05.