Vitamin-E-Foods

What is Vitamin E

Vitamin E is a fat-soluble nutrient found in many foods, added to others, and available as a dietary supplement. “Vitamin E” is the collective name for a group of fat-soluble compounds with distinctive antioxidant activities 1. Naturally occurring vitamin E exists in eight chemical forms (alpha-, beta-, gamma-, and delta-tocopherol and alpha-, beta-, gamma-, and delta-tocotrienol) that have varying levels of biological activity 1. Alpha- (or α-) tocopherol is the only form that is recognized to meet human requirements, but beta-, gamma-, and delta-tocopherols, 4 tocotrienols, and several stereoisomers may also have important biologic activity (see Figure 1). In the body, vitamin E acts as an antioxidant, helping to protect cells from the damage caused by free radicals. Free radicals are compounds formed when our bodies convert the food we eat into energy. People are also exposed to free radicals in the environment from cigarette smoke, air pollution, and ultraviolet light from the sun. Vitamin E is believed to serve as a chain-breaking antioxidant that stops the oxidative degradation of lipids, thus preventing free radical production and harm to the cell.

The body also needs vitamin E to boost its immune system so that it can fight off invading bacteria and viruses. It helps to widen blood vessels and keep blood from clotting within them. In addition, cells use vitamin E to interact with each other and to carry out many important functions. Scientists are investigating whether, by limiting free-radical production and possibly through other mechanisms, vitamin E might help prevent or delay the chronic diseases associated with free radicals.

Antioxidants protect cells from the damaging effects of free radicals, which are molecules that contain an unshared electron. Free radicals damage cells and might contribute to the development of cardiovascular disease and cancer 2. Unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS). The body forms ROS endogenously when it converts food to energy, and antioxidants might protect cells from the damaging effects of ROS. The body is also exposed to free radicals from environmental exposures, such as cigarette smoke, air pollution, and ultraviolet radiation from the sun. Reactive oxygen species (ROS) are part of signaling mechanisms among cells.

The main function of alpha tocopherol (α-tocopherol) in humans is that of a fat-soluble antioxidant. Vitamin E is a fat-soluble antioxidant that stops the production of reactive oxygen species (ROS) formed when fat undergoes oxidation. Fats, which are an integral part of all cell membranes, are vulnerable to damage through lipid peroxidation by free radicals. Alpha tocopherol is uniquely suited to intercept peroxyl radicals and thus prevent a chain reaction of lipid oxidation 3. When a molecule of α-tocopherol neutralizes a free radical, it is oxidized and its antioxidant capacity is lost. Other antioxidants, such as vitamin C, are capable of regenerating the antioxidant capacity of alpha tocopherol 4.

Aside from maintaining the integrity of cell membranes throughout the body, alpha tocopherol protects the fats in low-density lipoproteins (LDLs) from oxidation. Lipoproteins are particles composed of lipids and proteins that transport fats through the bloodstream. LDLs (bad cholesterol) specifically transport cholesterol from the liver to the tissues of the body. Oxidized LDLs (bad cholesterol) have been implicated in the development of cardiovascular disease 5.

In addition to its activities as an antioxidant, vitamin E is involved in immune function and, as shown primarily by in vitro studies of cells, cell signaling, regulation of gene expression, and other metabolic processes 1. Alpha-tocopherol inhibits the activity of protein kinase C, an enzyme involved in cell proliferation and differentiation in smooth muscle cells, platelets, and monocytes 6. Vitamin-E–replete endothelial cells lining the interior surface of blood vessels are better able to resist blood-cell components adhering to this surface. Vitamin E also increases the expression of two enzymes that suppress arachidonic acid metabolism, thereby increasing the release of prostacyclin from the endothelium, which, in turn, dilates blood vessels and inhibits platelet aggregation 6.

Vitamin E is absorbed in the intestinal lumen, which is dependent upon various factors such as pancreatic secretions, micelle formation, and most importantly, chylomicron secretions. Chylomicron secretion is necessary for vitamin E absorption. Vitamin E is found in sunflower seeds, nuts, some oils, spinach, butternut squash, and many other food sources. Vitamin E deficiency has been linked to peripheral neuropathy in addition to spinocerebellar ataxia, skeletal myopathy and pigmented retinopathy. Interestingly, studies have reported vitamin E level in association to the development of cataracts 7.

Serum concentrations of vitamin E (alpha-tocopherol) depend on the liver, which takes up the nutrient after the various forms are absorbed from the small intestine. The liver preferentially resecretes only alpha-tocopherol via the hepatic alpha-tocopherol transfer protein 1; the liver metabolizes and excretes the other vitamin E forms 8. As a result, blood and cellular concentrations of other forms of vitamin E are lower than those of alpha-tocopherol and have been the subjects of less research 9, 10. Plasma tocopherol levels vary with total plasma lipid levels. Normally, the plasma alpha-tocopherol level is 5 to 20 mcg/mL (11.6 to 46.4 mcmol/L) 11.

Vitamin E is safe for pregnancy and breastfeeding. Both vitamin K and omega-6 fatty acids requirements may increase with high doses of vitamin E.

Some food and dietary supplement labels still list vitamin E in International Units (IUs) rather than milligrams (mg). 1 IU of the natural form of vitamin E is equivalent to 0.67 mg. 1 IU of the synthetic form of vitamin E is equivalent to 0.45 mg.

International Units and Milligrams

Vitamin E is listed on the new Nutrition Facts and Supplement Facts labels in milligrams (mg) 12. The U.S. Food and Drug Administration (FDA) required manufacturers to use these new labels starting in January 2020, but companies with annual sales of less than $10 million may continue to use the old labels that list vitamin E in international units (IUs) until January 2021 13. Conversion rules are as follows:

To convert from mg to IU:

  • 1 mg of alpha-tocopherol is equivalent to 1.49 IU of the natural form or 2.22 IU of the synthetic form.

To convert from IU to mg:

  • 1 IU of the natural form is equivalent to 0.67 mg of alpha-tocopherol.
  • 1 IU of the synthetic form is equivalent to 0.45 mg of alpha-tocopherol.

For example, 15 mg of natural alpha-tocopherol would equal 22.4 IU (15 mg x 1.49 IU/mg = 22.4 IU). The corresponding value for synthetic alpha-tocopherol would be 33.3 IU (15 mg x 2.22 IU/mg).

Figure 1. Vitamin E chemical structures

Vitamin E chemical structure

What does Vitamin E do?

Vitamin E is a fat-soluble antioxidant that stops the production of reactive oxygen species (ROS) formed when fat undergoes oxidation. Scientists are investigating whether, by limiting free-radical production and possibly through other mechanisms, vitamin E might help prevent or delay the chronic diseases associated with free radicals.

Antioxidants protect cells from the damaging effects of free radicals, which are molecules that contain an unshared electron. Free radicals damage cells and might contribute to the development of cardiovascular disease and cancer 2. Unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species. The body forms reactive oxygen species endogenously when it converts food to energy, and antioxidants might protect cells from the damaging effects of reactive oxygen species. The body is also exposed to free radicals from environmental exposures, such as cigarette smoke, air pollution, and ultraviolet radiation from the sun. Reactive oxygen species are part of signaling mechanisms among cells.

The body also needs vitamin E to boost its immune system so that it can fight off invading bacteria and viruses. It helps to widen blood vessels and keep blood from clotting within them.

In addition to its activities as an antioxidant, vitamin E is involved in immune function and, as shown primarily by in vitro studies of cells, cell signaling, regulation of gene expression, and other metabolic processes 1. Alpha-tocopherol inhibits the activity of protein kinase C, an enzyme involved in cell proliferation and differentiation in smooth muscle cells, platelets, and monocytes 14. Vitamin-E–replete endothelial cells lining the interior surface of blood vessels are better able to resist blood-cell components adhering to this surface. Vitamin E also increases the expression of two enzymes that suppress arachidonic acid metabolism, thereby increasing the release of prostacyclin from the endothelium, which, in turn, dilates blood vessels and inhibits platelet aggregation 14.

Vitamin E inhibits platelet adhesion by preventing oxidative changes to low-density lipoprotein (LDL) cholesterol also called bad cholesterol and inhibition of platelet aggregation by reducing prostaglandin E2. Another effect is inhibiting protein kinase C causing smooth-muscle proliferation.

Even though research has shown that vitamin E assists with the prevention of heart disease and atherosclerosis it has not been approved for this use by the United States Food and Drug Administration (FDA).

Vitamin E Supplements

Vitamin E supplements come in different amounts and forms. Supplements of vitamin E typically provide only alpha-tocopherol, although “mixed” products containing other tocopherols and even tocotrienols are available such as gamma-tocopherol, tocotrienols, and mixed tocopherols. Scientists do not know if any of these forms are superior to alpha-tocopherol in supplements.

Two main things to consider when choosing a vitamin E supplement are:

  1. The amount of vitamin E: Most once-daily multivitamin-mineral supplements provide about 13.5 mg of vitamin E, whereas vitamin E-only supplements commonly contain 67 mg or more. The doses in most vitamin E-only supplements are much higher than the recommended amounts. Some people take large doses because they believe or hope that doing so will keep them healthy or lower their risk of certain diseases.
  2. The form of vitamin E: Although vitamin E sounds like a single substance, it is actually the name of eight related compounds in food, including alpha-tocopherol. Each form has a different potency, or level of activity in the body.

Naturally occurring alpha-tocopherol exists in one stereoisomeric form, commonly listed as ”D-alpha-tocopherol” on food packaging and supplement labels. In contrast, synthetically produced (laboratory-made) alpha-tocopherol contains equal amounts of its eight possible stereoisomers, commonly listed as ”DL-alpha-tocopherol”; serum and tissues maintain only four of these stereoisomers 14. A given amount of synthetic alpha-tocopherol (all rac-alpha-tocopherol; commonly labeled as “DL” or “dl”) is therefore only half as active as the same amount (by weight in mg) of the natural form (RRR-alpha-tocopherol; commonly labeled as “D” or “d”). People need approximately 50% more IU of synthetic alpha tocopherol from dietary supplements and fortified foods to obtain the same amount of the nutrient as from the natural form.

  • The natural vitamin E (D-alpha-tocopherol) is more potent; 1 mg vitamin E = 1 mg d-alpha-tocopherol (natural vitamin E) = 2 mg dl-alpha-tocopherol (synthetic vitamin E).

Some food and dietary supplement labels still list vitamin E in International Units (IUs) rather than mg. 1 IU of the natural form of vitamin E is equivalent to 0.67 mg. 1 IU of the synthetic form of vitamin E is equivalent to 0.45 mg.

Some vitamin E supplements provide other forms of the vitamin, such as gamma-tocopherol, tocotrienols, and mixed tocopherols. Scientists do not know if any of these forms are superior to alpha-tocopherol in supplements.

Most vitamin-E-only supplements provide ≥100 IU of the nutrient. These amounts are substantially higher than the recommended dietary allowances. The 1999–2000 National Health and Nutrition Examination Survey (NHANES) found that 11.3% of adults took vitamin E supplements containing at least 400 IU 15.

Alpha-tocopherol in dietary supplements and fortified foods is often esterified to prolong its shelf life while protecting its antioxidant properties. The body hydrolyzes and absorbs these esters (alpha-tocopheryl acetate and succinate) as efficiently as alpha-tocopherol 14.

Vitamin E interactions with medications

Vitamin E supplements have the potential to interact with several types of medications. A few examples are provided below. People taking these and other medications on a regular basis should discuss their vitamin E intakes with their healthcare providers.

Vitamin E has a few interactions with medications that are listed below:

  • Anticoagulation and antiplatelet medications: due to vitamin E inhibiting platelet aggregation and disrupting vitamin K clotting factors there is a protentional increase risk of bleeding combining these two. Vitamin E can inhibit platelet aggregation and antagonize vitamin K-dependent clotting factors. As a result, taking large doses with anticoagulant or antiplatelet medications, such as warfarin (Coumadin®), can increase the risk of bleeding, especially in conjunction with low vitamin K intake. The amounts of supplemental vitamin E needed to produce clinically significant effects are unknown but probably exceed 400 IU/day 6.
  • Simvastatin and niacin: Vitamin E can reduce the amount of high-density lipoprotein (HDL or “good” cholesterol) which is the opposite desired effect of taking simvastatin and/or niacin. Some people take vitamin E supplements with other antioxidants, such as vitamin C, selenium, and beta-carotene. This collection of antioxidant ingredients blunted the rise in high-density lipoprotein (HDL) cholesterol levels, especially levels of HDL, the most cardioprotective HDL component, among people treated with a combination of simvastatin (brand name Zocor®) and niacin 16.
  • Chemotherapy and radiotherapy: Oncologists generally advise against the use of antioxidant supplements during cancer chemotherapy or radiotherapy because they might reduce the effectiveness of these therapies by inhibiting cellular oxidative damage in cancerous cells 17. Although a systematic review of randomized controlled trials has called this concern into question 18, further research is needed to evaluate the potential risks and benefits of concurrent antioxidant supplementation with conventional therapies for cancer.

What are some vitamin E benefits on health?

Scientists are studying vitamin E to understand how it affects health. Here are several examples of what this research has shown.

Many claims have been made about vitamin E’s potential to promote health and prevent and treat disease. The mechanisms by which vitamin E might provide this protection include its function as an antioxidant and its roles in anti-inflammatory processes, inhibition of platelet aggregation, and immune enhancement.

A primary barrier to characterizing the roles of vitamin E in health is the lack of validated biomarkers for vitamin E intake and status to help relate intakes to valid predictors of clinical outcomes 14.

Coronary heart disease

For a time, vitamin E supplements looked like an easy way to prevent heart disease. Promising observational studies, including the Nurses’ Health Study 19 and Health Professionals Follow-Up Study 20,  suggested 20 to 40 percent reductions in coronary heart disease risk among individuals who took vitamin E supplements (usually containing 400 IU or more) for least two years 20.

The results of several randomized trials have dampened enthusiasm for vitamin E’s ability to prevent heart attacks or deaths from heart disease among individuals with heart disease or those at high risk for it. In the GISSI Prevention Trial, the results were mixed but mostly showed no preventive effects after more than three years of treatment with vitamin E among 11,000 heart attack survivors 21. Results from the Heart Outcomes Prevention Evaluation (HOPE) trial also showed no benefit of four years worth of vitamin E supplementation among more than 9,500 men and women already diagnosed with heart disease or at high risk for it 22, 23. In fact, when the HOPE trial was extended for another four years, researchers found that study volunteers who took vitamin E had a higher risk of heart failure 23. In the HOPE-TOO followup study, almost 4,000 of the original participants continued to take vitamin E or placebo for an additional 2.5 years 24. HOPE-TOO study found that vitamin E provided no significant protection against heart attacks, strokes, unstable angina, or deaths from cardiovascular disease or other causes after 7 years of treatment 24. Participants taking vitamin E, however, were 13% more likely to experience, and 21% more likely to be hospitalized for, heart failure, a statistically significant but unexpected finding not reported in other large studies.

The HOPE and HOPE-TOO trials provide compelling evidence that moderately high doses of vitamin E supplements do not reduce the risk of serious cardiovascular events among men and women >50 years of age with established heart disease or diabetes 25. These findings are supported by evidence from the Women’s Angiographic Vitamin and Estrogen study, in which 423 postmenopausal women with some degree of coronary stenosis took supplements with 400 IU vitamin E (form not specified) and 500 mg vitamin C twice a day or placebo for >4 years 26. Not only did the supplements provide no cardiovascular benefits, but all-cause mortality was significantly higher in the women taking the supplements. Based on such studies, the American Heart Association has concluded that “the scientific data do not justify the use of antioxidant vitamin supplements [such as vitamin E] for cardiovascular disease risk reduction.” 27.

It’s possible that in people who already have heart disease or are high risk of heart disease, the use of drugs such as aspirin, beta blockers, and ACE inhibitors mask a modest effect of vitamin E, and that vitamin E may have benefits among healthier people. But large randomized controlled trials of vitamin E supplementation in healthy women and men have yielded mixed results.

In the Women’s Health Study, which followed 40,000 healthy women ≥45 years of age who were randomly assigned to receive either vitamin E supplements of 600 IU of natural vitamin E (402 mg) on alternate days or placebo and who were followed for an average of 10 years 28. The investigators found no significant differences in rates of overall cardiovascular events (combined nonfatal heart attacks, strokes, and cardiovascular deaths) or all-cause mortality between the groups. However, the study did find two positive and significant results for women taking vitamin E: they had a 24% reduction in cardiovascular death rates, and those ≥65 years of age had a 26% decrease in nonfatal heart attack and a 49% decrease in cardiovascular death rates 28. A later analysis found that women who took the vitamin E supplements also had a lower risk of developing serious blood clots in the legs and lungs, with women at the highest risk of such blood clots receiving the greatest benefit 29.

The most recent published clinical trial of vitamin E and men’s cardiovascular health included almost 15,000 healthy physicians ≥50 years of age who were randomly assigned to receive 400 IU synthetic alpha-tocopherol (180 mg) every other day, 500 mg vitamin C daily, both vitamins, or placebo 30. During a mean follow-up period of 8 years, intake of vitamin E (and/or vitamin C) had no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, or cardiovascular morality. Furthermore, use of vitamin E was associated with a significantly increased risk of hemorrhagic stroke 30.

Other heart disease prevention trials in healthy people have not been as promising, however. The SU.VI.MAX trial found that seven years of low-dose vitamin E supplementation (as part of a daily antioxidant pill) reduced the risk of cancer and the risk of dying from any cause in men, but did not show these beneficial effects in women; the supplements did not offer any protection against heart disease in men or women 31. Discouraging results have also come from the Physicians’ Health Study II, an eight-year trial that involved nearly 15,000 middle-aged men, most of whom were free of heart disease at the start of the study. Researchers found that taking vitamin E supplements of 400 IU every other day, alone or with vitamin C, failed to offer any protection against heart attacks, strokes, or cardiovascular deaths 32.

More recent evidence suggests that vitamin E may have potential benefits only in certain subgroups of the general population: A trial of high dose vitamin E in Israel, for example, showed a marked reduction in coronary heart disease among people with type 2 diabetes who have a common genetic predisposition for greater oxidative stress 33. So we certainly have not heard the last word on vitamin E and heart disease prevention.

In general, clinical trials have not provided evidence that routine use of vitamin E supplements prevents cardiovascular disease or reduces its morbidity and mortality. However, participants in these studies have been largely middle-aged or elderly individuals with demonstrated heart disease or risk factors for heart disease. Some researchers have suggested that understanding the potential utility of vitamin E in preventing coronary heart disease might require longer studies in younger participants taking higher doses of the supplement 34. Further research is needed to determine whether supplemental vitamin E has any protective value for younger, healthier people at no obvious risk of cardiovascular disease.

Cancer

Antioxidant nutrients like vitamin E protect cell constituents from the damaging effects of free radicals that, if unchecked, might contribute to cancer development. Vitamin E might also block the formation of carcinogenic nitrosamines formed in the stomach from nitrites in foods and protect against cancer by enhancing immune function 35.

Evidence to date is insufficient to support taking vitamin E to prevent cancer. In fact, daily use of large-dose vitamin E supplements (400 IU of synthetic vitamin E [180 mg]) may increase the risk of prostate cancer. Taken as a whole, observational studies have not found vitamin E in food or supplements to offer much protection against cancer in general, or against specific cancers 36, 37, 38, 39, 40, 41, 42, 43, 44, 45. Some observational studies and clinical trials, however, suggested that vitamin E supplements might lower the risk of advanced prostate cancer in smokers 38, 46, 47, 48.

Investigators had hoped that the Selenium and Vitamin E Cancer Prevention Trial (SELECT) would give more definitive answers on vitamin E and prostate cancer. SELECT’s 18,000 men were assigned to follow one of four pill regimens—vitamin E plus selenium, vitamin E plus a selenium placebo, selenium plus a vitamin E placebo, or a double placebo—and were supposed to be tracked for 7 to 12 years. But investigators halted the study halfway though, in 2008, when early analyses showed that vitamin E offered no cancer or prostate cancer prevention benefit 49. Though the trial ended, researchers continued to follow the men who had participated. In 2011, they reported a 17 percent higher risk of prostate cancer among men assigned to take vitamin E; there was no significant increased risk of prostate cancer among men who took vitamin E and selenium 50. The additional 2011 data show that the men who took vitamin E alone had a 17 percent relative increase in numbers of prostate cancers compared to men on placebo. This difference in prostate cancer incidence between the vitamin E only group and the placebos only group is now statistically significant, and not likely to be due to chance 51.

Though these results, on the face of it, sound worrisome, two other major trials of vitamin E and prostate cancer had quite different results: The Alpha Tocopherol Beta Carotene (ATBC) randomized trial, for example, followed nearly 30,000 Finnish male smokers for an average of six years 46. It found that men assigned to take daily vitamin E supplements had a 32 percent lower risk of developing prostate cancer—and a 41 percent lower risk of dying from prostate cancer—than men given a placebo. However, there are many reasons why the vitamin E supplements may not have prevented prostate cancer. Two of the most likely reasons, looking back at the Alpha-Tocopherol Beta Carotene (ATBC) Cancer Prevention trial, a study designed to test vitamin E and beta carotene for lung cancer prevention in smokers 52. In the The Alpha Tocopherol Beta Carotene trial, a reduction in prostate cancer incidence was observed, but this secondary finding may have been due to chance, as the study was not designed to determine prostate cancer risk 51. Another possible reason that men in ATBC had a reduction in prostate cancer incidence, while men on SELECT did not, is that the dose of vitamin E used in SELECT (400 IU/day) was higher than the dose used in the ATBC (50 IU/day) 51. Researchers sometimes talk about a “U-shaped response curve” where very low or very high blood levels of a nutrient are harmful but more moderate levels are beneficial; while the ATBC dose may have been preventive, the SELECT dose may have been too large to have a prevention benefit 51.

The large and long-term Physicians’ Health Study II trial, meanwhile, found that vitamin E supplements had no effect on the risk of prostate cancer or any other cancer 53.

Bear in mind that prostate cancer develops slowly, and any study looking at prostate cancer prevention needs to track men for a long time. By stopping the SELECT trial early, there’s no way to tell if vitamin E could have helped protect against prostate cancer in some men if they had continued the trial over a longer period of time. Very few cases in the SELECT Trial were of advanced prostate cancer, further limiting the interpretation of the findings.

One study of women in Iowa provides evidence that higher intakes of vitamin E from foods and supplements could decrease the risk of colon cancer, especially in women <65 years of age 54. The overall relative risk for the highest quintile of intake (>35.7 IU/day, form not specified) compared to the lowest quintile (<5.7 IU/day, form not specified) was 0.32. However, prospective cohort studies of 87,998 women in the Nurses’ Health Study and 47,344 men in the Health Professionals Follow-up Study failed to replicate these results 55. Although some research links higher intakes of vitamin E with decreased incidence of breast cancer, an examination of the impact of dietary factors, including vitamin E, on the incidence of postmenopausal breast cancer in >18,000 women found no benefit from the vitamin 56.

The American Cancer Society conducted an epidemiologic study examining the association between use of vitamin C and vitamin E supplements and bladder cancer mortality. Of the almost one million adults followed between 1982 and 1998, adults who took supplemental vitamin E for 10 years or longer had a reduced risk of death from bladder cancer 57; vitamin C supplementation provided no protection.

Vitamin E and macular degeneration

Age-related macular degeneration (AMD) and cataracts are among the most common causes of significant vision loss in older people. Their causes are usually unknown, but the cumulative effects of oxidative stress have been postulated to play a role. If so, nutrients with antioxidant functions, such as vitamin E, could be used to prevent or treat these conditions.

Prospective cohort studies have found that people with relatively high dietary intakes of vitamin E (e.g., 20 mg/day [30 IU]) have an approximately 20% lower risk of developing age-related macular degeneration than people with low intakes (e.g., <10 mg/day [<15 IU]) 58. However, two randomized controlled trials in which participants took supplements of vitamin E (500 IU/day [335 mg] d-alpha-tocopherol in one study 59 and 111 IU/day (50 mg) dl-alpha-tocopheryl acetate combined with 20 mg/day beta-carotene in the other study 60 or a placebo failed to show a protective effect for vitamin E on age-related macular degeneration. The Age-Related Eye Disease Study (AREDS) 61, a large randomized clinical trial, found that participants at high risk of developing advanced age-related macular degeneration (i.e., those with intermediate age-related macular degeneration or those with advanced age-related macular degeneration in one eye) reduced their risk of developing advanced age-related macular degeneration by 25% by taking a daily supplement containing vitamin E (400 IU [180 mg] dl-alpha-tocopheryl acetate), beta-carotene (15 mg), vitamin C (500 mg), zinc (80 mg), and copper (2 mg) compared to participants taking a placebo over 5 years. A follow-up AREDS2 study 62 confirmed the value of this and similar supplement formulations in reducing the progression of age-related macular degeneration over a median follow-up period of 5 years.

Overall, the available evidence is inconsistent with respect to whether vitamin E supplements, taken alone or in combination with other antioxidants, can reduce the risk of developing age-related macular degeneration or cataracts. However, the formulations of vitamin E, other antioxidants, zinc, and copper used in AREDS hold promise for slowing the progression of age-related macular degeneration in people at high risk of developing advanced age-related macular degeneration.

Vitamin E and cataracts

Several observational studies have revealed a potential relationship between vitamin E supplements and the risk of cataract formation. One prospective cohort study found that lens clarity was superior in participants who took vitamin E supplements and those with higher blood levels of the vitamin 63. In another study, long-term use of vitamin E supplements was associated with slower progression of age-related lens opacification 64. However, in the AREDS trial, the use of a vitamin E-containing (as dl-alpha-tocopheryl acetate) formulation had no apparent effect on the development or progression of cataracts over an average of 6.3 years 65. The AREDS2 study, which also tested formulations containing 400 IU (180 mg) vitamin E, confirmed these findings 66.

Cognitive Function

The brain has a high oxygen consumption rate and abundant polyunsaturated fatty acids in the neuronal cell membranes. Researchers hypothesize that if cumulative free-radical damage to neurons over time contributes to cognitive decline and neurodegenerative diseases, such as Alzheimer’s disease, then ingestion of sufficient or supplemental antioxidants (such as vitamin E) might provide some protection 67. This hypothesis was supported by the results of a clinical trial in 341 patients with Alzheimer’s disease of moderate severity who were randomly assigned to receive a placebo, vitamin E (2,000 IU/day dl-alpha-tocopherol), a monoamine oxidase inhibitor (selegiline), or vitamin E and selegiline 67. Over 2 years, treatment with vitamin E and selegiline, separately or together, significantly delayed functional deterioration and the need for institutionalization compared to placebo. However, participants taking vitamin E experienced significantly more falls.

Vitamin E consumption from foods or supplements was associated with less cognitive decline over 3 years in a prospective cohort study of elderly, free-living individuals aged 65–102 years 68. However, a clinical trial in primarily healthy older women who were randomly assigned to receive 600 IU (402 mg) d-alpha-tocopherol every other day or a placebo for ≤4 years found that the supplements provided no apparent cognitive benefits 69. Another trial in which 769 men and women with mild cognitive impairment were randomly assigned to receive 2,000 IU/day vitamin E (form not specified), a cholinesterase inhibitor (donepezil), or placebo found no significant differences in the progression rate of Alzheimer’s disease between the vitamin E and placebo groups 70.

In summary, most research results do not support the use of vitamin E supplements by healthy or mildly impaired individuals to maintain cognitive performance or slow its decline with normal aging 71. More research is needed to identify the role of vitamin E, if any, in the management of cognitive impairment 72.

Neurodegenerative Diseases

The brain has a high oxygen consumption rate and abundant polyunsaturated fatty acids in the neuronal cell membranes. Researchers hypothesize that if cumulative free-radical damage to neurons over time contributes to cognitive decline and neurodegenerative diseases, such as Alzheimer’s disease, then ingestion of sufficient or supplemental antioxidants (such as vitamin E) might provide some protection 73. This hypothesis was supported by the results of a clinical trial in 341 patients with Alzheimer’s disease of moderate severity who were randomly assigned to receive a placebo, vitamin E (2,000 IU/day dl-alpha-tocopherol), a monoamine oxidase inhibitor (selegiline), or vitamin E and selegiline 74. Over 2 years, treatment with vitamin E and selegiline, separately or together, significantly delayed functional deterioration and the need for institutionalization compared to placebo. However, participants taking vitamin E experienced significantly more falls.

Scientists seeking to untangle the causes of Alzheimer’s, Parkinson’s, and other diseases of the brain and nervous system have focused on the role that free radical damage plays in these diseases’ development 75. But to date, there is little evidence as to whether vitamin E can help protect against these diseases or that it offers any benefit to people who already have these diseases.

Dementia

Some prospective studies suggest that vitamin E supplements, particularly in combination with vitamin C, may be associated with small improvements in cognitive function or lowered risk of Alzheimer’s disease and other forms of dementia, while other studies have failed to find any such benefit 76, 77, 78, 79. A three-year randomized controlled trial in people with mild cognitive impairment—often a precursor to Alzheimer’s disease—found that taking 2,000 IU of vitamin E daily failed to slow the progression to Alzheimer’s disease 80. Keep in mind, however, that the progression from mild cognitive impairment to Alzheimer’s disease can take many years, and this study was fairly short, so it is probably not the last word on vitamin E and dementia.

Parkinson’s disease

Some, but not all, prospective studies suggest that getting higher intakes of vitamin E from diet—not from high-dose supplements—is associated with a reduced risk of Parkinson’s disease 81, 82, 83. In people who already have Parkinson’s, high-dose vitamin E supplements do not slow the disease’s progression 84. Why the difference between vitamin E from foods versus that from supplements ? It’s possible that foods rich in vitamin E, such as nuts or legumes, contain other nutrients that protect against Parkinson’s disease. More research is needed.

Amyotrophic Lateral Sclerosis (ALS)

One large prospective study that followed nearly 1 million people for up to 16 years found that people who regularly took vitamin E supplements had a lower risk of dying from ALS than people who never took vitamin E supplements 85. More recently, a combined analysis of multiple studies with more than 1 million participants found that the longer people used vitamin E supplements, the lower their risk of ALS 86. Clinical trials of vitamin E supplements in people who already have ALS have generally failed to show any benefit, however 87. This may be a situation where vitamin E is beneficial for prevention, rather than treatment, but more research is needed.

Should men take vitamin E or selenium supplements for cancer prevention?

No. Scientists do not understand how these supplements really work and more importantly, the interactions that these supplements have together or with foods, drugs, or other supplements. There are no clinical trials that show a benefit from taking vitamin E or selenium to reduce the risk of prostate cancer or any other cancer or heart disease 88, 89, 90, 91, 92, 93. While the men in SELECT who took both vitamin E and selenium did not have a statistically significant increase in their risk for prostate cancer, they also did not have a reduced risk of prostate cancer or any other cancer or heart disease. SELECT researchers were surprised by the findings in the men who took both vitamin E and selenium, and while the 2014 analysis suggests possible reasons for the findings, the mechanism remains unclear 51.

Evidence to date is insufficient to support taking vitamin E to prevent cancer. In fact, daily use of large-dose vitamin E supplements (400 IU) may increase the risk of prostate cancer 94.

Vitamin E oil for Skin

Vitamin E is the most abundant lipophilic antioxidant found in human skin 95. In humans, levels of vitamin E in the epidermis are higher than the dermis 95. Although the predominant form of vitamin E in skin of unsupplemented individuals is alpha-tocopherol, skin may also contain measurable amounts of gamma-tocopherol 96 and other diet-derived tocopherols and tocotrienols 97.

Vitamin E first accumulates in the sebaceous glands before it is delivered to the skin surface through sebum 98. Following oral ingestion, it takes at least seven days before the vitamin E content of sebum is altered 99. There are no transport proteins specific for vitamin E in the skin. Sebum is secreted to the surface of the stratum corneum, where it concentrates in the lipid-rich extracellular matrix of this layer 96. Due to its lipophilic nature, vitamin E can also penetrate into all underlying layers of skin 100. Skin vitamin E levels are higher in individuals with increased sebum production, as well as in skin types that naturally produce more sebum (e.g., “oily’ skin on the face vs. drier skin on the arm) 100.

Exposures to UV light 101 or ozone 102 lower the vitamin E content in skin, primarily in the stratum corneum. Vitamin E concentrations in the human epidermis also decline with age 95. Since epidermal structure changes with age 103, this may be due to increased UV penetration of this layer.

Vitamin E deficiency may affect skin function, but there is little evidence from human studies. Vitamin E deficiency in rats has been reported to cause skin ulcerations 104 and changes in skin collagen cross-linking 105, but the underlying cause of these effects is unknown.

Many people believe that there are special healing qualities to vitamin E on skin. Anecdotal reports claim that vitamin E speeds wound healing and improves the cosmetic outcome of burns and other wounds. Many lay people use vitamin E on a regular basis to improve the outcome of scars and several physicians recommend topical vitamin E after skin surgery or resurfacing.

In a very small double blinded clinical trial 106 with 15 patients who had undergone skin cancer removal surgery. After the surgery, the patients were given two ointments each labeled A or B. A was a regular emollient, and the B was emollient mixed with vitamin E. The scars were randomly divided into parts A and B. Patients were asked to put the A ointment on part A and the B ointment on part B twice daily for 4 weeks. The physicians, a third blinded investigator and the patients independently evaluated the scars for cosmetic appearance on weeks 1, 4, and 12. The results of this study show that topically applied vitamin E does not help in improving the cosmetic appearance of scars and that the application of topical vitamin E may actually be detrimental to the cosmetic appearance of a scar. In 90% of the cases in this study, topical vitamin E either had no effect on, or actually worsened, the cosmetic appearance of scars. Of the patients studied, 33% developed a contact dermatitis to the vitamin E. Therefore the researchers conclude that use of topical vitamin E on surgical wounds should be discouraged 106.

Topical application

Topical application of vitamin E has been used in a wide variety of forms throughout history, ranging from the application of oils to the skin surface to the use of modern cosmetic formulations. Just as sebum provides a delivery mechanism for vitamin E to the stratum corneum, topical applications of vitamin E permeate the epidermis and dermis 107. The rate of percutaneous vitamin E absorption and factors that influence its penetration are largely unknown in humans, with a large range of concentrations and times used in various studies. It is generally assumed that solutions with vitamin E concentrations as low as 0.1% can increase vitamin E levels in the skin 108. Interestingly, vitamin E levels in the dermis increase greatly after topical application, likely accumulating in the sebaceous glands 107. However, although it is increased after topical delivery, the concentration of vitamin E in the dermis is lower than in the stratum corneum. Skin supplied only with dietary vitamin E primarily contains alpha- and gamma-tocopherol 99; by contrast, skin supplied with synthetic vitamin E topically can contain a mixture of different tocopherols and/or tocotrienols 109. In terms of penetration and absorption following topical application, tocotrienols and tocopherols accumulate in skin at varying rates, but the mechanisms governing these differences are unclear 107.

After topical application, vitamin E accumulates not only in cell membranes but also in the extracellular lipid matrix of the stratum corneum, where vitamin E contributes to antioxidant defenses. However, much of a topically applied dose of vitamin E alone will be destroyed in the skin following exposure to UV light 101. This suggests that although vitamin E is working as an antioxidant, it is unstable on its own and easily lost from the skin. Thus, improving the stability of topical applications with vitamin E is important. Products containing both vitamin C and vitamin E have shown greater efficacy in photoprotection than either antioxidant alone.

The stability of topical vitamin E solutions may also be increased by the use of vitamin E conjugates. These vitamin E derivatives are usually commercially produced esters of tocopherol (although tocotrienol esters have been formulated) that are resistant to oxidation but can still penetrate the skin layers. Vitamin E conjugates, however, do not have antioxidant functions. To be effective, the molecule conjugated to vitamin E must be removed by enzymes within a cell. Since the stratum corneum contains metabolically inactive cells and the remaining layers of the epidermis and dermis may contain a large volume of extracellular proteins, it is unclear how efficiently ester conjugates are converted to “free” vitamin E in skin. Depending on the compound and the model system used, the effectiveness of these formulations can vary greatly 110, and studies often do not compare the application of vitamin E conjugates to the application of unmodified vitamin E molecules.

Because vitamin E can absorb UV light to produce free radicals, there is the possibility that heavy sunlight exposure after topical application can cause skin reactions. However, concentrations of vitamin E between 0.1%-1.0% are generally considered safe and effective to increase vitamin E levels in the skin, but higher levels of α-tocopherol have been used with no apparent side effects 108. On the other hand, studies of dose-dependent vitamin E accumulation and effectiveness in skin protection are lacking. Some forms of vitamin E, especially ester conjugates, have led to adverse reactions in the skin, including allergic contact dermatitis and erythema. Although such reactions may be due to oxidation by-products, the emulsion creams used for topical delivery of compounds may also contribute to the observed effects 111.

Vitamin E functions in healthy skin

Photoprotection

The primary role of vitamin E in the skin is to prevent damage induced by free radicals and reactive oxygen species; therefore, the use of vitamin E in the prevention of ultraviolet (UV)-induced damage has been extensively studied. Although molecules in the vitamin E family can absorb light in the Ultraviolet B (UVB) spectrum, the “sunscreen” activity of vitamin E is considered limited since it cannot absorb Ultraviolet A (UVA) light or light in higher wavelengths of the Ultraviolet B (UVB) spectrum 112. Thus, the primary photoprotective effect of vitamin E is attributed to its role as a lipid-soluble antioxidant.

Many studies in cell culture models (in vitro studies) have found protective effects of vitamin E molecules on skin cells 113, but these models do not recreate the complex structure of skin tissues. Therefore, in vivo studies are needed.

Studies using orally administered vitamin E have reported mixed results on its photoprotective potential. An early study of vitamin E supplementation in hairless mice found no effect of dietary α-tocopherol acetate on UV-induced carcinogenesis 114. Three other mouse studies reported inhibition of UV-induced tumors in mice fed α-tocopherol acetate 115, but one of these studies utilized vitamin E doses that were toxic to animals when combined with the UV treatment 116. Another study in mice found a reduction of UV-induced DNA damage with dietary α-tocopherol acetate, but no effects on other free radical damage were observed in the skin 117. One human study reported that subjects taking 400 IU/day of α-tocopherol had reduced UV-induced lipid peroxidation in the skin but concluded there was no overall photoprotective effect 118. This was supported by another human study that found that 400 IU/day of α-tocopherol for six months provided no meaningful protection to skin 119. Furthermore, multiple human studies have shown no effect of vitamin E on the prevention or development of skin cancers 120.

In contrast to oral supplementation with α-tocopherol alone, multiple studies have found that the combination of vitamin C and vitamin E protects the skin against UV damage. Human subjects orally co-supplemented with vitamins C and E show increased Minimal Erythemal Dose, a measure of photoprotection from UV light in skin 121. The combination of the two vitamins was associated with lower amounts of DNA damage after UV exposure 122. Results of another study suggest a mixture of tocopherols and tocotrienols may be superior to α-tocopherol alone, as the mixture showed reduced sunburn reactions and tumor incidence after UV exposure in mice 123. However, further trials with dietary tocotrienol/tocopherol mixtures are needed in human subjects.

Topical application of vitamin E is generally effective for increasing photoprotection of the skin. In rodent models, the application of α-tocopherol or α-tocopherol acetate before UV exposure reduces UV-induced skin damage by reducing lipid peroxidation 124, limiting DNA damage 125, and reducing the many chemical and structural changes to skin after UV exposure 126. Vitamin E topical applications have also been shown to reduce UV-induced tumor formation in multiple mouse studies 115 and to reduce the effects of photo-activated toxins in the skin 127. Topical application of vitamin E also reduces the effects of UV radiation when applied after the initial exposure. In mice, α-tocopherol acetate prevents some of the erythema, edema, skin swelling, and skin thickening if applied immediately after UV exposure 128. A similar effect has been shown in rabbits, where applying α-tocopherol to skin immediately after UV increased the Minimal Erythemal Dose 129. While the greatest effect was seen when vitamin E was applied immediately after UV exposure, one study showed a significant effect of application eight hours after the insult 128. In human subjects, the use of vitamin E on skin lowers peroxidation of skin surface lipids 130, decreases erythema 131, and limits immune cell activation after UV exposure 132.

Like oral supplementation with vitamin C and vitamin E, topical preparations with both vitamins have also been successful. Together, the application of these antioxidants to the skin of animals before UV exposure has been shown to decrease sunburned cells 133, decrease DNA damage 134, inhibit erythema 133, and decrease skin pigmentation after UV exposure 135. Similar effects have been seen in human subjects 136.

While a majority of studies have found benefit of topical α-tocopherol, there is much less evidence for the activity of esters of vitamin E in photoprotection 130. As described above, vitamin E esters require cellular metabolism to produce “free” vitamin E. Thus, topical use of vitamin E esters may provide only limited benefit or may require a delay after administration to provide significant UV protection.

Anti-inflammatory effects

Vitamin E has been considered an anti-inflammatory agent in the skin, as several studies have supported its prevention of inflammatory damage after UV exposure. As mentioned above, topical vitamin E can reduce UV-induced skin swelling, skin thickness, erythema, and edema — all signs of skin inflammation. In cultured keratinocytes, α-tocopherol and γ-tocotrienol have been shown to decrease inflammatory prostaglandin synthesis, interleukin production, and the induction of cyclooxygenase-2 (COX-2) and NADPH oxidase by UV light 137, as well as limit inflammatory responses to lipid hydroperoxide exposure 138. In mice, dietary γ-tocotrienol suppresses UV-induced COX-2 expression in the skin 139. Furthermore, topical application of α-tocopherol acetate or a γ-tocopherol derivative inhibited the induction of COX-2 and nitric oxide synthase (iNOS) following UV exposure 140. In vitro studies have shown similar anti-inflammatory effects of α- and γ-tocopherol on immune cells 141.

Many of these anti-inflammatory effects of vitamin E supplementation have been reported in combination with its photoprotective effects, making it difficult to distinguish an anti-inflammatory action from an antioxidant action that would prevent inflammation from initially occurring. Despite these limitations, there are many reports of vitamin E being used successfully in chronic inflammatory skin conditions, either alone 142 or in combination with vitamin C 143 or vitamin D 144, thus suggesting a true anti-inflammatory action.

Wound healing

As mentioned above, skin lesions have been reported in rats suffering from vitamin E deficiency, although their origin is unclear. Vitamin E levels decrease rapidly at the site of a cutaneous wound, along with other skin antioxidants, such as vitamin C or glutathione 145. Since skin antioxidants slowly increase during normal wound healing, these observations have stimulated additional studies on the effect of vitamin E on the wound healing process. However, no studies have demonstrated a positive effect of vitamin E supplementation on wound repair in normal skin. Studies have shown that α-tocopherol supplementation decreases wound closure time in diabetic mice, but no effects have been observed in normal mice 146. Vitamin E increases the breaking strength of wounds pre-treated with ionizing radiation 147, but this is likely due to antioxidant functions at the wound site akin to a photoprotective effect. In contrast, intramuscular injection of α-tocopherol acetate in rats has been suggested to decrease collagen synthesis and inhibit wound repair 148.

In humans, studies with topical alpha-tocopherol have either found no effects on wound healing or appearance or have found negative effects on the appearance of scar tissue 149, 150. However, these studies are complicated by a high number of skin reactions to the vitamin E preparations, possibly due to uncontrolled formation of tocopherol radicals in the solutions used. Despite these results, vitamin E, along with zinc and vitamin C, is included in oral therapies for pressure ulcers (bed sores) and burns 151, 152.

Other functions

There is limited information concerning the effects of vitamin E supplementation on photodamage, which is commonly observed as skin wrinkling. Although vitamin E can protect mice exposed to UV from excessive skin wrinkling, this is a photoprotective effect rather than treatment of pre-existing wrinkles. Other reports using vitamin E to treat photodamage or reduce wrinkles are poorly controlled studies or unpublished observations 153. An analysis of the dietary intake of Japanese women showed no correlation between vitamin E consumption and skin wrinkling 154.

Vitamin E and oils containing tocopherols or tocotrienols have been reported to have moisturizing properties, but data supporting these roles are limited. Cross-sectional studies have shown no association between vitamin E consumption and skin hydration in healthy men and women 154, 155. However, two small studies have shown topical application of vitamin E can improve skin water-binding capacity after two to four weeks of use 156, 157. Long-term studies with topical vitamin E are needed to establish if these moisturizing effects can be sustained.

Environmental pollutants like ozone can decrease vitamin E levels in the skin 158 and lead to free radical damage that may compound the effects of UV exposure 102. Although not well studied, topical applications of vitamin E may reduce pollution-related free radical damage 109.

Vitamin E oil for skin summary

Vitamin E is an integral part of the skin’s antioxidant defenses, primarily providing protection against UV radiation and other free radicals that may come in contact with the epidermis. Oral supplementation with only vitamin E may not provide adequate protection for the skin, and co-supplementation of vitamin E and vitamin C may be warranted to effectively increase the photoprotection of skin through the diet. However, topical vitamin E seems to be an effective mechanism for both delivery to the skin and providing a photoprotective effect. Additional anti-inflammatory effects of topical vitamin E have been seen in the skin, although more studies are needed to determine if vitamin E primarily works as a free-radical scavenger or can have other effects on inflammatory signaling. Vitamin E is available commercially as a variety of synthetic derivatives, but the limited cellular metabolism in skin layers makes the use of such products problematic. Use of unesterified vitamin E, similar to that found in natural sources, has provided the most consistent data concerning its topical efficacy. The vitamin E family consists of eight different tocopherols and tocotrienols, and it will be important for future studies to determine if one or more of these molecules can have unique effects on skin function.

How much vitamin E do you need?

Intake recommendations for vitamin E and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies 14. DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender, include:

  • Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy people.
  • Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
  • Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects.

The FNB’s vitamin E recommendations are for alpha-tocopherol alone, the only form maintained in plasma. The FNB based these recommendations primarily on serum levels of the nutrient that provide adequate protection in a test measuring the survival of erythrocytes when exposed to hydrogen peroxide, a free radical. Acknowledging “great uncertainties” in these data, the FNB has called for research to identify other biomarkers for assessing vitamin E requirements.

RDAs for vitamin E are provided in milligrams (mg) and are listed in Table 1. Because insufficient data are available to develop RDAs for infants, AIs were developed based on the amount of vitamin E consumed by healthy breastfed babies.

At present, the vitamin E content of foods and dietary supplements is listed on labels in international units (IUs), a measure of biological activity rather than quantity. Naturally sourced vitamin E is called RRR-alpha-tocopherol (commonly labeled as d-alpha-tocopherol); the synthetically produced form is all rac-alpha-tocopherol (commonly labeled as dl-alpha-tocopherol). Conversion rules are as follows:

To convert from mg to IU:

  • 1 mg of alpha-tocopherol is equivalent to 1.49 IU of the natural form or 2.22 IU of the synthetic form.

To convert from IU to mg:

  • 1 IU of the natural form is equivalent to 0.67 mg of alpha-tocopherol.
  • 1 IU of the synthetic form is equivalent to 0.45 mg of alpha-tocopherol.

Table 1 lists the RDAs for alpha-tocopherol in both mg and IU of the natural form; for example, 15 mg x 1.49 IU/mg = 22.4 IU. The corresponding value for synthetic alpha-tocopherol would be 33.3 IU (15 mg x 2.22 IU/mg).

The amount of vitamin E you need each day depends on your age. Average daily recommended intakes are listed below in milligrams (mg) and in International Units (IU). Package labels list the amount of vitamin E in foods and dietary supplements in IU.

Table 1. Recommended Dietary Allowances (RDAs) for Vitamin E (Alpha-Tocopherol)

Life StageRecommended Amount
Birth to 6 months4 mg (6 IU)
Infants 7–12 months5 mg (7.5 IU)
Children 1–3 years6 mg (9 IU)
Children 4–8 years7 mg (10.4 IU)
Children 9–13 years11 mg (16.4 IU)
Teens 14–18 years15 mg (22.4 IU)
Adults15 mg (22.4 IU)
Pregnant teens and women15 mg (22.4 IU)
Breastfeeding teens and women19 mg (28.4 IU)

What foods provide vitamin E?

Numerous foods provide vitamin E. Nuts, seeds, and vegetable oils are among the best sources of alpha-tocopherol, and significant amounts are available in green leafy vegetables and fortified cereals (see Table 2 for a more detailed list) 159. Most vitamin E in American diets is in the form of gamma-tocopherol from soybean, canola, corn, and other vegetable oils and food products 10.

The U.S. Department of Agriculture’s (USDA’s) Nutrient Database website 160 lists the nutrient content of many foods, including, in some cases, the amounts of alpha-, beta-, gamma-, and delta-tocopherol arranged by nutrient content 161 and by food name 162.

Vitamin E is found naturally in foods and is added to some fortified foods. You can get recommended amounts of vitamin E by eating a variety of foods including the following:

  • Vegetable oils like wheat germ, sunflower, and safflower oils are among the best sources of vitamin E. Corn and soybean oils also provide some vitamin E.
  • Nuts (such as peanuts, hazelnuts, and, especially, almonds) and seeds (like sunflower seeds) are also among the best sources of vitamin E.
  • Green vegetables, such as spinach and broccoli, provide some vitamin E.
  • Food companies add vitamin E to some breakfast cereals, fruit juices, margarines and spreads, and other foods. To find out which ones have vitamin E, check the product labels.

Vitamin E from natural (food) sources is commonly listed as “d-alpha-tocopherol” on food packaging and supplement labels. Synthetic (laboratory-made) vitamin E is commonly listed as “dl-alpha-tocopherol”. The natural form is more potent. For example, 100 IU of natural vitamin E is equal to about 150 IU of the synthetic form.

Some vitamin E supplements provide other forms of the vitamin, such as gamma-tocopherol, tocotrienols, and mixed tocopherols. Scientists do not know if any of these forms are superior to alpha-tocopherol in supplements.

Table 2. Selected Food Sources of Vitamin E (Alpha-Tocopherol)

FoodMilligrams (mg)
per serving
Percent DV*
Wheat germ oil, 1 tablespoon20.3100
Sunflower seeds, dry roasted, 1 ounce7.437
Almonds, dry roasted, 1 ounce6.834
Sunflower oil, 1 tablespoon5.628
Safflower oil, 1 tablespoon4.625
Hazelnuts, dry roasted, 1 ounce4.322
Peanut butter, 2 tablespoons2.915
Peanuts, dry roasted, 1 ounce2.211
Corn oil, 1 tablespoon1.910
Spinach, boiled, ½ cup1.910
Broccoli, chopped, boiled, ½ cup1.26
Soybean oil, 1 tablespoon1.16
Kiwifruit, 1 medium1.16
Mango, sliced, ½ cup0.74
Tomato, raw, 1 medium0.74
Spinach, raw, 1 cup0.63

Footnote: *DV = Daily Value. DVs were developed by the FDA to help consumers compare the nutrient content of different foods within the context of a total diet. The DV for vitamin E is 30 IU (approximately 20 mg of natural alpha-tocopherol) for adults and children age 4 and older. However, the FDA does not require food labels to list vitamin E content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

[Source 163]
foods with vitamin E

Are you getting enough vitamin E?

The diets of most Americans provide less than the recommended amounts of vitamin E. Nevertheless, healthy people rarely show any clear signs that they are not getting enough vitamin E. The FNB suggests that mean intakes of vitamin E among healthy adults are probably higher than the RDA but cautions that low-fat diets might provide insufficient amounts unless people make their food choices carefully by, for example, increasing their intakes of nuts, seeds, fruits, and vegetables.

What happens if you don’t get enough vitamin E?

Vitamin E deficiency is very rare in healthy people. It is almost always linked to certain diseases where fat is not properly digested or absorbed. Examples include Crohn’s disease, cystic fibrosis, and certain rare genetic diseases such as abetalipoproteinemia and ataxia with vitamin E deficiency (AVED). Vitamin E needs some fat for the digestive system to absorb it.

Vitamin E deficiency can cause nerve and muscle damage that results in loss of feeling in the arms and legs, loss of body movement control, muscle weakness, and vision problems. Another sign of deficiency is a weakened immune system.

Vitamin E deficiency

Dietary vitamin E deficiency is common in developing countries; deficiency among adults in developed countries is uncommon and usually due to fat malabsorption 14. Premature babies of very low birth weight (<1,500 grams) might be deficient in vitamin E. Vitamin E supplementation in these infants might reduce the risk of some complications, such as those affecting the retina, but they can also increase the risk of infections 164.

Because the digestive tract requires fat to absorb vitamin E, people with fat-malabsorption disorders are more likely to become deficient than people without such disorders. Deficiency symptoms include peripheral neuropathy, ataxia, skeletal myopathy, retinopathy, and impairment of the immune response 14, 165. People with Crohn’s disease, cystic fibrosis, or an inability to secrete bile from the liver into the digestive tract, for example, often pass greasy stools or have chronic diarrhea; as a result, they sometimes require water-soluble forms of vitamin E, such as tocopheryl polyethylene glycol-1000 succinate 166.

Some people with abetalipoproteinemia, a rare inherited disorder resulting in poor absorption of dietary fat, require enormous doses of supplemental vitamin E (approximately 100 mg/kg or 5–10 g/day) 166. Vitamin E deficiency secondary to abetalipoproteinemia causes such problems as poor transmission of nerve impulses, muscle weakness, and retinal degeneration that leads to blindness 167. Ataxia and vitamin E deficiency (AVED) is another rare, inherited disorder in which the liver’s alpha-tocopherol transfer protein is defective or absent. People with AVED have such severe vitamin E deficiency that they develop nerve damage and lose the ability to walk unless they take large doses of supplemental vitamin E 167.

Vitamin E deficiency causes fragility of red blood cells and degeneration of neurons, particularly peripheral axons and posterior column neurons.

The main symptoms of vitamin E deficiency are hemolytic anemia and neurologic deficits. Diagnosis is based on measuring the ratio of plasma alpha-tocopherol to total plasma lipids; a low ratio suggests vitamin E deficiency. Treatment consists of oral vitamin E, given in high doses if there are neurologic deficits or if deficiency results from malabsorption.

Vitamin E deficiency causes

In developed countries, it is unlikely that vitamin E deficiency occurs due to diet intake insufficiency and the more common causes are below.

  • Premature low birth weight infants with a weight less than 1500 grams (3.3 pounds)
  • Mutations in the tocopherol transfer protein causing impaired fat metabolism
  • Disrupted fat malabsorption as the small intestine requires fat to absorb vitamin E
  • Patients with cystic fibrosis patients fail to secrete pancreatic enzymes to absorb vitamins A, D, E, and K
  • Short-bowel syndrome patients may take years to develop symptoms. Surgical resection, mesenteric vascular thrombosis, and pseudo-obstruction are a few examples of this issue
  • Chronic cholestatic hepatobiliary disease leads to a decrease in bile flow and micelle formation that is needed for vitamin E absorption
  • Crohn’s disease, exocrine pancreatic insufficiency, and liver disease may all not absorb fat
  • Abetalipoproteinemia an autosomal-recessive disease causes an error in lipoprotein production and transportation
  • Isolated vitamin E deficiency syndrome an autosomal recessive disorder of chromosome arm 8q

In developing countries, the most common cause is inadequate intake of vitamin E.

Vitamin E deficiency signs and symptoms

Vitamin E deficiency patients may present with one of the causative histories listed along with symptoms of ataxia, difficulty with upward gaze, and hyporeflexia. Not as common symptoms include muscle weakness and visual-field constriction. The most severe symptoms are blindness, dementia, and cardiac arrhythmias.

If vitamin E deficiency is expected, a full neurological exam is recommended as well as a standard physical exam. Patients presenting early may show hyporeflexia, decreased night vision, loss/decreased vibratory sense, however, have normal cognition. A more moderate stage of this deficiency may show limb and truncal ataxia, profuse muscle weakness, and limited upward gaze. Late presentations may show cardiac arrhythmias and possible blindness with reduced cognition. Ataxia is the most common exam finding.

Patients that have abetalipoproteinemia have eye problems often including pigmented retinopathy and visual field issues. However, patients suffering from cholestatic liver disease often have personality and behavioral disorders.

Vitamin E deficiency diagnosis

A low alpha-tocopherol level or low ratio serum alpha-tocopherol to serum lipids measurement is the mainstay of diagnosis. In adults, alpha-tocopherol levels should be less than 5 mcg/mL. In an adult with hyperlipidemia, the abnormal lipids may affect the vitamin E levels and a serum alpha-tocopherol to lipids level, needing to be less than 0.8 mg/g) is more accurate. A pediatric patient with abetalipoproteinemia will have serum alpha-tocopherol levels that are not detectable.

Vitamin E deficiency treatment

Treatment addresses the underlying cause of the deficiency (fat malabsorption, fat metabolism disorders, among others) and then provide oral vitamin E supplementation. Also, a modification in diet can assist in the supplementation, increase intake of leafy vegetables, whole grains, nuts, seeds, vegetable oils and fortified cereals is highly recommended. Though normally presented in our diets, adults need 15mg of vitamin E per day. A supplement of 15 to 25 mg/kg once per day or mixed tocopherols 200 IU can both be used. If a patient has issues with the small intestine and/or oral ingestion intramuscular injection is necessary 168. The recommended daily allowance of alpha-tocopherol is as follows.

  • Age 0 to 6 months: 3 mg
  • Age 6 to 12 months: 4 mg
  • Age 1 to 3 years: 6 mg
  • Age 4 to 10 years: 7 mg
  • Adults and elderly patients: 10 mg

Replacement recommendations vary by causing disease and are as follows 169:

  • Abetalipoproteinemia: 100 to 200 IU/kg per day
  • Chronic cholestasis: 15 to 25 IU/kg per day
  • Cystic fibrosis: 5 to 10 IU/kg per day
  • Short-bowel syndrome: 200 to 3600 IU per day
  • Isolated vitamin E deficiency: 800 to 3600 IU per day

Vitamin E deficiency prognosis

If left untreated, symptoms may worsen. However, once diagnosed, the outcome is very good as most symptoms will resolve quickly. However, as vitamin E deficiency becomes more pronounced, the therapy will be more restricted. Patients who are at risk for vitamin E deficiency should be tested and evaluated regularly.

Vitamin E Side Effects and Toxicity

Research has not found any adverse effects from consuming vitamin E in food 14. However, high doses of alpha-tocopherol supplements can cause hemorrhage, especially in patients already on anticoagulation or antiplatelet therapy and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation. Two clinical trials have found an increased risk of hemorrhagic stroke in participants taking alpha-tocopherol; one trial included Finnish male smokers who consumed 50 mg/day for an average of 6 years  170 and the other trial involved a large group of male physicians in the United States who consumed 400 IU every other day for 8 years 171. Because the majority of physicians in the latter study were also taking aspirin, this finding could indicate that vitamin E has a tendency to cause bleeding.

Bleeding episodes can occur anywhere in the body, and serious life-threatening hemorrhagic strokes have been reported. Other vitamin E toxicity complications include gastrointestinal manifestations, weakness, fatigue, and emotional lability. The treatment for vitamin E toxicity includes discontinuation of vitamin E supplementation and consideration of vitamin K therapy if serious bleeding occurs. To prevent vitamin E toxicity, supplementation of vitamin E should be kept to a lower dosage.

The Food and Nutrition Board at the Institute of Medicine of The National Academies has established Tolerable Upper Intake Levels (ULs – the maximum daily intake unlikely to cause adverse health effects) for vitamin E based on the potential for hemorrhagic effects (see Table 3). The Tolerable Upper Intake Levels (ULs) apply to all forms of supplemental alpha-tocopherol, including the eight stereoisomers present in synthetic vitamin E. Doses of up to 1,000 mg/day (1,500 IU/day of the natural form or 1,100 IU/day of the synthetic form) in adults appear to be safe, although the data are limited and based on small groups of people taking up to 3,200 mg/day of alpha-tocopherol for only a few weeks or months. Long-term intakes above the Tolerable Upper Intake Level (UL) increase the risk of adverse health effects 14. Vitamin E Tolerable Upper Intake Levels (ULs) for infants have not been established.

Table 3. Tolerable Upper Intake Levels (ULs) for Vitamin E

AgeMaleFemalePregnancyLactation
1–3 years200 mg
(300 IU)
200 mg
(300 IU)
4–8 years300 mg
(450 IU)
300 mg
(450 IU)
9–13 years600 mg
(900 IU)
600 mg
(900 IU)
14–18 years800 mg
(1,200 IU)
800 mg
(1,200 IU)
800 mg
(1,200 IU)
800 mg
(1,200 IU)
19+ years1,000 mg
(1,500 IU)
1,000 mg
(1,500 IU)
1,000 mg
(1,500 IU)
1,000 mg
(1,500 IU)
[Source 14 ]

Can vitamin E be harmful?

Eating vitamin E in foods is not risky or harmful 172. A patient who consumes vitamin E in their diet has, on average, a level of circulating alpha-tocopherol of approximately 20 micromol/L. Patients that have additional vitamin E supplementation have levels of 30 micromol/L or greater.

In supplement form, however, high doses of vitamin E might increase the risk of bleeding (by reducing the blood’s ability to form clots after a cut or injury) and of serious bleeding in the brain (known as hemorrhagic stroke) 173. High doses of alpha-tocopherol supplements can cause hemorrhage and interrupt blood coagulation in animals and test tube studies data suggest that high doses inhibit platelet aggregation. Two clinical trials have found an increased risk of hemorrhagic stroke in participants taking alpha-tocopherol; one trial included Finnish male smokers who consumed 50 mg/day for an average of 6 years 174 and the other trial involved a large group of male physicians in the United States who consumed 400 IU (180 mg) of synthetic vitamin E every other day for 8 years 30. Because the majority of physicians in the latter study were also taking aspirin, this finding could indicate that vitamin E has a tendency to cause bleeding.

Because of this risk, the upper limit for adults is 1,500 IU/day for supplements made from the natural form of vitamin E and 1,100 IU/day for supplements made from synthetic vitamin E. The upper limits for children are lower than those for adults. Some research suggests that taking vitamin E supplements even below these upper limits might cause harm. In one study, for example, men who took 400 IU of vitamin E each day for several years had an increased risk of prostate cancer.

Two meta-analyses of randomized trials have also raised questions about the safety of large doses of vitamin E, including doses lower than the Tolerable Upper Intake Level (UL). These meta-analyses linked supplementation to small but statistically significant increases in all-cause mortality. One analysis found an increased risk of death at doses of 400 IU/day (form not specified), although the risk began to increase at 150 IU 175. In the other analysis of studies of antioxidant supplements for disease prevention, the highest quality trials revealed that vitamin E, administered singly (dose range 10 IU–5,000 IU/day; mean 569 IU [form not specified]) or combined with up to four other antioxidants, significantly increased mortality risk 176.

The implications of these analyses for the potential adverse effects of high-dose vitamin E supplements are unclear 6. Participants in the studies included in these analyses were typically middle-aged or older and had chronic diseases or related risk factors. These participants often consumed other supplements in addition to vitamin E. Some of the studies analyzed took place in developing countries in which nutritional deficiencies are common. A review of the subset of studies in which vitamin E supplements were given to healthy individuals for the primary prevention of chronic disease found no convincing evidence that the supplements increased mortality 177.

However, results from the recently published, large SELECT trial show that vitamin E supplements (400 IU/day [180 mg] as dl-alpha-tocopheryl acetate) may harm adult men in the general population by increasing their risk of prostate cancer 178. Follow-up studies are assessing whether the cancer risk was associated with baseline blood levels of vitamin E and selenium prior to supplementation as well as whether changes in one or more genes might increase a man’s risk of developing prostate cancer while taking vitamin E.

Vitamin E toxicity complications

Although the major hazardous complications of elevated vitamin E levels include bleeding, there have been others mentioned. These include thyroid problems, weakness, emotional disorder, gastrointestinal derangement, tenderness of breasts, and thrombophlebitis 173.

Vitamin E toxicity diagnosis

To detect vitamin E toxicity, serum levels of circulating alpha-tocopherol can be obtained. The average range of plasma alpha-tocopherol in a patient that eats a well-balanced diet is 20 micromoles/liter 179. A patient on vitamin E supplementation may have plasma levels of 30 micromoles/liter or greater 179. The normal lab range for circulating alpha-tocopherols is 5.7 to 19.9 mg/L 180. The levels of circulating alpha-tocopherol are very dependent on the lipid content of the blood. In patients with extremely high or extremely low cholesterol levels, the levels of circulating alpha-tocopherol are not an accurate measure of vitamin E. In a patient with average cholesterol levels, the levels of circulating alpha-tocopherol are still not an accurate measure of vitamin E. This is due to the upregulation of biliary and urinary excretion once vitamin E levels are increased in the body 181. Because of these irregularities in vitamin E metabolism, there is no set cut-off level of circulating alpha-tocopherols considered universally toxic.

In a study performed on patients with intracranial hemorrhages and taking vitamin E supplementation, alpha-tocopherol levels ranged from 23.3 micromoles/L to 46.7 micromoles/L in patients that were discovered to have intracranial hemorrhages 180. In another study that correlated the vitamin E levels and risk of bleeding in patients taking oral anticoagulation, a ratio of circulating alpha-tocopherols to total serum cholesterol concentration was used. This was thought to most accurately represent the true circulating vitamin E levels 182. Although there is a concern regarding the reliability of these circulating levels of alpha-tocopherols correlating to vitamin E levels, this is still the most widely used test in the literature regarding quantifying vitamin E when describing its effects.

Vitamin E toxicity treatment

The mainstay treatment for vitamin E toxicity is stopping the exogenous vitamin supplementation. This is effective since vitamin E toxicity does not occur unless there is an exogenous supplementation 172. If there is significant bleeding, vitamin K supplementation should be considered in patients taking vitamin E supplementation. There can be inhibition of a clotting cascade that is vitamin K dependent when there are higher concentrations of vitamin E. This can occur whether the patient is on warfarin or not. Vitamin E also impedes platelet aggregation. This can occur regardless of whether the patient takes antiplatelet agents. Therefore, giving vitamin K to patients who are actively bleeding or have a severe hemorrhage should be considered 182.

References
  1. Traber MG. Vitamin E. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006;396-411.
  2. Verhagen H, Buijsse B, Jansen E, Bueno-de-Mesquita B. The state of antioxidant affairs. Nutr Today 2006;41:244-50.
  3. Vitamin E. https://lpi.oregonstate.edu/mic/vitamins/vitamin-E
  4. Traber MG. Vitamin E. In: Erdman JWJ, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed. Washington, D.C.: Wiley-Blackwell; 2012:214-229.
  5. Trpkovic A, Resanovic I, Stanimirovic J, Radak D, Mousa SA, Cenic-Milosevic D, Jevremovic D, Isenovic ER. Oxidized low-density lipoprotein as a biomarker of cardiovascular diseases. Crit Rev Clin Lab Sci. 2015;52(2):70-85. doi: 10.3109/10408363.2014.992063
  6. Vitamin E. https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional
  7. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, D.C.: National Academy Press; 2000.
  8. Traber MG. Vitamin E regulatory mechanisms. Annu Rev Nutr 2007;27:347-62. https://www.ncbi.nlm.nih.gov/pubmed/17439363?dopt=Abstract
  9. Sen CK, Khanna S, Roy S. Tocotrienols: vitamin E beyond tocopherols. Life Sci 2006;78:2088-98. Sen CK, Khanna S, Roy S. Tocotrienols: vitamin E beyond tocopherols. Life Sci 2006;78:2088-98.
  10. Dietrich M, Traber MG, Jacques PF, Cross CE, Hu Y, Block G. Does γ-tocopherol play a role in the primary prevention of heart disease and cancer? A review. Am J Coll Nutr 2006;25:292-9. https://www.ncbi.nlm.nih.gov/pubmed/16943450?dopt=Abstract
  11. Merck Sharp & Dohme Corp., Merck Manual. Vitamin E (Tocopherol). https://www.merckmanuals.com/professional/nutritional-disorders/vitamin-deficiency,-dependency,-and-toxicity/vitamin-e
  12. Food Labeling: Revision of the Nutrition and Supplement Facts Labels. https://www.federalregister.gov/documents/2016/05/27/2016-11867/food-labeling-revision-of-the-nutrition-and-supplement-facts-labels
  13. Food Labeling: Revision of the Nutrition and Supplement Facts Labels and Serving Sizes of Foods That Can Reasonably Be Consumed at One Eating Occasion; Dual-Column Labeling; Updating, Modifying, and Establishing Certain Reference Amounts Customarily Consumed; Serving Size for Breath Mints; and Technical Amendments; Proposed Extension of Compliance Dates. https://www.federalregister.gov/documents/2017/10/02/2017-21019/food-labeling-revision-of-the-nutrition-and-supplement-facts-labels-and-serving-sizes-of-foods-that
  14. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. https://www.nap.edu/catalog/9810/dietary-reference-intakes-for-vitamin-c-vitamin-e-selenium-and-carotenoids
  15. Ford ES, Ajani UA, Mokdad AH. Brief communication: the prevalence of high intake of vitamin E from the use of supplements among U.S. adults. Ann Intern Med 2005;143:116-20. https://www.ncbi.nlm.nih.gov/pubmed/16027453?dopt=Abstract
  16. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001 Nov 29;345(22):1583-92. doi: 10.1056/NEJMoa011090
  17. Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. 2008 Jun 4;100(11):773-83. doi: 10.1093/jnci/djn148
  18. Block KI, Koch AC, Mead MN, Tothy PK, Newman RA, Gyllenhaal C. Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials. Cancer Treat Rev. 2007 Aug;33(5):407-18. doi: 10.1016/j.ctrv.2007.01.005
  19. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328:1444-9. https://www.ncbi.nlm.nih.gov/pubmed/8479463
  20. Rimm EB, Stampfer MJ. Antioxidants for vascular disease. Med Clin North Am. 2000;84:239-49. https://www.ncbi.nlm.nih.gov/pubmed/10685137
  21. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999;354:447-55. https://www.ncbi.nlm.nih.gov/pubmed/10465168
  22. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:154-60. https://www.ncbi.nlm.nih.gov/pubmed/10639540
  23. 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;293:1338-47. https://www.ncbi.nlm.nih.gov/pubmed/15769967
  24. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR; HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005 Mar 16;293(11):1338-47. doi: 10.1001/jama.293.11.1338
  25. Brown BG, Crowley J. Is there any hope for vitamin E? JAMA. 2005 Mar 16;293(11):1387-90. doi: 10.1001/jama.293.11.1387
  26. Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes M, Gordon DJ, Proschan M, Younes N, Verter JI. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. 2002 Nov 20;288(19):2432-40. doi: 10.1001/jama.288.19.2432
  27. Kris-Etherton PM, Lichtenstein AH, Howard BV, Steinberg D, Witztum JL. Antioxidant vitamin supplements and cardiovascular disease. Circulation. 2004;110:637-41. https://www.ncbi.nlm.nih.gov/pubmed/15289389
  28. Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. JAMA. 2005 Jul 6;294(1):56-65. doi: 10.1001/jama.294.1.56
  29. Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women’s Health Study. Circulation. 2007;116:1497-503. https://www.ncbi.nlm.nih.gov/pubmed/17846285
  30. Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2008 Nov 12;300(18):2123-33. doi: 10.1001/jama.2008.600
  31. Hercberg S, Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004;164:2335-42. https://www.ncbi.nlm.nih.gov/pubmed/15557412
  32. 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;300:2123-33. https://www.ncbi.nlm.nih.gov/pubmed/18997197
  33. 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. 2008;28:341-7. https://www.ncbi.nlm.nih.gov/pubmed/18032779
  34. Blumberg JB, Frei B. Why clinical trials of vitamin E and cardiovascular diseases may be fatally flawed. Commentary on “The relationship between dose of vitamin E and suppression of oxidative stress in humans.” Free Radic Biol Med 2007;43:1374-6. https://www.ncbi.nlm.nih.gov/pubmed/17936183
  35. Weitberg AB, Corvese D. Effect of vitamin E and beta-carotene on DNA strand breakage induced by tobacco-specific nitrosamines and stimulated human phagocytes. J Exp Clin Cancer Res. 1997 Mar;16(1):11-4.
  36. Hunter DJ, Manson JE, Colditz GA, et al. A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med. 1993;329:234-40. https://www.ncbi.nlm.nih.gov/pubmed/8292129
  37. Willett WC, Polk BF, Underwood BA, et al. Relation of serum vitamins A and E and carotenoids to the risk of cancer. N Engl J Med. 1984;310:430-4. https://www.ncbi.nlm.nih.gov/pubmed/6537988
  38. Chan JM, Stampfer MJ, Ma J, Rimm EB, Willett WC, Giovannucci EL. Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev. 1999;8:893-9. https://www.ncbi.nlm.nih.gov/pubmed/10548318
  39. van Dam RM, Huang Z, Giovannucci E, et al. Diet and basal cell carcinoma of the skin in a prospective cohort of men. Am J Clin Nutr. 2000;71:135-41. https://www.ncbi.nlm.nih.gov/pubmed/10617958
  40. Wu K, Willett WC, Chan JM, et al. A prospective study on supplemental vitamin e intake and risk of colon cancer in women and men. Cancer Epidemiol Biomarkers Prev. 2002;11:1298-304. https://www.ncbi.nlm.nih.gov/pubmed/12433706
  41. Fung TT, Spiegelman D, Egan KM, Giovannucci E, Hunter DJ, Willett WC. Vitamin and carotenoid intake and risk of squamous cell carcinoma of the skin. Int J Cancer. 2003;103:110-5. https://www.ncbi.nlm.nih.gov/pubmed/12455062
  42. Feskanich D, Willett WC, Hunter DJ, Colditz GA. Dietary intakes of vitamins A, C, and E and risk of melanoma in two cohorts of women. Br J Cancer. 2003;88:1381-7. https://www.ncbi.nlm.nih.gov/pubmed/12778065
  43. Cho E, Spiegelman D, Hunter DJ, et al. Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:713-20. https://www.ncbi.nlm.nih.gov/pubmed/12917201
  44. Cho E, Hunter DJ, Spiegelman D, et al. Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: a pooled analysis of 8 prospective studies. Int J Cancer. 2006;118:970-8. https://www.ncbi.nlm.nih.gov/pubmed/16152626
  45. Lee JE, Giovannucci E, Smith-Warner SA, Spiegelman D, Willett WC, Curhan GC. Intakes of fruits, vegetables, vitamins A, C, and E, and carotenoids and risk of renal cell cancer. Cancer Epidemiol Biomarkers Prev. 2006;15:2445-52. https://www.ncbi.nlm.nih.gov/pubmed/17164369
  46. 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;90:440-6. https://www.ncbi.nlm.nih.gov/pubmed/9521168
  47. Kirsh VA, Hayes RB, Mayne ST, et al. Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst. 2006;98:245-54. https://www.ncbi.nlm.nih.gov/pubmed/16478743
  48. 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. https://www.ncbi.nlm.nih.gov/pubmed/17943452
  49. 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;301:39-51. https://www.ncbi.nlm.nih.gov/pubmed/19066370
  50. Klein EA, Thompson IM, Jr., Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306:1549-56. www.ncbi.nlm.nih.gov/pubmed/21990298
  51. National Cancer Institute. Selenium and Vitamin E Cancer Prevention Trial (SELECT): Questions and Answers. https://www.cancer.gov/types/prostate/research/select-trial-results-qa
  52. 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):2123-33.
  53. 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;301:52-62. https://www.ncbi.nlm.nih.gov/pubmed/19066368
  54. Bostick RM, Potter JD, McKenzie DR, Sellers TA, Kushi LH, Steinmetz KA, Folsom AR. Reduced risk of colon cancer with high intake of vitamin E: the Iowa Women’s Health Study. Cancer Res. 1993 Sep 15;53(18):4230-7
  55. Wu K, Willett WC, Chan JM, Fuchs CS, Colditz GA, Rimm EB, Giovannucci EL. A prospective study on supplemental vitamin e intake and risk of colon cancer in women and men. Cancer Epidemiol Biomarkers Prev. 2002 Nov;11(11):1298-304.
  56. Graham S, Zielezny M, Marshall J, Priore R, Freudenheim J, Brasure J, Haughey B, Nasca P, Zdeb M. Diet in the epidemiology of postmenopausal breast cancer in the New York State Cohort. Am J Epidemiol. 1992 Dec 1;136(11):1327-37. doi: 10.1093/oxfordjournals.aje.a116445
  57. Jacobs EJ, Henion AK, Briggs PJ, Connell CJ, McCullough ML, Jonas CR, Rodriguez C, Calle EE, Thun MJ. Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women. Am J Epidemiol. 2002 Dec 1;156(11):1002-10. doi: 10.1093/aje/kwf147
  58. Evans J. Primary prevention of age related macular degeneration. BMJ. 2007 Oct 13;335(7623):729. doi: 10.1136/bmj.39351.478924.BE
  59. Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ. Vitamin E supplementation and macular degeneration: randomised controlled trial. BMJ. 2002 Jul 6;325(7354):11. doi: 10.1136/bmj.325.7354.11
  60. Teikari JM, Virtamo J, Rautalahti M, Palmgren J, Liesto K, Heinonen OP. Long-term supplementation with alpha-tocopherol and beta-carotene and age-related cataract. Acta Ophthalmol Scand. 1997 Dec;75(6):634-40. doi: 10.1111/j.1600-0420.1997.tb00620.x
  61. Age-Related Eye Disease Study Research Group (2001). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Archives of ophthalmology (Chicago, Ill. : 1960), 119(10), 1417–1436. https://doi.org/10.1001/archopht.119.10.1417
  62. The Age-Related Eye Disease Study 2 (AREDS2) Research Group*. Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial. JAMA. 2013;309(19):2005–2015. doi:10.1001/jama.2013.4997 https://jamanetwork.com/journals/jama/fullarticle/1684847
  63. Leske MC, Chylack LT Jr, He Q, Wu SY, Schoenfeld E, Friend J, Wolfe J. Antioxidant vitamins and nuclear opacities: the longitudinal study of cataract. Ophthalmology. 1998 May;105(5):831-6. doi: 10.1016/s0161-6420(98)95021-7
  64. Jacques PF, Taylor A, Moeller S, Hankinson SE, Rogers G, Tung W, Ludovico J, Willett WC, Chylack LT Jr. Long-term nutrient intake and 5-year change in nuclear lens opacities. Arch Ophthalmol. 2005 Apr;123(4):517-26. doi: 10.1001/archopht.123.4.517
  65. Age-Related Eye Disease Study Research Group (2001). A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. Archives of ophthalmology (Chicago, Ill. : 1960), 119(10), 1439–1452. https://doi.org/10.1001/archopht.119.10.1439
  66. Age-Related Eye Disease Study 2 (AREDS2) Research Group, Chew, E. Y., SanGiovanni, J. P., Ferris, F. L., Wong, W. T., Agron, E., Clemons, T. E., Sperduto, R., Danis, R., Chandra, S. R., Blodi, B. A., Domalpally, A., Elman, M. J., Antoszyk, A. N., Ruby, A. J., Orth, D., Bressler, S. B., Fish, G. E., Hubbard, G. B., Klein, M. L., … Bernstein, P. (2013). Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. JAMA ophthalmology, 131(7), 843–850. https://doi.org/10.1001/jamaophthalmol.2013.4412
  67. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N Engl J Med. 1997 Apr 24;336(17):1216-22. doi: 10.1056/NEJM199704243361704
  68. Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS. Vitamin E and cognitive decline in older persons. Arch Neurol. 2002 Jul;59(7):1125-32. doi: 10.1001/archneur.59.7.1125
  69. Kang JH, Cook N, Manson J, Buring JE, Grodstein F. A randomized trial of vitamin E supplementation and cognitive function in women. Arch Intern Med. 2006 Dec 11-25;166(22):2462-8. doi: 10.1001/archinte.166.22.2462
  70. Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, Jin S, Kaye J, Levey A, Pfeiffer E, Sano M, van Dyck CH, Thal LJ; Alzheimer’s Disease Cooperative Study Group. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005 Jun 9;352(23):2379-88. doi: 10.1056/NEJMoa050151
  71. Espeland MA, Henderson VW. Preventing cognitive decline in usual aging. Arch Intern Med. 2006 Dec 11-25;166(22):2433-4. doi: 10.1001/archinte.166.22.2433
  72. Isaac MG, Quinn R, Tabet N. Vitamin E for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD002854. doi: 10.1002/14651858.CD002854.pub2. Update in: Cochrane Database Syst Rev. 2012;11:CD002854
  73. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzehimer’s disease. N Engl J Med 1997;336:1216-22. https://www.ncbi.nlm.nih.gov/pubmed/9110909
  74. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzehimer’s disease. N Engl J Med 1997;336:1216-22. https://www.ncbi.nlm.nih.gov/pubmed/9110909?dopt=Abstract
  75. Kamat CD, Gadal S, Mhatre M, Williamson KS, Pye QN, Hensley K. Antioxidants in central nervous system diseases: preclinical promise and translational challenges. J Alzheimers Dis. 2008;15:473-93. https://www.ncbi.nlm.nih.gov/pubmed/18997301
  76. Grodstein F, Chen J, Willett WC. High-dose antioxidant supplements and cognitive function in community-dwelling elderly women. Am J Clin Nutr. 2003;77:975-84. https://www.ncbi.nlm.nih.gov/pubmed/12663300
  77. Zandi PP, Anthony JC, Khachaturian AS, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004;61:82-8. https://www.ncbi.nlm.nih.gov/pubmed/14732624
  78. Laurin D, Masaki KH, Foley DJ, White LR, Launer LJ. Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. Am J Epidemiol. 2004;159:959-67. https://www.ncbi.nlm.nih.gov/pubmed/15128608
  79. Gray SL, Anderson ML, Crane PK, et al. Antioxidant vitamin supplement use and risk of dementia or Alzheimer’s disease in older adults. J Am Geriatr Soc. 2008;56:291-5. https://www.ncbi.nlm.nih.gov/pubmed/18047492
  80. 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. https://www.ncbi.nlm.nih.gov/pubmed/15829527
  81. Zhang SM, Hernan MA, Chen H, Spiegelman D, Willett WC, Ascherio A. Intakes of vitamins E and C, carotenoids, vitamin supplements, and PD risk. Neurology. 2002;59:1161-9. https://www.ncbi.nlm.nih.gov/pubmed/12391343?dopt=Citation
  82. Etminan M, Gill SS, Samii A. Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson’s disease: a meta-analysis. Lancet Neurol. 2005;4:362-5. https://www.ncbi.nlm.nih.gov/pubmed/15907740
  83. Morens DM, Grandinetti A, Waslien CI, Park CB, Ross GW, White LR. Case-control study of idiopathic Parkinson’s disease and dietary vitamin E intake. Neurology. 1996;46:1270-4. https://www.ncbi.nlm.nih.gov/pubmed/8628465
  84. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. The Parkinson Study Group. N Engl J Med. 1993;328:176-83. https://www.ncbi.nlm.nih.gov/pubmed/8417384
  85. Ascherio A, Weisskopf MG, O’Reilly E J, et al. Vitamin E intake and risk of amyotrophic lateral sclerosis. Ann Neurol. 2005;57:104-10. https://www.ncbi.nlm.nih.gov/pubmed/15529299
  86. Wang H, O’Reilly EJ, Weisskopf MG, et al. Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies. Am J Epidemiol. 2011;173:595-602. https://www.ncbi.nlm.nih.gov/pubmed/21335424
  87. Orrell RW, Lane RJ, Ross M. Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease. Cochrane Database Syst Rev. 2007:CD002829. https://www.ncbi.nlm.nih.gov/pubmed/17253482
  88. Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers. JAMA 2009; 301(1). Published online December 9, 2008. Print edition January 2009.
  89. EA Klein, IM Thompson, CM Tangen, et al. Vitamin E and the Risk of Prostate Cancer: Results of The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011; 306(14) 1549-1556.
  90. 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. JNCI 1998; 90(6):440-446.
  91. Kristal AR, Darke AK, Morris S, et al. Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk. J Natl Cancer Inst 2014.
  92. Clark LC, Combs GF Jr., Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial: Nutritional Prevention of Cancer Study Group. JAMA 1996; 276(24):1957-1963.
  93. Duffield-Lillico AJ, Reid ME, Turnbull BW, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: A summary report of the Nutritional Prevention of Cancer Trial. Cancer Epidemiology, Biomarkers & Prevention 2002; 11(7):630-639.
  94. National Institute of Health, Office of Dietary Supplements. Vitamin E. https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/
  95. Rhie G, Shin MH, Seo JY, Choi WW, Cho KH, Kim KH, Park KC, Eun HC, Chung JH. Aging- and photoaging-dependent changes of enzymic and nonenzymic antioxidants in the epidermis and dermis of human skin in vivo. J Invest Dermatol. 2001 Nov;117(5):1212-7. doi: 10.1046/j.0022-202x.2001.01469.x. Erratum in: J Invest Dermatol 2002 Apr;118(4):741.
  96. Thiele JJ, Traber MG, Packer L. Depletion of human stratum corneum vitamin E: an early and sensitive in vivo marker of UV induced photo-oxidation. J Invest Dermatol. 1998 May;110(5):756-61. doi: 10.1046/j.1523-1747.1998.00169.x
  97. Ikeda S, Toyoshima K, Yamashita K. Dietary sesame seeds elevate alpha- and gamma-tocotrienol concentrations in skin and adipose tissue of rats fed the tocotrienol-rich fraction extracted from palm oil. J Nutr. 2001 Nov;131(11):2892-7. doi: 10.1093/jn/131.11.2892
  98. Ekanayake-Mudiyanselage S, Kraemer K, Thiele JJ. Oral supplementation with all-Rac- and RRR-alpha-tocopherol increases vitamin E levels in human sebum after a latency period of 14-21 days. Ann N Y Acad Sci. 2004 Dec;1031:184-94. doi: 10.1196/annals.1331.017
  99. Vaule H, Leonard SW, Traber MG. Vitamin E delivery to human skin: studies using deuterated alpha-tocopherol measured by APCI LC-MS. Free Radic Biol Med. 2004 Feb 15;36(4):456-63. doi: 10.1016/j.freeradbiomed.2003.11.020
  100. Thiele JJ, Weber SU, Packer L. Sebaceous gland secretion is a major physiologic route of vitamin E delivery to skin. J Invest Dermatol. 1999 Dec;113(6):1006-10. doi: 10.1046/j.1523-1747.1999.00794.x
  101. Weber C, Podda M, Rallis M, Thiele JJ, Traber MG, Packer L. Efficacy of topically applied tocopherols and tocotrienols in protection of murine skin from oxidative damage induced by UV-irradiation. Free Radic Biol Med. 1997;22(5):761-9. doi: 10.1016/s0891-5849(96)00346-2
  102. Valacchi G, Weber SU, Luu C, Cross CE, Packer L. Ozone potentiates vitamin E depletion by ultraviolet radiation in the murine stratum corneum. FEBS Lett. 2000 Jan 21;466(1):165-8. doi: 10.1016/s0014-5793(99)01787-1
  103. Baumann L. Skin ageing and its treatment. J Pathol. 2007 Jan;211(2):241-51. doi: 10.1002/path.2098
  104. Machlin LJ, Filipski R, Nelson J, Horn LR, Brin M. Effects of a prolonged vitamin E deficiency in the rat. J Nutr. 1977 Jul;107(7):1200-8. doi: 10.1093/jn/107.7.1200
  105. Igarashi A, Uzuka M, Nakajima K. The effects of vitamin E deficiency on rat skin. Br J Dermatol. 1989 Jul;121(1):43-9. doi: 10.1111/j.1365-2133.1989.tb01398.x
  106. Dermatol Surg. 1999 Apr;25(4):311-5.10.1046/j.1524-4725.1999.08223. The effects of topical vitamin E on the cosmetic appearance of scars. https://www.ncbi.nlm.nih.gov/pubmed/10417589/
  107. Traber MG, Rallis M, Podda M, Weber C, Maibach HI, Packer L. Penetration and distribution of alpha-tocopherol, alpha- or gamma-tocotrienols applied individually onto murine skin. Lipids. 1998 Jan;33(1):87-91. doi: 10.1007/s11745-998-0183-0
  108. Thiele JJ, Ekanayake-Mudiyanselage S. Vitamin E in human skin: organ-specific physiology and considerations for its use in dermatology. Mol Aspects Med. 2007 Oct-Dec;28(5-6):646-67. doi: 10.1016/j.mam.2007.06.001
  109. Thiele JJ, Traber MG, Podda M, Tsang K, Cross CE, Packer L. Ozone depletes tocopherols and tocotrienols topically applied to murine skin. FEBS Lett. 1997 Jan 20;401(2-3):167-70. doi: 10.1016/s0014-5793(96)01463-9
  110. Nada A, Krishnaiah YS, Zaghloul AA, Khattab I. In vitro and in vivo permeation of vitamin E and vitamin E acetate from cosmetic formulations. Med Princ Pract. 2011;20(6):509-13. doi: 10.1159/000329883
  111. Kosari P, Alikhan A, Sockolov M, Feldman SR. Vitamin E and allergic contact dermatitis. Dermatitis. 2010 May-Jun;21(3):148-53.
  112. Kagan V, Witt E, Goldman R, Scita G, Packer L. Ultraviolet light-induced generation of vitamin E radicals and their recycling. A possible photosensitizing effect of vitamin E in skin. Free Radic Res Commun. 1992;16(1):51-64. doi: 10.3109/10715769209049159
  113. Jin GH, Liu Y, Jin SZ, Liu XD, Liu SZ. UVB induced oxidative stress in human keratinocytes and protective effect of antioxidant agents. Radiat Environ Biophys. 2007 Mar;46(1):61-8. doi: 10.1007/s00411-007-0096-1
  114. Pauling L, Willoughby R, Reynolds R, Blaisdell BE, Lawson S. Incidence of squamous cell carcinoma in hairless mice irradiated with ultraviolet light in relation to intake of ascorbic acid (vitamin C) and of D, L-alpha-tocopheryl acetate (vitamin E). Int J Vitam Nutr Res Suppl. 1982;23:53-82.
  115. Burke KE, Clive J, Combs GF Jr, Nakamura RM. Effects of topical L-selenomethionine with topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice. J Am Acad Dermatol. 2003 Sep;49(3):458-72. doi: 10.1067/s0190-9622(03)00900-9
  116. Gerrish KE, Gensler HL. Prevention of photocarcinogenesis by dietary vitamin E. Nutr Cancer. 1993;19(2):125-33. doi: 10.1080/01635589309514243
  117. Record IR, Dreosti IE, Konstantinopoulos M, Buckley RA. The influence of topical and systemic vitamin E on ultraviolet light-induced skin damage in hairless mice. Nutr Cancer. 1991;16(3-4):219-25. doi: 10.1080/01635589109514160
  118. McArdle F, Rhodes LE, Parslew RA, Close GL, Jack CI, Friedmann PS, Jackson MJ. Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced oxidative stress in human skin. Am J Clin Nutr. 2004 Nov;80(5):1270-5. doi: 10.1093/ajcn/80.5.1270
  119. Werninghaus K, Meydani M, Bhawan J, Margolis R, Blumberg JB, Gilchrest BA. Evaluation of the photoprotective effect of oral vitamin E supplementation. Arch Dermatol. 1994 Oct;130(10):1257-61.
  120. van der Pols JC, Heinen MM, Hughes MC, Ibiebele TI, Marks GC, Green AC. Serum antioxidants and skin cancer risk: an 8-year community-based follow-up study. Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1167-73. doi: 10.1158/1055-9965.EPI-08-1211
  121. 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 Dec;25(9):1006-12. doi: 10.1016/s0891-5849(98)00132-4
  122. Placzek M, Gaube S, Kerkmann U, Gilbertz KP, Herzinger T, Haen E, Przybilla B. Ultraviolet B-induced DNA damage in human epidermis is modified by the antioxidants ascorbic acid and D-alpha-tocopherol. J Invest Dermatol. 2005 Feb;124(2):304-7. doi: 10.1111/j.0022-202X.2004.23560.x
  123. Yamada Y, Obayashi M, Ishikawa T, Kiso Y, Ono Y, Yamashita K. Dietary tocotrienol reduces UVB-induced skin damage and sesamin enhances tocotrienol effects in hairless mice. J Nutr Sci Vitaminol (Tokyo). 2008 Apr;54(2):117-23. doi: 10.3177/jnsv.54.117
  124. Saral Y, Uyar B, Ayar A, Naziroglu M. Protective effects of topical alpha-tocopherol acetate on UVB irradiation in guinea pigs: importance of free radicals. Physiol Res. 2002;51(3):285-90.
  125. McVean M, Liebler DC. Prevention of DNA photodamage by vitamin E compounds and sunscreens: roles of ultraviolet absorbance and cellular uptake. Mol Carcinog. 1999 Mar;24(3):169-76. doi: 10.1002/(sici)1098-2744(199903)24:3<169::aid-mc3>3.0.co;2-a
  126. Ritter EF, Axelrod M, Minn KW, Eades E, Rudner AM, Serafin D, Klitzman B. Modulation of ultraviolet light-induced epidermal damage: beneficial effects of tocopherol. Plast Reconstr Surg. 1997 Sep;100(4):973-80. doi: 10.1097/00006534-199709001-00021
  127. Beijersbergen van Henegouwen GM, Junginger HE, de Vries H. Hydrolysis of RRR-alpha-tocopheryl acetate (vitamin E acetate) in the skin and its UV protecting activity (an in vivo study with the rat). J Photochem Photobiol B. 1995 Jul;29(1):45-51. doi: 10.1016/1011-1344(95)90251-1
  128. Trevithick JR, Shum DT, Redae S, Mitton KP, Norley C, Karlik SJ, Groom AC, Schmidt EE. 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 Dec;7(4):1269-81.
  129. Roshchupkin DI, Pistsov MY, Potapenko AY. Inhibition of ultraviolet light-induced erythema by antioxidants. Arch Dermatol Res. 1979 Aug;266(1):91-4. doi: 10.1007/BF00412867
  130. Thiele JJ, Hsieh SN, Ekanayake-Mudiyanselage S. Vitamin E: critical review of its current use in cosmetic and clinical dermatology. Dermatol Surg. 2005 Jul;31(7 Pt 2):805-13; discussion 813. doi: 10.1111/j.1524-4725.2005.31724
  131. Zhai H, Behnam S, Villarama CD, Arens-Corell M, Choi MJ, Maibach HI. Evaluation of the antioxidant capacity and preventive effects of a topical emulsion and its vehicle control on the skin response to UV exposure. Skin Pharmacol Physiol. 2005 Nov-Dec;18(6):288-93. doi: 10.1159/000088014
  132. Chung JH, Seo JY, Lee MK, Eun HC, Lee JH, Kang S, Fisher GJ, Voorhees JJ. Ultraviolet modulation of human macrophage metalloelastase in human skin in vivo. J Invest Dermatol. 2002 Aug;119(2):507-12. doi: 10.1046/j.1523-1747.2002.01844.x
  133. Lin JY, Selim MA, Shea CR, Grichnik JM, Omar MM, Monteiro-Riviere NA, Pinnell SR. UV photoprotection by combination topical antioxidants vitamin C and vitamin E. J Am Acad Dermatol. 2003 Jun;48(6):866-74. doi: 10.1067/mjd.2003.425
  134. Lin FH, Lin JY, Gupta RD, Tournas JA, Burch JA, Selim MA, Monteiro-Riviere NA, Grichnik JM, Zielinski J, Pinnell SR. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. J Invest Dermatol. 2005 Oct;125(4):826-32. doi: 10.1111/j.0022-202X.2005.23768.x
  135. Quevedo WC Jr, Holstein TJ, Dyckman J, McDonald CJ, Isaacson EL. Inhibition of UVR-induced tanning and immunosuppression by topical applications of vitamins C and E to the skin of hairless (hr/hr) mice. Pigment Cell Res. 2000 Apr;13(2):89-98. doi: 10.1034/j.1600-0749.2000.130207.x
  136. Murray JC, Burch JA, Streilein RD, Iannacchione MA, Hall RP, Pinnell SR. A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation. J Am Acad Dermatol. 2008 Sep;59(3):418-25. doi: 10.1016/j.jaad.2008.05.004
  137. Kato E, Sasaki Y, Takahashi N. Sodium dl-α-tocopheryl-6-O-phosphate inhibits PGE₂ production in keratinocytes induced by UVB, IL-1β and peroxidants. Bioorg Med Chem. 2011 Nov 1;19(21):6348-55. doi: 10.1016/j.bmc.2011.08.067
  138. Nakagawa K, Shibata A, Maruko T, Sookwong P, Tsuduki T, Kawakami K, Nishida H, Miyazawa T. gamma-Tocotrienol reduces squalene hydroperoxide-induced inflammatory responses in HaCaT keratinocytes. Lipids. 2010 Sep;45(9):833-41. doi: 10.1007/s11745-010-3458-4
  139. Shibata A, Nakagawa K, Kawakami Y, Tsuzuki T, Miyazawa T. Suppression of gamma-tocotrienol on UVB induced inflammation in HaCaT keratinocytes and HR-1 hairless mice via inflammatory mediators multiple signaling. J Agric Food Chem. 2010 Jun 9;58(11):7013-20. doi: 10.1021/jf100691g
  140. Yoshida E, Watanabe T, Takata J, Yamazaki A, Karube Y, Kobayashi S. Topical application of a novel, hydrophilic gamma-tocopherol derivative reduces photo-inflammation in mice skin. J Invest Dermatol. 2006 Jul;126(7):1633-40. doi: 10.1038/sj.jid.5700236
  141. Han SN, Meydani SN. Impact of vitamin E on immune function and its clinical implications. Expert Rev Clin Immunol. 2006 Jul;2(4):561-7. doi: 10.1586/1744666X.2.4.561
  142. Tsoureli-Nikita E, Hercogova J, Lotti T, Menchini G. Evaluation of dietary intake of vitamin E in the treatment of atopic dermatitis: a study of the clinical course and evaluation of the immunoglobulin E serum levels. Int J Dermatol. 2002 Mar;41(3):146-50. doi: 10.1046/j.1365-4362.2002.01423.x
  143. Hayakawa R, Ueda H, Nozaki T, Izawa Y, Yokotake J, Yazaki K, Azumi T, Okada Y, Kobayashi M, Usuda T, Ishida J, Kondo T, Adachi A, Kawase A, Matsunaga K. Effects of combination treatment with vitamins E and C on chloasma and pigmented contact dermatitis. A double blind controlled clinical trial. Acta Vitaminol Enzymol. 1981;3(1):31-8.
  144. Javanbakht MH, Keshavarz SA, Djalali M, Siassi F, Eshraghian MR, Firooz A, Seirafi H, Ehsani AH, Chamari M, Mirshafiey A. Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis. J Dermatolog Treat. 2011 Jun;22(3):144-50. doi: 10.3109/09546630903578566
  145. Shukla A, Rasik AM, Patnaik GK. Depletion of reduced glutathione, ascorbic acid, vitamin E and antioxidant defence enzymes in a healing cutaneous wound. Free Radic Res. 1997 Feb;26(2):93-101. doi: 10.3109/10715769709097788
  146. Musalmah M, Nizrana MY, Fairuz AH, NoorAini AH, Azian AL, Gapor MT, Wan Ngah WZ. Comparative effects of palm vitamin E and alpha-tocopherol on healing and wound tissue antioxidant enzyme levels in diabetic rats. Lipids. 2005 Jun;40(6):575-80. doi: 10.1007/s11745-005-1418-9
  147. Taren DL, Chvapil M, Weber CW. Increasing the breaking strength of wounds exposed to preoperative irradiation using vitamin E supplementation. Int J Vitam Nutr Res. 1987;57(2):133-7.
  148. Ehrlich HP, Tarver H, Hunt TK. Inhibitory effects of vitamin E on collagen synthesis and wound repair. Ann Surg. 1972 Feb;175(2):235-40. doi: 10.1097/00000658-197202000-00013
  149. Baumann LS, Spencer J. The effects of topical vitamin E on the cosmetic appearance of scars. Dermatol Surg. 1999 Apr;25(4):311-5. doi: 10.1046/j.1524-4725.1999.08223.x
  150. Jenkins M, Alexander JW, MacMillan BG, Waymack JP, Kopcha R. Failure of topical steroids and vitamin E to reduce postoperative scar formation following reconstructive surgery. J Burn Care Rehabil. 1986 Jul-Aug;7(4):309-12. doi: 10.1097/00004630-198607000-00002
  151. Barbosa E, Faintuch J, Machado Moreira EA, Gonçalves da Silva VR, Lopes Pereima MJ, Martins Fagundes RL, Filho DW. Supplementation of vitamin E, vitamin C, and zinc attenuates oxidative stress in burned children: a randomized, double-blind, placebo-controlled pilot study. J Burn Care Res. 2009 Sep-Oct;30(5):859-66. doi: 10.1097/BCR.0b013e3181b487a8
  152. Ellinger S, Stehle P. Efficacy of vitamin supplementation in situations with wound healing disorders: results from clinical intervention studies. Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):588-95. doi: 10.1097/MCO.0b013e328331a5b5
  153. Burke KE. Photodamage of the skin: protection and reversal with topical antioxidants. J Cosmet Dermatol. 2004 Jul;3(3):149-55. doi: 10.1111/j.1473-2130.2004.00067.x
  154. Nagata C, Nakamura K, Wada K, Oba S, Hayashi M, Takeda N, Yasuda K. Association of dietary fat, vegetables and antioxidant micronutrients with skin ageing in Japanese women. Br J Nutr. 2010 May;103(10):1493-8. doi: 10.1017/S0007114509993461
  155. Boelsma E, van de Vijver LP, Goldbohm RA, Klöpping-Ketelaars IA, Hendriks HF, Roza L. Human skin condition and its associations with nutrient concentrations in serum and diet. Am J Clin Nutr. 2003 Feb;77(2):348-55. doi: 10.1093/ajcn/77.2.348
  156. Gehring W, Fluhr J, Gloor M. Influence of vitamin E acetate on stratum corneum hydration. Arzneimittelforschung. 1998 Jul;48(7):772-5.
  157. Gönüllü U, Sensoy D, Uner M, Yener G, Altinkurt T. Comparing the moisturizing effects of ascorbic acid and calcium ascorbate against that of tocopherol in emulsions. J Cosmet Sci. 2006 Nov-Dec;57(6):465-73.
  158. Weber SU, Thiele JJ, Cross CE, Packer L. Vitamin C, uric acid, and glutathione gradients in murine stratum corneum and their susceptibility to ozone exposure. J Invest Dermatol. 1999 Dec;113(6):1128-32. doi: 10.1046/j.1523-1747.1999.00789.x
  159. U.S. Department of Agriculture, Agricultural Research Service. 2011. USDA National Nutrient Database for Standard Reference, Release 24. Nutrient Data Laboratory Home Page. https://www.ars.usda.gov/northeast-area/beltsville-md/beltsville-human-nutrition-research-center/nutrient-data-laboratory/
  160. The USDA Food Composition Databases. https://ndb.nal.usda.gov/ndb/
  161. The USDA Food Composition Databases. Vitamin E Content. https://ods.od.nih.gov/pubs/usdandb/VitaminE-Content.pdf
  162. The USDA Food Composition Databases. Foods Vitamin E Content. https://ods.od.nih.gov/pubs/usdandb/VitaminE-Food.pdf
  163. U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference, Release 27. Nutrient Data Laboratory home page, 2014. https://ndb.nal.usda.gov/ndb/
  164. Brion LP, Bell EF, Raghuveer TS. Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev;4:CD003665. https://www.ncbi.nlm.nih.gov/pubmed/14583988?dopt=Abstract
  165. Kowdley KV, Mason JB, Meydani SN, Cornwall S, Grand RJ. Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption. Gastroenterology 1992;102:2139-42. https://www.ncbi.nlm.nih.gov/pubmed/1587435?dopt=Abstract
  166. Traber MG. Vitamin E. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006;396-411
  167. Tanyel MC, Mancano LD. Neurologic findings in vitamin E deficiency. Am Fam Physician 1997;55:197-201. https://www.ncbi.nlm.nih.gov/pubmed/9012278?dopt=Abstract
  168. Boltshauser E, Weber KP. Laboratory investigations. Handb Clin Neurol. 2018;154:287-298. doi: 10.1016/B978-0-444-63956-1.00017-5
  169. Kemnic TR, Coleman M. Vitamin E Deficiency. [Updated 2020 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519051
  170. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-35. https://www.ncbi.nlm.nih.gov/pubmed/8127329?dopt=Abstract
  171. Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA 2008;300:2123-33. https://www.ncbi.nlm.nih.gov/pubmed/18997197?dopt=Abstract
  172. Diab L, Krebs NF. Vitamin Excess and Deficiency. Pediatr Rev. 2018 Apr;39(4):161-179. doi: 10.1542/pir.2016-0068
  173. Owen KN, Dewald O. Vitamin E Toxicity. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564373
  174. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994 Apr 14;330(15):1029-35. doi: 10.1056/NEJM199404143301501
  175. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. doi: 10.7326/0003-4819-142-1-200501040-00110
  176. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007 Feb 28;297(8):842-57. doi: 10.1001/jama.297.8.842. Erratum in: JAMA. 2008 Feb 20;299(7):765-6.
  177. Huang HY, Caballero B, Chang S, Alberg A, Semba R, Schneyer C, et al. Multivitamin/Mineral Supplements and Prevention of Chronic Disease. Evidence Report/Technology Assessment No. 139. (Prepared by The Johns Hopkins University Evidence-based Practice Center under Contract No. 290-02-0018). AHRQ Publication No. 06-E012. Rockville, MD: Agency for Healthcare Research and Quality. May 2008.
  178. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011 Oct 12;306(14):1549-56. doi: 10.1001/jama.2011.1437
  179. Traber MG. Vitamin E inadequacy in humans: causes and consequences. Adv Nutr. 2014 Sep;5(5):503-14. doi: 10.3945/an.114.006254
  180. Le NK, Kesayan T, Chang JY, Rose DZ. Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels. J Stroke Cerebrovasc Dis. 2020 May;29(5):104747. doi: 10.1016/j.jstrokecerebrovasdis.2020.104747
  181. Traber MG. Mechanisms for the prevention of vitamin E excess. J Lipid Res. 2013 Sep;54(9):2295-306. doi: 10.1194/jlr.R032946
  182. Pastori D, Carnevale R, Cangemi R, Saliola M, Nocella C, Bartimoccia S, Vicario T, Farcomeni A, Violi F, Pignatelli P. Vitamin E serum levels and bleeding risk in patients receiving oral anticoagulant therapy: a retrospective cohort study. J Am Heart Assoc. 2013 Oct 28;2(6):e000364. doi: 10.1161/JAHA.113.000364
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