- What is Vitamin E
- What does Vitamin E do?
- Vitamin E Supplements
- What are some vitamin E benefits on health?
- Vitamin E oil for Skin
- How much vitamin E do you need?
- What foods provide vitamin E?
- Vitamin E deficiency
- Vitamin E Side Effects and Toxicity
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
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:
- 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.
- 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.
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.
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.
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.
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.
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 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
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.
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.
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.
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 Stage||Recommended Amount|
|Birth to 6 months||4 mg (6 IU)|
|Infants 7–12 months||5 mg (7.5 IU)|
|Children 1–3 years||6 mg (9 IU)|
|Children 4–8 years||7 mg (10.4 IU)|
|Children 9–13 years||11 mg (16.4 IU)|
|Teens 14–18 years||15 mg (22.4 IU)|
|Adults||15 mg (22.4 IU)|
|Pregnant teens and women||15 mg (22.4 IU)|
|Breastfeeding teens and women||19 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)
|Wheat germ oil, 1 tablespoon||20.3||100|
|Sunflower seeds, dry roasted, 1 ounce||7.4||37|
|Almonds, dry roasted, 1 ounce||6.8||34|
|Sunflower oil, 1 tablespoon||5.6||28|
|Safflower oil, 1 tablespoon||4.6||25|
|Hazelnuts, dry roasted, 1 ounce||4.3||22|
|Peanut butter, 2 tablespoons||2.9||15|
|Peanuts, dry roasted, 1 ounce||2.2||11|
|Corn oil, 1 tablespoon||1.9||10|
|Spinach, boiled, ½ cup||1.9||10|
|Broccoli, chopped, boiled, ½ cup||1.2||6|
|Soybean oil, 1 tablespoon||1.1||6|
|Kiwifruit, 1 medium||1.1||6|
|Mango, sliced, ½ cup||0.7||4|
|Tomato, raw, 1 medium||0.7||4|
|Spinach, raw, 1 cup||0.6||3|
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]
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
|1–3 years||200 mg|
|4–8 years||300 mg|
|9–13 years||600 mg|
|14–18 years||800 mg|
|19+ years||1,000 mg|
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
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