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 2). 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). These compounds act as antioxidants, which prevent lipid peroxidation of polyunsaturated fatty acids in cellular membranes 3). Alpha tocopherol (α-tocopherol) is also likely involved in strengthening certain aspects of cell-mediated immunity.

The main function of alpha tocopherol (α-tocopherol) in humans is that of a fat-soluble antioxidant. 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 4). 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 5).

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 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 6).

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 7); 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 14). 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 15). Alpha-tocopherol inhibits the activity of protein kinase C, an enzyme involved in cell proliferation and differentiation in smooth muscle cells, platelets, and monocytes 16). 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 17).

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 18). 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).

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 19).

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 20).

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.
  • Simvastatin and niacin: Vitamin E can reduce the amount of high-density lipoprotein (HDL) which is the opposite desired effect of taking simvastatin and/or niacin.

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 21).

  • 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 22) and Health Professionals Follow-Up Study 23),  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 24).

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 25). 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 26), 27). 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 28). 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.” 29)

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 women for 10 years, vitamin E supplements of 600 IU every other day did not significantly reduce the risk of so-called “major cardiac events” (heart attack, stroke, or cardiovascular death). But there was some encouraging news in the findings: When these major cardiac events were analyzed separately, vitamin E supplementation was linked to a 24 percent lower risk of cardiovascular death 30). And among women ages 65 and older, vitamin E supplementation reduced the risk of major cardiac events by 26 percent. 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 31).

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 32). 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 33).

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 34). 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 CHD might require longer studies in younger participants taking higher doses of the supplement 35). 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 36).

The story on vitamin E and cancer prevention has been a bit less encouraging than the story on vitamin E and heart disease. 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 37), 38), 39), 40), 41), 42), 43), 44), 45), 46). Some observational studies and clinical trials, however, suggested that vitamin E supplements might lower the risk of advanced prostate cancer in smokers 47), 48), 49), 50).

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 51). 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 52). 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 53).

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 54). 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 55). 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 56). 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) 57). 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 58).

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 59).

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.

  • Eye disorders

Age-related macular degeneration (AMD) and cataracts are among the most common causes of significant vision loss in older people. Their etiologies 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.

A six-year trial found that vitamin E, in combination with vitamin C, beta carotene, and zinc, offers some protection against the development of advanced age-related macular degeneration (AMD), but not cataract, in people who were at high risk of the disease 60), 61). On its own, however, vitamin E does not seem to offer much benefit against either AMD or cataract 62), 63).

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 AMD or cataracts. However, the formulations of vitamin E, other antioxidants, zinc, and copper used in AREDS hold promise for slowing the progression of AMD in people at high risk of developing advanced AMD.

  • Cognitive Function and 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 64). 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 65). 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 66). 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 67), 68), 69), 70). 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 71). 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 72), 73), 74). In people who already have Parkinson’s, high-dose vitamin E supplements do not slow the disease’s progression 75). 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 76). 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 77). Clinical trials of vitamin E supplements in people who already have ALS have generally failed to show any benefit, however 78). 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 79), 80), 81), 82), 83), 84). 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 85).

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 86).

Vitamin E oil for Skin

Vitamin E is the most abundant lipophilic antioxidant found in human skin 87). In humans, levels of vitamin E in the epidermis are higher than the dermis 88). Although the predominant form of vitamin E in skin of unsupplemented individuals is alpha-tocopherol, skin may also contain measurable amounts of gamma-tocopherol 89) and other diet-derived tocopherols and tocotrienols 90).

Vitamin E first accumulates in the sebaceous glands before it is delivered to the skin surface through sebum 91). Following oral ingestion, it takes at least seven days before the vitamin E content of sebum is altered 92). 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 93). Due to its lipophilic nature, vitamin E can also penetrate into all underlying layers of skin 94). 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) 95).

Exposures to UV light 96) or ozone 97) lower the vitamin E content in skin, primarily in the stratum corneum. Vitamin E concentrations in the human epidermis also decline with age 98). Since epidermal structure changes with age 99), 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 100) and changes in skin collagen cross-linking 101), 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 102) 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 103).

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 104). 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 105). Interestingly, vitamin E levels in the dermis increase greatly after topical application, likely accumulating in the sebaceous glands 106). 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 107); by contrast, skin supplied with synthetic vitamin E topically can contain a mixture of different tocopherols and/or tocotrienols 108). 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 109).

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 110). 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 111), 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 112). 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 113).

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 114). 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 115), 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 116). Three other mouse studies reported inhibition of UV-induced tumors in mice fed α-tocopherol acetate 117), but one of these studies utilized vitamin E doses that were toxic to animals when combined with the UV treatment 118). 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 119). 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 120). 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 121). Furthermore, multiple human studies have shown no effect of vitamin E on the prevention or development of skin cancers 122).

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 123). The combination of the two vitamins was associated with lower amounts of DNA damage after UV exposure 124). 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 125). 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 126), limiting DNA damage 127), and reducing the many chemical and structural changes to skin after UV exposure 128). Vitamin E topical applications have also been shown to reduce UV-induced tumor formation in multiple mouse studies 129) and to reduce the effects of photo-activated toxins in the skin 130). 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 131). A similar effect has been shown in rabbits, where applying α-tocopherol to skin immediately after UV increased the Minimal Erythemal Dose 132). 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 133). In human subjects, the use of vitamin E on skin lowers peroxidation of skin surface lipids 134), decreases erythema 135), and limits immune cell activation after UV exposure 136).

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 137), decrease DNA damage 138), inhibit erythema 139), and decrease skin pigmentation after UV exposure 140). Similar effects have been seen in human subjects 141).

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 142). 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 143), as well as limit inflammatory responses to lipid hydroperoxide exposure 144). In mice, dietary γ-tocotrienol suppresses UV-induced COX-2 expression in the skin 145). 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 146). In vitro studies have shown similar anti-inflammatory effects of α- and γ-tocopherol on immune cells 147).

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 148) or in combination with vitamin C 149) or vitamin D 150), 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 151). 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 152). Vitamin E increases the breaking strength of wounds pre-treated with ionizing radiation 153), 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 154).

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 155), 156). 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 157), 158).

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 159). An analysis of the dietary intake of Japanese women showed no correlation between vitamin E consumption and skin wrinkling 160).

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 161), 162). However, two small studies have shown topical application of vitamin E can improve skin water-binding capacity after two to four weeks of use 163), 164). 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 165) and lead to free radical damage that may compound the effects of UV exposure 166). Although not well studied, topical applications of vitamin E may reduce pollution-related free radical damage 167).

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 168). 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) 169). Most vitamin E in American diets is in the form of gamma-tocopherol from soybean, canola, corn, and other vegetable oils and food products 170).

The U.S. Department of Agriculture’s (USDA’s) Nutrient Database website 171) lists the nutrient content of many foods, including, in some cases, the amounts of alpha-, beta-, gamma-, and delta-tocopherol arranged by nutrient content 172) and by food name 173).

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 174)]
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 175). 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 176).

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 177), 178). 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 179).

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) 180). Vitamin E deficiency secondary to abetalipoproteinemia causes such problems as poor transmission of nerve impulses, muscle weakness, and retinal degeneration that leads to blindness 181). 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 182).

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 183). 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 184):

  • 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 185). 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  186) 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 187). 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 has established Upper Intake Levels (ULs) for vitamin E based on the potential for hemorrhagic effects (see Table 3). The 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 at least 2,000 IU for a few weeks or months. Long-term intakes above the UL increase the risk of adverse health effects 188). Vitamin E ULs for infants have not been established.

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

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 189) ]

Can vitamin E be harmful?

Eating vitamin E in foods is not risky or harmful 190). 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) 191). 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.

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 192).

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 193). A patient on vitamin E supplementation may have plasma levels of 30 micromoles/liter or greater 194). The normal lab range for circulating alpha-tocopherols is 5.7 to 19.9 mg/L 195). 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 196). 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 197). 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 198). 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 199). 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 200).

References   [ + ]