Vitamin E is a fat-soluble nutrient in various foods that acts as an antioxidant to protect cells from free radical damage. It also plays a crucial role in immune system support, contributes to blood vessel dilation and clotting prevention, and facilitates cell communication and essential bodily functions.

As per guidelines from the U.S. Institute of Medicine of the National Academies, adults with plasma alpha-tocopherol (one form of vitamin E) concentrations below 516 micrograms per deciliter are considered insufficient in vitamin E. Deficiency in serum alpha-tocopherol levels has been observed in only 0.1 percent of adults aged 20 and above in the United States. Vitamin E deficiency may result in the fragility of red blood cells and the degeneration of neurons.

The primary signs and symptoms of vitamin E deficiency are:

• Mild hemolytic anemia, which involves the rapid destruction of red blood cells (hemolysis) that surpasses the body’s ability to produce new ones
• General neurological issues

Symptoms of vitamin E deficiency may vary according to the condition’s development. In the early stages, people might experience:

• Slower reflexes
• Reduced night vision
• A loss of feeling or less sensitivity to vibrations

In the middle stages, people may have:

• Difficulty coordinating movements
• Muscle weakness
• Difficulty looking upward

In the later stages, there could be:

• Heart rhythm issues
• Blindness
• Declined cognition

In infants, especially premature ones, vitamin E deficiency may cause:

• Retrolental fibroplasia, identified by an incomplete formation of blood vessels in the rim of the eye’s retina, which is followed by overgrowth of blood vessels centrally, resulting in the retina’s destruction. It takes place almost exclusively in premature infants who require supplemental oxygen.
• Intraventricular hemorrhage, which is bleeding that occurs within the brain’s ventricular system (normally only containing spinal fluid)
• Subependymal hemorrhage, or bleeding that occurs under the membrane lining the brain’s side ventricles
• Muscle weakness

Complications

Complications of vitamin E deficiency include:

• Ataxia, characterized by a lack of coordination, results in the loss of muscle control in various body parts, including arms, legs, hands, and eye muscles, leading to difficulties in balance and walking
• Cognitive impairment and memory problems caused by degeneration of neurons
• Decreased immune function

When we eat foods containing vitamin E (including tocopherols and tocotrienols), the compounds mix with dietary fats in the stomach. Tocopherols and tocotrienols are absorbed in the small intestine and enter enterocytes, the absorption cells lining the small and large intestines. Fat-soluble vitamin E is then packed into droplets of fat called chylomicrons.

The liver selectively distinguishes among different forms of vitamin E and favors the release of alpha-tocopherol into the bloodstream, primarily as a component of very-low-density lipoproteins (VLDL). The alpha-tocopherol transfer protein facilitates this process. Excess alpha-tocopherol is excreted mainly in the urine. Alpha-tocopherol is also stored in the body’s fat tissues.

The following are the benefits vitamin E provides:

• Antioxidant properties: Vitamin E plays an essential role in preventing the formation of reactive oxygen species (ROS) during the oxidation of fats. As an antioxidant, it safeguards cells from the harmful impact of free radicals. Free radicals, formed during processes such as food conversion to energy, can damage cells and potentially contribute to conditions such as heart disease and cancer. Vitamin E inhibits the spread of oxidation among saturated fatty acids within cell membranes. It can potentially hinder the oxidation of “bad” cholesterol, low-density lipoproteins (LDL), lowering the risk of heart disease. Vitamin E also protects us from free radicals from environmental exposures such as cigarette smoke, air pollution, and sunlight.
• Protection from blood clots: Vitamin E promotes the expression of enzymes that modulate the metabolism of arachidonic acid, an omega-6 fatty acid, leading to increased release of prostacyclin. Prostacyclin facilitates blood vessel dilation and hinders platelet clumping.
• Improved immunity: Alpha-tocopherol regulates the activity of protein kinase C, an enzyme crucial for cell proliferation and differentiation in smooth muscle cells, platelets, and monocytes. Endothelial cells, which line blood vessels, benefit from adequate vitamin E levels, exhibiting enhanced resistance to clot or plaque formation. In addition, vitamin E decreases the production of prostaglandin E2, which plays a significant role in the inflammatory process involving rheumatoid arthritis and osteoarthritis, and serum lipid peroxides, products of the oxidative breakdown of lipids formed through a chain reaction initiated by free radicals. Vitamin E also promotes the multiplication of lymphocytes, white blood cells that play a vital role in immunity.
• Anti-inflammatory activities: Vitamin E influences the function of T-cells by directly affecting their membrane integrity, signal transfers, and cell division. T-cells can eliminate infected or cancerous cells directly and contribute to the immune response by assisting B lymphocytes in eliminating invading pathogens. Vitamin E also has an indirect impact by influencing inflammatory mediators produced by other immune cells. This modulation of immune function affects the body’s vulnerability to infectious diseases like respiratory infections and allergic conditions such as asthma.
• Skin health: Vitamin E helps maintain healthy skin by reacting with ROS and absorbing UV light energy. Its photoprotective properties help prevent free radical damage induced by UV light.

Vitamin E Prevents Certain Conditions

There is some evidence that vitamin E can help prevent the following diseases.

Heart Disease

As aforementioned, vitamin E prevents the oxidation of LDL cholesterol, considered a critical initial stage in the development of atherosclerosis, and inhibits platelet aggregation, which can contribute to heart attacks and blood clots. In one study involving nearly 90,000 nurses, those with the highest vitamin E intake, mainly from supplements, had a 34 percent lower risk of major coronary disease compared to participants who consumed the least amount of vitamin E after taking factors such as age and smoking into consideration.

Yet the effectiveness of vitamin E supplements in preventing coronary heart disease is brought into question by randomized clinical trials. For instance, in the Heart Outcomes Prevention Evaluation (HOPE) study, which tracked nearly 10,000 high-risk patients from the Americas and Europe for 4.5 years, those who took 400 international units (IU), or 268 milligrams, a day of natural vitamin E did not experience a significant reduction in cardiovascular events compared to participants who took a placebo. In the HOPE-TOO follow-up study, nearly 4,000 of the initial participants extended their use of either vitamin E or a placebo for an extra 2.5 years. In comparing the group taking vitamin E and the one taking the placebo, no variations in cancer incidence, cancer-related deaths, or major cardiovascular events were found. Instead, there were increased rates of heart failure and hospitalizations related to heart failure in the vitamin E group.

However, some experts have since criticized the HOPE study designs and the researchers’ interpretations of the trial results. Therefore, while research suggests that vitamin E may aid in preventing heart disease and atherosclerosis, it has not received approval from the U.S. Food and Drug Administration (FDA) for these purposes.

Cancer

Vitamin E is capable of shielding cell components from the harmful impact of free radicals, thus potentially preventing the development of cancer. It has been found to reduce the risk of certain types of cancer, including breast, lung (mouse model), and colon (mouse model) cancer. However, vitamin E’s effect on prostate cancer has been mixed.

Age-Related Eye Diseases

Age-related macular degeneration (AMD) and cataracts are common causes of vision loss in older people. Research on the preventive effects of vitamin E on these conditions has produced inconsistent results. However, for those at high risk of advanced AMD, a supplement containing high doses of vitamin E, along with other antioxidants, zinc, and copper, has had some encouraging results in slowing vision loss.

Neurodegenerative Diseases

Limited evidence exists regarding the potential protective effects of vitamin E against diseases related to the brain and nervous system, including the following:

• Alzheimer’s disease: Vitamin E levels are lower in individuals with Alzheimer’s than in those without, suggesting that vitamin E might be a promising candidate for exerting beneficial effects against the disease. However, in one three-year study involving participants with mild cognitive impairment, a common precursor to Alzheimer’s, the administration of 2,000 IU of daily vitamin E did not impede disease progression.
• Parkinson’s disease: A cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018 involving 13,340 participants revealed that vitamin E intake seemed to lessen the risk of new-onset Parkinson’s in individuals over 40. However, vitamin E was not found to relieve symptoms in patients already diagnosed with the disease. The findings suggest that vitamin E supplementation could be considered as an intervention strategy to reduce the occurrence of Parkinson’s disease.
• Amyotrophic lateral sclerosis (ALS): In a pooled analysis of data from five prospective cohort studies spanning from the 1970s to the mid-2000s and comprising more than 1 million participants, long-term use of vitamin E supplements was linked to lower rates of ALS. The potential protective effect of vitamin E warrants additional investigation.

Diabetes

Research has indicated that the onset of diabetes is linked to higher oxidative damage to various molecules in the body. A four-year study involving 944 nondiabetic Finnish men revealed that those with below-median plasma vitamin E levels had nearly a fourfold higher relative risk of developing non-insulin-dependent diabetes.

Increased oxidative stress also plays a significant role in the development of diabetic complications. One study found that vitamin E was associated with better glucose control, lower cholesterol, and better blood pressure.

Vitamin E comprises eight compounds: alpha-, beta-, gamma-, and delta-tocopherol, as well as alpha-, beta-, gamma-, and delta-tocotrienol. Every form possesses unique biological activity, determining its potency within the body. Among the compounds, the more important are alpha-tocopherol and gamma-tocopherol.

Gamma-tocopherol is a significant form of vitamin E in the U.S. diet (due to corn and soybean oil) and the second most abundant in the blood and tissues. It possesses distinctive antioxidant and anti-inflammatory properties. Research indicates that supplementing with gamma-tocopherol can alleviate inflammation and symptoms in animal models with induced conditions such as inflammation, asthma, and cancer. One study revealed that a mixture of tocopherols rich in gamma-tocopherol suppressed tumor formation in the colon, prostate, breast, and lungs in animal models.

Tocotrienols are present in various vegetable oils, wheat germ, barley, and specific nuts and grains. They are associated with lipoproteins, fat deposits, and cellular membranes, safeguarding polyunsaturated fatty acids (PUFAs) from peroxidation reactions. With their unsaturated chain, tocotrienols efficiently penetrate tissues with saturated fatty layers, such as the brain and liver. Studies suggest that tocotrienols may be beneficial against inflammation-related diseases, showcasing properties such as neuroprotection, anti-cancer effects, anti-inflammatory action, and cholesterol reduction.

The recommended dietary allowance (RDA) of vitamin E for different age groups differs depending on the authorities making the recommendations.

One IU of the natural form equals 0.67 milligram of alpha-tocopherol, while 1 IU of the synthetic form equals 0.45 milligram of alpha-tocopherol.

Vitamin E supplements typically include all alpha-tocopherol isomers, with an activity level approximately half that of natural sources. They are available in various forms, the most common being alpha-tocopherol supplements, and standard measures for dietary sufficiency also focus on the alpha form or equivalent compounds. These supplements may come in different formulations, including:

• Alpha-tocopherol: These contain the alpha-tocopherol form, which is the most biologically active.
• Mixed tocopherol: Some supplements combine different tocopherol forms, such as alpha-, beta-, gamma-, and delta-tocopherol. Researchers have not determined whether these forms outperform alpha-tocopherol in supplement formulations.
• Mixed tocotrienol
• Multivitamin/mineral: Most daily multivitamin/mineral supplements typically supply around 13.5 milligrams of vitamin E.

Vitamin E supplements can be derived from natural sources, such as plant oils, or synthesized in a lab. The artificial version of vitamin E is only 50 percent as effective as the natural form.

Vitamin E supplements are available in capsules, tablets, soft gels, topical oils, and liquids. Most typically offer at least 67 milligrams (equivalent to 100 IU of natural vitamin E), exceeding the RDAs. High doses, such as 400 IU of synthetic supplements, may increase prostate cancer risk, along with other health risks. One hazard of high doses of supplemental vitamin E is an increased risk of bleeding, especially into the brain, or difficulty clotting after a significant injury. Vitamin E from food does not appear to increase risks.

Regular non-food vitamin E supplementation is not advised for individuals without a deficiency. Over-the-counter oral supplements are available in cases of detected deficiency or conditions causing low vitamin E levels.

The best approach to supply your body with vitamin E involves consuming a balanced diet, emphasizing the benefits of whole foods for overall health.

Vitamin E is present in various foods and oils, including nuts, seeds, and vegetable oils, which are particularly rich in alpha-tocopherol. Green leafy vegetables and fortified cereals also contribute significant amounts of vitamin E. Gamma-tocopherol, found in soybean, canola, corn, and other oils, is a prevalent source in American diets.

Expressing vitamin E activity as alpha-tocopherol equivalents in food is a way to measure and standardize the total vitamin E content, considering the potency of alpha-tocopherol, which allows for a more accurate assessment of the effectiveness of various forms of vitamin E present in the food. The following are the alpha-tocopherol content of some common foods and oils:

• Wheat germ oil: 20.3 milligrams per tablespoon
• Sunflower seeds: Dry-roasted (7.4 milligrams per ounce)
• Almonds: Dry-roasted (6.8 milligrams per ounce)
• Sunflower oil: 5.6 milligrams per tablespoon
• Hazelnuts: Dry-roasted (4.3 milligrams per ounce)
• Spinach: Boiled (3.8 milligrams per cup)
• Broccoli: Chopped and boiled (2.4 milligrams per cup)
• Peanuts: Dry-roasted (2.2 milligrams per ounce)
• Corn oil: 1.9 milligrams per tablespoon
• Peanut butter: 1.45 milligrams per tablespoon
• Soybean oil: 1.1 milligrams per tablespoon

The interaction of vitamin E with other antioxidants may elucidate why some foods with modest vitamin E content, such as olive oil, offer more benefits than higher doses of vitamin E alone. The impact of food-supplied antioxidants on endogenous alpha-tocopherol kinetics suggests that other antioxidant compounds may be necessary for a beneficial response. Still, additional studies are required to confirm this possibility.

Vitamin E is obtained through diet and supplements. However, topical vitamin E products are also available for skin care. Vitamin E has been used in experimental and clinical dermatology for six or seven decades. Advances in research have led to the development of various formulations for cosmetics and skin care products. Experimental evidence suggests that both topical and oral vitamin E may possess anti-tumor, photoprotective, and skin barrier-stabilizing properties. However, controlled clinical studies are needed to assess the clinical benefits, especially in areas such as atopic dermatitis or the prevention of UV-induced carcinogenesis. Vitamin E has been shown repeatedly to not affect scar appearance during or after healing beyond simple moisturizing.

Vitamin E deficiency is unlikely without a history of inadequate intake or predisposing factors. Confirmation typically involves measuring the vitamin E level. Testing red blood cell hemolysis in response to peroxide can suggest the deficiency but lacks specificity. Hemolysis increases as vitamin E deficiency impairs red blood cell stability.

The primary diagnostic indicators are a low alpha-tocopherol level or a low ratio of serum alpha-tocopherol to serum lipids. A vitamin E (tocopherol) test is a blood test that measures the concentration of alpha-tocopherol. Vitamin E deficiency is suggested if alpha-tocopherol is less than 5 micrograms per milliliter in adults. In individuals with hyperlipidemia, a low ratio of serum alpha-tocopherol to lipids (under 0.8 milligram per gram total lipid) is the most accurate indicator due to potential lipid level influence on vitamin E status.

In individuals with abetalipoproteinemia, a rare autosomal recessive disorder characterized by low or absent plasma cholesterol, LDL, and VLDL, serum alpha-tocopherol levels are typically undetectable. This condition results in progressive neurologic and visual decline early in life. The prognosis is improved with multiple vitamin supplementations.

Since vitamin E deficiency is rare in healthy individuals, it is typically associated with conditions that hinder proper vitamin absorption. When formulating a differential diagnosis, health care providers must contemplate alternative potential vitamin deficiencies and these medical conditions, including Crohn’s disease, liver disease, cerebral palsy, abetalipoproteinemia, and paraneoplastic (cancer-related) syndrome.

The treatment for vitamin E deficiency involves addressing the root cause, such as fat malabsorption or metabolism disorders, followed by oral vitamin E supplementation. Dietary modifications, including an increased intake of leafy vegetables, whole grains, nuts and seeds, and other foods high in vitamin E are recommended to support supplementation. Different treatment options include:

• Alpha-tocopherol intake: An oral dose of alpha-tocopherol at 15 to 25 milligrams per kilogram daily is recommended for patients suffering from vitamin E deficiency due to malabsorption.
• Mixed tocopherols: 200 IU (134 milligrams) of mixed tocopherols can be administered as an alternative to the above treatment plan.
• Alpha-tocopherol injection: Larger doses of alpha-tocopherol via injection may be necessary to treat early-stage neuropathy or address absorption and transport issues in abetalipoproteinemia. If a patient has problems with oral ingestion, injection can also be used.
• Supplements for newborns: Vitamin E supplements are provided to prevent disorders in premature newborns, while most full-term newborns generally receive sufficient vitamin E from breast milk or formulas and do not require supplements.
• Specialized vitamin E forms: Patients experiencing fat malabsorption due to impaired biliary secretion often struggle to absorb orally administered vitamin E. Therefore, they are treated with specialized forms of vitamin E, such as alpha-tocopheryl polyethylene glycol succinate. This water-soluble form of vitamin E can construct micelles (which are like tiny, invisible soap bubbles that form in water) spontaneously, thus eliminating the reliance on bile acids for absorption.

High-Risk Populations

The following factors put one at a higher risk of vitamin E deficiency:

• Disrupted fat malabsorption can contribute to vitamin E deficiency since fat is needed for vitamin E absorption.
• Cystic fibrosis is a life-threatening inherited disease that impacts multiple organs. It causes excessive sodium and water absorption and is characterized by dysfunction in the glands producing sweat and mucus. Patients with cystic fibrosis may fail to secrete pancreatic enzymes necessary for the absorption of fat-soluble vitamins.
• Genetic problems impacting the transportation of alpha-tocopherol, such as deficiencies in the alpha-tocopherol transfer protein or apolipoprotein B.
• Short-bowel syndrome, resulting from factors such as surgical resection of the bowel or pseudo-obstruction impairing absorption, may cause patients to take years to develop symptoms related to vitamin E deficiency.
• Chronic cholestatic hepatobiliary disease can lead to decreased bile flow and micelle formation, which are necessary for vitamin E absorption.
• Digestive disorders: Conditions such as Crohn’s disease (which can affect any part of the digestive tract), exocrine pancreatic insufficiency (the pancreas does not produce enough enzymes to digest food properly), celiac disease, and liver disease may impede the absorption of fats, consequently affecting vitamin E absorption.
• Abetalipoproteinemia is an autosomal recessive disorder, meaning an inheritance pattern, that causes lipoprotein production and transportation errors, thus impacting vitamin E metabolism.
• Isolated vitamin E deficiency syndrome, an autosomal recessive disorder.
• Premature low birth weight infants under 3.3 pounds are at risk of vitamin E deficiency.
• Low-fat diet: Vegetable oils serve as the primary source of this vitamin, and vitamin E is most effectively absorbed when consumed with some fat.
• Medical conditions that interfere with fat or vitamin E absorption: This could include severe congestive heart failure with swelling of the bowel walls.

Excessive vitamin E intake, known as hypervitaminosis E, is rare, and vitamin E is considered the least toxic among the fat-soluble vitamins. No documented evidence of toxicity is associated with obtaining vitamin E solely from food sources. However, vitamin E toxicity can take place with supplements.

Research on high-dose vitamin E supplementation indicates a potential increase in overall mortality. Increased serum vitamin E levels can also impede the absorption of other fat-soluble vitamins, impair bone mineralization, coagulation problems, and reduced vitamin A storage.

The FNB’s highest tolerable upper intake levels (ULs) for vitamin E for both males and females are as follows:

• 1 to 3 years: 200 milligrams
• 4 to 8 years: 300 milligrams
• 9 to 13 years: 600 milligrams
• 14 to 18 years: 800 milligrams
• Over 19 years: 1,000 milligrams

Common adverse events of taking alpha-tocopherol supplements may include:

• Nausea
• Headache
• Vision changes
• Stomach discomfort
• Increased bleeding risk
• Hemorrhagic stroke risk
• A slight rise in urine creatinine
• Necrotizing enterocolitis, which is a life-threatening condition that predominantly impacts newborns, with a mortality rate reaching up to 50 percent. The condition involves inflammation in the intestine, leading to bacterial invasion, cellular damage, and necrosis of the colon and intestine.

Vitamin E may interact with the following medications:

• Anticoagulation and anti-platelet medications: Combining vitamin E with these medications may increase bleeding risk, as vitamin E can inhibit platelet clumping and interfere with vitamin K clotting factors.
• Simvastatin and niacin: When combined with simvastatin and niacin, vitamin E may counteract the desired effect of these medications by reducing the levels of high-density lipoprotein (HDL), or “good” cholesterol.
• Chemotherapy and radiotherapy: Oncologists typically discourage the use of antioxidant supplements during cancer chemotherapy or radiotherapy due to concerns that they may diminish the effectiveness of these treatments by impeding oxidative damage in cancer cells.
• Antidepressant drugs: Vitamin E can interfere with the absorption of the antidepressant desipramine, a tricyclic antidepressant belonging to the same class as imipramine and nortriptyline.
• Antipsychotic drugs: Vitamin E may interfere with the body’s absorption of the antipsychotic medication chlorpromazine, a type of phenothiazine.
• Beta blockers: Vitamin E may interfere with the absorption of propranolol, a beta blocker used to treat high blood pressure. Other beta blockers include acebutolol, atenolol, bisoprolol, carvedilol, metoprolol, nadolol, and many others.
• Bile acid sequestrants: Bile acid sequestrants, such as cholestyramine and cholestipol, prescribed to lower cholesterol, may decrease the body’s absorption of vitamin E.
• Tamoxifen: Tamoxifen, a breast cancer medication, may elevate triglyceride levels, thus increasing the risk of high cholesterol. Vitamin E, when taken with tamoxifen, can enhance the anti-cancer impact of this medication.

Vitamin E relies significantly on vitamins C and B3, selenium, and glutathione. A vitamin E-rich diet may not achieve maximum effectiveness unless it includes foods abundant in these complementary nutrients.

• Vitamin C: Evidence supports a collaborative interaction between vitamins C and E.
• Vitamin K: Large doses of vitamin E supplements in humans can potentially counteract the effects of vitamin K.
• Thiols: Thiols, which include glutathione and are formerly called mercaptans, are a group of organic compounds containing sulfur. The collaboration among thiols, tocopherols, and other compounds boosts the efficiency of the cellular antioxidant defense system.

The controversies surrounding vitamin E supplementation include:

• The scarcity of clear evidence for significant health benefits
• The debate centering on the different forms of vitamin E and their effectiveness in preventing or treating various conditions
• Different standards regarding upper limits of supplementation
• Potentially increased mortality: Per one meta-analysis of 19 clinical trials involving 135,967 participants, 400 IU (268 milligrams) of vitamin E supplements per day may elevate the risk of all-cause mortality. This dosage is much lower than the existing U.S. upper limit of 1,000 milligrams daily for adults aged 19 and over.
• Actual prevalence of vitamin E deficiency: Based on the National Health and Nutrition Examination Survey (NHANES) 2005–2006 data, the prevalence of vitamin E inadequacy in U.S. adults (over 20 years) was less than 1 percent of the population. This contradicts dietary surveys suggesting widespread inadequacy (over 90 percent), which might be attributed to underreporting of fat intake, inaccuracies in nutrient databases, and the absence of correction for circulating vitamin E concentrations to lipid levels. This raises questions about the need to reevaluate the nutritional requirement for vitamin E.
• Optimal daily intakes: The 2000 U.S. Dietary Reference Intakes (DRIs) review utilized data from past studies to establish vitamin E recommendations, resulting in significantly higher values than previous U.S. RDIs. The estimated average requirement was determined by considering the amount of dietary vitamin E needed to reduce plasma alpha-tocopherol to a level associated with low hemolysis. However, challenges arise in interpreting these data concerning the plasma alpha-tocopherol level where adverse effects occur, given the absence of data for concentrations between 5 and 12 micromoles per liter.