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AntioxidantImmune Support

Vitamin E

Evidence Level
Moderate
6 Clinical Trials
4 Documented Benefits
3/5 Evidence Score

Vitamin E is a family of fat-soluble compounds, and alpha-tocopherol is the form the body keeps. It is the main antioxidant in cell membranes, and EU regulators accept that it contributes to the protection of cells from oxidative stress. Nuts, seeds and vegetable oils are the richest sources. The adult RDA is 15 mg a day, and US surveys find most diets fall short of it, yet clear deficiency is rare in healthy people. Supplement trials have been disappointing. In older adults, 200 mg a day improved some immune test responses, but trials counting infections gave mixed results. Large trials found no protection against heart disease or cancer: 400 IU a day raised heart failure risk in people with vascular disease or diabetes and prostate cancer risk in healthy men, and a pooled analysis linked 400 IU a day or more to higher death rates. High doses can also add to bleeding risk with blood thinners.

Studied Dose Adult RDA 15 mg a day; upper limit 1,000 mg a day (1,500 IU natural or 1,100 IU synthetic). Trials used 200 mg (immune), 400 IU (heart and cancer) and up to 3,200 IU (oxidative stress); 400 IU or more was linked to higher death rates.
Active Compound Alpha-tocopherol: natural d-alpha-tocopherol (RRR) or synthetic dl-alpha-tocopherol (all-rac); some products add mixed tocopherols.
Deficiency information View details

Vitamin E deficiency is rare in healthy adults. Almost all cases come from fat malabsorption disorders or rare genetic conditions that affect how vitamin E is carried in the body. Severe deficiency causes progressive nerve damage, including loss of balance and coordination (ataxia) and peripheral neuropathy. Premature infants are also vulnerable because they have small stores at birth.

Common symptoms

  • Loss of balance and coordination (ataxia)
  • Loss of position and vibration sense (proprioceptive loss)
  • Muscle weakness
  • Loss of deep tendon reflexes (areflexia)
  • Numbness or tingling in hands and feet (peripheral neuropathy)
  • Eye problems such as limited upward gaze, retinal damage and reduced vision
  • Hemolytic anemia (red blood cells more susceptible to oxidative damage)
  • Difficulty walking, especially in the dark
  • Slurred speech (dysarthria) in advanced cases

At-risk groups

  • People with fat malabsorption disorders such as cystic fibrosis, cholestatic liver disease or short-bowel syndrome
  • People with abetalipoproteinemia (rare genetic disorder of fat metabolism)
  • People with ataxia with vitamin E deficiency (AVED, caused by TTPA gene mutations)
  • Premature or low birth weight infants
  • People who've had extensive intestinal surgery
  • People with chronic pancreatic insufficiency
  • Note: vitamin E deficiency from inadequate diet alone is essentially unheard of
When to see a doctor: See a doctor for a neurological check that includes a blood alpha-tocopherol test if you notice worsening balance or clumsiness, loss of vibration sense or muscle weakness, especially in a young person or someone with known fat malabsorption. In the genetic forms, early treatment with high-dose vitamin E can halt progression and partly reverse symptoms.
Explore related deficiencies →
Sources: NIH ODS: Vitamin E Health Professional Fact Sheet · Vitamin E Deficiency, StatPearls (NBK519051)

Benefits

Antioxidant protection

Alpha-tocopherol is the main fat-soluble antioxidant in cell membranes, and EU regulators accept that vitamin E contributes to the protection of cells from oxidative stress. In a dose-ranging trial in adults with high cholesterol, a blood marker of lipid damage fell significantly only at 1,600 IU a day or more, above the upper limit.

Supported by Trial 5

Immune function in older adults

In healthy adults over 65, 200 mg a day for about 8 months improved skin test immune responses and hepatitis B vaccine antibodies. Trials counting infections gave mixed results: in nursing home residents fewer people had a cold but total infections did not fall, and in older adults living at home infections were no less frequent and were more severe.

Supported by Trial 2, Trial 3

LDL oxidation and heart outcomes

Vitamin E slows the oxidation of LDL cholesterol in laboratory studies, a step in plaque formation. In the HOPE trial, 400 IU a day did not reduce heart attacks, strokes or cardiovascular deaths in people with vascular disease or diabetes and raised the risk of heart failure. A lab effect on LDL should not be read as a heart benefit.

Supported by Trial 1

Skin response to UV light

In a 50-day randomized trial, 2 g a day of vitamin E alone produced no significant change in how easily skin burned in UV light. Only the combination with 3 g a day of vitamin C raised the sunburn threshold. The vitamin E dose was twice the adult upper limit, so this is not a reason to take vitamin E for skin.

Supported by Trial 6

Mechanism of action

1

Lipid peroxidation termination

Alpha-tocopherol donates a hydrogen atom to lipid peroxyl radicals (LOO•), converting them to lipid hydroperoxides and generating a tocopheroxyl radical, which is then regenerated by vitamin C. This interrupts the chain reaction of lipid peroxidation.

2

Gene expression regulation

In laboratory studies tocopherols change the activity of genes involved in inflammation (the NF-kB pathway), cell adhesion and immune cell development, apart from their antioxidant action.

3

Platelet aggregation inhibition

Vitamin E reduces platelet clumping in laboratory studies. This is the reason high doses can add to bleeding risk, and the US upper limit is based on this bleeding effect. It has not translated into fewer heart attacks or strokes in large trials.

Clinical trials

1
HOPE and HOPE-TOO: Vitamin E and Cardiovascular Events
PubMed

Randomized double-blind placebo-controlled trial of 400 IU a day of natural vitamin E in 9,541 people aged 55 or older with vascular disease or diabetes; the extension followed participants for a median 7 years. (Lonn et al. 2005, JAMA)

9,541 adults with vascular disease or diabetes.

No significant difference in cancer (RR 0.94), cancer deaths (RR 0.88) or major cardiovascular events (RR 1.04). Heart failure (RR 1.13) and hospitalization for heart failure (RR 1.21) were more common on vitamin E.

2
Vitamin E and Immune Responses in Healthy Older Adults
PubMed

Randomized double-blind placebo-controlled trial of 60, 200 or 800 mg a day of vitamin E or placebo for 235 days. (Meydani et al. 1997, JAMA)

88 healthy free-living adults aged 65 or older.

The 200 mg group had a 65% increase in skin test (DTH) response and a 6-fold rise in hepatitis B vaccine antibodies, versus 17% and 3-fold on placebo, plus a rise in tetanus antibodies. There was no effect on diphtheria antibodies, immunoglobulin levels or T and B cell counts.

3
Vitamin E and Respiratory Infections in Nursing Home Residents
PubMed

Randomized double-blind placebo-controlled trial of 200 IU a day of vitamin E for 1 year at 33 Boston-area nursing homes; all participants also got a half-RDA multivitamin. (Meydani et al. 2004, JAMA)

617 nursing home residents aged 65 or older; 451 completed.

No significant effect on the number of infections or infection days, overall, upper or lower. Fewer people on vitamin E had at least one respiratory infection (60% vs 68%, P=0.048) or at least one cold (40% vs 48%, P=0.05). Antibiotic use did not differ.

4
Vitamin E and Respiratory Infections in Older Adults Living at Home
PubMed

Randomized double-blind placebo-controlled 2 x 2 factorial trial of 200 mg a day of vitamin E, a multivitamin, both or placebo, median 441 days. (Graat et al. 2002, JAMA)

652 well-nourished adults aged 60 or older in the Netherlands.

Vitamin E did not lower the rate of acute respiratory infections (rate ratio 1.12, P=0.21). Infections in the vitamin E groups lasted longer (median 19 vs 14 days), had more symptoms and more often caused fever and restricted activity.

5
Vitamin E Dose and Oxidative Stress Markers
PubMed

Randomized dose-ranging study of 0, 100, 200, 400, 800, 1,600 or 3,200 IU a day of natural vitamin E for 16 weeks, after a 20-week time-course study. (Roberts et al. 2007, Free Radic Biol Med)

Adults with polygenic high cholesterol and raised oxidative stress.

Plasma F2-isoprostanes, a marker of lipid peroxidation, fell in a dose-related way, reaching significance only at 1,600 IU (35% drop) and 3,200 IU (49% drop). The full effect took 16 weeks to appear.

6
Oral Vitamin E, Vitamin C and Sunburn Response
PubMed

Prospective randomized placebo-controlled trial of 2 g a day of vitamin E, 3 g a day of vitamin C, both, or placebo for 50 days, testing skin redness after simulated sunlight. (Fuchs and Kern 1998, Free Radic Biol Med)

Healthy volunteers.

Vitamin E alone raised vitamin E levels in skin cells but did not significantly change the sunburn response. Only the combination raised the minimal erythema dose, from 103 to 183 mJ/cm2.

Side effects and drug interactions

Common Potential side effects

Research has not found harmful effects from vitamin E in food; the risks below come from high-dose supplements.
Bleeding risk at high doses, which is what the adult upper limit of 1,000 mg a day is based on; take extra care with blood thinners, antiplatelet drugs or before surgery.
High-dose supplements (about 400 IU a day or more) were linked to higher all-cause death rates in a pooled analysis of 19 trials, and 400 IU a day raised prostate cancer risk by about 17% in healthy men in the SELECT trial.

Important Drug interactions

Blood thinners and antiplatelet drugs such as warfarin: vitamin E can slow platelet clumping and work against vitamin K clotting factors, so large doses taken with these drugs can raise bleeding risk, especially when vitamin K intake is low. The dose that matters is unknown but is probably above 400 IU a day.
Simvastatin plus niacin: an antioxidant mix of vitamin E, vitamin C, selenium and beta carotene blunted the rise in HDL cholesterol in people treated with this drug pair.
Cancer chemotherapy and radiotherapy: oncologists generally advise against antioxidant supplements during treatment because they might reduce its effect. Ask your cancer care team before use.

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Frequently asked questions about Vitamin E

How much vitamin E should I take?

The RDA is 15 mg (about 22 IU natural) per day. Supplements often contain far more, such as 100 to 400 IU. High-dose vitamin E long-term is not generally recommended, so moderation is wise.

Natural or synthetic vitamin E, which is better?

Natural vitamin E (labeled d-alpha-tocopherol) is more potent and better retained than synthetic (dl-alpha-tocopherol). Look for 'd-' not 'dl-' on the label. Mixed tocopherols and tocotrienols more closely reflect the forms found in food.

What is vitamin E used for?

Vitamin E is an essential nutrient that protects cell membranes from oxidative damage. Supplements are mainly useful to correct a shortfall. Trials have not shown that extra vitamin E prevents heart disease or cancer, and results for infections in older adults were mixed. Take it with a meal that contains fat for best absorption.

Does vitamin E thin the blood?

At high doses vitamin E can have a blood-thinning effect. If you take anticoagulants, are scheduled for surgery, or take other supplements that thin the blood, talk to your doctor and avoid high doses.

What is Vitamin E?

Vitamin E is a family of fat-soluble compounds, and alpha-tocopherol is the form the body keeps. It is the main antioxidant in cell membranes, and EU regulators accept that it contributes to the protection of cells from oxidative stress. Nuts, seeds and vegetable oils are the richest sources.

What are the signs of Vitamin E deficiency?

Vitamin E deficiency is rare in healthy adults. Almost all cases come from fat malabsorption disorders or rare genetic conditions that affect how vitamin E is carried in the body. Severe deficiency causes progressive nerve damage, including loss of balance and coordination (ataxia) and peripheral neuropathy.

Is Vitamin E safe, and does it have side effects?

Side effects and cautions reported for Vitamin E include: Research has not found harmful effects from vitamin E in food; the risks below come from high-dose supplements. Bleeding risk at high doses, which is what the adult upper limit of 1,000 mg a day is based on; take extra care with blood thinners, antiplatelet drugs or before surger… It may also interact with some medications. Vitamin E is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Vitamin E interact with any medications?

Possible interactions include: Blood thinners and antiplatelet drugs such as warfarin: vitamin E can slow platelet clumping and work against vitamin K clotting factors, so large doses taken with these drugs can raise bleeding risk, especially when vitamin K intake is low. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Vitamin E?

NutraSmarts rates the evidence for Vitamin E as Moderate (3 out of 5). It is backed by 6 study summaries and 10 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(10 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR, HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005;293(11):1338-47. doi: 10.1001/jama.293.11.1338.PubMedUsed to support: HOPE and HOPE-TOO RCT in 9,541 people aged 55 or older with vascular disease or diabetes: 400 IU a day of natural vitamin E did not reduce cancer, cancer deaths or major cardiovascular events (median follow-up 7 years in the extension) and raised heart failure risk (RR 1.13).
  2. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37-46. doi: 10.7326/0003-4819-142-1-200501040-00110.PubMedUsed to support: Dose-response meta-analysis (19 trials): high-dose vitamin E (>=400 IU/d) was associated with increased all-cause mortality. A core harm signal arguing against high-dose supplementation.
  3. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-56. doi: 10.1001/jama.2011.1437.PubMedUsed to support: SELECT RCT in 35,533 relatively healthy men: 400 IU a day of synthetic vitamin E increased prostate cancer risk (HR 1.17), an absolute increase of 1.6 cases per 1,000 person-years.
  4. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2012;2012(3):CD007176. doi: 10.1002/14651858.CD007176.pub2.PubMedUsed to support: Cochrane review (78 RCTs, ~296,000 participants): antioxidant supplements did not reduce mortality, and beta-carotene and vitamin E appeared to increase mortality. Reinforces that vitamin E's value is as an essential nutrient, not a high-dose preventive.
  5. Meydani SN, Meydani M, Blumberg JB, Leka LS, Siber G, Loszewski R, Thompson C, Pedrosa MC, Diamond RD, Stollar BD. Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA. 1997;277(17):1380-6. doi: 10.1001/jama.1997.03540410058031.PubMedUsed to support: RCT in 88 healthy adults aged 65 or older given 60, 200 or 800 mg a day or placebo for 235 days: 200 mg a day gave the largest gains in skin test response and hepatitis B antibodies, with no change in diphtheria antibodies, immunoglobulins or T and B cell counts.
  6. Meydani SN, Leka LS, Fine BC, Dallal GE, Keusch GT, Singh MF, Hamer DH. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA. 2004;292(7):828-36. doi: 10.1001/jama.292.7.828.PubMedUsed to support: RCT in 617 nursing home residents: 200 IU a day for 1 year did not change the number of respiratory infections or infection days, but fewer participants had at least one upper respiratory infection or cold.
  7. Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. JAMA. 2002;288(6):715-21. doi: 10.1001/jama.288.6.715.PubMedUsed to support: RCT in 652 adults aged 60 or older living at home: 200 mg a day of vitamin E did not reduce respiratory infections, and infections were longer and more severe in those taking it.
  8. Roberts LJ 2nd, Oates JA, Linton MF, Fazio S, Meador BP, Gross MD, Shyr Y, Morrow JD. The relationship between dose of vitamin E and suppression of oxidative stress in humans. Free Radic Biol Med. 2007;43(10):1388-93. doi: 10.1016/j.freeradbiomed.2007.06.019.PubMedUsed to support: Dose-ranging RCT in adults with high cholesterol: plasma F2-isoprostanes fell with dose, significantly only at 1,600 IU (35%) and 3,200 IU (49%) a day of natural vitamin E after 16 weeks.
  9. Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med. 1998;25(9):1006-12. doi: 10.1016/s0891-5849(98)00132-4.PubMedUsed to support: Randomized placebo-controlled trial in healthy volunteers: 2 g a day of vitamin E alone for 50 days did not significantly change the sunburn response; vitamin E plus 3 g a day of vitamin C raised the minimal erythema dose from 103 to 183 mJ/cm2.
  10. European Commission Commission Regulation (EU) No 432/2012 of 16 May 2012 establishing a list of permitted health claims made on foods, other than those referring to the reduction of disease risk and to children's development and health Official Journal of the European Union. 2012;OJ L 136, 25.5.2012, p. 1. Based on EFSA Journal 2010;8(10):1816..SourceUsed to support: Not PubMed-indexed. Lists the authorised claim that vitamin E contributes to the protection of cells from oxidative stress, for foods that are at least a source of vitamin E.