Vitamin E · The Ingredient Files

①

Evidence by effect

Evidence strength (A–D, color) and effect size (dots, fill) are shown separately. The two axes are independent.

Claimed effect

Evidence strength

Effect size

One-line summary · key source

Improving liver tissue in non-alcoholic steatohepatitisA state of fat-laden liver with inflammation and cell injury; the non-alcoholic type is called NASH. (NASH) in non-diabetic adultsEvidence type: RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.

B Moderate

Moderate

This is essentially the only evidence-based use of a vitamin E supplement, and the one context where 'antioxidant' genuinely helped. In a large randomized trial (PIVENS) of 247 non-diabetic adults with non-alcoholic steatohepatitisA state of fat-laden liver with inflammation and cell injury; the non-alcoholic type is called NASH. (NASH), the group taking vitamin E 800 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form. a day for 96 weeks had significantly greater improvement in liver tissue (histology) than placeboAn inert dummy treatment used as the comparison baseline. (43% vs 19%), with reductions in liver enzymes (ALT/AST), fat accumulation, and lobular inflammation. But fibrosis (scarring) scores did not improve significantly, the result is limited to non-diabetic adults, and the dose used (800 IU) is the high dose linked to mortality and cancer risk in other settings. So it is an indication used under specialist care in a specific patient group, not grounds to extend it into a general antioxidant or liver-health supplement. PMID: 20427778

Preventing cardiovascular disease (the belief)Evidence type: RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.

D Insufficient

None

The belief that 'as an antioxidant it is good for blood vessels' collapsed in large trials, which instead showed a harmful signal. In the HOPE-TOO trial, giving natural vitamin E 400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form. daily to about 9,500 patients aged 55+ with vascular disease or diabetes over a median 7 years, the vitamin E group had no difference from placeboAn inert dummy treatment used as the comparison baseline. in major cardiovascular events (heart attack, stroke, cardiovascular death; relative risk 1.04). But heart failureA condition in which the heart cannot pump enough blood to meet the body's needs. risk was actually higher (relative risk 1.13), as were heart-failure hospitalizations (1.21). The authors concluded that in patients with vascular disease or diabetes, long-term vitamin E does not reduce cardiovascular events and may raise heart-failure risk. So supplementing vitamin E for heart health offers no benefit and only potential harm. PMID: 15769967

Preventing cancer (the belief) - increased prostate cancer riskEvidence type: RCTRandomized controlled trial - a high-reliability trial that randomly assigns participants to compare effects.

D Insufficient

None

The hope that vitamin E prevents cancer also turned out the opposite in a large trial. In SELECT, which randomized about 35,000 relatively healthy men to vitamin E (400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day), selenium, both, or placeboAn inert dummy treatment used as the comparison baseline., the vitamin E group developed significantly more prostate cancer than placebo (hazard ratio 1.17, P=0.008). In absolute terms that was 1.6 extra cases per 1,000 person-years, and the authors concluded vitamin E supplementation significantly increased prostate cancer risk in healthy men. In HOPE-TOO too, cancer incidence and cancer death did not differ from placebo. So vitamin E does not reduce cancer, and in healthy men it may actually raise the risk of a specific cancer. PMID: 21990298

High-dose long-term use - mortality risk (the 'antioxidant equals longevity' belief)Evidence type: Meta-analysis

D Insufficient

None

Beyond individual diseases, high-dose vitamin E was linked to overall mortality itself. In a meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of 19 randomized trials and 135,967 people, 9 of 11 trials testing high-dose (400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day or more) vitamin E leaned toward increased all-cause mortality, amounting to about 39 excess deaths per 10,000 people (P=0.035). A dose-response analysis showed rising mortality risk above 150 IU a day. The authors concluded that high-dose (400 IU or more) vitamin E supplements may increase all-cause mortality and 'should be avoided.' One caveat: many high-dose trials were small studies in people with chronic diseases, so generalizing to healthy adults is uncertain. Even so, the idea that 'it is an antioxidant, so more is better' runs against the evidence. PMID: 15537682

Evidence strength A Strong · B Moderate · C Weak · D Insufficient/refuted

Effect size Large → None

②

Who benefits / who should be cautious

The statements in this section are translated directly from institutional sources (NIH-ODS, etc.), not our own interpretation. Consult a professional before use.

Benefit

Almost the only case where vitamin E supplementation has evidence is non-diabetic adults with non-alcoholic steatohepatitisA state of fat-laden liver with inflammation and cell injury; the non-alcoholic type is called NASH. (NASH), where a large trial improved liver tissue. But this is a specific indication diagnosed and managed by a specialist, not grounds to extend it for general health or antioxidant purposes. source↗

Original text

Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes.
Caution

There is no reason to take vitamin E for heart health. In a large trial of patients with vascular disease or diabetes, vitamin E did not reduce cardiovascular events and instead raised the risk of heart failureA condition in which the heart cannot pump enough blood to meet the body's needs.. source↗

Original text

In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.
Caution

Vitamin E does not reduce cancer, and in healthy men it actually raised prostate cancer risk. Taking vitamin E supplements in the hope of preventing cancer is unsupported and carries potential harm. source↗

Original text

Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.
Caution

Avoid high-dose vitamin E. A large meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. found that high-dose vitamin E of 400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form. a day or more may increase all-cause mortality, and the authors said it should be avoided. The idea that 'more antioxidant is better' is dangerous. source↗

Original text

High-dosage (> or =400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.

③

Form & dosage evidence

Trial doses by effect

Non-alcoholic steatohepatitis (NASH, trial dose): Vitamin E 800 IU/day in non-diabetic adults under specialist care (PIVENS) - not a general supplement recommendation [20427778]

④

Balanced conclusion

Vitamin E is a two-faced ingredient: 'an essential nutrient amply supplied by food, but with no benefit as a supplement and real risk at high doses.' As a fat-soluble antioxidant nutrient that protects cell membranes, its deficiency is serious, but that is very rare outside special situations like fat malabsorption, and an ordinary diet with nuts, seeds, and vegetable oils easily meets the daily requirement (about 15 mg). By contrast, the high-dose supplements sold under an 'antioxidant equals heart, cancer, anti-aging' image collapsed in large trials. In HOPE-TOO, 400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form. did not prevent cardiovascular events and increased heart failureA condition in which the heart cannot pump enough blood to meet the body's needs.; in SELECT, it raised prostate cancer risk in healthy men; and in a meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of 19 trials and 136,000 people, high-dose (400 IU or more) was linked to all-cause mortality, with the authors saying it should be avoided. The one evidence-based supplement use is confined to non-diabetic NASH patients as a specific indication under specialist care. In short, a healthy person has no reason to take high-dose vitamin E supplements expecting antioxidant, heart, anti-aging, or immune benefits, and the amount needed is safely and amply obtained from a balanced diet.

Apply - Get it from food

Examples of foods rich in Vitamin E. Amounts are shown for reference against the doses used in the trials.

Note: eating these foods does not guarantee immediate treatment or prevention of any disease.

The recommended intake of vitamin E for adults is about 15 mg (alpha-tocopherol) a day. It is abundant in the vegetable oils, nuts, and seeds below and also present in leafy greens and avocado, so a balanced diet meets it without difficulty. For reference, the 400 IU common in supplements is roughly 180-270 mg, more than ten times the recommendation - a high dose that offers no benefit and carries safety signals. Being fat-soluble, vitamin E is absorbed better when eaten with some oil.

Sunflower oil100 g ~41 mg [source]
Sunflower seeds, dried100 g ~35 mg [source]
Almonds100 g ~26 mg [source]
Hazelnuts100 g ~15 mg [source]
Avocado, raw100 g ~2.1 mg [source]
Spinach, boiled100 g ~2.1 mg [source]

⑤

Sources

Each source shows its one-line summary and key summary up front. Expand the collapsed section to read the original abstract. Every citation is verified by re-resolving through the API.

PMID 20427778 Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis Randomized controlled trial (PIVENS) · N Engl J Med, 2010 247 people, 96 weeks - vitamin E 800 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day beat placeboAn inert dummy treatment used as the comparison baseline. for NASH histology (43% vs 19%), lowered enzymes/fat/inflammation, but not fibrosis. Non-diabetic adults only.

Key summary

A randomized trial (PIVENS) of 247 non-diabetic adults with non-alcoholic steatohepatitisA state of fat-laden liver with inflammation and cell injury; the non-alcoholic type is called NASH. (NASH) assigned to pioglitazone (30 mg/day), vitamin E (800 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day), or placeboAn inert dummy treatment used as the comparison baseline. for 96 weeks. The primary outcome was improvement in liver histology. The vitamin E group had a significantly higher rate of histologic improvement than placebo (43% vs 19%, P=0.001), with reductions in liver enzymes (ALT/AST), fat accumulation, and lobular inflammation, but no significant improvement in fibrosis. Pioglitazone was not significant on the primary outcome versus placebo and caused more weight gain. The authors concluded vitamin E was superior to placebo in non-diabetic NASH adults. The 800 IU dose is high and should be read alongside the safety concerns in other settings.

Show original abstract

BACKGROUND: Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. METHODS: We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily (80 subjects), vitamin E at a dose of 800 IU daily (84 subjects), or placebo (83 subjects), for 96 weeks. The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis, as assessed with the use of a composite of standardized scores for steatosis, lobular inflammation, hepatocellular ballooning, and fibrosis. Given the two planned primary comparisons, P values of less than 0.025 were considered to indicate statistical significance. RESULTS: Vitamin E therapy, as compared with placebo, was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis (43% vs. 19%, P=0.001), but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant (34% and 19%, respectively; P=0.04). Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pioglitazone, as compared with placebo (P<0.001 for both comparisons), and both agents were associated with reductions in hepatic steatosis (P=0.005 for vitamin E and P<0.001 for pioglitazone) and lobular inflammation (P=0.02 for vitamin E and P=0.004 for pioglitazone) but not with improvement in fibrosis scores (P=0.24 for vitamin E and P=0.12 for pioglitazone). Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo; the rates of other side effects were similar among the three groups. CONCLUSIONS: Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes. There was no benefit of pioglitazone over placebo for the primary outcome; however, significant benefits of pioglitazone were observed for some of the secondary outcomes. (ClinicalTrials.gov number, NCT00063622.) ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

View original ↗

PMID 15769967 Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial Randomized controlled trial (HOPE-TOO) · JAMA, 2005 9,500 vascular/diabetes patients, 7 years - vitamin E 400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day did not cut cancer or CV events (RR 1.04), but raised heart failureA condition in which the heart cannot pump enough blood to meet the body's needs. (RR 1.13) and HF hospitalization (1.21).

Key summary

A large randomized trial (HOPE and its extension HOPE-TOO) of long-term vitamin E supplementation for cancer and cardiovascular outcomes in patients aged 55+ with vascular disease or diabetes. Natural vitamin E 400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form. or placeboAn inert dummy treatment used as the comparison baseline. was given daily, with a median 7 years of follow-up. The vitamin E group did not differ significantly from placebo in cancer incidence (relative risk 0.94), cancer death (0.88), or major cardiovascular events (1.04). But heart-failure risk was higher (1.13), as were heart-failure hospitalizations (1.21), with the same pattern in the extension cohort. The authors concluded that in patients with vascular disease or diabetes, long-term vitamin E does not prevent cancer or major cardiovascular events and may increase heart-failure risk.

Show original abstract

CONTEXT: Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. OBJECTIVE: To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. INTERVENTION: Daily dose of natural source vitamin E (400 IU) or matching placebo. MAIN OUTCOME MEASURES: Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. RESULTS: Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. CONCLUSION: In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

View original ↗

PMID 21990298 Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) Randomized controlled trial (SELECT) · JAMA, 2011 ~35,000 healthy men - vitamin E 400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day significantly increased prostate cancer risk (HR 1.17, P=0.008); 1.6 extra cases per 1,000 person-years.

Key summary

A large randomized trial (SELECT) of selenium and vitamin E for prostate cancer prevention in about 35,000 relatively healthy men. Participants were assigned to selenium (200 µg/day), vitamin E (400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day of all rac-α-tocopheryl acetate), both, or placeboAn inert dummy treatment used as the comparison baseline.. Over long-term follow-up, 620 men in the vitamin E group developed prostate cancer versus 529 in placebo, a significant increase (hazard ratio 1.17, 99% CI 1.004-1.36, P=0.008). Selenium alone and the combination were not significant. The absolute increase for vitamin E was 1.6 cases per 1,000 person-years. The authors concluded that vitamin E supplementation significantly increased prostate cancer risk in healthy men.

Show original abstract

CONTEXT: The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. OBJECTIVE: To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS: A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. INTERVENTIONS: Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. MAIN OUTCOME MEASURES: Prostate cancer incidence. RESULTS: This report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. CONCLUSION: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

View original ↗

PMID 15537682 Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality Meta-analysis · Ann Intern Med, 2005 19 trials, 136,000 people - high-dose (>=400 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day) vitamin E raised all-cause mortality (+39 per 10,000, P=0.035), dose-response above 150 IU/day. 'Should be avoided.'

Key summary

A meta-analysisA statistical synthesis combining results of multiple studies into one conclusion. of the dose-response between vitamin E supplementation and all-cause mortality (19 randomized trials, 135,967 people, doses 16.5-2000 IUInternational unit - a measure of a vitamin biological activity; for vitamin E, 1 IU is roughly 0.45 to 0.67 mg depending on the form./day, median 400). Of 11 trials testing high-dose (400 IU/day or more) vitamin E, 9 leaned toward increased all-cause mortality, amounting to 39 excess deaths per 10,000 people (P=0.035); low-dose trials showed no such signal. A dose-response analysis showed rising mortality risk above 150 IU a day. The authors concluded high-dose vitamin E supplements may increase all-cause mortality and should be avoided, while noting the limitation that many high-dose trials were small studies in people with chronic diseases, so generalizing to healthy adults is uncertain.

Show original abstract

BACKGROUND: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. PURPOSE: To perform a meta-analysis of the dose-response relationship between vitamin E supplementation and total mortality by using data from randomized, controlled trials. PATIENTS: 135,967 participants in 19 clinical trials. Of these trials, 9 tested vitamin E alone and 10 tested vitamin E combined with other vitamins or minerals. The dosages of vitamin E ranged from 16.5 to 2000 IU/d (median, 400 IU/d). DATA SOURCES: PubMed search from 1966 through August 2004, complemented by a search of the Cochrane Clinical Trials Database and review of citations of published reviews and meta-analyses. No language restrictions were applied. DATA EXTRACTION: 3 investigators independently abstracted study reports. The investigators of the original publications were contacted if required information was not available. DATA SYNTHESIS: 9 of 11 trials testing high-dosage vitamin E (> or =400 IU/d) showed increased risk (risk difference > 0) for all-cause mortality in comparisons of vitamin E versus control. The pooled all-cause mortality risk difference in high-dosage vitamin E trials was 39 per 10,000 persons (95% CI, 3 to 74 per 10,000 persons; P = 0.035). For low-dosage vitamin E trials, the risk difference was -16 per 10,000 persons (CI, -41 to 10 per 10,000 persons; P > 0.2). A dose-response analysis showed a statistically significant relationship between vitamin E dosage and all-cause mortality, with increased risk of dosages greater than 150 IU/d. LIMITATIONS: High-dosage (> or =400 IU/d) trials were often small and were performed in patients with chronic diseases. The generalizability of the findings to healthy adults is uncertain. Precise estimation of the threshold at which risk increases is difficult. CONCLUSION: High-dosage (> or =400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided. ※ The abstract text as collected and stored via the API by the pipeline. The key summary is written based solely on this text.

View original ↗

USDA FoodData Central Oil, sunflower, linoleic (approx. 65%) (FDC 171025)