Vitamin E

What it is

Vitamin E is a group of fat-soluble compounds called tocopherols and tocotrienols; alpha-tocopherol is the form the body mainly uses [1][2]. It cannot be made by the body and comes from food, and recommended adult intakes are generally 15 to 30 mg a day [1]. Dietary sources include nuts and seeds [1]. Deficiency is uncommon in adults in industrialised countries, and there are few solid data on how often low vitamin E status occurs in these populations [1]. When deficiency does occur it is usually caused by fat malabsorption (conditions such as coeliac disease, cystic fibrosis, chronic cholestasis, or after bariatric surgery), liver disease, or the rare inherited disorder ataxia with vitamin E deficiency; the main symptoms are neurological and visual, including reduced reflexes, impaired vibration sense, distal muscle weakness, unsteadiness, and later vision problems [1].

How it might work

Vitamin E is an antioxidant that protects cell membranes and fats from oxidative damage by free radicals, which is the proposed reason it was once expected to reduce the artery damage and cell changes behind heart disease and cancer [1]. It also has anticoagulant effects, the proposed explanation for its interaction with blood-thinning medicines and for the small bleeding signal in the pooled trial data [2].

What the research says

Fatty liver disease (formerly NAFLD and NASH, now often called MASLD) is the one condition where randomised trials show vitamin E helping. A 2024 Cochrane review pooled 16 trials in 1,066 adults and children and found that vitamin E at 298 to 1,000 IU a day lowered ALT by 9.29 U/L on average (95% CI 13.69 to 4.89 lower) and AST by 4.90 U/L (2.57 to 7.24 lower) compared with placebo or no intervention, with moderate certainty; effects on death, serious side effects and quality of life were too uncertain to judge [3]. In the PIVENS trial, 247 adults with NASH and without diabetes took 800 IU a day for 96 weeks: 43% improved on liver biopsy versus 19% on placebo (P=0.001) and liver enzymes fell, but fibrosis scores did not improve [4]. A 2024 meta-analysis of eight trials found vitamin E reduced steatosis, lobular inflammation and hepatocyte ballooning and roughly doubled the chance of MASH resolution (RR 1.9, 95% CI 1.20 to 3.02), again without a clear improvement in fibrosis [5]. An earlier review found the liver-benefit signals mainly in adults, with only one of four paediatric trials showing significant improvement [6].

Large, long-term randomised trials agree that vitamin E does not prevent cardiovascular events. In HOPE, 9,541 people with vascular disease or diabetes took 400 IU a day for a mean of 4.5 years, and the combined rate of heart attack, stroke and cardiovascular death was 16.2% versus 15.5% (relative risk 1.05, 95% CI 0.95 to 1.16) [7]. In the Women's Health Study, 39,876 healthy women took 600 IU every other day for about 10 years: major cardiovascular events fell a non-significant 7% (RR 0.93, 0.82 to 1.05), while cardiovascular deaths were 24% lower (RR 0.76, 0.59 to 0.98) [8]. In the Physicians' Health Study II, 14,641 men took 400 IU every other day for a mean of 8 years with no effect on major cardiovascular events (HR 1.01, 0.90 to 1.13) [9]. A 2022 systematic review for the US Preventive Services Task Force pooled four trials of 62,136 people and found no effect on cardiovascular events (OR 0.96, 0.90 to 1.04) [10]. A 2022 meta-analysis of 884 randomised trials also found no effect of vitamin E on cardiovascular disease or type 2 diabetes risk [11], and a 2013 meta-analysis of 50 trials (294,478 participants) found no reduction in major cardiovascular events (RR 1.00, 0.98 to 1.02) [12].

For cancer overall the results are similarly null. The Women's Health Study found no difference in total invasive cancer (RR 1.01, 0.94 to 1.08) [8], and the Physicians' Health Study II found no difference in total cancer in men (HR 1.04, 0.95 to 1.13) [13]. In HOPE-TOO, the extended follow-up of HOPE to a median of 7 years, cancer was diagnosed in 11.6% of the vitamin E group versus 12.3% of the placebo group (RR 0.94, 0.84 to 1.06) and cancer deaths were 3.3% versus 3.7% (RR 0.88, 0.71 to 1.09) [14]. The US Preventive Services Task Force review pooled five trials (76,777 participants) and found no effect on cancer incidence (OR 1.02, 0.98 to 1.08) [10]. In the ATBC trial of 29,133 male smokers, alpha-tocopherol did not reduce lung cancer incidence (change of -2%, 95% CI -14 to 12%) [15].

Prostate cancer is the one cancer where trial results point in different directions. In SELECT, 34,887 men took 400 IU a day for up to 12 years: prostate cancer was diagnosed in 620 men on vitamin E versus 529 on placebo (hazard ratio 1.17, 99% CI 1.004 to 1.36, P=0.008), an absolute increase of 1.6 cases per 1,000 person-years [16]. The Physicians' Health Study II found no change in prostate cancer risk (HR 0.97, 0.85 to 1.09) [13], and its post-trial follow-up also found no difference over about 10 years (HR 0.99, 0.89 to 1.10) [17]. The older ATBC trial observed fewer prostate cancers among men who received alpha-tocopherol [15], while a 2022 meta-analysis of intake studies found no significant link overall (dietary RR 0.97, 0.92 to 1.02; supplemental RR 0.99, 0.94 to 1.04) [18].

Pooled trial data suggest vitamin E slightly increases bleeding-type strokes. A 2010 meta-analysis of nine trials (118,765 participants) found haemorrhagic stroke risk 22% higher with vitamin E (RR 1.22, 95% CI 1.00 to 1.48) while ischaemic stroke risk was 10% lower (RR 0.90, 0.82 to 0.99); in absolute terms that was one extra haemorrhagic stroke per 1,250 people and one ischaemic stroke prevented per 476 [19]. The Physicians' Health Study II found haemorrhagic strokes 74% more common with vitamin E (HR 1.74, 1.04 to 2.91) [9], and the ATBC trial reported more deaths from haemorrhagic stroke in the alpha-tocopherol groups [15]. A 2024 meta-analysis of 16 trials found vitamin E alone did not change stroke rates, and the higher haemorrhagic stroke risk (RR 1.22, 1.00 to 1.48) appeared when vitamin E was combined with other antioxidants [20].

The mortality data are mixed. A 2005 dose-response meta-analysis of 19 trials (135,967 participants) found that doses of 400 IU a day and above were associated with about 39 extra deaths per 10,000 people (95% CI 3 to 74 per 10,000), with a dose-response increase above about 150 IU a day [21]. A larger analysis restricted to trials at low risk of bias (53 trials, 241,883 participants) found vitamin E above the recommended daily allowance was associated with a 3% higher mortality risk (RR 1.03, 1.00 to 1.05) [22]. However, meta-analyses in apparently healthy people found no increase: RR 1.01 (0.97 to 1.05) across 18 trials and 142,219 participants taking 23 to 800 IU a day [23], and RR 1.00 (0.98 to 1.02) across 57 trials (246,371 participants) with no dose relationship up to 5,500 IU a day [24]. The US Preventive Services Task Force review also found no mortality effect (OR 1.02, 0.97 to 1.07) [10].

For scars the evidence is weak. A systematic review of six prospective studies found insufficient evidence that topical vitamin E alone improves scar appearance, with two studies reporting contact dermatitis, itching or rash [25]. In a double-blind split-scar trial of 15 patients, topical vitamin E did not improve cosmetic appearance, in 90% of cases it had no effect or made the scar look worse, and 33% of patients developed contact dermatitis [26].

Doses used in studies

Prevention trials used 400 IU a day (HOPE and HOPE-TOO, SELECT), 400 IU every other day (Physicians' Health Study II), 600 IU every other day (Women's Health Study) and 50 mg a day of alpha-tocopherol (ATBC), with follow-up from about 4.5 to 12 years [7][14][16][9][8][15]. NASH trials used 800 IU a day for 96 weeks (PIVENS) [4], and the Cochrane review of NAFLD trials covered 298 to 1,000 IU a day for 2 to 24 months [3]. The mortality meta-analysis pooled doses from 16.5 to 2,000 IU a day, with a median of 400 IU a day [21].

Safety and interactions

Common side effects: in the large trials vitamin E was generally well tolerated, with side-effect rates similar to placebo [7][4]. Applied to the skin it caused contact dermatitis in one in three patients in a small scar trial, and reviews report itching and rash [26][25]. In pregnancy trials of vitamin E combined with other supplements, women reported more abdominal pain (RR 1.66, 95% CI 1.16 to 2.37) and more term prelabour rupture of membranes (RR 1.77, 1.37 to 2.28) [27].

Upper limits: the tolerable upper intake level for vitamin E set by the US Institute of Medicine is 1,000 mg a day for adults, and a 2005 safety review judged supplements up to 1,600 IU (about 1,073 mg) a day safe for most adults [28]. However, one dose-focused meta-analysis linked 400 IU a day and above to a small increase in deaths, and a pooled analysis found a 22% higher rate of haemorrhagic stroke, so high-dose use is the main safety question [21][19].

Interactions: vitamin E is listed among therapies with documented reports of interaction with warfarin, and its anticoagulant effect is the proposed reason it can increase bleeding risk when combined with blood thinners such as warfarin or aspirin [29][2]. Some medicines that reduce fat absorption, including orlistat, cholestyramine and colestipol, antiepileptic drugs, and mineral oil laxatives, can also lower vitamin E absorption [1].

Pregnancy and breastfeeding: a Cochrane review of 21 trials (22,129 women) found no clear benefit of vitamin E given with other supplements for stillbirth, pre-eclampsia, preterm birth or growth restriction; it was associated with fewer placental abruptions (RR 0.64, 0.44 to 0.93) but more abdominal pain and term membrane rupture, and the review did not support routine use in pregnancy [27]. No breastfeeding-specific trial data were identified [27].

Conditions to be careful with: in people with vascular disease or diabetes, long-term 400 IU a day was associated with a 13% higher risk of heart failure (RR 1.13, 95% CI 1.01 to 1.26) and 21% more heart-failure hospitalisations (RR 1.21, 1.00 to 1.47) [14]. People who take blood thinners, have bleeding disorders or heart failure, or who are pregnant or breastfeeding should ask a doctor before using high-dose vitamin E; this page is not medical advice [19][14].

Caveats and open questions

Most prevention trials enrolled adults without known vitamin E deficiency, often older people followed for under 10 years, so they do not answer what supplementation does in people with genuinely low vitamin E status [10][30]. Vitamin E also did not prevent age-related macular degeneration in a Cochrane review of four trials (55,614 participants): no effect on any AMD (RR 0.97, 0.90 to 1.06), with a non-significant higher risk of late AMD (RR 1.22, 0.89 to 1.67) [31]. In fatty liver disease, effects on death, serious side effects and quality of life remain too uncertain to judge, and fibrosis has not improved in pooled analyses [3][5]. Ongoing trials listed below are testing tocotrienols in precancerous pancreatic cysts and an alpha-tocopherol combination for pneumonitis prevention.