[1] Tocopherols and tocotrienols both occur in α (alpha), β (beta), γ (gamma), and δ (delta) forms, as determined by the number and position of methyl groups on the chromanol ring.

[1][6] All eight of these vitamers feature a chromane double ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals, and a hydrophobic side chain that allows for penetration into biological membranes.

Both natural and synthetic tocopherols are subject to oxidation, so dietary supplements are esterified, creating tocopheryl acetate for stability purposes.

The molecules that contribute α-tocopherol activity are four tocopherols and four tocotrienols, within each group of four identified by the prefixes alpha- (α-), beta- (β-), gamma- (γ-), and delta- (δ-).

The oxidized α-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol.

A number of health benefits of tocotrienols have been proposed, including decreased risk of age-associated cognitive impairment, heart disease and cancer.

[4] In contrast, the U.S. Dietary Reference Intake text for vitamin E concluded that a plasma concentration of 12 μmol/L was sufficient to achieve normal ex vivo hydrogen peroxide-induced hemolysis.

[5][1] The amounts of alpha-tocopherol, other tocopherols, and tocotrienols that are components of dietary vitamin E, when consumed from foods, do not appear to cause any interactions with drugs.

Consumption of alpha-tocopherol as a dietary supplement in amounts in excess of 300 mg/day may lead to interactions with aspirin, warfarin, tamoxifen and cyclosporine A in ways that alter function.

[41] The US National Institutes of Health, Office of Dietary Supplements, raises a concern that co-administration of vitamin E could counter the mechanisms of anti-cancer radiation therapy and some types of chemotherapy, and so advises against its use in these patient populations.

[1] The U.S. National Academy of Medicine updated estimated average requirements (EARs) and recommended dietary allowances (RDAs) for vitamin E in 2000.

It identified that no adverse effects were observed in a human trial as 540 mg/day, used an uncertainty factor of 2 to derive an upper limit of half of that, then rounded to 300 mg/day.

For vitamin E labeling purposes 100% of the daily value was 30 international units (IUs), but as of May 2016, it was revised to 15 mg to bring it into agreement with the RDA.

[60] Tocotrienols and tocopherols, the latter including the stereoisomers of synthetic alpha-tocopherol, are absorbed from the intestinal lumen, incorporated into chylomicrons, and secreted into the portal vein, leading to the liver.

Bile is necessary for chylomicron formation, so disease conditions such as cystic fibrosis result in biliary insufficiency and vitamin E malabsorption.

Large intakes of α-tocopherol result in increased urinary α-CEHC, so this appears to be a means of disposing of excess vitamin E.[5][14] Alpha-tocopherol transfer protein is coded by the TTPA gene on chromosome 8.

Tocotrienols are also a poor fit because the double bonds in the phytic tail create a rigid configuration that is a mismatch with the α-TTP pocket.

[37] The role of α-TTP is to move α-tocopherol to the plasma membrane of hepatocytes (liver cells), where it can be incorporated into newly created very low density lipoprotein (VLDL) molecules.

In the US, the vitamin is widely available as an over-the-counter supplement; however, medical evidence supporting its effectiveness and safety for treating or preventing a variety of health conditions is mixed.

[63] In a 2022 update of an earlier report, the United States Preventive Services Task Force recommended against the use of vitamin E supplements for the prevention of cardiovascular disease or cancer, concluding there was insufficient evidence to assess the balance of benefits and harms, yet also concluding with moderate certainty that there is no net benefit of supplementation.

[82] One review reported a modest increase in cancer risk with vitamin E supplementation while stating that more than 90% of the cited clinical trials used the synthetic, racemic form dl-alpha-tocopherol.

A further revision, May 2012, allowed that vitamin E may reduce risk of renal, bladder and colorectal cancers, with a more concise qualifier sentence added: "FDA has concluded that there is very little scientific evidence for this claim."

[85][86] In a 2022 update of an earlier report, the United States Preventive Services Task Force recommended against the use of vitamin E supplements for the prevention of cardiovascular disease or cancer, concluding there was insufficient evidence to assess the balance of benefits and harms, yet also concluding with moderate certainty that there is no net benefit of supplementation.

[87] An inverse relation has been observed between coronary heart disease and the consumption of foods high in vitamin E, and also higher serum concentration of alpha-tocopherol.

[87] A meta-analysis of randomized clinical trials (RCTs) reported that when consumed without any other antioxidant nutrient, the relative risk of heart attack was reduced by 18%.

[94] The U.S. National Institutes of Health reviewed literature published up to 2008 and concluded "In general, clinical trials have not provided evidence that routine use of vitamin E supplements prevents cardiovascular disease or reduces its morbidity and mortality.

[101] For Parkinson's disease, there is an observed inverse correlation seen with dietary vitamin E, but no confirming evidence from placebo-controlled clinical trials.

[107][108] There are also reports of allergic contact dermatitis from use of vitamin-E derivatives such as tocopheryl linoleate and tocopherol acetate in skin care products.

[112] By November 2019, the CDC had identified vitamin E acetate as a very strong culprit of concern in the vaping-related illnesses, but has not ruled out other chemicals or toxicants as possible causes.

From 1949 onward there were trials with premature infants suggesting that oral alpha-tocopherol was protective against edema, intracranial hemorrhage, hemolytic anemia and retrolental fibroplasia.