Vitamin E
Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols.[1][2] Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitamin E,[3] can cause nerve problems.[4] Vitamin E is a fat-soluble antioxidant which may help protect cell membranes from reactive oxygen species.[2][4] Worldwide, government organizations recommend adults consume in the range of 3 to 15 mg per day. As of 2016, consumption was below recommendations according to a worldwide summary of more than one hundred studies that reported a median dietary intake of 6.2 mg per day for alpha-tocopherol.[5] Foods rich in vitamin E include seeds and nuts, seed oils, peanut butter, and vitamin E-fortified foods, such as margarine.[2][4]
Population studies suggested that people who consumed foods with more vitamin E, or who chose on their own to consume a vitamin E dietary supplement, had lower incidence of cardiovascular diseases, cancer, dementia, and other diseases. However, placebo-controlled clinical trials using alpha-tocopherol as a supplement, with daily amounts as high as 2,000 mg per day, could not always replicate these findings.[2] In the United States vitamin E supplement use peaked around 2002, but has declined by more than half by 2006. The authors theorized that declining use may have been due to publications of large placebo-controlled studies that showed either no benefits or actual negative consequences from high-dose vitamin E.[6][7][8]
Both natural and synthetic tocopherols are subject to oxidation, so dietary supplements are esterified, creating tocopheryl acetate for stability purposes.[2][9] 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.[4][10] 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.
Vitamin E was discovered in 1922, isolated in 1935, and first synthesized in 1938. Because the vitamin activity was first identified as essential for fertilized eggs to result in live births (in rats), it was given the name "tocopherol" from Greek words meaning birth and to bear or carry. Alpha-tocopherol, either naturally extracted from plant oils or, most commonly, as the synthetic tocopheryl acetate, is sold as a popular dietary supplement, either by itself or incorporated into a multivitamin product, and in oils or lotions for use on skin.
Drug interactions[edit]
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 and cyclosporine A in ways that alter function.[4][34] For aspirin and warfarin, high amounts of vitamin E may potentiate anti-blood clotting action.[4][34] In multiple clinical trials, vitamin E lowered blood concentration of the immunosuppressant medication, cyclosporine A.[34] 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. The references it cited reported instances of reduced treatment adverse effects, but also poorer cancer survival, raising the possibility of tumor protection from the intended oxidative damage by the treatments.[4]
Testing for levels[edit]
A worldwide summary of more than one hundred human studies reported a median of 22.1 μmol/L for serum α-tocopherol, and defined α-tocopherol deficiency as less than 12 μmol/L. It cited a recommendation that serum α-tocopherol concentration be ≥30 μmol/L to optimize health benefits.[5] 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.[3] A 2014 review defined less than 9 μmol/L as deficient, 9-12 μmol/L as marginal, and greater than 12 μmol/L as adequate.[52]
Serum concentration increases with age. This is attributed to the fact that vitamin E circulates in blood incorporated into lipoproteins, and serum lipoprotein concentrations increase with age. Infants and young children have a higher risk of being below the deficiency threshold.[5] Cystic fibrosis and other fat malabsorption conditions can result in low serum vitamin E. Dietary supplements will raise serum vitamin E.[3]
History[edit]
Vitamin E was discovered in 1922 by Herbert McLean Evans and Katharine Scott Bishop[108] and first isolated in a pure form by Evans and Gladys Anderson Emerson in 1935 at the University of California, Berkeley.[109] Because the vitamin activity was first identified as a dietary fertility factor in rats, it was given the name "tocopherol" from the Greek words "τόκος" [tókos, birth], and "φέρειν", [phérein, to bear or carry] meaning in sum "to carry a pregnancy," with the ending "-ol" signifying its status as a chemical alcohol. George M. Calhoun, Professor of Greek at the University of California, was credited with helping with the naming process.[110] Erhard Fernholz elucidated its structure in 1938 and shortly afterward the same year, Paul Karrer and his team first synthesized it.[111]
Nearly 50 years after the discovery of vitamin E, an editorial in the Journal of the American Medical Association titled "Vitamin in search of a disease" read in part "...research revealed many of the vitamin's secrets, but no certain therapeutic use and no definite deficiency disease in man." The animal discovery experiments had been a requirement for successful pregnancy, but no benefits were observed for women prone to miscarriage. Evidence for vascular health was characterized as unconvincing. The editorial closed with mention of some preliminary human evidence for protection against hemolytic anemia in young children.[112]
A role for vitamin E in coronary heart disease was first proposed in 1946 by Evan Shute and colleagues.[113][114] More cardiovascular work from the same research group followed,[115] including a proposal that megadoses of vitamin E could slow down and even reverse the development of atherosclerosis.[116] Subsequent research showed no association between vitamin E supplementation and cardiovascular events such as nonfatal stroke or myocardial infarction, or cardiovascular mortality.[117]
There is a long history of belief that topical application of vitamin E containing oil benefits burn and wound healing.[98] This belief persists even though scientific reviews refuted this claim.[99][100][101]
The role of vitamin E in infant nutrition has a long research history. 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.[118] A more recent review concluded that vitamin E supplementation in preterm infants reduced the risk of intercranial hemorrhage and retinopathy, but noted an increased risk of sepsis.[119]