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Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four
tocotrienol The vitamin E family comprise four tocotrienols (alpha, beta, gamma, delta) and four tocopherols (alpha, beta, gamma, delta). The critical chemical structural difference between tocotrienols and tocopherols is that tocotrienols have unsaturated ...
s. 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, can cause nerve problems. Vitamin E is a
fat-soluble Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves li ...
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...
which may help protect
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
s from reactive oxygen species. 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. 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 A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
, had lower incidence of cardiovascular diseases,
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
,
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
, and other diseases. However,
placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...
-controlled
clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...
s using alpha-tocopherol as a supplement, with daily amounts as high as 2,000 mg per day, could not always replicate these findings. 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. There is use of vitamin E in skincare and wound-treatment products, but no clinical evidence that it is effective. Both natural and synthetic tocopherols are subject to oxidation, and so in dietary supplements are
ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
ified, creating tocopheryl acetate for stability purposes. 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. All eight of these vitamers feature a chromane double ring, with a hydroxyl group that can donate a hydrogen atom to reduce
free radicals In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spon ...
, and a
hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, ...
side chain which 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 A multivitamin is a preparation intended to serve as a dietary supplement with vitamins, dietary minerals, and other nutritional elements. Such preparations are available in the form of tablets, capsules, pastilles, powders, liquids, or injecta ...
product, and in oils or lotions for use on skin.


Chemistry

The nutritional content of vitamin E is defined by equivalency to 100% RRR-configuration α-tocopherol activity. 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-). For alpha(α)-tocopherol each of the three "R" sites has a methyl group (CH3) attached. For beta(β)-tocopherol: R1 = methyl group, R2 = H, R3 = methyl group. For gamma(γ)-tocopherol: R1 = H, R2 = methyl group, R3 = methyl group. For delta(δ)-tocopherol: R1 = H, R2 = H, R3 = methyl group. The same configurations exist for the tocotrienols, except that the hydrophobic side chain has three carbon-carbon double bonds whereas the tocopherols have a saturated side chain.


Stereoisomers

In addition to distinguishing tocopherols and tocotrienols by position of methyl groups, the tocopherols have a phytyl tail with three chiral points or centers that can have a right or left orientation. The naturally occurring plant form of alpha-tocopherol is RRR-α-tocopherol, also referred to as d-tocopherol, whereas the synthetic form ( all-racemic or ''all-rac'' vitamin E, also dl-tocopherol) is equal parts of eight stereoisomers RRR, RRS, RSS, SSS, RSR, SRS, SRR and SSR with progressively decreasing biological equivalency, so that 1.36 mg of dl-tocopherol is considered equivalent to 1.0 mg of d-tocopherol, the natural form. Rephrased, the synthetic has 73.5% of the potency of the natural.


Tocopherols

Alpha-tocopherol is a
lipid-soluble Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipoph ...
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...
functioning within the glutathione peroxidase pathway, and protecting
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...
s from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This removes the free radical intermediates and prevents the
oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
reaction from continuing. 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 Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) and ...
,
retinol Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family found in food and used as a dietary supplement. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xeroph ...
or
ubiquinol A ubiquinol is an electron-rich (reduced) form of coenzyme Q (ubiquinone). The term most often refers to ubiquinol-10, with a 10-unit tail most commonly found in humans. The natural ubiquinol form of coenzyme Q is 2,3-dimethoxy-5-methyl-6-poly p ...
. Other forms of vitamin E have their own unique properties; for example, γ-tocopherol is a
nucleophile In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they ar ...
that can react with
electrophilic In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carr ...
mutagens.


Tocotrienols

The four
tocotrienol The vitamin E family comprise four tocotrienols (alpha, beta, gamma, delta) and four tocopherols (alpha, beta, gamma, delta). The critical chemical structural difference between tocotrienols and tocopherols is that tocotrienols have unsaturated ...
s (alpha, beta, gamma, delta) are similar in structure to the four tocopherols, with the main difference being that the former have hydrophobic side chains with three carbon-carbon double bonds, whereas the tocopherols have saturated side chains. For ''alpha(α)''-tocotrienol each of the three "R" sites has a methyl group (CH3) attached. For ''beta(β)''-tocotrienol: R1 = methyl group, R2 = H, R3 = methyl group. For ''gamma(γ)''-tocotrienol: R1 = H, R2 = methyl group, R3 = methyl group. For ''delta(δ)''-tocotrienol: R1 = H, R2 = H, R3 = methyl group. Palm oil is a good source of alpha and gamma tocotrienols. Tocotrienols have only a single chiral center, which exists at the 2' chromanol ring carbon, at the point where the isoprenoid tail joins the ring. The other two corresponding centers in the phytyl tail of the corresponding tocopherols do not exist as chiral centers for tocotrienols due to unsaturation (C-C double bonds) at these sites. Tocotrienols extracted from plants are always dextrorotatory stereoisomers, signified as d-tocotrienols. In theory, levorotatory forms of tocotrienols (l-tocotrienols) could exist as well, which would have a 2S rather than 2R configuration at the molecules' single chiral center, but unlike synthetic dl-alpha-tocopherol, the marketed tocotrienol
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
s are extracted from palm oil. A number of health benefits of tocotrienols have been proposed, included decreased risk of are-associated cognitive impairment, heart disease and cancer. The evidence is not conclusive.


Functions

Vitamin E may have various roles as a vitamin. Many biological functions have been postulated, including a role as a
fat-soluble Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves li ...
antioxidant Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...
. In this role, vitamin E acts as a radical scavenger, delivering a hydrogen (H) atom to free radicals. At 323 kJ/ mol, the O-H bond in tocopherols is about 10% weaker than in most other
phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it r ...
s. This weak bond allows the vitamin to donate a hydrogen atom to the peroxyl radical and other
free radicals In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spon ...
, minimizing their damaging effect. The thus-generated tocopheryl radical is recycled to tocopherol by a
redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or ...
reaction with a hydrogen donor, such as
vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) ...
. Vitamin E affects
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. T ...
and is an enzyme activity regulator, such as for protein kinase C (PKC) – which plays a role in
smooth muscle Smooth muscle is an involuntary non- striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit ...
growth – with vitamin E participating in deactivation of PKC to inhibit smooth muscle growth.


Synthesis


Biosynthesis

Photosynthesizing plants,
algae Algae (; singular alga ) is an informal term for a large and diverse group of photosynthetic eukaryotic organisms. It is a polyphyletic grouping that includes species from multiple distinct clades. Included organisms range from unicellular micr ...
and
cyanobacteria Cyanobacteria (), also known as Cyanophyta, are a phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's common name, bl ...
synthesize tocochromanols, the chemical family of compounds made up of four tocopherols and four tocotrienols; in a nutrition context this family is referred to as Vitamin E. Biosynthesis starts with formation of the closed-ring part of the molecule as homogentisic acid (HGA). The side chain is attached (saturated for tocopherols, polyunsaturated for
tocotrienol The vitamin E family comprise four tocotrienols (alpha, beta, gamma, delta) and four tocopherols (alpha, beta, gamma, delta). The critical chemical structural difference between tocotrienols and tocopherols is that tocotrienols have unsaturated ...
s). The pathway for both is the same, so that gamma- is created and from that alpha-, or delta- is created and from that the beta- compounds. Biosynthesis takes place in the plastids. As to why plants synthesize tocochromanols, the major reason appears to be for antioxidant activity. Different parts of plants, and different species, are dominated by different tocochromanols. The predominant form in leaves, and hence leafy green vegetables is α-tocopherol. Location is in chloroplast membranes, in close proximity to the photosynthetic process. The function is to protect against damage from the ultraviolet radiation of sunlight. Under normal growing conditions the presence of α-tocopherol does not appear to be essential, as there are other photo-protective compounds, and plants that through mutations have lost the ability to synthesize α-tocopherol demonstrate normal growth. However, under stressed growing conditions such as drought, elevated temperature or salt-induced oxidative stress, the plants' physiological status is superior if it has the normal synthesis capacity. Seeds are lipid-rich, to provide energy for
germination Germination is the process by which an organism grows from a seed or spore. The term is applied to the sprouting of a seedling from a seed of an angiosperm or gymnosperm, the growth of a sporeling from a spore, such as the spores of fungi, fe ...
and early growth. Tocochromanols protect the seed lipids from oxidizing and becoming rancid. The presence of tocochromanols extends seed longevity, and promotes successful germination and seedling growth. Gamma-tocopherol dominates in seeds of most plant species, but there are exceptions. For canola, corn and soy bean oils, there is more γ-tocopherol than α-tocopherol, but for safflower, sunflower and olive oils the reverse is true. Of the commonly used food oils, palm oil is unique in that tocotrienol content is higher than tocopherol content. Seed tocochromanols content is also dependent on environmental stressors. In almonds, for example, drought or elevated temperature increase α-tocopherol and γ-tocopherol content of the nuts. The same article mentions that drought increases the tocopherol content of olives, and heat likewise for soybeans. Vitamin E biosynthesis occurs in the plastid and goes through two different pathways: the Shikimate pathway and the Methylerythritol Phosphate pathway (MEP pathway). The Shikimate pathway generates the chromanol ring from the Homogentisic Acid (HGA) and the MEP pathway produces the hydrophobic tail which differs between tocopherol and tocotrienol. The synthesis of the specific tail is dependent on which molecule it originates from. In a tocopherol, its prenyl tail emerges from the geranylgeranyl diphosphate (GGDP) group, while the phytyl tail of a tocotrienol stems from a phytyl diphosphate. Focusing on tocopherols, the synthesis of its derivatives stems from the reaction between the HGA and the Phytyl-PP which generates 2-Methyl-6-phytylhydroquinone. At this point of the synthesis, 2-Methyl-6-phytylhydroquinone can go through two different pathways. The first path takes the molecule and methylates it at C3. This results in a 2,3-Dimethyl-5-phytylhydroquinone. Then, the cyclization of the hydroxyl group at C1 generates the first derivative, γ-Tocopherol. Following the cyclization, another methylation is done at C5 of the γ-Tocopherol resulting in the production of α-Tocopherol. The second path takes the same 2-Methyl-6-phytylhydroquinone and cyclizes the hydroxyl group at C1 which produces the δ-Tocopherol. Afterward, a round of methylation at C5 results in the last derivative, β-Tocopherol. This whole synthesis occurs similarly for tocotrienol with prenyl-PP, which is generated from a GGDP group, replacing the phytyl-PP.


Industrial synthesis

The synthetic product is all-rac-alpha-tocopherol, also referred to as dl-alpha tocopherol. It consists of eight stereoisomers (RRR, RRS, RSS, RSR, SRR, SSR, SRS and SSS) in equal quantities. "It is synthesized from a mixture of toluene and 2,3,5-trimethyl-hydroquinone that reacts with isophytol to all-rac-alpha-tocopherol, using iron in the presence of hydrogen chloride gas as catalyst. The reaction mixture obtained is filtered and extracted with aqueous caustic soda. Toluene is removed by evaporation and the residue (all rac-alpha-tocopherol) is purified by vacuum distillation." The synthetic is in contrast to what is extracted from plants, all RRR-alpha tocopherol, referred to as d-alpha-tocopherol. The synthetic has 73.5% of the potency of the natural. Manufacturers of dietary supplements and fortified foods for humans or domesticated animals convert the phenol form of the vitamin to an
ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
using either acetic acid or succinic acid because the esters are more chemically stable, providing for a longer shelf-life.


Deficiency

Vitamin E deficiency is rare in humans, occurring as a consequence of abnormalities in dietary fat absorption or metabolism rather than from a diet low in vitamin E. One example of a genetic abnormality in metabolism is mutations of genes coding for alpha-tocopherol transfer protein (α-TTP). Humans with this genetic defect exhibit a progressive neurodegenerative disorder known as
ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
with vitamin E deficiency (AVED) despite consuming normal amounts of vitamin E. Large amounts of alpha-tocopherol as a dietary supplement are needed to compensate for the lack of α-TTP Vitamin E deficiency due to either malabsorption or metabolic anomaly can cause nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function. In addition to ataxia, vitamin E deficiency can cause peripheral neuropathy, myopathies, retinopathy, and impairment of immune responses.


Drug interactions

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 Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
, warfarin and
cyclosporine A Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disea ...
in ways that alter function. For aspirin and warfarin, high amounts of vitamin E may potentiate anti-blood clotting action. In multiple clinical trials, vitamin E lowered blood concentration of the immunosuppressant medication, cyclosporine A. The US
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the lat ...
, 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.


Dietary recommendations

The U.S. National Academy of Medicine updated estimated average requirements (EARs) and recommended dietary allowances (RDAs) for vitamin E in 2000. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements. Adequate intakes (AIs) are identified when there is not sufficient information to set EARs and RDAs. The EAR for vitamin E for women and men ages 14 and up is 12 mg/day. The RDA is 15 mg/day. As for safety, tolerable upper intake levels ("upper limits" or ULs) are set for vitamins and minerals when evidence is sufficient. Hemorrhagic effects in rats were selected as the critical endpoint to calculate the upper limit via starting with the lowest-observed-adverse-effect-level. The result was a human upper limit set at 1000 mg/day. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes. The European Food Safety Authority (EFSA) refers to the collective set of information as dietary reference values, with population reference intakes (PRIs) instead of RDAs, and average requirements instead of EARs. AIs and ULs are defined the same as in the United States. For women and men ages 10 and older, the PRIs are set at 11 and 13 mg/day, respectively. PRI for pregnancy is 11 mg/day, for lactation 11 mg/day. For children ages 1–9 years the PRIs increase with age from 6 to 9 mg/day. The EFSA used an effect on blood clotting as a safety-critical effect. It identified that no adverse effects were observed in a human trial as 540 mg/day, used an uncertainty factor of 2 to get to a suggest an upper limit of half of that, then rounded to 300 mg/day. The Japan National Institute of Health and Nutrition set adult AIs at 6.5 mg/day (females) and 7.0 mg/day (males), and 650–700 mg/day (females), and 750–900 mg/day (males) for upper limits, amounts depending on age. India recommends an intake of 8–10 mg/day and does not set an upper limit. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
recommends that adults consume 10 mg/day. The United Kingdom is an outlier, in that it recommends 4 mg/day for adult men and 3 mg/day for adult women. Consumption is below these government recommendations. Government survey results in the United States reported average consumption for adult females at 8.4 mg/d and adult males 10.4 mg/d. Both are below the RDA of 15 mg/day. A worldwide summary of more than one hundred studies reported a median dietary intake of 6.2 mg/d for alpha-tocopherol.


Food labeling

For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of daily value. For vitamin E labeling purposes 100% of the daily value was 30 international units, but as of 27 May 2016 it was revised to 15 mg to bring it into agreement with the RDA. Compliance with the updated labeling regulations was required by 1 January 2020 for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for manufacturers with lower volume food sales. A table of the old and new adult daily values is provided at
Reference Daily Intake The Reference Daily Intake (RDI) used in nutrition labeling on food and dietary supplement products in the U.S. and Canada is the daily intake level of a nutrient that is considered to be sufficient to meet the requirements of 97–98% of healt ...
. European Union regulations require that labels declare energy, protein, fat, saturated fat, carbohydrates, sugars, and salt. Voluntary nutrients may be shown if present in significant amounts. Instead of daily values, amounts are shown as percent of reference intakes (RIs). For vitamin E, 100% RI was set at 12 mg in 2011. The
international unit In pharmacology, the international unit (IU) is a unit of measurement for the effect, not mass of a substance; the variance is based on the biological activity or effect, for the purpose of easier comparison across similar ''forms'' of substanc ...
measurement was used by the United States in 1968–2016. 1 IU is the biological equivalent of about 0.667 mg d (RRR)-alpha-tocopherol (2/3 mg exactly), or of 0.90 mg of dl-alpha-tocopherol, corresponding to the then-measured relative potency of stereoisomers. In May 2016, the measurements have been revised, such that 1 mg of "Vitamin E" is 1 mg of d-alpha-tocopherol or 2 mg of dl-alpha-tocopherol. The change was originally started in 2000, when forms of Vitamin E other than alpha-tocopherol was dropped from dietary calculations by the IOM. The UL amount disregards any conversion. The EFSA has never used an IU unit, and their measurement only considers RRR-alpha-tocopherol.


Sources

Worldwide, consumption is below recommendations according to a summary of more than one hundred studies that reported a median dietary intake of 6.2 mg per day for alpha-tocopherol. Of the many different forms of vitamin E, gamma-tocopherol (
γ-tocopherol γ-Tocopherol is a tocopherol and one of the chemical compounds that comprise vitamin E. As a food additive, it has E number E308. See also * α-Tocopherol * β-Tocopherol * δ-Tocopherol δ-Tocopherol is a tocopherol and one of the che ...
) is the most common form found in the North American diet, but alpha-tocopherol (
α-tocopherol α-Tocopherol is a type of vitamin E. It has E number "E307". Vitamin E exists in eight different forms, four tocopherols and four tocotrienols. All feature a chromane ring, with a hydroxyl group that can donate a hydrogen atom to reduce free r ...
) is the most biologically active. Palm oil is a source of tocotrienols. The U.S. Department of Agriculture (USDA), Agricultural Research Services, maintains a food composition database. The last major revision was Release 28, September 2015. In addition to the naturally occurring sources shown in the table, certain ready-to-eat cereals, infant formulas, liquid nutrition products and other foods are fortified with alpha-tocopherol.


Supplements

Vitamin E is fat soluble, so dietary supplement products are usually in the form of the vitamin, esterified with acetic acid to generate tocopheryl acetate, and dissolved in vegetable oil in a softgel capsule. For alpha-tocopherol, amounts range from 100 to 1000 IU per serving. Smaller amounts are incorporated into multi-vitamin/mineral tablets. Gamma-tocopherol and tocotrienol supplements are also available from dietary supplement companies. The latter are extracts from palm oil.


Fortification

The World Health Organization does not have any recommendations for food fortification with vitamin E. The Food Fortification Initiative does not list any countries that have mandatory or voluntary programs for vitamin E. Infant formulas have alpha-tocopherol as an ingredient. In some countries, certain brands of ready-to-eat cereals, liquid nutrition products and other foods have alpha-tocopherol as an added ingredient.


Non-nutrient food additives

Various forms of vitamin E are common food additive in oily food, used to deter rancidity caused by peroxidation. Those with an
E number E numbers ("E" stands for "Europe") are codes for substances used as food additives, including those found naturally in many foods such as vitamin C, for use within the European Union (EU) and European Free Trade Association (EFTA). Commonly ...
include: # E306 Tocopherol-rich extract (mixed, natural, can include tocotrienol) # E307 Alpha-tocopherol (synthetic) # E308 Gamma-tocopherol (synthetic) # E309 Delta-tocopherol (synthetic) These E numbers include all racemic forms and acetate esters thereof. Commonly found on
food label The packaging and labeling of food is subject to regulation in most regions/jurisdictions, both to prevent false advertising and to promote food safety. Regulations by type Multi-faceted * Codex Alimentarius (international voluntary standard) ...
s in Europe and some other countries, their safety assessment and approval are the responsibility of the European Food Safety Authority.


Metabolism

Tocotrienols and tocopherols, the latter including the stereoisomers of synthetic alpha-tocopherol, are absorbed from the intestinal lumen, incorporated into
chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small particle''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (8 ...
s, and secreted into the
portal vein The portal vein or hepatic portal vein (HPV) is a blood vessel that carries blood from the gastrointestinal tract, gallbladder, pancreas and spleen to the liver. This blood contains nutrients and toxins extracted from digested contents. Approx ...
, leading to the liver. Absorption efficiency is estimated at 51% to 86%, and that applies to all of the vitamin E family – there is no discrimination among the vitamin E vitamers during absorption. Unabsorbed vitamin E is excreted via feces. Additionally, vitamin E is excreted by the liver via
bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bi ...
into the intestinal lumen, where it will either be reabsorbed or excreted via feces, and all of the vitamin E vitamers are metabolized and then excreted via urine. Upon reaching the liver, RRR-alpha-tocopherol is preferentially taken up by alpha-tocopherol transfer protein (α-TTP). All other forms are degraded to 2'-carboxethyl-6-hydroxychromane (CEHC), a process that involves truncating the phytic tail of the molecule, then either sulfated or glycuronidated. This renders the molecules water-soluble and leads to excretion via urine. Alpha-tocopherol is also degraded by the same process, to 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychromane (α-CEHC), but more slowly because it is partially protected by α-TTP. Large intakes of α-tocopherol result in increased urinary α-CEHC, so this appears to be a means of disposing of excess vitamin E. Alpha-tocopherol transfer protein is coded by the TTPA gene on chromosome 8. The binding site for RRR-α-tocopherol is a hydrophobic pocket with a lower affinity for beta-, gamma-, or delta-tocopherols, or for the stereoisomers with an S configuration at the chiral 2 site. 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. A rare genetic defect of the TTPA gene results in people exhibiting a progressive neurodegenerative disorder known as ataxia with vitamin E deficiency (AVED) despite consuming normal amounts of vitamin E. Large amounts of alpha-tocopherol as a dietary supplement are needed to compensate for the lack of α-TTP 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. These convey α-tocopherol to cells in the rest of the body. As an example of a result of the preferential treatment, the US diet delivers approximately 70 mg/d of γ-tocopherol and plasma concentrations are on the order of 2–5 µmol/L; meanwhile, dietary α-tocopherol is about 7 mg/d but plasma concentrations are in the range of 11–37 µmol/L. Affinity of α-TTP for vitamin E vitamers


Testing for levels

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. 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. 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. 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. Cystic fibrosis and other fat malabsorption conditions can result in low serum vitamin E. Dietary supplements will raise serum vitamin E.


Research

For the conditions described below, the results of randomized clinical trials (RCTs) do not always concur with the observational evidence. This could be a matter of amount. Observational studies compare low consumers to high consumers based on intake from food. Diets higher in vitamin E may contain other compounds that convey health benefits, or be consumed by people who make non-diet lifestyle choices that lower disease risk, so that the observed effect may not be due to the vitamin E content. Meanwhile, many of the published RCTs used amounts of alpha-tocopherol 20X to 30X higher than what can be achieved from food.


Declining supplement use

In the United States, vitamin E supplement use by female health professionals was 16.1% in 1986, 46.2% in 1998, 44.3% in 2002, but decreased to 19.8% in 2006. Similarly, for male health professionals, rates for same years were 18.9%, 52.0%, 49.4% and 24.5%. The authors theorized that declining use in these populations may have been due to publications of studies that showed either no benefits or negative consequences from vitamin E supplements. Within the U.S. military services, vitamin prescriptions written for active, reserve and retired military, and their dependents, were tracked over years 2007–2011. Vitamin E prescriptions decreased by 53% while vitamin C remained constant and vitamin D increased by 454%. A report on vitamin E sales volume in the US documented a 50% decrease between 2000 and 2006, with a potential reason being a meta-analysis that concluded high-dosage (≥400 IU/d for at least 1 year) vitamin E was associated with an increase in all-cause mortality.


All-cause mortality

Two meta-analyses concluded that as a dietary supplement, vitamin E neither improved nor impaired all-cause mortality. An older meta-analysis had concluded high-dosage (≥400 IU/d for at least 1 year) vitamin E was associated with an increase in all-cause mortality. The authors acknowledged that the cited high-dose trials were often small and performed with people who already had chronic diseases. A meta-analysis of long-term clinical trials reported a non-significant 2% increase in all-cause mortality when alpha-tocopherol was the only supplement used. The same meta-analysis reported a statistically significant 3% increase for results when alpha-tocopherol was used in combination with other nutrients (vitamin A, vitamin C, beta-carotene, selenium).


Age-related macular degeneration

A Cochrane review reported no change to risk of developing age-related macular degeneration from long-term vitamin E suplementation.


Alzheimer's disease

An older review of dietary intake studies reported that higher consumption of vitamin E from foods lowered the risk of developing Alzheimer's disease (AD) by 24%. A 2017 Cochrane review reported on vitamin E as a potential dietary benefit for mild cognitive impairment (MCI) and Alzheimer's disease. Based on evidence from one trial in each of the categories, the study found insufficient evidence for supplemental vitamin E to prevent progression from MCI to dementia, but it did indicate slowing of functional decline in people with AD. Given the small number of trials and subjects, the authors recommended further research. A 2018 meta-analysis found lower vitamin E blood levels in AD people compared to healthy, age-matched people. In 2017, a consensus statement from the British Association for Psychopharmacology concluded that, until further information is available, vitamin E cannot be recommended for treatment or prevention of Alzheimer's disease.


Cancer

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. As for literature on different types of cancer, an inverse relationship between dietary vitamin E and kidney cancer and
bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become ma ...
is seen in observational studies. The risk reduction was 19% when highest and lowest intake groups were compared. The authors concluded that
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
s (RCTs) are needed. A large study comparing placebo to an all rac-alpha-tocopherol group consuming 400 IU/day reported no difference in bladder cancer cases. An inverse relationship between dietary vitamin E and
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, mali ...
was reported in observational studies. The relative risk reduction was 16% when highest and lowest intake groups were compared. The benefit was progressive as dietary intake increased from 2 mg/day to 16 mg/day. The authors noted that the findings need to be confirmed by prospective studies. One such large trial, which compared 50 mg alpha-tocopherol to placebo in male tobacco smokers, reported no impact on lung cancer. A trial which tracked people who chose to consume a vitamin E dietary supplement reported an increased risk of lung cancer for those consuming more than 215 mg/day. For prostate cancer, there are also conflicting results. A meta-analysis based on serum alpha-tocopherol content reported an inverse correlation, with the difference between lowest and highest a 21% reduction in relative risk. In contrast, a meta-analysis of observational studies reported no relationship for dietary vitamin E intake. There were also conflicting results from large RCTs. The ATBC trial administered placebo or 50 mg/day alpha-tocopherol to male tobacco smokers for 5 to 8 years and reported a 32% decrease in the incidence of prostate cancer. Conversely, the SELECT trial of selenium and vitamin E for prostate cancer enrolled men ages 55 or older, mostly non-smokers, to consume a placebo or a 400 IU/day dietary supplement. It reported relative risk as a statistically significant 17% higher for the vitamin group. For colorectal cancer, a systematic review identified RCTs of vitamin E and placebo followed for 7–10 years. There was a non-significant 11% decrease in relative risk. The SELECT trial (men over 55 years, placebo or 400 IU/day) also reported on colorectal cancer. There was a non-significant 3% increase in adenoma occurrence compared to placebo. The Women's Health Study compared placebo to 600 IU of natural-source vitamin E on alternate days for an average of 10.1 years. There were no significant differences for incidences of all types of cancer, cancer deaths, or specifically for breast, lung or colon cancers. Potential confounding factors are the form of vitamin E used in prospective studies and the amounts. Synthetic, racemic mixtures of vitamin E isomers are not bioequivalent to natural, non-racemic mixtures, yet are widely used in clinical trials and as dietary supplement ingredients. 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.


Cancer health claims

The U.S. Food and Drug Administration initiated a process of reviewing and approving food and dietary supplement health claims in 1993. Reviews of petitions results in proposed claims being rejected or approved. If approved, specific wording is allowed on package labels. In 1999, a second process for claims review was created. If there is not a scientific consensus on the totality of the evidence, a Qualified Health Claim (QHC) may be established. The FDA does not "approve" qualified health claim petitions. Instead, it issues a Letter of Enforcement Discretion that includes very specific claim language and the restrictions on using that wording. The first QHCs relevant to vitamin E were issued in 2003: "Some scientific evidence suggests that consumption of antioxidant vitamins may reduce the risk of certain forms of cancer." In 2009, the claims became more specific, allowing that vitamin E might reduce the risk of renal, bladder and colorectal cancers, but with required mention that the evidence was deemed weak and the claimed benefits highly unlikely. A petition to add brain, cervical, gastric and lung cancers was rejected. 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." Any company product label making the cancer claims has to include a qualifier sentence. The European Food Safety Authority (EFSA) reviews proposed health claims for the
European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are located primarily in Europe, Europe. The union has a total area of ...
countries. As of September 2022,, EFSA has not evaluated any vitamin E and cancer prevention claims.


Cataracts

A meta-analysis from 2015 reported that for studies which reported serum tocopherol, higher serum concentration was associated with a 23% reduction in relative risk of age-related cataracts (ARC), with the effect due to differences in nuclear cataract rather than cortical or posterior subcapsular cataract – the three major classifications of age-related cataracts. However, this article and a second meta-analysis reporting on clinical trials of alpha-tocopherol supplementation reported no statistically significant change to risk of ARC when compared to placebo.


Cardiovascular diseases

In an 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. Research on the effects of vitamin E on cardiovascular disease has produced conflicting results. In theory, oxidative modification of LDL-cholesterol promotes blockages in coronary arteries that lead to atherosclerosis and
heart attacks A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
, so vitamin E functioning as an antioxidant would reduce oxidized cholesterol and lower risk of cardiovascular disease. Vitamin E status has also been implicated in the maintenance of normal endothelial cell function of cells lining the inner surface of arteries, anti-inflammatory activity and inhibition of platelet adhesion and aggregation. 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. In one of the largest observational studies, almost 90,000 healthy nurses were tracked for eight years. Compared to those in the lowest fifth for reported vitamin E consumption (from food and dietary supplements), those in the highest fifth were at a 34% lower risk of major coronary disease. The problem with observational studies is that these cannot confirm a relation between the lower risk of coronary heart disease and vitamin E consumption because of confounding factors. Diet higher in vitamin E may also be higher in other, unidentified components that promote heart health, or people choosing such diets may be making other healthy lifestyle choices. There is some supporting evidence from randomized clinical trials (RCTs). A meta-analysis on the effects of alpha-tocopherol supplementation in RCTs on aspects of cardiovascular health reported that when consumed without any other antioxidant nutrient, the relative risk of heart attack was reduced by 18%. The results were not consistent for all of the individual trials incorporated into the meta-analysis. For example, the Physicians' Health Study II did not show any benefit after 400 IU every other day for eight years, for heart attack, stroke, coronary mortality or all-cause mortality. The HOPE/HOPE-TOO trial, which enrolled people with pre-existing vascular disease or diabetes into a multi-year trial of 400 IU/day, reported a higher risk of heart failure in the alpha-tocopherol group. The effects of vitamin E supplementation on incidence of
stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
were summarized in 2011. There were no significant benefits for vitamin E versus placebo. Subset analysis for ischaemic stroke, haemorrhagic stroke, fatal stroke, non-fatal stroke – all no significant difference in risk. Likewise for subset analysis of natural or synthetic vitamin E, or only above or below 300 IU/day, or whether the enrolled people were healthy or considered to be at higher than normal risk. The authors concluded that there was a lack of clinically important benefit of vitamin E supplementation in the prevention of stroke. One large, multi-year study in which post-menopausal women consumed either placebo or 600 IU of natural-sourced vitamin E on alternate days reported no effect on stroke, but did report a 21% reduction in relative risk of developing a deep vein clot or pulmonary embolism. The beneficial effect was strongest is the subset of women who had a history of a prior thrombotic event or who were genetically coded for clot risk (
factor V Leiden Factor V Leiden (rs6025 or ''F5'' p.R506Q) is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an antico ...
or prothrombin mutation).


Cardiovascular health claims

In 2001, the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
rejected proposed health claims for vitamin E and cardiovascular health. 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." The European Food Safety Authority (EFSA) reviews proposed health claims for the
European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are located primarily in Europe, Europe. The union has a total area of ...
countries. In 2010, the EFSA reviewed and rejected claims that a cause and effect relationship has been established between the dietary intake of vitamin E and maintenance of normal cardiac function or of normal blood circulation.


Nonalcoholic fatty liver disease

Meta-analyses reported that supplemental vitamin E significantly reduced elevated liver enzymes, steatosis, inflammation and fibrosis, suggesting that the vitamin may be useful for treatment of nonalcoholic fatty liver disease (NAFLD) and the more extreme subset known as nonalcoholic steatohepatitis (NASH) in adults, but not in children.


Parkinson's disease

For
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
, there is an observed inverse correlation seen with dietary vitamin E, but no confirming evidence from placebo-controlled clinical trials.


Pregnancy

Antioxidant vitamins as dietary supplements have been proposed as having benefits if consumed during pregnancy. For the combination of vitamin E with vitamin C supplemented to pregnant women, a Cochrane review concluded that the data do not support vitamin E supplementation – majority of trials alpha-tocopherol at 400 IU/day plus vitamin C at 1,000 mg/day – as being efficacious for reducing risk of
stillbirth Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...
, neonatal death,
preterm birth Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is betwee ...
,
preeclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...
or any other maternal or infant outcomes, either in healthy women or those considered at risk for pregnancy complications. The review identified only three small trials in which vitamin E was supplemented without co-supplementation with vitamin C. None of these trials reported any clinically meaningful information.


Topical

Although there is widespread use of tocopheryl acetate as a
topical medication A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...
, with claims for improved wound healing and reduced
scar A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a ...
tissue, reviews have repeatedly concluded that there is insufficient evidence to support these claims. There are reports of vitamin E-induced allergic contact dermatitis from use of vitamin-E derivatives such as tocopheryl linoleate and tocopherol acetate in skin care products. Incidence is low despite widespread use.


Vaping-associated lung injury

On 5 September 2019, the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
announced that 10 out of 18, or 56% of the samples of vape liquids sent in by states, linked to recent vaping related lung disease outbreak in the United States, tested positive for vitamin E acetate which had been used as a
thickening agent A thickening agent or thickener is a substance which can increase the viscosity of a liquid without substantially changing its other properties. Edible thickeners are commonly used to thicken sauces, soups, and puddings without altering the ...
by illicit THC vape cartridge manufacturers. On 8 November 2019, the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
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. These findings were based on fluid samples from the lungs of 29 patients with
vaping-associated pulmonary injury Vaping-associated pulmonary injury (VAPI), also known as vaping-associated lung injury (VALI) or e-cigarette, or vaping, product use associated lung injury (E/VALI), is an umbrella term, used to describe lung diseases associated with the use of v ...
, which provided direct evidence of vitamin E acetate at the primary site of injury in all the 29 lung fluid samples tested. A review confirmed vitamin E acetate as a causitive agent.
Pyrolysis The pyrolysis (or devolatilization) process is the thermal decomposition of materials at elevated temperatures, often in an inert atmosphere. It involves a change of chemical composition. The word is coined from the Greek-derived elements '' ...
of vitamin E acetate produces a range of toxic gases.


History

Vitamin E was discovered in 1922 by Herbert McLean Evans and Katharine Scott Bishop and first isolated in a pure form by Evans and
Gladys Anderson Emerson Gladys Ludwina Anderson Emerson (July 1, 1903 – January 18, 1984) was an American historian, biochemist and nutritionist who researched the impact of vitamins on the body. She was the first person to isolate Vitamin E in a pure form, and won th ...
in 1935 at the
University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant un ...
. 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" ókos, birth and "φέρειν", hérein, to bear or carrymeaning 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. Erhard Fernholz elucidated its structure in 1938 and shortly afterwards the same year, Paul Karrer and his team first synthesized it. 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. A role for vitamin E in coronary heart disease was first proposed in 1946 by Evan Shute and colleagues. More cardiovascular work from the same research group followed, including a proposal that megadoses of vitamin E could slow down and even reverse the development of atherosclerosis. However, a 2004 meta-analysis showed no association between vitamin E supplementation and cardiovascular events (nonfatal stroke or myocardial infarction) or cardiovascular mortality. There is a long history of belief that topical application of vitamin E containing oil benefits burn and wound healing. This belief persists even though scientific reviews repeatedly refuted this claim. 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 Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
,
intracranial hemorrhage Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds (intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural blee ...
, hemolytic anemia and
retrolental fibroplasia Retinopathy of prematurity (ROP), also called retrolental fibroplasia (RLF) and Terry syndrome, is a disease of the eye affecting prematurely born babies generally having received neonatal intensive care, in which oxygen therapy is used due to ...
. A 2003 Cochrane review concluded that vitamin E supplementation in preterm infants reduced the risk of intercranial hemorrhage and retinopathy, but noted an increased risk of sepsis.


References


External links

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