Vitamin E

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Vitamin E
Drug class
Tocopherol, alpha-.svg
The α-tocopherol form of vitamin E
Class identifiers
Use Vitamin E deficiency, antioxidant
ATC code A11H
Biological target Reactive oxygen species
Clinical data
Drugs.com MedFacts Natural Products
External links
MeSH D014810
In Wikidata

Vitamin E is a group of eight compounds that include four tocopherols and four tocotrienols. All eight feature a chromane double ring, with a hydroxyl group that can donate a hydrogen atom to reduce free radicals, and a hydrophobic side chain which allows for penetration into biological membranes. Both the tocopherols and tocotrienols 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][2] Of the many different forms of vitamin E, gamma-tocopherol (γ-tocopherol) is the most common form found in the North American diet.[3] γ-Tocopherol is the major tocopherol in corn oil and soybean oil.[3][4] Alpha-tocopherol (α-tocopherol), the most biologically active form of vitamin E, is the second-most common form of vitamin E in the diet, this variant can be found most abundantly in wheat germ oil, sunflower oil, and safflower oil.[3][5] As fat-soluble antioxidants, tocopherols interrupt the propagation of reactive oxygen species that spread through biological membranes or through fat when its lipid content undergoes oxidation by reacting with lipid radicals.[1][3][6]

Worldwide, government organizations recommend adults consume in the range of 7 to 15 mg per day, as of 2016, consumption is 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.[7] Research with alpha-tocopherol as a dietary supplement, with daily amounts as high as 2000 mg per day, has had mixed results. 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, but placebo-controlled clinical trials could not always replicate these findings, and there were some indications that vitamin E supplementation actually was associated with a modest increase in all-cause mortality.[8] As of 2017, vitamin E continues to be a topic of active clinical research.[9]

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.[10][11][12][13] Vitamin E is sold as a dietary supplement, either by itself or incorporated into a multivitamin product, it is also sold in topical products, although there is little evidence for any benefit.[14]

Functions[edit]

Sample of α-tocopherol, one of the various forms of vitamin E, in an oil solution

Vitamin E has many biological functions, including its role as a fat-soluble antioxidant.[1][15]

Tocopherols function by donating H atoms to radicals (X).

Mechanism of action[edit]

Vitamin E acts as a radical scavenger, delivering an H atom to free radicals, at 323 kJ/mol, the O-H bond in tocopherols is about 10% weaker than in most other phenols.[16] This weak bond allows the vitamin to donate a hydrogen atom to the peroxyl radical and other free radicals, minimizing their damaging effect, the thus generated tocopheryl radical is relatively unreactive but revert to tocopherol by a redox reaction with a hydrogen donor such as vitamin C.[17] As it is fat-soluble, it is incorporated into cell membranes, which are protected from oxidative damage by vitamin E.

Other functions[edit]

Vitamin E is an enzyme activity regulator, such as for protein kinase C (PKC) – which plays a role in smooth muscle growth – vitamin E participates in deactivation of PKC to inhibit smooth muscle growth.[18]

Vitamin E affects gene expression, such as for scavenger receptor CD36, a receptor upregulated by oxidized low density lipoprotein (LDL) and binding it.[19] Treatment with vitamin E downregulated expression of the CD36 scavenger receptor gene[19] and modulated expression of connective tissue growth factor.[20][21]

Deficiency[edit]

Main article: Vitamin E 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,[22] it can cause nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function. Vitamin E deficiency can cause: peripheral neuropathy, myopathies, ataxia, retinopathy, impairment of immune responses and red blood cell destruction.[1][22][23][24][25]

Uses[edit]

Observational studies that measure dietary intake and/or serum concentration, and experimental studies that ideally are randomized clinical trials (RCTs), are two means of examining the effects or lack thereof of a proposed intervention on human health.[26] Healthcare outcomes are expected to be in accord between reviews of observational and experimental studies. If, however, there is a lack of agreement, then factors other than study design need to be considered.[27]

For the conditions described below, the results of 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, whereas RCTS often used amounts of alpha-tocopherol 20X to 30X higher than what can be achieved from food. Diets higher in vitamin E may contain other compounds that convey health benefits, so the observed effect may not be due to the vitamin E content. There is also a concern that supplementing with alpha-tocopherol in multiples much higher than is possible via diet will suppress absorption and retention of other tocopherols, with unknown effects on health. Supplementing alpha-tocopherol is known to reduced serum gamma- and delta-tocopherol concentrations,[28] from one large survey, consumption of alpha-tocopherol as a supplement lowered serum gamma-tocopherol from 6.0 micromol/L for people not consuming any supplement to 2.1 micromol/L for those consuming greater than or equal to 400 IU/day.[29]

Supplement popularity over time[edit]

In the US, the popularity for vitamin E as a dietary supplement may have peaked around 2000, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) tracked dietary supplement use by people over the age of 40 during years 1986-2006. For women, user prevalence was 16.1% in 1986, 46.2% in 1998, 44.3% in 2002, but had decreased to 19.8% in 2006. Similarly, for men, prevalence for same years was 18.9%, 52.0%, 49.4% and 24.5%. The authors theorized that declining use in these health science aware populations may have due to publications of studies that showed either no benefits or negative consequences from vitamin E supplements.[30] There is other evidence for declining use of vitamin E. Within the US 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%.[31] A report on vitamin E sales volume in the US documented a 50% decrease between 2000 and 2006,[32] with a significant cause attributed to a well-publicized meta-analysis that had concluded that high-dosage vitamin E increased all-cause mortality.[8]

Age-related macular degeneration[edit]

A Cochrane review published in 2017 on antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration (AMD) identified only one vitamin E clinical trial. That trial compared 500 IU/day of alpha-tocopherol to placebo for four years and reported no effect on the progression of AMD in people already diagnosed with the condition.[33] Another Cochrane review, same year, same authors, reviewed the literature on alpha-tocopherol preventing the development of AMD, this review identified four trials, duration 4–10 years, and reported no change to risk of developing AMD.[34] A large clinical trial known as AREDS compared beta-carotene (15 mg), vitamin C (500 mg) and alpha-tocopherol (400 IU) to placebo for up to 10 years, with a conclusion that the anti-oxidant combination significantly slowed progression. However, because there was no group in the trial receiving only vitamin E, no conclusions could be drawn as to the contribution of the vitamin to the effect.[35]

Antioxidant theory[edit]

Main article: Antioxidant

Tocopherol is described as functioning as an antioxidant. A dose-ranging trial was conducted in people with chronic oxidative stress attributed to elevated serum cholesterol. Plasma F2-isoprostane concentration was selected as a biomarker of free radical-mediated lipid peroxidation. Only the two highest doses - 1600 and 3200 IU/day - significantly lowered F2-isoprostane.[36]

Alzheimer's disease[edit]

Alzheimer's disease (AD) and vascular dementia are common causes of decline of brain functions that occur with age. AD is a chronic neurodegenerative disease that worsens over time,[37] the disease process is associated with plaques and tangles in the brain.[38] Vascular dementia can be caused by ischemic or hemorrhagic infarcts affecting multiple brain areas, including the anterior cerebral artery territory, the parietal lobes, or the cingulate gyrus.[39] Both types of dementia may be present. Vitamin E status (and that of other antioxidant nutrients) is conjectured as having a possible impact on risk of Alzheimer's disease and vascular dementia. A review of dietary intake studies reported that higher consumption of vitamin E from foods lowered the risk of developing AD by 24%.[40] A second review examined serum vitamin E levels and reported lower serum vitamin E in AD patients compared to healthy, age-matched people.[41] A Cochrane review reported on vitamin E as treatment for mild cognitive impairment (MCI) and Alzheimer's disease. Based on evidence from only one trial in each of the categories, the authors' conclusions were that there was not sufficient evidence for supplemental vitamin E preventing the progression from MCI to dementia, but that it did slow functional decline in people with AD. Given the small number of trials and subjects, the authors recommended further research;[42] in 2017 a consensus statement from the British Association for Psychopharmacology included that until further information is available, vitamin E cannot be recommended for treatment or prevention of Alzheimer's disease.[43]

Cancer[edit]

An inverse relationship between dietary vitamin E and kidney cancer risk was reported in a meta-analysis of observational studies, the relative risk reduction was 19% when highest and lowest intake groups were compared. The authors concluded that randomized controlled trials (RCTs) are needed.[44] An inverse relationship between dietary vitamin E and bladder cancer was reported in a meta-analysis of observational studies, the relative risk reduction was 18% when highest and lowest intake groups were compared. The authors concluded that large prospective studies are needed to confirm this association.[45] A very large multi-year comparing placebo to an all rac-alpha-tocopherol group consuming 400 IU/day reported no statistically significant difference in bladder cancer cases.[46] An inverse relationship between dietary vitamin E and lung cancer risk was reported in a meta-analysis of 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 needs to be confirmed by prospective studies.[47] One such large trial, which compared 50 mg alpha-tocopherol to placebo in male tobacco smokers, reported no impact on lung cancer.[48] A very large 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.[49]

For prostate cancer, there are 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 realative risk;[50] in contrast, a meta-analysis of observational studies reported no relationship for dietary vitamin E intake.[51] 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.[52] 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.[53]

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,[54] 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,[55] 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 for breast, lung or colon cancers.[56]

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.[57] 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.[58]

Cancer health claims[edit]

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,[59] 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.[60] The European Food Safety Authority (EFSA) reviews proposed health claims for the European Union countries, as of March 2018, EFSA has not evaluated any vitamin E and cancer prevention claims.

Cataracts[edit]

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.[61] 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.[61][62]

Cardiovascular diseases[edit]

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, 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.[63] 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;[63][64] 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,[65] 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.[63][65]

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%,[66] 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,[67] 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.[68]

The effects of vitamin E supplementation on incidence of stroke 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.[69] 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,[56] 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 or prothrombin mutation).[70]

Cardiovascular health claims[edit]

In 2001 the U.S. Food and Drug Administration rejected proposed health claims for vitamin E and cardiovascular health.[71] 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."[1] The European Food Safety Authority (EFSA) reviews proposed health claims for the European Union 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.[72]

Parkinson's disease[edit]

There is an observed inverse correlation seen with dietary vitamin E, but no confirming evidence from placebo-controlled clinical trials. A meta-analysis published in 2005 concluded that diets higher in vitamin E content lowered risk of developing Parkinson's disease,[73] from what appears to be the only clinical trial of tocopherol supplementation in people with early Parkinson's disease, 2000 IU/day for 14 months had no effect on rate of disease progression.[74]

Pregnancy[edit]

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 of 21 clinical trials concluded that the data do not support vitamin E supplementation - majority of trials alpha-tocopherol at 400 IU/day plus vitamin C at 1000 mg/day - as being efficacious for reducing risk of stillbirth, neonatal death, preterm birth, preeclampsia or any other maternal or infant outcomes, either in healthy women or those considered at risk for pregnancy complications.[75] 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.[75]

Topical[edit]

Although there is widespread use of tocopheryl acetate as a topical medication, with claims for improved wound healing and reduced scar tissue,[76] reviews have repeatedly concluded that there is insufficient evidence to support these claims.[14][77] 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.[78]

Side effects[edit]

The US Food and Nutrition Board set a Tolerable upper intake level (UL) at 1,000 mg (1,500 IU) per day derived from animal models that demonstrated bleeding at high doses.[22] The European Food Safety Authority reviewed the same safety question and set a UL at 300 mg/day.[79] 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 by itself or in combination with other nutrients (vitamin A, vitamin C, beta-carotene, selenium).[80] Another meta-analysis reported a non-significant 1% increase in all-cause mortality when alpha-tocopherol was the only supplement. Subset analysis reported no difference between natural (plant extracted) or synthetic alpha-tocopherol, or whether the amount used was less than or more than 400 IU/day.[81] 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.[78]

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, tamoxifen and cyclosporine A in ways that alter function. For aspirin and warfarin, high amounts of vitamin E may potentiate anti-blood clotting action.[1][82] One small trial demonstrated that vitamin E at 400 mg/day reduced blood concentration of the anti-breast cancer drug tamoxifen. In multiple clinical trials, vitamin E lowered blood concentration of the immuno-suppressant drug, cyclosporine A,[82] 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.[1]

Diet[edit]

Recommendations[edit]

US vitamin E recommendations (mg per day)[22]
AI (children ages 0–6 months) 4
AI (children ages 7–12 months) 5
RDA (children ages 1–3 years) 6
RDA (children ages 4–8 years) 7
RDA (children ages 9–13 years) 11
RDA (children ages 14–18 years) 15
RDA (adults ages 19+) 15
RDA (pregnancy) 15
RDA (lactation) 19
UL (adults) 1,000

The U.S. Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for vitamin E in 2000, the current EAR for vitamin E for women and men ages 14 and up is 12 mg/day. The RDA is 15 mg/day. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements, for infants up to 12 months the Adequate Intake (AI) is 4–5 mg/day. As for safety, the IOM sets Tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. Hemorrhagic effects in rats were selected as the critical endpoint to calculate the UL via starting with the lowest-observed-adverse-effect-level (LOAEL) and processing that through an uncertainty factor calculation, the end result was the UL set at 1000 mg/day.[22] Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes (DRIs).[22]

The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in 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. These PRIs are lower than the U.S. RDAs,[83] the European Food Safety Authority reviewed the same safety question and set a UL at 300 mg/day. The EU used an effect on blood clotting as a critical effect, 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 UL of 270 mg/day, then rounded up to 300 mg/day.[79]

The Japan National Institute of Health and Nutrition set lower AIs than the US RDAs or EU PRIs, and intermediate ULs: 6.5 mg/day (females) and 7.0 mg/day (males) for adult AIs, and 650–700 mg/day (females) and 750–900 mg/day (males) for adult ULs, amount depending on age.[84] India recommends an intake of 8–10 mg/day and does not set a UL.[85] The World Health Organization recommends that adults consume 10 mg/day.[7]

Consumption is below government recommendations. A worldwide summary of more than one hundred studies reported a median dietary intake of 6.2 mg/d for alpha-tocopherol.[7] Government survey results in the US reported average consumption for adult females at 8.4 mg/d and adult males 10.4 mg/d[86] - both below the RDA of 15 mg/day.

Food labeling[edit]

For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For vitamin E labeling purposes 100% of the Daily Value was 30 IU, but as of May 27, 2016 it was revised to 15 mg to bring it into agreement with the RDA.[87] A table of the old and new adult Daily Values is provided at Reference Daily Intake, the original deadline to be in compliance was July 28, 2018, but on September 29, 2017 the FDA released a proposed rule that extended the deadline to January 1, 2020 for large companies and January 1, 2021 for small companies.[88] 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.[89]

Sources[edit]

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.[90]

Plant source[90] Amount
(mg / 100g)
Wheat germ oil 150
Hazelnut oil 47
Canola/rapeseed oil 44
Sunflower oil 41.1
Safflower oil 34.1
Almond oil 39.2
Grapeseed oil 28.8
Sunflower seed kernels 26.1
Almonds 25.6
Almond butter 24.2
Wheat germ 19
Plant source[90] Amount
(mg / 100g)
Canola oil 17.5
Palm oil 15.9
Peanut oil 15.7
Margarine, tub 15.4
Hazelnuts 15.3
Corn oil 14.8
Olive oil 14.3
Soybean oil 12.1
Pine nuts 9.3
Peanut butter 9.0
Peanuts 8.3
Plant source[90] Amount
(mg / 100g)
Popcorn 5.0
Pistachio nuts 2.8
Mayonnaise 3.3
Avocados 2.6
Spinach, raw 2.0
Asparagus 1.5
Broccoli 1.4
Cashew nuts 0.9
Bread 0.2-0.3
Rice, brown 0.2
Potato, Pasta <0.1
Animal source[90] Amount
(mg / 100g)
Fish 1.0-2.8
Oysters 1.7
Butter 1.6
Cheese 0.6-0.7
Eggs 1.1
Chicken 0.3
Beef 0.1
Pork 0.1
Milk, whole 0.1
Milk, skim 0.01

Supplements[edit]

Softgel capsules used for large amounts of vitamin E

Vitamin E is fat soluble, so dietary supplement products are usually in the form of the vitamin 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 available from a few dietary supplement companies.

Fortification[edit]

The World Health Organization does not have any recommendations for food fortification with vitamin E,[91] the Food Fortification Initiative does not list any countries that have mandatory or voluntary programs for vitamin E.[92] 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.[90]

Chemistry[edit]

The nutritional content of vitamin E is defined by α-tocopherol activity, the molecules that contribute α-tocopherol activity are four tocopherols and four tocotrienols, identified by the prefixes alpha- (α-), beta- (β-), gamma- (γ-), and delta- (δ-).[93] Natural tocopherols occur in the RRR-configuration only, the synthetic form contains eight different stereoisomers and is called 'all-rac'-α-tocopherol.[94]

Form Structure
alpha-Tocopherol Tocopherol, alpha-.svg
beta-Tocopherol Beta-tocopherol.png
gamma-Tocopherol Gamma-tocopherol.png
delta-Tocopherol Delta-tocopherol.png

Tocopherols[edit]

General chemical structure of tocotrienols.

alpha-Tocopherol is a lipid-soluble antioxidant functioning within the glutathione peroxidase pathway,[95] and protecting cell membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction.[3][96] This removes the free radical intermediates and prevents the oxidation 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, retinol or ubiquinol.[97] Other forms of vitamin E have their own unique properties; for example, γ-tocopherol is a nucleophile that can react with electrophilic mutagens.[98]

Tocotrienols[edit]

The four tocotrienols (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, R2 = H, R3= Methyl, for gamma(γ)-tocotrienol: R1 = H, R2 = Methyl, R3= Methyl. For delta(δ)-tocotrienol: R1 = H, R2 = H, R3= Methyl. Palm oil is a source. Preliminary clinical trials on dietary supplement tocotrienols indicate potential for anti-disease activity.[99]

Testing for levels[edit]

Cystic fibrosis and other fat malabsorption conditions can result in low serum vitamin E. Dietary supplements will raise serum vitamin E.[22] A worldwide summary of more than one hundred studies reported a median of 22.1 µmol/L for serum α-tocopherol (2.2 µmol/L for serum γ-tocopherol), defined deficiency as less than 12 µmol/L, and cited a recommendation that serum α-tocopherol concentration be ≥30 µmol/L to optimize health benefits.[7] Serum concentration increases with age, this is attributed to 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.[7]

Synthesis[edit]

Photosynthesizing plants, algae and cyanobacteria make vitamin E, for commercial uses, vitamin E can be extracted from plants, typically as a by-product of making vegetable oils, or through an entirely synthetic process.

Biosynthesis[edit]

Photosynthesizing plants, algae and cyanobacteria 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 tocotrienols). The pathway for both types branches so that gamma-(tocopherol or tocotrienol) is created and from that the two alpha- types, or else delta-(tocopherol or tocotrienol) is created and from that the two beta- types,[100][101] as to why plants synthesize tocochromanols, the major reason appears to be for antioxidant activity. Seeds are lipid-rich, to provide energy for germination and early growth. Tocochromanols protect the seed lipids from oxidizing and becoming rancid.[100][101] When seed crops such as soybeans are processed to extract oil, the oils are additionally processed to separate out vitamin E and sell it as natural vitamin E (as opposed to synthetic). Tocochromanols are also incorporated into leaves, where the activity combats damage from the ultraviolet radiation of sunlight. Under normal growing conditions the presence of tocochromanols may not be essential, as there are other photo-protective compounds, this has been demonstrated by research on plant mutations unable to synthesize these compounds. However, under stressed growing conditions such as drought or salt-induced oxidative stress, the plants' physiological status is superior if it has the normal sysnthesis capacity.[102]

Different parts of plants, and different species, are dominated by different tocochromals, the predominant form in leaves, and hence leafy green vegetables, is alpha-tocopherol. Gamma-tocopherol dominates in seeds, but there are exceptions.[100][101][103] For canola, corn and soy bean oils, there is more gamma-tocopherol than alpha-tocopherol, but for safflower, sunflower and olive oils the reverse is true. Of the commonly used food oils, palm oil is unique in that the tocotrienol content is higher than the tocopherol content.[103]

Industrial synthesis[edit]

Naturally sourced d-alpha-tocopherol can be extracted and purified from seed oils, or gamma-tocopherol can be extracted, purified, and methylated to create d-alpha-tocopherol; in contrast to alpha-tocopherol extracted from plants, which is also called d-alpha-tocopherol, industrial synthesis creates dl-alpha-tocopherol. "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." Specification for the ingredient is >97% pure.[104] This synthetic dl-alpha-tocopherol has approximately 50% of the potency of d-alpha-tocopherol. Manufacturers of dietary supplements and fortified foods for humans or domesticated animals convert the phenol form of the vitamin to an ester using either acetic acid or succinic acid because the esters are more chemically stable, providing for a longer shelf-life. The ester forms are de-esterified in the gut and absorbed as free alpha-tocopherol.

History[edit]

Vitamin E was discovered in 1922 by Herbert McLean Evans and Katharine Scott Bishop[10] and first isolated in a pure form by Evans and Gladys Anderson Emerson in 1935 at the University of California, Berkeley.[11] 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.[12] Erhard Fernholz elucidated its structure in 1938 and shortly afterwards the same year, Paul Karrer and his team first synthesized it.[13]

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.[105]

A role for vitamin E in coronary heart disease had first been proposed in 1946.[106][107] More cardiovascular work from the same research group followed,[108] including a proposal that megadoses of vitamin E could slow down and even reverse the development of atherosclerosis.[109] However, a 2004 meta-analysis showed no association between vitamin E supplementation and cardiovascular events (nonfatal stroke or myocardial infarction) or cardiovascular mortality.[110] There is a long history of belief that topical application of vitamin E containing oil benefits burn and wound healing,[76] this belief persists even though scientific reviews repeatedly refuted this claim.[14][77][111]

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.[112] 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.[113]

Research[edit]

As of 2018 there are at least 10 trials actively recruiting subjects for conditions including liver disease, burn injury, skin aging, and type 2 diabetes.[114] Trial topics included exercise, infection, preventing atherosclerosis, burn injury, retinopathy in premature infants, male infertility and type 2 diabetes.[115]

See also[edit]

References[edit]

  1. ^ a b c d e f g "Vitamin E — Health Professional Fact Sheet". Office of Dietary Supplements, US National Institutes of Health. 9 May 2016. Retrieved 5 February 2015. 
  2. ^ Brigelius-Flohé R, Traber MG (1999). "Vitamin E: function and metabolism" (PDF). FASEB J. 13 (10): 1145–1155. doi:10.1096/fasebj.13.10.1145. PMID 10385606. 
  3. ^ a b c d e "Vitamin E". Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR. May 2015. Retrieved 7 March 2017. 
  4. ^ Bieri JG, Evarts RP (1974). "γ-Tocopherol: metabolism, biological activity and significance in human vitamin E nutrition". American Journal of Clinical Nutrition. 27 (9): 980–986. doi:10.1093/ajcn/27.8.980. PMID 4472121. 
  5. ^ Reboul E, Richelle M, Perrot E, Desmoulins-Malezet C, Pirisi V, Borel P; Richelle; Perrot; Desmoulins-Malezet; Pirisi; Borel (15 November 2006). "Bioaccessibility of carotenoids and vitamin E from their main dietary sources". Journal of Agricultural and Food Chemistry. 54 (23): 8749–8755. doi:10.1021/jf061818s. PMID 17090117. 
  6. ^ Choe, Eunok; Min, David B (October 2009). "Mechanisms of Antioxidants in the Oxidation of Foods". Comprehensive Reviews in Food Science and Food Safety. 8 (4): 345–358. doi:10.1111/j.1541-4337.2009.00085.x. Retrieved 4 September 2016. 
  7. ^ a b c d e Péter S, Friedel A, Roos FF, Wyss A, Eggersdorfer M, Hoffmann K, Weber P (July 2016). "A Systematic Review of Global Alpha-Tocopherol Status as Assessed by Nutritional Intake Levels and Blood Serum Concentrations". Int J Vitam Nutr Res. 85 (5–6): 1–21. doi:10.1024/0300-9831/a000281. PMID 27414419. 
  8. ^ a b Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (January 2005). "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Ann. Intern. Med. 142 (1): 37–46. PMID 15537682. 
  9. ^ Galli, F; Azzi, A; Birringer, M; Cook-Mills, J. M; Eggersdorfer, M; Frank, J; Cruciani, G; Lorkowski, S; Özer, N. K (2017). "Vitamin E: Emerging aspects and new directions". Free Radical Biology and Medicine. 102: 16–36. doi:10.1016/j.freeradbiomed.2016.09.017. PMID 27816611. 
  10. ^ a b Evans HM, Bishop KS; Bishop (1922). "On the existence of a hitherto unrecognized dietary factor essential for reproduction". Science. 56 (1458): 650–651. Bibcode:1922Sci....56..650E. doi:10.1126/science.56.1458.650. JSTOR 1647181. PMID 17838496. 
  11. ^ a b Elizabeth H. Oakes (2007), "Emerson, Gladys Anderson", Encyclopedia of World Scientists, pp. 211–212, ISBN 1438118821 
  12. ^ a b Evans HM; Emerson OH; Emerson GA. (1 February 1936). "The isolation from wheat germ oil of an alcohol, a-tocopherol, having the properties of vitamin E". Journal of Biological Chemistry. 113 (1): 319–332. 
  13. ^ a b Karrer P, Fritzsche H, Ringier BH, Salomon H (1938). "Synthesis of α-Tocopherol (Vitamin E)". Nature. 141 (3580): 1057. doi:10.1038/1411057d0. 
  14. ^ a b c Sidgwick GP, McGeorge D, Bayat A (2015). "A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring". Arch. Dermatol. Res. 307 (6): 461–477. doi:10.1007/s00403-015-1572-0. PMC 4506744 Freely accessible. PMID 26044054. 
  15. ^ Galli, F. Azzi, A. Birringer, M. Cook-Mills, J. M. Eggersdorfer, M. Frank, J. Cruciani, G. Lorkowski, S. Ozer, N. K. (2017). "Vitamin E: Emerging aspects and new directions". Free Radic Biol Med. 102: 16–36. doi:10.1016/j.freeradbiomed.2016.09.017. PMID 27816611. 
  16. ^ Lide, David R., ed. (2006). CRC Handbook of Chemistry and Physics (87th ed.). Boca Raton, FL: CRC Press. ISBN 0-8493-0487-3. 
  17. ^ Traber MG, Stevens JF; Stevens (2011). "Free Radical Biology and Medicine – Vitamins C and E: Beneficial effects from a mechanistic perspective". Free Radical Biology and Medicine. 51 (5): 1000–1013. doi:10.1016/j.freeradbiomed.2011.05.017. PMC 3156342 Freely accessible. PMID 21664268. 
  18. ^ Schneider C (2005). "Chemistry and biology of vitamin E". Mol Nutr Food Res. 49 (1): 7–30. doi:10.1002/mnfr.200400049. PMID 15580660. 
  19. ^ a b Devaraj S, Hugou I, Jialal I; Hugou; Jialal (2001). "-Tocopherol decreases CD36 expression in human monocyte-derived macrophages". J Lipid Res. 42 (4): 521–527. PMID 11290823. 
  20. ^ Azzi A, Stocker A; Stocker (2000). "Vitamin E: non-antioxidant roles". Prog Lipid Res. 39 (3): 231–255. doi:10.1016/S0163-7827(00)00006-0. PMID 10799717. 
  21. ^ Villacorta L, Graça-Souza AV, Ricciarelli R, Zingg JM, Azzi A; Graça-Souza; Ricciarelli; Zingg; Azzi (2003). "α-Tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-α-mediated downregulation in human smooth muscle cells". Circ. Res. 92 (1): 104–110. doi:10.1161/01.RES.0000049103.38175.1B. PMID 12522127. 
  22. ^ a b c d e f g Institute of Medicine (2000). "Vitamin E". Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: The National Academies Press. pp. 186–283. 
  23. ^ Whitney, Ellie; Sharon Rady Rolfes (2011). Peggy Williams, ed. Understanding Nutrition (Twelfth ed.). California: Wadsworth, Cengage Learning. ISBN 0-538-73465-5. 
  24. ^ Kowdley KV, Mason JB, Meydani SN, Cornwall S, Grand RJ; Mason; Meydani; Cornwall; Grand (1992). "Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption". Gastroenterology. 102 (6): 2139–2142. doi:10.1016/0016-5085(92)90344-x. PMID 1587435. 
  25. ^ Brigelius-Flohé R, Traber MG; Traber (1 July 1999). "Vitamin E: function and metabolism". FASEB J. 13 (10): 1145–1155. doi:10.1096/fasebj.13.10.1145. PMID 10385606. 
  26. ^ Munnangi S, Boktor SW (18 December 2018). "Epidemiology, Study Design". StatPearls[Internet]. PMID 29262004. 
  27. ^ Anglemyer A, Horvath HT, Bero L (April 2014). "Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials". Cochrane Database Syst Rev (4): MR000034. doi:10.1002/14651858.MR000034.pub2. PMID 24782322. 
  28. ^ Huang, HY; Appel, LJ (2003). "Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans". The Journal of Nutrition. 133 (10): 3137–40. PMID 14519797. 
  29. ^ Ford ES, Ajani UA, Mokdad AH (July 2005). "Brief communication: The prevalence of high intake of vitamin E from the use of supplements among U.S. adults". Ann. Intern. Med. 143 (2): 116–120. PMID 16027453. 
  30. ^ Kim HJ, Giovannucci E, Rosner B, Willett WC, Cho E (March 2014). "Longitudinal and secular trends in dietary supplement use: Nurses' Health Study and Health Professionals Follow-Up Study, 1986-2006". J Acad Nutr Diet. 114 (3): 436–43. doi:10.1016/j.jand.2013.07.039. PMC 3944223 Freely accessible. PMID 24119503. 
  31. ^ Morioka TY, Bolin JT, Attipoe S, Jones DR, Stephens MB, Deuster PA (July 2015). "Trends in Vitamin A, C, D, E, K Supplement Prescriptions From Military Treatment Facilities: 2007 to 2011". Mil Med. 180 (7): 748–53. doi:10.7205/MILMED-D-14-00511. PMID 26126244. 
  32. ^ Tilburt JC, Emanuel EJ, Miller FG (September 2008). "Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results". J Gen Intern Med. 23 (9): 1495–8. doi:10.1007/s11606-008-0704-z. PMC 2518024 Freely accessible. PMID 18618194. 
  33. ^ Evans JR, Lawrenson JG (July 2017). "Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration". Cochrane Database Syst Rev. 7: CD000254. doi:10.1002/14651858.CD000254.pub4. PMID 28756618. 
  34. ^ Evans JR, Lawrenson JG (July 2017). "Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration". Cochrane Database Syst Rev. 7: CD000253. doi:10.1002/14651858.CD000253.pub4. PMID 28756617. 
  35. ^ Chew EY, Clemons TE, Agrón E, Sperduto RD, Sangiovanni JP, Kurinij N, Davis MD (August 2013). "Long-term effects of vitamins C and E, β-carotene, and zinc on age-related macular degeneration: AREDS report no. 35". Ophthalmology. 120 (8): 1604–1611.e4. doi:10.1016/j.ophtha.2013.01.021. PMC 3728272 Freely accessible. PMID 23582353. 
  36. ^ Robertsii, L; Oates, J; Linton, M; Fazio, S; Meador, B; Gross, M; Shyr, Y; Morrow, J (2007). "The relationship between dose of vitamin E and suppression of oxidative stress in humans". Free Radical Biology and Medicine. 43 (10): 37–46. doi:10.1016/j.freeradbiomed.2007.06.019. PMC 2072864 Freely accessible. PMID 17936185. 
  37. ^ Burns A, Iliffe S (5 February 2009). "Alzheimer's disease". The BMJ. 338: b158. doi:10.1136/bmj.b158. PMID 19196745. 
  38. ^ Ballard C, Gauthier S, Corbett A, et al. (19 March 2011). "Alzheimer's disease". Lancet. 377 (9770): 1019–1031. doi:10.1016/S0140-6736(10)61349-9. PMID 21371747. 
  39. ^ Love, S (1 December 2005). "Neuropathological Investigation of Dementia: A Guide for Neurologists". Journal of Neurology, Neurosurgery & Psychiatry. 76 (supplement 5): v8–v14. doi:10.1136/jnnp.2005.080754. PMC 1765714 Freely accessible. 
  40. ^ Li FJ, Shen L, Ji HF (2012). "Dietary intakes of vitamin E, vitamin C, and β-carotene and risk of Alzheimer's disease: a meta-analysis". J. Alzheimers Dis. 31 (2): 253–258. doi:10.3233/JAD-2012-120349. PMID 22543848. 
  41. ^ Dong Y, Chen X, Liu Y, Shu Y, Chen T, Xu L, Li M, Guan X (February 2018). "Do low-serum vitamin E levels increase the risk of Alzheimer disease in older people? Evidence from a meta-analysis of case-control studies". Int J Geriatr Psychiatry. 33 (2): e257–e263. doi:10.1002/gps.4780. PMID 28833475. 
  42. ^ Farina N, Llewellyn D, Isaac M, Tabet N (April 2017). "Vitamin E for Alzheimer's dementia and mild cognitive impairment". Cochrane Database Syst Rev. 4: CD002854. doi:10.1002/14651858.CD002854.pub5. PMID 28418065. 
  43. ^ O'Brien JT, Holmes C, Jones M, Jones R, Livingston G, McKeith I, Mittler P, Passmore P, Ritchie C, Robinson L, Sampson EL, Taylor JP, Thomas A, Burns A (February 2017). "Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology". J. Psychopharmacol. (Oxford). 31 (2): 147–168. doi:10.1177/0269881116680924. PMID 28103749. 
  44. ^ Shen C, Huang Y, Yi S, Fang Z, Li L (November 2015). "Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta-Analysis of Observational Studies". Med. Sci. Monit. 21: 3420–3426. PMC 4644018 Freely accessible. PMID 26547129. 
  45. ^ Wang YY, Wang XL, Yu ZJ (2014). "Vitamin C and E intake and risk of bladder cancer: a meta-analysis of observational studies". Int J Clin Exp Med. 7 (11): 4154–4164. PMC 4276184 Freely accessible. PMID 25550926. 
  46. ^ Lotan Y, Goodman PJ, Youssef RF, Svatek RS, Shariat SF, Tangen CM, Thompson IM, Klein EA (June 2012). "Evaluation of vitamin E and selenium supplementation for the prevention of bladder cancer in SWOG coordinated SELECT". J. Urol. 187 (6): 2005–2010. doi:10.1016/j.juro.2012.01.117. PMC 4294531 Freely accessible. PMID 22498220. 
  47. ^ Zhu YJ, Bo YC, Liu XX, Qiu CG (March 2017). "Association of dietary vitamin E intake with risk of lung cancer: a dose-response meta-analysis". Asia Pac J Clin Nutr. 26 (2): 271–277. doi:10.6133/apjcn.032016.04. PMID 28244705. 
  48. ^ Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994). "The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers". New England Journal of Medicine. 330 (15): 1029–1035. doi:10.1056/NEJM199404143301501. PMID 8127329. 
  49. ^ Slatore CG, Littman AJ, Au DH, Satia JA, White E (March 2008). "Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not reduce the risk of lung cancer". Am. J. Respir. Crit. Care Med. 177 (5): 524–530. doi:10.1164/rccm.200709-1398OC. PMC 2258445 Freely accessible. PMID 17989343. 
  50. ^ Cui R, Liu ZQ, Xu Q (2014). "Blood α-tocopherol, γ-tocopherol levels and risk of prostate cancer: a meta-analysis of prospective studies". PLoS ONE. 9 (3): e93044. doi:10.1371/journal.pone.0093044. PMC 3965522 Freely accessible. PMID 24667740. 
  51. ^ Kim Y, Wei J, Citronberg J, Hartman T, Fedirko V, Goodman M (September 2015). "Relation of Vitamin E and Selenium Exposure to Prostate Cancer Risk by Smoking Status: A Review and Meta-Analysis". Anticancer Res. 35 (9): 4983–4996. PMID 26254398. 
  52. ^ Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, Haapakoski J, Malila N, Rautalahti M, Ripatti S, Mäenpää H, Teerenhovi L, Koss L, Virolainen M, Edwards BK (March 1998). "Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial". J. Natl. Cancer Inst. 90 (6): 440–446. PMID 9521168. 
  53. ^ Klein EA, Thompson IM, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL, Baker LH (October 2011). "Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT)". JAMA. 306 (14): 1549–1556. doi:10.1001/jama.2011.1437. PMC 4169010 Freely accessible. PMID 21990298. 
  54. ^ Arain MA, Abdul Qadeer A (April 2010). "Systematic review on "vitamin E and prevention of colorectal cancer"". Pak J Pharm Sci. 23 (2): 125–130. PMID 20363687. 
  55. ^ Lance P, Alberts DS, Thompson PA, Fales L, Wang F, San Jose J, Jacobs ET, Goodman PJ, Darke AK, Yee M, Minasian L, Thompson IM, Roe DJ (January 2017). "Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention". Cancer Prev Res (Phila). 10 (1): 45–54. doi:10.1158/1940-6207.CAPR-16-0104. PMC 5510661 Freely accessible. PMID 27777235. 
  56. ^ a b Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE (July 2005). "Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial". JAMA. 294 (1): 56–65. doi:10.1001/jama.294.1.56. PMID 15998891. 
  57. ^ Jensen, SK; Lauridsen, C (2007). "Alpha-tocopherol stereoisomers". Vitamins and hormones. Vitamins & Hormones. 76: 281–308. doi:10.1016/S0083-6729(07)76010-7. ISBN 9780123735928. PMID 17628178. 
  58. ^ Slatore, C. G.; Littman, A. J.; Au, D. H.; Satia, J. A.; White, E. (2007). "Long-Term Use of Supplemental Multivitamins, Vitamin C, Vitamin E, and Folate Does Not Reduce the Risk of Lung Cancer". American Journal of Respiratory and Critical Care Medicine. 177 (5): 524–530. doi:10.1164/rccm.200709-1398OC. PMC 2258445 Freely accessible. PMID 17989343. 
  59. ^ Qualified Health Claims Overview from the U.S. Food & Drug Administration.
  60. ^ Alliance for Natural Health v. Sebelius, Case No. 09-1546 (D.D.C.) U.S. Food & Drug Administration May 17, 2012
  61. ^ a b Zhang Y, Jiang W, Xie Z, Wu W, Zhang D (October 2015). "Vitamin E and risk of age-related cataract: a meta-analysis". Public Health Nutr. 18 (15): 2804–2814. doi:10.1017/S1368980014003115. PMID 25591715. 
  62. ^ Mathew MC, Ervin AM, Tao J, Davis RM; Ervin; Tao; Davis (2012). "Routine Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract". Cochrane Database Syst Rev. 6 (6): CD004567. doi:10.1002/14651858.CD004567.pub2. PMC 4410744 Freely accessible. PMID 22696344. 
  63. ^ a b c Kirmizis D, Chatzidimitriou D (2009). "Antiatherogenic effects of vitamin E: the search for the Holy Grail". Vasc Health Risk Manag. 5: 767–774. PMC 2747395 Freely accessible. PMID 19774218. 
  64. ^ Gaziano, JM (2004). "Vitamin E and cardiovascular disease: observational studies". Annals of the New York Academy of Sciences. 1031: 280–291. doi:10.1196/annals.1331.028. PMID 15753154. 
  65. ^ a b Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC (May 1993). "Vitamin E consumption and the risk of coronary disease in women". N. Engl. J. Med. 328 (20): 1444–1449. doi:10.1056/NEJM199305203282003. PMID 8479463. 
  66. ^ Loffredo L, Perri L, Di Castelnuovo A, Iacoviello L, De Gaetano G, Violi F (April 2015). "Supplementation with vitamin E alone is associated with reduced myocardial infarction: a meta-analysis". Nutr Metab Cardiovasc Dis. 25 (4): 354–363. doi:10.1016/j.numecd.2015.01.008. PMID 25779938. 
  67. ^ Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM (November 2008). "Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial". JAMA. 300 (18): 2123–2133. doi:10.1001/jama.2008.600. PMC 2586922 Freely accessible. PMID 18997197. 
  68. ^ Lonn E, Bosch J, Yusuf S, Sheridan P, Pogue J, Arnold JM, Ross C, Arnold A, Sleight P, Probstfield J, Dagenais GR (March 2005). "Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial". JAMA. 293 (11): 1338–1347. doi:10.1001/jama.293.11.1338. PMID 15769967. 
  69. ^ Bin Q, Hu X, Cao Y, Gao F (April 2011). "The role of vitamin E (tocopherol) supplementation in the prevention of stroke. A meta-analysis of 13 randomised controlled trials". Thromb. Haemost. 105 (4): 579–585. doi:10.1160/TH10-11-0729. PMID 21264448. 
  70. ^ Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE (September 2007). "Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study". Circulation. 116 (13): 1497–1503. doi:10.1161/CIRCULATIONAHA.107.716407. PMID 17846285. 
  71. ^ Letter Regarding Dietary Supplement Health Claim for Vitamin E and Heart Disease (Docket No 99P-4375) U.S. Food and Drug Administration.
  72. ^ Scientific Opinion on the substantiation of health claims related to vitamin E and protection of DNA, proteins and lipids from oxidative damage (ID 160, 162, 1947),... maintenance of normal cardiac function (ID 166),... maintenance of normal blood circulation (ID 216)... pursuant to Article 13(1) of Regulation (EC) No 1924/2006 European Food Safety Authority EFSA Journal 2010;8(10):1816.
  73. ^ Etminan, Mahyar; Gill, Sudeep S; Samii, Ali (2005). "Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis". The Lancet Neurology. 4 (6): 362–365. doi:10.1016/S1474-4422(05)70097-1. 
  74. ^ Shoulson I (September 1998). "DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism". Ann. Neurol. 44 (3 Suppl 1): S160–S166. PMID 9749589. 
  75. ^ a b Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA (September 2015). "Vitamin E supplementation in pregnancy". Cochrane Database Syst Rev (9): CD004069. doi:10.1002/14651858.CD004069.pub3. PMID 26343254. 
  76. ^ a b Panin G, Strumia R, Ursini F (December 2004). "Topical alpha-tocopherol acetate in the bulk phase: eight years of experience in skin treatment". Ann. N. Y. Acad. Sci. 1031: 443–447. doi:10.1196/annals.1331.069. PMID 15753192. 
  77. ^ a b Tanaydin V, Conings J, Malyar M, van der Hulst R, van der Lei B (September 2016). "The Role of Topical Vitamin E in Scar Management: A Systematic Review". Aesthet Surg J. 36 (8): 959–965. doi:10.1093/asj/sjw046. PMID 26977069. 
  78. ^ a b Kosari P, Alikhan A, Sockolov M, Feldman SR (2010). "Vitamin E and allergic contact dermatitis". Dermatitis. 21 (3): 148–153. PMID 20487657. 
  79. ^ a b Tolerable Upper Intake Levels For Vitamins And Minerals (PDF), European Food Safety Authority, 2006 
  80. ^ Bjelakovic G, Nikolova D, Gluud C (2013). "Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: do we have evidence for lack of harm?". PLoS ONE. 8 (9): e74558. doi:10.1371/journal.pone.0074558. PMC 3765487 Freely accessible. PMID 24040282. 
  81. ^ Curtis AJ, Bullen M, Piccenna L, McNeil JJ (December 2014). "Vitamin E supplementation and mortality in healthy people: a meta-analysis of randomised controlled trials". Cardiovasc Drugs Ther. 28 (6): 563–573. doi:10.1007/s10557-014-6560-7. PMID 25398301. 
  82. ^ a b Podszun M, Frank J (December 2014). "Vitamin E-drug interactions: molecular basis and clinical relevance". Nutr Res Rev. 27 (2): 215–231. doi:10.1017/S0954422414000146. PMID 25225959. 
  83. ^ "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies" (PDF). 2017. 
  84. ^ Dietary Reference Intakes for Japanese 2010: Fat-Soluble Vitamins Journal of Nutritional Science and Vitaminology 2013(59):S57-S55.
  85. ^ "Nutrient Requirements and Recommended Dietary Allowances for Indians: A Report of the Expert Group of the Indian Council of Medical Research. pp.283-295 (2009)" (PDF). Archived (PDF) from the original on June 15, 2016. 
  86. ^ "TABLE 1: Nutrient Intakes from Food and Beverages" Archived February 24, 2017, at the Wayback Machine. What We Eat In America, NHANES 2012-2014
  87. ^ "Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels. FR page 33982" (PDF). 
  88. ^ "Changes to the Nutrition Facts Panel - Compliance Date" Archived March 12, 2017, at the Wayback Machine.
  89. ^ Regulation (EU) No 1169/2011 of the European Parliament and of the Council Official Journal of the European Union. page 304/61. (2009).
  90. ^ a b c d e f USDA Food Composition Databases United States Department of Agriculture, Agricultural Research Service. Release 28 (2015)
  91. ^ Guidelines on food fortification with micronutrients World Health Organization (2006)
  92. ^ Food Fortification Initiative Food Fortification Initiative, Enhancing Grains for Better Lives (accessed Feb 2018).
  93. ^ Traber, M.G. "19". In Ross, A. Catherine. Modern Nutrition in Health and Disease (11 ed.). Philadelphia, PA: Lippincott Williams & Wilkins. pp. 293–294. ISBN 9781605474618. 
  94. ^ Traber, MG. "Chapter 15: vitamin E". In Bowman BA and Russell RM. Current Knowledge in Nutrition. I (9 ed.). Washington DC, USA: ILSI. ISBN 978-1-57881-199-1. 
  95. ^ Wefers H, Sies H; Sies (1988). "The protection of ascorbate and glutathione against microsomal lipid peroxidation is dependent on Vitamin E". European Journal of Biochemistry. 174 (2): 353–357. doi:10.1111/j.1432-1033.1988.tb14105.x. PMID 3383850. 
  96. ^ Traber MG, Atkinson J; Atkinson (2007). "Vitamin E, Antioxidant and Nothing More". Free Radical Biology & Medicine. 43 (1): 4–15. doi:10.1016/j.freeradbiomed.2007.03.024. PMC 2040110 Freely accessible. PMID 17561088. 
  97. ^ Wang X, Quinn PJ; Quinn (1999). "Vitamin E and its function in membranes". Progress in Lipid Research. 38 (4): 309–336. doi:10.1016/S0163-7827(99)00008-9. PMID 10793887. 
  98. ^ Brigelius-Flohé R, Traber MG; Traber (1999). "Vit amin E: function and metabolism". FASEB J. 13 (10): 1145–1155. doi:10.1096/fasebj.13.10.1145. PMID 10385606. 
  99. ^ Meganathan P, Fu JY (2016). "Biological Properties of Tocotrienols: Evidence in Human Studies". Int J Mol Sci. 17 (11): E1682. doi:10.3390/ijms17111682. PMC 5133770 Freely accessible. PMID 27792171. 
  100. ^ a b c Mène-Saffrané L (December 2017). "Vitamin E Biosynthesis and Its Regulation in Plants". Antioxidants (Basel). 7 (1): 2. doi:10.3390/antiox7010002. PMC 5789312 Freely accessible. PMID 29295607. 
  101. ^ a b c Fritsche S, Wang X, Jung C (December 2017). "Recent Advances in our Understanding of Tocopherol Biosynthesis in Plants: An Overview of Key Genes, Functions, and Breeding of Vitamin E Improved Crops". Antioxidants (Basel). 6 (4): 99. doi:10.3390/antiox6040099. PMC 5745509 Freely accessible. PMID 29194404. 
  102. ^ Falk J, Munné-Bosch S (June 2010). "Tocochromanol functions in plants: antioxidation and beyond". J. Exp. Bot. 61 (6): 1549–1566. doi:10.1093/jxb/erq030. PMID 20385544. 
  103. ^ a b Shahidi F, de Camargo AC (October 2016). "Tocopherols and Tocotrienols in Common and Emerging Dietary Sources: Occurrence, Applications, and Health Benefits". Int J Mol Sci. 17 (10): 1745. doi:10.3390/ijms17101745. PMC 5085773 Freely accessible. PMID 27775605. 
  104. ^ Scientific Opinion on the safety and efficacy of synthetic alpha-tocopherol for all animal species (2012) European Food Safety Authority EFSA Journal 2012;10(7):2784
  105. ^ "VITAMIN IN SEARCH OF A DISEASE". JAMA: the Journal of the American Medical Association. 201 (3): 195–196. 1967. doi:10.1001/jama.1967.03130030065018. 
  106. ^ Vogelsang A, Shute EV (June 1946). "Effect of vitamin E in coronary heart disease". Nature. 157 (3997): 772. doi:10.1038/157772b0. PMID 21064771. 
  107. ^ Skelton F, Shute E, Skinner HG, Waud RA (1946). "Antipurpuric Action of A-Tocopherol (Vitamin E)". Science. 103 (2687): 762. doi:10.1126/science.103.2687.762-b. PMID 17836459. 
  108. ^ Shute EV, Vogelsang AB, Skelton FB, Shute WE (January 1948). "The influence of vitamin E on vascular disease". Surg Gynecol Obstet. 86 (1): 1–8. PMID 18920873. 
  109. ^ Shute WE, Shute EV. Alpha Tocopherol (Vitamin E) in Cardiovascular Disease. Toronto, Ontario, Canada: Ryerson Press, 1954
  110. ^ Eidelman, R.S; Hollar, D; Hebert, P.R; Lamas, G.A; Hennekens, C.H (2004). "Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease". Archives of Internal Medicine. 164 (14): 1552–1556. doi:10.1001/archinte.164.14.1552. PMID 15277288. 
  111. ^ Pehr K, Forsey RR (November 1993). "Why don't we use vitamin E in dermatology?". CMAJ. 149 (9): 1247–1253. PMC 1485678 Freely accessible. PMID 8221479. 
  112. ^ Bell EF (1987). "History of vitamin E in infant nutrition". American Journal of Clinical Nutrition. 46 (1 Suppl): 183–186. doi:10.1093/ajcn/46.1.183. PMID 3300257. 
  113. ^ Brion LP, Bell EF, Raghuveer TS (2003). "Vitamin E supplementation for prevention of morbidity and mortality in preterm infants". Cochrane Database Syst Rev (4): CD003665. doi:10.1002/14651858.CD003665. PMID 14583988. 
  114. ^ Vitamin E clinical trials limited to actively recruiting subjects clinicaltrials.gov Search conducted March 18, 2018.
  115. ^ Vitamin E clinical trials clinicaltrials.gov Search conducted March 18, 2018.

External links[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Vitamin_E&oldid=846265937"