Editing Tocopherol (section)

==Uses==
{{Main|Vitamin E}}
Observational studies that measure dietary intake and/or serum concentration, and experimental studies that ideally are [[randomized clinical trial]]s (RCTs), are two means of examining the effects or lack thereof of a proposed intervention on human health.<ref>{{cite book |vauthors=Munnangi S, Boktor SW |chapter=Epidemiology of Study Design |title=StatPearls |date=18 December 2018 |publisher=StatPearls |pmid=29262004 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK470342/}}</ref> Healthcare outcomes may be expected to be in accord between reviews of observational and experimental studies. If there is a lack of agreement, then factors other than design need to be considered.<ref>{{Cite journal |last1=Toews |first1=Ingrid |last2=Anglemyer |first2=Andrew |last3=Nyirenda |first3=John Lz |last4=Alsaid |first4=Dima |last5=Balduzzi |first5=Sara |last6=Grummich |first6=Kathrin |last7=Schwingshackl |first7=Lukas |last8=Bero |first8=Lisa |date=2024-01-04 |title=Healthcare outcomes assessed with observational study designs compared with those assessed in randomized trials: a meta-epidemiological study |journal=The Cochrane Database of Systematic Reviews |volume=1 |issue=1 |pages=MR000034 |doi=10.1002/14651858.MR000034.pub3 |issn=1469-493X |pmc=10765475 |pmid=38174786}}</ref> In observational studies on vitamin E, an inverse correlation between dietary intake and risk of a disease, or serum concentration and risk of a disease, may be considered suggestive, but any conclusions also should rest on randomized clinical trials of sufficient size and duration to measure clinically significant results. One concern with correlations is that other nutrients and non-nutrient compounds (such as polyphenols) may be higher in the same diets that are higher in vitamin E. Another concern for the relevance of RCTs described below is that while observational studies are comparing disease risk between low and high dietary intake of naturally occurring vitamin E from food (when worldwide, the adult median dietary intake is 6.2&nbsp;mg/d for d-α-tocopherol; 10.2&nbsp;mg/day when all of the tocopherol and tocotrienol isomers are included),<ref name=Peter2016>{{cite journal | vauthors = Péter S, Friedel A, Roos FF, Wyss A, Eggersdorfer M, Hoffmann K, Weber P | title = A Systematic Review of Global Alpha-Tocopherol Status as Assessed by Nutritional Intake Levels and Blood Serum Concentrations | journal = International Journal for Vitamin and Nutrition Research | volume = 85 | issue = 5–6 | pages = 261–281 | date = December 2015 | pmid = 27414419 | doi = 10.1024/0300-9831/a000281 | doi-access = free }}</ref> the prospective RCTs often used 400 IU/day of synthetic dl-α-tocopherol as the test product, equivalent to 268&nbsp;mg of α-tocopherol equivalents.<ref name="GOVe"/>

===Supplement popularity over time===
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 been due to publications of studies that showed either no benefits or negative consequences from vitamin E supplements.<ref>{{cite journal | vauthors = Kim HJ, Giovannucci E, Rosner B, Willett WC, Cho E | title = Longitudinal and secular trends in dietary supplement use: Nurses' Health Study and Health Professionals Follow-Up Study, 1986-2006 | journal = Journal of the Academy of Nutrition and Dietetics | volume = 114 | issue = 3 | pages = 436–43 | date = March 2014 | pmid = 24119503 | pmc = 3944223 | doi = 10.1016/j.jand.2013.07.039 }}</ref> There is other evidence for declining use of vitamin E. 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%.<ref>{{cite journal | vauthors = Morioka TY, Bolin JT, Attipoe S, Jones DR, Stephens MB, Deuster PA | title = Trends in Vitamin A, C, D, E, K Supplement Prescriptions From Military Treatment Facilities: 2007 to 2011 | journal = Military Medicine | volume = 180 | issue = 7 | pages = 748–53 | date = July 2015 | pmid = 26126244 | doi = 10.7205/MILMED-D-14-00511 | doi-access = free }}</ref> A report on vitamin E sales volume in the USA documented a 50% decrease between 2000 and 2006,<ref>{{cite journal | vauthors = Tilburt JC, Emanuel EJ, Miller FG | title = Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results | journal = Journal of General Internal Medicine | volume = 23 | issue = 9 | pages = 1495–8 | date = September 2008 | pmid = 18618194 | pmc = 2518024 | doi = 10.1007/s11606-008-0704-z }}</ref> with a significant cause attributed to a well-publicized meta-analysis that had concluded that high-dosage vitamin E increased all-cause mortality.<ref name=Miller2005>{{cite journal | vauthors = Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E | title = Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality | journal = Annals of Internal Medicine | volume = 142 | issue = 1 | pages = 37–46 | date = January 2005 | pmid = 15537682 | doi = 10.7326/0003-4819-142-1-200501040-00110 | s2cid = 35030072 }}</ref>

=== Age-related macular degeneration ===
A Cochrane review published in 2017 (updated in 2023) on antioxidant vitamin and mineral supplements for slowing the progression of [[Macular degeneration|age-related macular degeneration]] (AMD) identified only one vitamin E clinical trial.<ref name=":0">{{Cite journal |last1=Evans |first1=Jennifer R. |last2=Lawrenson |first2=John G. |date=2023-09-13 |title=Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=9 |pages=CD000254 |doi=10.1002/14651858.CD000254.pub5 |issn=1469-493X |pmc=10498493 |pmid=37702300 }}</ref> That trial compared 500 IU/day of α-tocopherol to placebo for four years and reported no effect on the progression of AMD in people already diagnosed with the condition.<ref name=":0" /> Another Cochrane review, same year, same authors, reviewed the literature on α-tocopherol preventing the development of AMD. This review identified four trials, duration 4–10 years, and reported no change to risk of developing AMD.<ref>{{cite journal | vauthors = Evans JR, Lawrenson JG | title = Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | pages = CD000253 | date = July 2017 | issue = 7 | pmid = 28756617 | pmc = 6483250 | doi = 10.1002/14651858.CD000253.pub4 }}</ref> A large clinical trial known as AREDS compared [[β-carotene]] (15&nbsp;mg), [[vitamin C]] (500&nbsp;mg), and α-tocopherol (400 IU) to placebo for up to ten 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.<ref>{{cite journal | vauthors = Chew EY, Clemons TE, Agrón E, Sperduto RD, Sangiovanni JP, Kurinij N, Davis MD | title = Long-term effects of vitamins C and E, β-carotene, and zinc on age-related macular degeneration: AREDS report no. 35 | journal = Ophthalmology | volume = 120 | issue = 8 | pages = 1604–11.e4 | date = August 2013 | pmid = 23582353 | pmc = 3728272 | doi = 10.1016/j.ophtha.2013.01.021 }}</ref>

=== Complementary and alternative medicine ===
Proponents of [[megavitamin therapy]] and [[orthomolecular medicine]] advocate ''natural tocopherols.''<ref name="gamma">{{cite journal | vauthors = Jiang Q, Christen S, Shigenaga MK, Ames BN | title = gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention | journal = The American Journal of Clinical Nutrition | volume = 74 | issue = 6 | pages = 714–22 | date = December 2001 | pmid = 11722951 | doi = 10.1093/ajcn/74.6.714 | doi-access = free }}</ref> Meanwhile, clinical trials have largely concentrated on use of either a synthetic, all-racemic d-α-tocopheryl acetate or synthetic dl-α-tocopheryl acetate.{{citation needed|date=April 2018}}

====Antioxidant theory====
{{Main|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.<ref>{{cite journal | vauthors = Roberts LJ, Oates JA, Linton MF, Fazio S, Meador BP, Gross MD, Shyr Y, Morrow JD | title = The relationship between dose of vitamin E and suppression of oxidative stress in humans | journal = Free Radical Biology & Medicine | volume = 43 | issue = 10 | pages = 1388–93 | date = November 2007 | pmid = 17936185 | pmc = 2072864 | doi = 10.1016/j.freeradbiomed.2007.06.019 }}</ref>

=== Alzheimer's disease ===
[[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.<ref>{{cite journal | vauthors = Burns A, Iliffe S | title = Alzheimer's disease | journal = BMJ | volume = 338 | pages = b158 | date = February 2009 | pmid = 19196745 | doi = 10.1136/bmj.b158 | s2cid = 8570146 }}</ref> The disease process is associated with [[Senile plaques|plaques]] and [[Neurofibrillary tangle|tangles]] in the brain.<ref name=Lancet2011>{{cite journal | vauthors = Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E | title = Alzheimer's disease | journal = Lancet | volume = 377 | issue = 9770 | pages = 1019–31 | date = March 2011 | pmid = 21371747 | doi = 10.1016/S0140-6736(10)61349-9 | s2cid = 20893019 }}</ref> Vascular dementia may be caused by ischemic or hemorrhagic [[infarct]]s affecting multiple brain areas, including the [[anterior cerebral artery]] territory, the [[parietal lobe]]s, or the [[cingulate gyrus]].<ref>{{cite journal | vauthors = Love S | title = Neuropathological investigation of dementia: a guide for neurologists | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 76 Suppl 5 | issue = supplement 5 | pages = v8-14 | date = December 2005 | pmid = 16291923 | pmc = 1765714 | doi = 10.1136/jnnp.2005.080754 }}</ref> 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%.<ref>{{cite journal | vauthors = Li FJ, Shen L, Ji HF | title = Dietary intakes of vitamin E, vitamin C, and β-carotene and risk of Alzheimer's disease: a meta-analysis | journal = Journal of Alzheimer's Disease | volume = 31 | issue = 2 | pages = 253–8 | date = 2012 | pmid = 22543848 | doi = 10.3233/JAD-2012-120349 }}</ref> A second review examined serum vitamin E levels and reported lower serum vitamin E in AD patients compared to healthy, age-matched people.<ref>{{cite journal | vauthors = Dong Y, Chen X, Liu Y, Shu Y, Chen T, Xu L, Li M, Guan X | title = Do low-serum vitamin E levels increase the risk of Alzheimer disease in older people? Evidence from a meta-analysis of case-control studies | journal = International Journal of Geriatric Psychiatry | volume = 33 | issue = 2 | pages = e257–e263 | date = February 2018 | pmid = 28833475 | doi = 10.1002/gps.4780 | s2cid = 44859128 }}</ref> 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.<ref>{{cite journal | vauthors = 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 | title = Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology | journal = Journal of Psychopharmacology | volume = 31 | issue = 2 | pages = 147–168 | date = February 2017 | pmid = 28103749 | doi = 10.1177/0269881116680924 | s2cid = 52848530 | url = https://eprints.soton.ac.uk/408021/1/BAP_Guidelines_AntiDementia.pdf }}</ref>

===Cancer===
From reviews of observational studies, diets higher in vitamin E content were associated with a lower relative risk of [[kidney cancer]],<ref name=Shen2015>{{cite journal | vauthors = Shen C, Huang Y, Yi S, Fang Z, Li L | title = Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta-Analysis of Observational Studies | journal = Medical Science Monitor | volume = 21 | pages = 3420–6 | date = November 2015 | pmid = 26547129 | pmc = 4644018 | doi = 10.12659/MSM.896018 }}</ref> [[bladder cancer]],<ref name=Wang2014>{{cite journal | vauthors = Wang YY, Wang XL, Yu ZJ | title = Vitamin C and E intake and risk of bladder cancer: a meta-analysis of observational studies | journal = International Journal of Clinical and Experimental Medicine | volume = 7 | issue = 11 | pages = 4154–64 | date = 2014 | pmid = 25550926 | pmc = 4276184 }}</ref> and [[lung cancer]]<ref name=Zhu2017>{{cite journal | vauthors = Zhu YJ, Bo YC, Liu XX, Qiu CG | title = Association of dietary vitamin E intake with risk of lung cancer: a dose-response meta-analysis | journal = Asia Pacific Journal of Clinical Nutrition | volume = 26 | issue = 2 | pages = 271–277 | date = March 2017 | pmid = 28244705 | doi = 10.6133/apjcn.032016.04 }}</ref> When comparisons were made between the lowest and highest groups for dietary vitamin E consumption from food, the average reductions in relative risk were in the range of 16-19%. For all of these reviews, the authors noted that the findings needed to be confirmed by prospective studies.<ref name=Shen2015/><ref name=Wang2014/><ref name=Zhu2017/> From [[randomized clinical trial]]s (RCTs) in which α-tocopherol was administered as a dietary supplement, results differed from the dietary intake reviews. A RCT of 400 IU/day of α-tocopherol did not reduce risk of bladder cancer.<ref>{{cite journal | vauthors = Lotan Y, Goodman PJ, Youssef RF, Svatek RS, Shariat SF, Tangen CM, Thompson IM, Klein EA | title = Evaluation of vitamin E and selenium supplementation for the prevention of bladder cancer in SWOG coordinated SELECT | journal = The Journal of Urology | volume = 187 | issue = 6 | pages = 2005–10 | date = June 2012 | pmid = 22498220 | pmc = 4294531 | doi = 10.1016/j.juro.2012.01.117 }}</ref> In male tobacco smokers, 50&nbsp;mg/day had no impact on developing lung cancer.<ref>{{cite journal | title = The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers | journal = The New England Journal of Medicine | volume = 330 | issue = 15 | pages = 1029–35 | date = April 1994 | pmid = 8127329 | doi = 10.1056/NEJM199404143301501 | last1 = Alpha-Tocopherol | first1 = Beta Carotene Cancer Prevention Study Group | doi-access = free }}</ref> A review of RCTs for [[colorectal cancer]] reported lack of a statistically significant reduction in risk.<ref>{{cite journal | vauthors = Arain MA, Abdul Qadeer A | title = Systematic review on "vitamin E and prevention of colorectal cancer" | journal = Pakistan Journal of Pharmaceutical Sciences | volume = 23 | issue = 2 | pages = 125–30 | date = April 2010 | pmid = 20363687 }}</ref> In male tobacco smokers, 50&nbsp;mg/day reduced prostate cancer risk by 32%,<ref>{{cite journal | vauthors = 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 | title = Prostate cancer and supplementation with α-tocopherol and beta-carotene: incidence and mortality in a controlled trial | journal = Journal of the National Cancer Institute | volume = 90 | issue = 6 | pages = 440–6 | date = March 1998 | pmid = 9521168 | doi = 10.1093/jnci/90.6.440 | doi-access = free }}</ref> but in a different trial, majority non-smokers, 400 IU/day increased risk by 17%.<ref>{{cite journal | vauthors = 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 | title = Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) | journal = JAMA | volume = 306 | issue = 14 | pages = 1549–56 | date = October 2011 | pmid = 21990298 | pmc = 4169010 | doi = 10.1001/jama.2011.1437 }}</ref> In women who consumed either placebo or 600 IU of natural-source vitamin E on alternate days for an average of 10.1 years there were no significant differences for [[breast cancer]], lung cancer, or colon cancer.<ref>{{cite journal | vauthors = Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE | title = Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial | journal = JAMA | volume = 294 | issue = 1 | pages = 56–65 | date = July 2005 | pmid = 15998891 | doi = 10.1001/jama.294.1.56 | doi-access = free }}</ref>

The U.S. [[Food and Drug Administration]] initiated a process of reviewing and approving food and dietary supplement health claims in 1993. A Qualified Health Claim issued in 2012 allows product label claims that vitamin E may reduce risk of renal, bladder, and colorectal cancers, with a stipulation that the label must include a mandatory qualifier sentence: “FDA has concluded that there is very little scientific evidence for this claim.”<ref name=FDA2012>[https://wayback.archive-it.org/7993/20171114183722/https://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm306866.htm Alliance for Natural Health v. Sebelius, Case No. 09-1546 (D.D.C.)] U.S. Food & Drug Administration May 17, 2012</ref> 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===
A meta-analysis from 2015 reported that for studies that reported serum tocopherol, higher serum concentration was associated with a 23% reduction in relative risk of age-related [[cataract]]s (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.<ref name=Zhang2015>{{cite journal | vauthors = Zhang Y, Jiang W, Xie Z, Wu W, Zhang D | title = Vitamin E and risk of age-related cataract: a meta-analysis | journal = Public Health Nutrition | volume = 18 | issue = 15 | pages = 2804–14 | date = October 2015 | pmid = 25591715 | doi = 10.1017/S1368980014003115 | pmc = 10271701 | doi-access = free }}</ref> However, this article and a second meta-analysis reporting on clinical trials of α-tocopherol supplementation reported no statistically significant change to risk of ARC when compared to placebo.<ref name=Zhang2015/><ref name="pmid22696344">{{cite journal | vauthors = Mathew MC, Ervin AM, Tao J, Davis RM | title = Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract | journal = The Cochrane Database of Systematic Reviews | issue = 6 | pages = CD004567 | date = June 2012 | volume = 2012 | pmid = 22696344 | pmc = 4410744 | doi = 10.1002/14651858.CD004567.pub2 }}</ref>

===Cardiovascular diseases===
Research on the effects of vitamin E on [[cardiovascular disease]] has produced conflicting results. 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 α-tocopherol.<ref name=Kirmizis2009>{{cite journal | vauthors = Kirmizis D, Chatzidimitriou D | title = Antiatherogenic effects of vitamin E: the search for the Holy Grail | journal = Vascular Health and Risk Management | volume = 5 | pages = 767–74 | date = 2009 | pmid = 19774218 | pmc = 2747395 | doi = 10.2147/vhrm.s5532 | doi-access = free }}</ref> 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.<ref name=Stampher1993>{{cite journal | vauthors = Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC | title = Vitamin E consumption and the risk of coronary disease in women | journal = The New England Journal of Medicine | volume = 328 | issue = 20 | pages = 1444–9 | date = May 1993 | pmid = 8479463 | doi = 10.1056/NEJM199305203282003 | doi-access = free }}</ref> Diet higher in vitamin E also may be higher in other, unidentified components that promote heart health, or people choosing such diets may be making other healthy lifestyle choices.<ref name=Kirmizis2009/><ref name=Stampher1993/> There is some supporting evidence from [[randomized clinical trial]]s (RCTs). A meta-analysis on the effects of α-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%.<ref name=Loffredo2015>{{cite journal | vauthors = Loffredo L, Perri L, Di Castelnuovo A, Iacoviello L, De Gaetano G, Violi F | title = Supplementation with vitamin E alone is associated with reduced myocardial infarction: a meta-analysis | journal = Nutrition, Metabolism, and Cardiovascular Diseases | volume = 25 | issue = 4 | pages = 354–63 | date = April 2015 | pmid = 25779938 | doi = 10.1016/j.numecd.2015.01.008 }}</ref> 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.<ref name=Sesso2008>{{cite journal | vauthors = Sesso HD, Buring JE, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Glynn RJ, Gaziano JM | title = Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial | journal = JAMA | volume = 300 | issue = 18 | pages = 2123–33 | date = November 2008 | pmid = 18997197 | pmc = 2586922 | doi = 10.1001/jama.2008.600 }}</ref> The effects of vitamin E supplementation on incidence of stroke were summarized in 2011. There were no significant benefits for vitamin E versus placebo for risk of stroke, or for subset analysis for [[ischaemic stroke]], [[haemorrhagic stroke]], fatal stroke, or non-fatal stroke.<ref>{{cite journal | vauthors = Bin Q, Hu X, Cao Y, Gao F | title = The role of vitamin E (tocopherol) supplementation in the prevention of stroke. A meta-analysis of 13 randomised controlled trials | journal = Thrombosis and Haemostasis | volume = 105 | issue = 4 | pages = 579–85 | date = April 2011 | pmid = 21264448 | doi = 10.1160/TH10-11-0729 | s2cid = 23237227 }}</ref>

In 2001 the U.S. [[Food and Drug Administration]] rejected proposed health claims for vitamin E and cardiovascular health.<ref>[https://wayback.archive-it.org/7993/20171115122059/https://www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ucm073251.htm Letter Regarding Dietary Supplement Health Claim for Vitamin E and Heart Disease (Docket No 99P-4375)] U.S. Food and Drug Administration.</ref> The U.S. National Institutes of Health also reviewed the literature and concluded there was not sufficient evidence to support the idea that routine use of vitamin E supplements prevents cardiovascular disease or reduces its morbidity and mortality.<ref name="GOVe"/> In 2010 the [[European Food Safety Authority]] 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.<ref>[https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2010.1816 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.</ref>

=== 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 of 21 clinical trials concluded that the data do not support vitamin E supplementation - majority of trials α-tocopherol at 400 IU/day plus vitamin C at 1000&nbsp;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.<ref name=CochraneVitE>{{cite journal | vauthors = Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA | title = Vitamin E supplementation in pregnancy | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD004069 | date = September 2015 | volume = 2016 | pmid = 26343254 | doi = 10.1002/14651858.CD004069.pub3 | pmc = 8406700 }}</ref> 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.<ref name=CochraneVitE/>

=== Topical ===
Although there is widespread use of vitamin E as a [[topical medication]], with claims for improved [[wound healing]] and reduced [[scar]] tissue, reviews have repeatedly concluded that there is insufficient evidence to support these claims.<ref name=Sidgwick2015>{{cite journal | vauthors = Sidgwick GP, McGeorge D, Bayat A | title = A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring | journal = Archives of Dermatological Research | volume = 307 | issue = 6 | pages = 461–77 | date = August 2015 | pmid = 26044054 | pmc = 4506744 | doi = 10.1007/s00403-015-1572-0 }}</ref><ref name=Tanaydin2016>{{cite journal | vauthors = Tanaydin V, Conings J, Malyar M, van der Hulst R, van der Lei B | title = The Role of Topical Vitamin E in Scar Management: A Systematic Review | journal = Aesthetic Surgery Journal | volume = 36 | issue = 8 | pages = 959–65 | date = September 2016 | pmid = 26977069 | doi = 10.1093/asj/sjw046 | doi-access = free }}</ref>