Editing Vitamin E (section)

== Chemistry ==
[[File:Tocopherols.svg|350px|right|thumb|class=skin-invert-image|General chemical structure of tocopherols]]
[[File:Alpha-Tocopherol Structural Formulae V.1.svg|350px|thumb|class=skin-invert-image|RRR alpha-tocopherol; chiral points are where the three dashed lines connect to the side chain]]
The nutritional content of vitamin E is defined by equivalency to 100% RRR-configuration α-tocopherol activity. The molecules that contribute α-tocopherol activity are four tocopherols and four tocotrienols, within each group of four identified by the prefixes alpha- (α-), beta- (β-), gamma- (γ-), and delta- (δ-). For alpha(α)-tocopherol each of the three "R" sites has a methyl group (CH<sub>3</sub>) attached. For beta(β)-tocopherol: R1 = methyl group, R2 = H, R3 = methyl group. For gamma(γ)-tocopherol: R1 = H, R2 = methyl group, R3 = methyl group. For delta(δ)-tocopherol: R1 = H, R2 = H, R3 = methyl group. The same configurations exist for the tocotrienols, except that the unsaturated side chain has three carbon-carbon double bonds whereas the tocopherols have a saturated side chain.<ref name=Manolescu2008>{{cite journal |vauthors = Manolescu B, Atanasiu V, Cercasov C, Stoian I, Oprea E, Buşu C |title = So many options but one choice: the human body prefers alpha-tocopherol. A matter of stereochemistry |journal = Journal of Medicine and Life |volume = 1 |issue = 4 |pages = 376–82 | date = October–December 2008 |pmid = 20108516 |pmc = 5654212 }}</ref>

=== Stereoisomers ===
In addition to distinguishing tocopherols and tocotrienols by position of methyl groups, the tocopherols have a phytyl tail with three [[Chirality|chiral]] points or centers that can have a right or left orientation. The naturally occurring plant form of alpha-tocopherol is RRR-α-tocopherol, also referred to as d-tocopherol, whereas the synthetic form ([[Racemic mixture|all-racemic]] or ''all-rac'' vitamin E, also dl-tocopherol) is equal parts of eight [[stereoisomer]]s RRR, RRS, RSS, SSS, RSR, SRS, SRR and SSR with progressively decreasing biological equivalency, so that 1.36&nbsp;mg of dl-tocopherol is considered equivalent to 1.0&nbsp;mg of d-tocopherol, the natural form. Rephrased, the synthetic has 73.5% of the potency of the natural.<ref name=Manolescu2008 />
{| class="wikitable"
|-
! Form || Structure
|-
| [[alpha-Tocopherol|''alpha''-Tocopherol]] || [[File:Tocopherol, alpha-.svg|300px|class=skin-invert-image]]
|-
| [[beta-Tocopherol|''beta''-Tocopherol]] || [[File:Beta-tocopherol.png|300px|class=skin-invert-image]]
|-
| [[gamma-Tocopherol|''gamma''-Tocopherol]] || [[File:Gamma-tocopherol.png|300px|class=skin-invert-image]]
|-
| [[delta-Tocopherol|''delta''-Tocopherol]] || [[File:Delta-tocopherol.png|300px|class=skin-invert-image]]
|-
| [[Tocopheryl acetate]] || [[File:Tocopheryl acetate.png|300px|class=skin-invert-image]]
|}

=== Tocopherols ===
[[Alpha-tocopherol]] is a [[fat-soluble]] [[antioxidant]] functioning within the [[glutathione peroxidase]] pathway,<ref>{{cite journal | vauthors = Wefers H, Sies H | title = The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E | journal = European Journal of Biochemistry | volume = 174 | issue = 2 | pages = 353–7 | date = June 1988 | pmid = 3383850 | doi = 10.1111/j.1432-1033.1988.tb14105.x | doi-access = free | title-link = doi }}</ref> and protecting [[cell membrane]]s from oxidation by reacting with lipid radicals produced in the [[lipid peroxidation]] [[chain reaction]].<ref name=lpi /><ref name=traber>{{cite journal | vauthors = Traber MG, Atkinson J | title = Vitamin E, antioxidant and nothing more | journal = Free Radical Biology & Medicine | volume = 43 | issue = 1 | pages = 4–15 | date = July 2007 | pmid = 17561088 | pmc = 2040110 | doi = 10.1016/j.freeradbiomed.2007.03.024 }}</ref> 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 [[Organic redox reaction|reduction]] by other [[antioxidant]]s, such as [[ascorbate]], [[retinol]] or [[ubiquinol]].<ref>{{cite journal | vauthors = Wang X, Quinn PJ | title = Vitamin E and its function in membranes | journal = Progress in Lipid Research | volume = 38 | issue = 4 | pages = 309–36 | date = July 1999 | pmid = 10793887 | doi = 10.1016/S0163-7827(99)00008-9 }}</ref> Other forms of vitamin E have their own unique properties; for example, γ-tocopherol is a [[nucleophile]] that can react with [[electrophile|electrophilic]] [[mutagen]]s.<ref name=Brigelius1999>{{cite journal | vauthors = Brigelius-Flohé R, Traber MG | title = Vitamin E: function and metabolism | journal = FASEB Journal | volume = 13 | issue = 10 | pages = 1145–55 | date = July 1999 | pmid = 10385606 | doi = 10.1096/fasebj.13.10.1145 | s2cid = 7031925 | doi-access = free | title-link = doi }}</ref>

=== Tocotrienols ===
The four [[tocotrienol]]s (alpha, beta, gamma, delta) are similar in structure to the four tocopherols, with the main difference being that the former have hydrophobic side chains with three carbon-carbon double bonds, whereas the tocopherols have saturated side chains. For ''alpha(α)''-tocotrienol each of the three "R" sites has a methyl group (CH<sub>3</sub>) attached. For ''beta(β)''-tocotrienol: R1 = methyl group, R2 = H, R3 = methyl group. For ''gamma(γ)''-tocotrienol: R1 = H, R2 = methyl group, R3 = methyl group. For ''delta(δ)''-tocotrienol: R1 = H, R2 = H, R3 = methyl group. Tocotrienols have only a single [[chirality|chiral center]], which exists at the 2' chromanol ring carbon, at the point where the isoprenoid tail joins the ring. The other two corresponding centers in the phytyl tail of the corresponding tocopherols do not exist as chiral centers for tocotrienols due to unsaturation (C-C double bonds) at these sites. Tocotrienols extracted from plants are always [[dextrorotatory]] stereoisomers, signified as d-tocotrienols. In theory, [[levorotatory]] forms of tocotrienols (l-tocotrienols) could exist as well, which would have a 2S rather than 2R configuration at the molecules' single chiral center, but unlike synthetic dl-alpha-tocopherol, the marketed tocotrienol [[dietary supplement]]s are extracted from palm oil or rice bran oil.<ref name="Ahsan2015">{{cite journal |vauthors=Ahsan H, Ahad A, Siddiqui WA |title=A review of characterization of tocotrienols from plant oils and foods |journal=J Chem Biol |volume=8 |issue=2 |pages=45–59 |date=April 2015 |pmid=25870713 |pmc=4392014 |doi=10.1007/s12154-014-0127-8 }}</ref>

Tocotrienols are not essential nutrients; government organizations have not specified an estimated average requirement or recommended dietary allowance. A number of health benefits of tocotrienols have been proposed, including decreased risk of age-associated cognitive impairment, heart disease and cancer. Reviews of human research linked tocotrienol treatment to improved [[Biomarker (medicine)|biomarkers]] for [[inflammation]] and [[cardiovascular disease]], although those reviews did not report any information on clinically significant disease outcomes.<ref>{{cite journal |url = http://www.eurekaselect.com/article/19696 |vauthors = Prasad K |title = Tocotrienols and cardiovascular health |journal = Current Pharmaceutical Design |volume = 17 |issue = 21 |pages = 2147–54 |date = 2011 |pmid = 21774782 |doi = 10.2174/138161211796957418 |access-date = 12 December 2022 |archive-date = 10 December 2022 |archive-url = https://web.archive.org/web/20221210053123/http://www.eurekaselect.com/article/19696 |url-status = live }}</ref><ref>{{cite journal |vauthors=Khor BH, Tiong HC, Tan SC, Wong SK, Chin KY, Karupaiah T, Ima-Nirwana S, Abdul Gafor AH |title=Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials |journal=PLOS ONE |volume=16 |issue=7 |pages=e0255205 |date=2021 |pmid=34297765 |pmc=8301652 |doi=10.1371/journal.pone.0255205 | doi-access = free | title-link = doi |bibcode=2021PLoSO..1655205K |url=}}</ref><ref>{{cite journal |vauthors=Rafique S, Khan DA, Farhat K, Khan MA, Noor M, Sharif M |title=Comparative efficacy of tocotrienol and tocopherol (vitamin E) on atherosclerotic cardiovascular diseases in humans |journal=J Pak Med Assoc |volume=74 |issue=6 |pages=1124–29 |date=June 2024 |pmid=38948984 |doi=10.47391/JPMA.9227 |url=| doi-access = free | title-link = doi |doi-broken-date=17 February 2025 }}</ref> Biomarkers for other diseases were not affected by tocotrienol supplementation.<ref>{{cite journal |vauthors=Li F, Xu B, Soltanieh S, Zanghelini F, Abu-Zaid A, Sun J |title=The effects of tocotrienols intake on obesity, blood pressure, inflammation, liver and glucose biomarkers: a meta-analysis of randomized controlled trials |journal=Crit Rev Food Sci Nutr |volume=62 |issue=26 |pages=7154–67 |date=2022 |pmid=33909529 |doi=10.1080/10408398.2021.1911926 |url=}}</ref>