Vitamin E: Structure, Properties and Functions

EtsuoNiki*a and KouichiAbeb a university of Tokyo, Research facility for advanced Science and an innovation (RCAST), Komaba, Tokyo 153-8904, Japan. E-mail: etsuo-niki
emer.rcast.u-tokyo.ac.jp b SSCI Laboratories, Faculty the Pharmacology, Musashino University, Nishi-Tokyo-Shi, Tokyo 202-0023, Japan.

Vitamin E is the collective name because that lipophilic, naturally arising compounds whose molecular structure is made up of a chromanol ring through a next chain situated at the C2 position and also includes four tocopherols and also four tocotrienols. Vitamin E, found as a dietary factor crucial for regular reproduction, is now welcomed as a major free radical scavenging antioxidant in humans and protects biological molecules native detrimental oxidative modifications. The structures and properties of vitamin E homologues and their sources, functions, and also applications room summarized.

1.1 advent

In 1922, Evans and Bishop prove the visibility of a hitherto i could not recognize it dietary factor essential for common reproduction in the rat.1 that was accepted at the time that the many striking duty of vitamin E to be to provide a regular gestation in a pregnant rat to stop the resorption of the embryos which invariably emerged in that absence.2 This unknown dietary element X was uncovered to be existing in green lettuce, dried alfalfa leaves, wheat, and also oats. Evans isolated the element X indigenous wheat germ oil, detailed the chemistry formula C29H50O2 and also proposed the surname α-tocopherol in 1936.3 The structural formula because that α-tocopherol was listed by Fernholz in 1938.4 Tocotrienols were found much later on than tocopherol and named in the early 1960s.5,6

Olcott found that the lipid fountain of vegetable oils had antioxidants versus the oxidative degradation of lard.7 because then, it has been unequivocally demonstrated the vitamin E plot as vital antioxidant in vivo and also in vitro and also plays critical role in the avoidance of detrimental oxidative damage of biological molecules.8–11 much more recently, the non-antioxidant functions of vitamin E, consisting of cellular signaling, gene regulation, membrane processes, and also nerve functions, have additionally received lot attention.12–14 However, many problems are quiet controversial and also remain to it is in elucidated. Sound information based upon solid chemical evidence is essential for expertise the role of vitamin E in vivo and in vitro.

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1.2 Homologues: Nomenclature and also Structure

Vitamin E is a plant-derived, lipid-soluble substance whose molecular framework is consisted of of a chromanol ring v a side chain located at the C2 position. Vitamin E refers to a team of eight different compounds: α-, β-, γ-, and also δ-tocopherols and the equivalent four tocotrienols. The 4 tocopherols have a saturated phytyl next chain, when tocotrienols have actually an unsaturated isoprenyl side chain comprise three twin bonds at C3′, C7′, and C11′. The twin bonds that tocotrienols' side chains at C3′ and also C7′ have a trans-configuration. The α-, β-, γ-, and δ-forms differ with respect come the number and position the methyl groups on the chromanol ring. The α-forms of tocopherol and also tocotrienol have actually three methyl teams at the C5, C7, and also C8-positions of the chromanol ring, when the β- and also γ-forms have two and also the δ-forms have actually one methyl group as depicted in figure 1.1.


*
Fig. 1.1 Chemical structure of vitamin E homologues.

In addition to tocopherols and also tocotrienols, tocomonoenols and also tocodienols include a solitary and two twin bond unsaturation, respectively, have likewise been found in nature. For example, a tocomonoenol with a single twin bond at carbon 11′, 2,5,7,8-tetramethy1-2-(4′,8′,12′-trimethyltrideca-11′-enyl)-6-chromanol, to be isolated from palm and also rice bran oils.15 due to the fact that then, several groups have detected tocomonoenols in plants and plant foods, such together α-tocomonoenol in palm oil,16–22 pumpkin seed oil (Cucurbita pepo L.),23 and also sunflower oil (Helianthus annuus),24 γ-tocomonoenol in pumpkin particle oil,22,23 δ-tocomonoenol in kiwi (Actinidia chinensis),25 and also β-, γ-, and also δ-tocomonoenol in the leaves of Kalanchoe daigremontiana and also Phaseolus coccineus.26 A tocomonoenol v an unsaturation in ~ the isoprenoid-chain terminus was additionally found in the organization of salmon.27 Furthermore, tocodienols v two twin bonds at carbon 7′ and also 11′ were established in palm oil.16,21

Tocopherols contain 3 chiral carbons, one at C2 in the chromanol ring and also two in the next chain at C4′ and also C8′. Naturally emerging α-tocopherol contains chiral carbons in the R-conformation, 2R, 4′R, and also 8′R-α-tocopherol. α-Tocotrienol has one chiral center at C2 in the chromanol ring and also natural tocotrienols occur as the R-isoform. ~ above the various other hand, the chemistry synthesis of α-tocopherol to produce an equimolar mixture that eight different stereoisomers: RRR, SRR, RSR, RRS, RSS, SSR, SRS, and SSS. The artificial α-tocopherol is referred to as all-rac-α-tocopherol. An equimolar mixture the RRR-α-tocopherol and also SRR-α-tocopherol is called 2-ambo-α-tocopherol. The IUPAC name of RRR-α-tocopherol and also RRR-α-tocotrienol room (2R)-2,5,7,8-tetramethyl-2-<(4R,8R)-(4,8,12-trimethyltridecyl)>chroman-6-ol and (2R)-2,5,7,8-tetramethyl-2-<(3E,7E)-4,8,12-trimethyltrideca-3,7,11-trienyl>-3,4-dihydrochromen-6-ol, respectively.

Ester creates of tocopherol and tocotrienols, consisting of acetate, nicotinate, succinate, and phosphate, have actually been prepared and also their activity and potential applications have actually been studied. Vitamin E is quickly oxidized as soon as subjected to heat, light, and alkaline conditions, however esters are less susceptible to oxidation and also therefore much more appropriate for food, cosmetic, and also pharmaceutical applications compared to the totally free form. Polyethylene glycol conjugates the tocopherols and tocotrienols have the capacity to form miscible micelles in water as result of amphiphilic properties and also enhance bioavailability in animals and humans via enhancing their water solubility and also absorption.28 It was reported the RRR-α-tocopheryl polyethylene glycol 1000 succinate acted together a safe and effective type of vitamin E because that reversing or preventing vitamin E deficiency throughout chronic childhood cholestasis.29

1.3 Physicochemical properties

The tocopherols room viscous oil at room temperature, insoluble in water yet soluble in ethanol and aprotic solvents. Vitamin E is a contempt yellow to amber, practically odorless, clear, viscous oil, which darkens on exposure come air or light by oxidation. The physicochemical properties of α-tocopherol, the many abundant and active type of vitamin E in humans, are summarized in Table 1.1.30 The melting suggest of RRR-α-tocopherol is 3 °C. The optical rotations the tocopherols room very little and count on the nature of the solvent. The ultraviolet absorption spectra of tocopherols and also tocotrienols in ethanol present an absorption maximum in ~ 292–298 nm, if the infrared spectra display OH (2.8 ± 3.0 µm) and CH (3.4 ± 3.5 µm) stretching and also a characteristic band at 8.6 µm. α-Tocopherol is fluorescent with an emissions maximum about 325 nm in a hydrophobic solution. The shortcut dissociation power of α-tocopherol's O–H shortcut is 77.1 kcal mol−1.31 The pKa values for α-, β-, γ-, and also δ-tocopherol in a micellar equipment were reported as 13.1, 12.8, 12.7, and also 12.6 respectively.32


a bond dissociation energy.31
IUPAC name (2R)-2,5,7,8-Tetramethyl-2-<(4R,8R)-4,8,12-trimethyltridecyl>-3,4-dihydrochromen-6-ol
Molecular formula C29H50O2
Molecular weight 430.7 g mol−1
Physical description Slightly yellow to amber, nearly odorless, clear, viscous oil
Melting point 3 °C
Boiling point 235 °C
Solubility Insoluble in water (1.9 × 10−6 mg L−1 in ~ 25 °C), soluble in ethanol
Density 0.950 g cm−3 at 25 °C
Partition coefficient log P = 12.2
Stability Unstable come UV light, alkaline, and also oxidation
Dissociation constant pKa = 10.8
UV absorb maximum 292 nm in ethanol
Fluorescence Excitation 290–295 nm, emission 320–335 nm
BDE (O–H)a 77.1 kcal mol−1

The partition coefficient the α-tocopherol is 12.2, while that for ascorbic mountain is −1.85,30 reflecting their lipophilic and hydrophilic characters, respectively.

1.4 sources

plenty of foods carry out vitamin E. Seeds and fruits are amongst the finest sources that vitamin E. Eco-friendly leafy vegetable are likewise important sources. Just plants and photosynthetic organisms are able to synthesize vitamin E.33,34 The synthesis is assisted in by enzyme to create stereospecific tocopherols: RRR-tocopherols.35 Tocopherols and tocotrienols have the right to be extracted and also purified or focused from vegetable oils and also other higher plant materials. Diet supplements space another source of vitamin E. Many vitamin E supplements save substantially higher amounts that vitamin E 보다 foods. Vitamin E in diet supplements and fortified foods items is frequently esterified to expand its shelf life if protecting that antioxidant properties.

The contents and composition that tocopherols and also tocotrienols in herbal oils differ markedly in between the plant species and even within the exact same species. Tocopherols are widely dispersed in higher plants, whereas tocotrienols occur only in some non-photosynthetic tissues. Some instances of the contents in natural edible oils embraced from numerous reports36–41 are shown in Table 1.2. α-Tocopherol is the significant tocopherol in palm, olive, and sunflower oils, whereas the components of γ-tocopherol in some edible oil such together corn, rapeseed, and soybean oil are higher than α-tocopherol.


Table 1.2The components of tocopherols (T) and tocotrienols (T3) in representative edible oils. Adjusted from ref. 36–41 a
Oil αT βT γT δT αT3 βT3 γT3 δT3 a In mg per 100 g oil. Significant components are displayed in bold.
Corn 1825 1 4475 2–3 1 0 1–2

The major sources of tocotrienols space palm, rice, and annatto, the ratio of tocopherol–tocotrienol in every being 25 : 75, 50 : 50, and also 0.1 : 99.9, respectively.42 Palm oil contains considerable quantities of α-, γ-, and also δ-tocotrienols. γ-Tocotrienol is the significant vitamin E isoform in the oil extracted from rice bran39,43 if β-tocopherol is one of the major isoforms discovered in wheat germ oil.36,37 Interestingly, the lipid portion of annatto (Bixa orellana L.) seeds included only tocotrienols, mainly δ-tocotrienol, yet no tocopherols.44

1.5 chemical Synthesis

due to wide applications in the pharmaceutical, food, and also cosmetic industries, about 35 000 lots of vitamin E is made per year worldwide.45 All-racemic-α-tocopherol, all-rac-α-tocopherol, an equimolar mixture of every eight stereoisomers, is industrially the most crucial product and is prepared either by complete synthesis or originates from organic sources. The is mainly used as an acetate ester. The industrial synthesis is composed of three significant parts: the ready of 2,3,5-trimethylhydroquinone, the production of the next chain component, and also the condensation reaction.45

Pure RRR-α-tocopherol is chemically prepared by semi-synthesis. Vegetable oils polished on a big scale and also isolated through a mix of number of separation methods contain mixture of RRR-tocopherols, which space converted to RRR-α-tocopherol through permethylation reactions. The efforts and strategies come synthesize tocopherols and also tocotrienols have been described in detail.45

1.6 evaluation

Natural products contain mixture of isomeric tocopherols and tocotrienols together with minor amounts of tocomonoenols and also tocodienols. They room metabolized and also oxidized to produce many kinds of compounds. The biological samples contain facility mixtures the vitamin E isoforms and also their metabolites and also oxidation products. The identification and also quantitation of vitamin E isoforms and also their products are necessary for elucidating their duty and functions. Sample ready is the most time-consuming and also important action in analysis, because it is the main resource of errors. Countless analytical methods consisting of colorimetric, fluorometric, gas chromatographic (GC), high performance fluid chromatographic (HPLC),46 GC-MS,47 and also HPLC-MS47,48 have actually been report (see likewise Chapter 2). Concerning public files for the quantitative determination an approach of vitamin E in energetic pharmaceutical ingredients, united States and also European Pharmacopeia embrace the GC method, while Japanese Pharmacopeia adopts the HPLC method. Every of this methods has its merits and demerits. At the existing time, HPLC techniques are the most widely applied.

HPLC problems for vitamin E analysis have been summarized in numerous reviews.46,47,49,50 Vitamin E and products are acquired from natural products, food matrices, and also biological samples by direct extraction, solid-phase extraction, and saponification. Care should it is in taken to protect against artifactual oxidation and decomposition during preparation of samples and also analysis. The use of electrochemical (amperometric), fluorometric (Ex. 290–295 nm, Em. 320–330 nm), or multiple sclerosis detection is much much more sensitive and particular than the conventional UV detection. Tocol, 2-methyl-2-(4,8,12-trimethyltridecyl)-6-chromanol, may be the ideal compound to use as an inner standard because its characteristics are similar to vitamin E. Deuterium-labelled α-tocopherol acetate is typically used together a typical in ms analysis. In many vitamin E analyses, atmospheric pressure chemical ionization (APCI) is offered in the optimistic ionization mode. It may be listed that supercritical-fluid chromatography making use of CO2 and ethanol as a mobile phase, NH2 as a stationary phase, and mass spectrometry for the detection and also quantification of vitamin E homologues has actually been proposed as a “greener” analysis strategy.51,52

1.7 Functions and Applications

Vitamin E is a physiologically necessary micronutrient and also has been used in various fields including medicine, pharmaceutics, cosmetics, and foods. Vitamin E is assumed to play an important role in the promo of health and also prevention and/or therapy of part diseases and also disorders. The everyday recommended entry is 15 mg (22.4 IU, international Unit) for adults .

Multiple features of vitamin E have been prove or proposed, consisting of (1) antioxidant by scavenging complimentary radicals, especially peroxyl radicals, and also singlet oxygen, (2) membrane stabilization by creating complexes through destabilizing molecules so as to prevent disturbance the the amphipathic balance in ~ the structure, (3) physiological regulator the enzyme activity, cellular signaling, cell proliferation, and gene expression, i beg your pardon is not straight related to antioxidant action, (4) inhibition the platelet coagulation, (5) prevention of conditions including neurological disorders, cardiovascular diseases, age-related eye and skin damage, and infertility, and (6) biocompatible comprehensive of biomaterials and medical devices, for example in high molecular load polyethylene used in hip and knee implants. It has actually been suggested that tocotrienols possess extr positive wellness effects past those of tocopherols including, for example, induction that immune responses and also lowering of serum cholesterol levels.53–55

among these functions, the duty of vitamin E as an antioxidant against totally free radical-mediated lipid peroxidation has been unequivocally demonstrated and also it shows up that this is the most necessary physiological function of this vitamin. Vitamin E additionally inhibits air oxidation of foods, oils, and industrial materials to extend their lifetime. The physiological significance of other features that room not concerned antioxidant function must be established in a future study.

Vitamin E is widely used as a dietary supplement, by chin or in addition to other means of means such together vitamin C, to promote health and also to alleviate the hazard of or prevent conditions that room assumed come arise indigenous detrimental oxidative modification of organic molecules. Vitamin E is supplied to fortify some foods and also beverages.

Deficiency the vitamin E is unusual as usual diets appear to carry out sufficient amounts, return malnutrition and also genetic disorders may result in vitamin E deficiency. Premature birth babies of very low birth weight might be deficient in vitamin E. Further, civilization with fat-malabsorption disorders56 and inherited disorders in i beg your pardon the liver's α-tocopherol move protein (α-TTP) is defective or absent57 or there are lessened levels the selenoproteins58 are an ext likely to end up being vitamin E deficient and require high doses of supplemental vitamin E.

The potential duty of vitamin E versus periodontal disease,59 nonalcoholic steatohepatitis,60 and sarcopenia61 has actually received attention. Inadequate micronutrient intake (vitamins and also phosphorus) was significantly linked with severity of periodontal disease.62 A systematic review showed far-reaching improvement the periodontal parameters by vitamin E and also lycopene.63 Vitamin E may mitigate age-associated skeleton dysfunction and also enhance muscle regeneration, for this reason attenuating sarcopenia.64

Vitamin E is likewise used for biomedical materials. α-Tocopherol is combined to a dialysis membrane because that clinical monitoring of chronic hemodialysis patients to boost stability and also functions.65 Vitamin E-blended ultra-high molecular load polyethylene (UHMWPE) has been developed as a product for use in complete knee and also hip replacements.66 α-Tocopherol is accepted to boost oxidation resistance while maintaining wear resistance and also fatigue strength.

The poor water solubility the vitamin E has greatly minimal its application. Investigations to improve both oral and also topical encapsulation and also formulations that vitamin E have been widely lugged out and also various delivery systems because that vitamin E have actually been emerged to conquer this problem and also to boost solubility, permeation, and also bioavailability. Liposomes,67 nano-emulsions, and lipid nanoparticles68 space some examples.69 The tocopheryl ester the polyethylene glycol and also tocopheryl phosphate room water soluble. Polyethylene conjugates of tocotrienols have additionally been studied.28

diet polyphenols such together quercetin room converted to glucoside and/or sulfate derivatives, or their O-methyl derivatives, throughout absorption right into the body, and presents together these conjugated metabolites in turn around blood. Development of the metabolites the tocopherol such together glucoside, sulfate, and O-methyl derivatives in vivo has not to be reported yet α-tocopherol glucoside was synthesized from 2-hydroxymethyl-2,5,7,8-tetramethylchroman-6-ol and also maltose by transglycosylation through α-glucosidase from Saccharomyces species.70 The glycosylated product, 2-(α-d-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, is water soluble and also acts together a radical scavenging antioxidant.70,71 δ-Tocopherol glucoside was prepared and also its effects throughout its topical application on skin to be studied.72

One crucial question is even if it is or not each vitamin E isoform exerts its very own specific duty which is not shared with various other isoforms. It has been suggested that tocotrienol exerts some features that tocopherol go not, and also that tocopherol interferes with such tocotrienol functions.42 this important problems must it is in clarified in future studies.

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1.8 security

Vitamin E is secure at approximately temperature, but it is easily oxidized in ~ high temperature, under light or in one alkaline medium. Frying is among the most usual methods that food preparation and during the frying process, usually between 160–190 °C, vitamin E is oxidized to give facility mixtures of commodities including tocored (5,6-tocopheryldione) and dimers that room assumed come be formed by a recombination that tocopheroxyl radicals. α-Tocopherol is oxidized come α-tocopheroxyl radical by change metal ion such together ferric ions (Fe3+) and cupric ion (Cu2+).