Tocopherol

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of RRR tocopherol
( RRR ) isomer of tocopherol (α-tocopherol)
General
Common name Vitamin E.
other names
  • α-tocopherol
  • (2 R ) -2,5,7,8-Tetramethyl-2 - [(4 R , 8 R ) -4,8,12-trimethyltridecyl] -3,4-dihydro-2 H -chromen-6-ol
  • E  307
  • TOCOPHEROL ( INCI )
Molecular formula C 29 H 50 O 2
CAS number 10191-41-0
PubChem 14985
ATC code

A11 HA03

DrugBank DB00163
Brief description yellow to brown liquid
Occurrence Cereals, nuts, seeds, vegetable oils, milk, eggs
physiology
function antioxidant
Daily need 10 mg
Consequences in case of deficiency Infertility, non-specific symptoms such as: dry, wrinkled skin, tiredness, decreased wound healing
Overdose > 300 mg / day
properties
Molar mass 430.71 g / mol
Physical state liquid
density 0.95 g cm −3
Melting point

2.5-3.5 ° C

boiling point
  • 393 ° C
  • 200–220 ° C at 0.1 hPa
solubility fat soluble, <1 mg / l in water
safety instructions
Please note the restricted labeling requirements for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 317
P: 261-273-280-333 + 313-362 + 364-501
Toxicological data
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Vitamin E (or tocopherol ) is a collective term for fat-soluble substances with mostly antioxidant effects. The most common vitamin E forms are called tocopherol e and tocotrienol e (derived from the ancient Greek words τόκος tókos "birth, offspring" and φέρειν phérein "carry, bring"). There are also tocomonoenols (T1) and MDT ( marine derived tocopherols ). Vitamin E is part of all membranes of animal cells, but is only formed by photosynthetically active organisms such as plants and cyanobacteria . Often the term vitamin E is used solely for α-tocopherol, the best-researched form of vitamin E.

history

Vitamin E was discovered as a "fertility vitamin ". Herbert M. Evans and Katherine S. Bishop (two American researchers) were the first to point out in 1922 a hitherto unknown fat-soluble factor that was necessary for the reproduction of rats. In the years that followed, this factor was isolated mainly from wheat germ oil , oats and corn, recognized as a vitamin and now called vitamin E due to the already known vitamins A , B , C and D. In 1938 the structure of vitamin E (here α-tocopherol) was clarified, and the first chemical synthesis took place in the same year. Representatives of the tocotrienols, which also belong to the vitamin E forms, were first described and synthesized in 1956.

description

The basic structure of all vitamin E forms is a chroman ring hydroxylated at position 6 , the methylation of which divides them into an α, β, γ or δ form. Four families are again distinguished by differently saturated side chains, namely the

  • Tocopherols with a saturated side chain
  • Tocomonoenols (T1) and marine tocopherols (MDT) with a monounsaturated side chain and the
  • Tocotrienols (T3) with a triple unsaturated side chain.

Other naturally occurring tocopherols are 5,7-dimethyltocol and 7-methyltocol. Both were isolated from rice germ oil in 1956 . The synthesis for 5,7-dimethyltocol took place as early as 1938 and for 7-methyltocol in 1958.

Tocopherols are naturally present in an ( RRR ) configuration . The naturally occurring ( RRR ) form of vitamin E is the formerly called the D form, as in D -alpha-tocopherol, the synthetic form (all-rac) the formerly called DL -form, as in DL -alpha-tocopherol.

Surname Structure of the ( RRR ) isomers R 1 R 2
α-tocopherol (RRR) -Tocopherols Structural Formulas V.1.svg CH 3 CH 3
β-tocopherol CH 3 H
γ-tocopherol H CH 3
δ-tocopherol H H
Surname Structure of the ( R ) isomers R 1 R 2
α- tocotrienol (R) -Tocotrienol (R3 = CH3) V.1.svg CH 3 CH 3
β-tocotrienol CH 3 H
γ-tocotrienol H CH 3
δ-tocotrienol H H
Surname Structure of the ( RRR ) isomers R 1 R 2
α-tocomonoenol (RRR) -Tocomonoenols Structural Formulas V.1.svg CH 3 CH 3
β-tocomonoenol CH 3 H
γ-tocomonoenol H CH 3
δ-tocomonoenol H H
Surname Structure of the ( RRR ) isomers R 1 R 2
α-MDT (RRR) -Tocomonoenols terminal Structural Formulas V.1.svg CH 3 CH 3
β-MDT CH 3 H
γ-MDT H CH 3
δ-MDT H H

Plastochromanol

Plastochromanols are a group of molecules that are produced by plants against lipid peroxidation and that can prevent the possible prooxidative activity of alpha-tocopherol. Gamma- tocotrienol is plastochromanol-3. Plastochromanole are, for example linseed oil , camelina oil , Sacha Inchi and Arabidopsis ago.

Task / function in the body

Reduction of a fatty acid radical by α-tocopherol. R 1 stands for the unbranched alkyl radical of the fatty acid.

One of its most important functions is that of a lipid-soluble antioxidant , which is able to protect polyunsaturated fatty acids in membrane lipids, lipoproteins and depot fat from being destroyed by oxidation ( lipid peroxidation ). Free radicals would attack the double bonds of the fatty acids in the cell and organelle membranes. Tocopherol acts as a radical scavenger, in that it itself becomes an inert, since it becomes a mesomeric-stabilized radical. The tocopherol radical is then reduced to form an ascorbate radical . The ascorbate radical is regenerated with the help of glutathione (GSH). Two monomers (GSH) are oxidized to a dimer (GSSG).

Vitamin E has functions in the control of the gonads and is therefore also known as the anti-sterility vitamin.

The human body can best store and transport ( RRR ) -α-tocopherol. The reason for this: The α-tocopherol transfer protein (α-TTP) in the liver, which is responsible for transporting vitamin E via VLDL into the bloodstream, has the highest affinity for natural α-tocopherol. Due to the storage capacity, a single dose can work for a longer period of time. The γ-tocopherol, which is mainly found in soy products, shows less activity. Recently, however, there has been a discussion as to whether this should be assigned a special role. In human LDL , a lipoprotein , α-tocopherol and, in low concentrations, γ-tocopherol are also present.

Special properties of α-tocopherol

α-Tocopherol, the most widely used and also synthetically produced isomer of vitamin E, has some positive and less positive properties compared to other tocochromanols:

  • It is preferentially transported by the transport protein TTP in mammals and stored in the liver.
  • It can even have a pro-oxidative effect, i.e. worsen the shelf life of lipids (cooking oils). This pro-oxidative effect is prevented by plastochromanols .
  • While very small amounts slightly reduce cholesterol production, larger amounts (in animal experiments with guinea pigs from 5 mg / d) cause a significant increase in plasma cholesterol.
  • The cholesterol-lowering property of tocotrienols is greatly reduced by alpha-tocopherol.

α-tocopherol equivalents

Information about the vitamin E requirement is correctly given in mg TE (also aTE or aTÄ). These mgTE indicate the "vitamin E activity", which is the relative effect as an anti-sterility vitamin. The individual isomers are included in the calculation of the aTE with a significantly different factor. Here is a list of the relative aTE of the eight common natural isomers. 1 mg aTE correspond to:

  • 1 mg alpha-tocopherol ( RRR -α-tocopherol or D -α-T0)
  • 2 mg beta-tocopherol
  • 4 mg of gamma tocopherol
  • 100 mg delta-tocopherol
  • 3.3 mg alpha-tocotrienol
  • 6.6 mg beta-tocotrienol
  • 13.2 mg gamma tocotrienol
  • there is no official conversion for delta-tocotrienol

The indication of the aTE does not correlate with the antioxidant effect. On the contrary, tocotrienols and generally delta and gamma isomers show a significantly higher antioxidant activity. In the case of tocotrienols, a 40-fold higher antioxidant protective effect against lipid peroxidation on cell membranes was demonstrated.

Synthetic products with vitamin E effects have a reduced effect compared to natural vitamin E because they consist of mixtures ("all-RAC") of different isomers in the structure of the phytyl residue. The older IE were based on the relative vitamin E activity of all- rac -α-tocopheryl acetate (1.49) and should no longer be used.

Occurrence

Sunflower oil and sunflower

Vegetable oils such as sea ​​buckthorn pulp oil ( 3304 mg / kg total tocopherol with 1844 mg / kg α-tocopherol), wheat germ oil (up to 2435 mg / kg total tocopherol with 70% α-tocopherol) and other germ oils , sunflower oil (454– ) have particularly high levels of vitamin E 810 mg / kg total tocopherol with 86–99% α-tocopherol), red palm oil (800 mg / kg total vitamin E, including 152 α-tocopherol and 600 mg / kg tocotrienols) and olive oil (46–224 mg / kg total tocopherol with 89-100% α-tocopherol). The dose- and matrix-dependent absorption rate averages 30%.

Even the grain of wheat contains is consumed during germination much vitamin E,.

Vitamin E is also synthetically [u. a. by BASF , E. Merck (India) and DSM Nutritional Products] as a racemic mixture. Synthetic tocopherol, however, is relatively unstable and is therefore usually provided with an acetyl group (see also dl-α-tocopheryl acetate ). This has no antioxidant properties. However, up to 50% of it can be converted into natural vitamin E in the body.

Α-Tocomonoenol has also been detected in palm oil , while some marine organisms contain the so-called marine tocopherol ( marine derived tocopherol , MDT).

stability

Vitamin E is relatively stable against heat. Even after several hours of heating at up to 180 ° C (e.g. when deep-frying), the losses remained in the range of 15% -60%. All eight vitamin E isomers have a clearly positive influence on the formation of undesirable oxidation products. The lower the temperature and the shorter the heating, the more vitamin E is obtained.

requirement

The minimum requirement is 4 mg / d, plus about 0.4 mg per gram of polyunsaturated fatty acids . In order to achieve the plasma level considered protective by various authors, an intake of 20 to 35 mg / d is necessary. Due to the low toxicity, doses of 268 mg / d are sometimes recommended. The plasma level should be above 30 µmol / l (with a cholesterol level of 220 mg / dl).

Due to its prostaglandin interaction, vitamin E intensifies the effect of anticoagulants (anticoagulants), which is why the therapy must be carefully monitored when using oral anticoagulants and in the case of vitamin K deficiency in order to avoid an increased risk of bleeding .

In patients with neurodermatitis , supplementation with 268 mg / d for eight months led to a significant improvement in symptoms.

Pharmacoepidemiological studies on tocopherol

For Pharmacoepidemiology of α-tocopherol extensive data about the German Cardiovascular Prevention Study (DHP) and from the from the National Reconnaissance Surveys Federal Health Survey for the local population. The regular use of α-tocopherol-containing preparations then leads to a dose-dependent and statistically significant reduction in the β- and γ-tocopherol in the serum. Health aspects of a possible increased bleeding tendency under co-medication with acetylsalicylic acid preparations are discussed in the literature. Also to tocopherol oxidation products, such as. For example, tocopherol quinone is available from survey data.

Data on the tocopherol content in the serum of the study participants are also available from the Berlin study on vegetarians . Despite a higher intake of tocopherols, the tocopherol levels in the serum of the vegetarians were lower than that of the comparison persons.

A large-scale study of 35,533 men examined whether vitamin E protects against prostate cancer. 400 IU / d of all rac-α-tocopheryl acetate (synthetically produced dl-α-tocopheryl acetate ) were used. As a result, prostate cancer was 17 percent more common compared to the control group. In contrast, several in vitro studies with the gamma isomers (gTP or gTE) have shown an apoptotic effect on prostate cancer cells. A multicenter study with more than 2000 study participants, taking into account nutritional epidemiological data on tocopherol intake with food, came to similar positive results with regard to the protective effect of tocopherols .

Deficiency symptoms (hypovitaminosis)

Deficiency symptoms in humans are very rare these days in Europe, as tocopherol can be stored very well in the liver and in adipose tissue. Proven deficiency symptoms usually only occur in connection with diseases such as B. exocrine pancreatic insufficiency or a reduction in the flow of bile, in which the absorption of fats is disturbed.

The consequences of hypovitaminosis are:

Overdose (hypervitaminosis)

UL α-tocopherol from EFSA
for children and adolescents
Age UL (mg / day)
1-3 100
4-6 120
7-10 160
11-14 220
15-17 260

Just like the fat-soluble vitamins vitamin A , vitamin D and vitamin K , ( RRR ) -α-tocopherol and the ( 2R ) -stereoisomers [( RSR ) -, ( RRS ) - and ( RSS ) -α-tocopherol] in adipose tissue or The body's blood plasma is enriched. The synthetically produced ( 2S ) -stereoisomers [( SRR ) -, ( SSR ) -, ( SRS ) - and ( SSS ) -α-tocopherol], however, are not stored in the blood plasma.

The European Food Safety Authority (EFSA) defines 300 mg (~ 450 IU ) of α-tocopherol or its equivalents as the tolerable upper intake level (UL), i.e. the amount that a healthy adult can consume daily for life without any health risks.

For children, a study identified amounts of 25 mg per kilogram of body weight per day as non-toxic and 10 mg per 418  kJ (= 100  kcal ) of food energy when given orally as a safe guideline.

In three meta-analyzes , which found dissenting votes, an increased mortality rate (all causes) was found for doses> 400 IU.

The mean lethal dose (LD50) of α-tocopherol is> 2000 mg per kg of body weight; tested on mice, rats and rabbits.

use

Tocopherols are used as antioxidants in the food industry . They are listed in the EU as food additives with the numbers E 306 (extracts containing tocopherol), E 307 (alpha), E 308 (gamma-) and E 309 (delta tocopherol) for all foodstuffs permitted for additives, partly (in Form of tocopherol-containing extracts of natural origin) also approved for " organic " food (E 306).

In addition to food, vitamin E is also added to cosmetics (sunscreens) and paints, as well as in artificial joints for greater resistance to oxidation of the plastic used . In the case of condoms , a vitamin E coating should u. a. increase the tear resistance.

Esterified with sebacic acid and polyethylene glycol , the nonionic surfactant polyoxyethanyl-α-tocopheryl sebacate (PTS) is obtained, which can be used as an aid in phase transfer catalysis .

Analytics

The methods used almost exclusively today for the reliable qualitative and quantitative determination of the individual tocopherols are HPLC , gas chromatography and the coupling processes of HPLC-MS and GC / MS . Both methods are used in food chemistry analysis as well as in pharmaceutical and physiological issues. The mass spectrum of tocopherol can also be found in the spectrum library of the NIST . Depending on the matrices to be examined , appropriate sample preparation methods such as B. extraction methods , also using solid phase extraction columns or other extraction aids such as. B. Extrelut made from diatomaceous earth. The photometric methods that were frequently used in the past are almost no longer used, as they generally do not allow any distinction between the individual tocopherols. Stereoisomeric racemic alpha-tocopherol can be separated both by HPLC and by gas chromatography.

See also

Individual evidence

  1. ↑ Entry on E 307: Alpha-tocopherol in the European database for food additives, accessed on August 7, 2020.
  2. ↑ Entry on TOCOPHEROL in the CosIng database of the EU Commission, accessed on February 25, 2020.
  3. ↑ a b c d e f g Data sheet (±) -α-Tocopherol, synthetic, ≥96% (HPLC) from Sigma-Aldrich , accessed on December 29, 2019 ( PDF ).
  4. ^ HM Evans, KS Bishop: On the existence of a hitherto unrecognized dietary factor essential for reproduction. In: Science . Volume 56, Number 1458, December 1922, pp. 650-651, doi: 10.1126 / science.56.1458.650 , PMID 17838496 .
  5. ^ Merck Index, 14th Ed. with CD-ROM, Merck, Whitehouse Station NJ , ISBN 978-0-911910-00-1 .
  6. ↑ a b B. Nowicka, J. Gruszka, J. Kruk: Function of plastochromanol and other biological prenyllipids in the inhibition of lipid peroxidation-A comparative study in model systems. In: Biochimica et Biophysica Acta . Volume 1828, number 2, February 2013, pp. 233-240, doi: 10.1016 / j.bbamem.2012.08.018 , PMID 22959712 .
  7. ^ R. Szymańska, J. Kruk: Identification of hydroxy-plastochromanol in Arabidopsis leaves. In: Acta biochimica Polonica. Volume 57, Number 1, 2010, pp. 105-108, PMID 20234882 .
  8. ↑ a b c d Use of vitamins in food. Toxicological and nutritional aspects (PDF; 1.3 MB) Federal Institute for Risk Assessment, p. 88 ff .; Retrieved July 9, 2009
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