Tocopherol

• α -tocopherol

A11HA03

2.5-3.5 ° C

• 393 ° C
• 200-220 ° C at 0.1 hPa

Vitamin E is a collective term for fat-soluble substances with antioxidant and non- antioxidant effects. The most common vitamin E forms are called tocopherols and tocotrienols (derived from the Ancient Greek words τόκος / Tokoš, "birth" and φέρειν / pherein, "to carry", " bring "). There are also Tocomonoenole (T1) and MDT (marine derived tocopherols ). Vitamin E is a component of all membranes of animal cells, but is formed only by photosynthetic organisms such as plants and cyanobacteria. Frequently, the term vitamin E is erroneously used alone for α -tocopherol, the best studied form of vitamin E.

History

Vitamin E was discovered as a " fertility vitamin ". Herbert M. Evans and Katherine S. Bishop ( two U.S. researchers ) reported in 1922 as first in a hitherto unknown fat-soluble factor out, which was necessary for the reproduction of rats. In subsequent years, this factor was isolated mainly from wheat germ oil, oats and corn, recognized as a vitamin and because of the already known vitamins A, B, C and D now called vitamin e. In 1938 the structure of vitamin E ( α -tocopherol here ) established, and it came in the same year for the first chemical synthesis. Representatives also counted among the vitamin E tocotrienols forms have been described and synthesized for the first time in 1956.

Description

The basic structure of all forms of Vitamin E is a hydroxylated at position 6 of the chroman ring, this latter compound is divided into a α -, β -, γ - or δ - form. Through different saturated side chains four families are distinguished again, namely the

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

Other naturally occurring tocopherols are 5.7 - and 7- Dimethyltocol methyltocol. Both were 1956 isolated from rice bran oil. The synthesis of 5,7- Dimethyltocol took place in 1938 and for 7- methyltocol 1958.

Tocopherols are natural hand form in one ( RRR ) configuration.

Plastochromanol

Plastochromanole are a group of molecules that are produced by plants against lipid peroxidation and prevent the possible prooxidant activity of alpha -tocopherol. In gamma -tocotrienol is plastochromanol - third Plastochromanole occur, for example in linseed oil, camelina oil, Sacha Inchi and Arabidopsis.

Task / function in the body

One of its main features is that of a lipid-soluble antioxidant that is able to repeatedly protect unsaturated fatty acids in membrane lipids, lipoproteins and fat depot from destruction by oxidation ( lipid peroxidation). Free radicals would attack the double bonds of the fatty acids of cell and organelle membranes. Tocopherol acts as a free radical scavenger by itself becomes an inert, since resonance stabilized radical. The tocopherol radical is then reduced to form a Ascorbatradikals. The Ascorbatradikal is regenerated by means of glutathione ( GSH). Two monomers are (GSH) to form a dimer (GSSG ) is oxidized.

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

The human body is capable of storing the most RRR - α -tocopherol and transport. The reason is the located in the liver α -tocopherol transfer protein ( α -TTP ), which is responsible for the transport of vitamin E via VLDL in the circulation has the highest affinity to the natural α -tocopherol. Due to the memory a single dose for extended periods may affect. The essentially occurring in soy products γ -tocopherol shows a lower activity. Recently, however, discuss whether this a special role must be ascribed. In human LDL, a lipoprotein, α -tocopherol and γ -tocopherol and low concentrations are present.

Special properties of α -tocopherol

α -tocopherol, the most widely used, and also synthetic isomer of Vitamin E has a number of positive and less positive features compared to other Tocochromanolen:

• It is preferably transported by the transport protein TTP in mammals and stored in the liver
• It can even be per - oxidation, thus deteriorating the durability of lipids ( edible oils ). These pro- oxidative effect is prevented by Plastochromanolen.
• While very small amounts easily throttle the production of cholesterol, causing greater amounts ( in animal experiments in guinea pigs from 5 mg / d) a significant increase in plasma cholesterol
• The cholesterol-lowering property of tocotrienols is greatly reduced by alpha -tocopherol

α -tocopherol equivalents

Information on Vitamin D needs to be done correctly in mg TE ( also aTE or ATAE ). This MgTe enter the " vitamin E activity ", which is the relative effect as an anti- sterility vitamin. The individual isomers go with a significantly different factor in the bill's aTE. Here is a list of the relative aTE the eight frequent natural isomers. 1 mg aTE meet:

Specifying ATE does not correlate with the anti-oxidative effect. On the contrary, show tocotrienols and generally delta- and gamma- isomers of a much higher antioxidant activity. In tocotrienols to a 40 -fold higher antioxidant protective effect against lipid peroxidation of cell membranes has been demonstrated.

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

Occurrence

Very high levels of vitamin E have vegetable oils such as wheat germ oil (up to 2435 mg / kg Gesamttocopherol with 70% α -tocopherol ), sunflower oil ( from 454 to 810 mg / kg Gesamttocopherol with 86-99 % α -tocopherol), red palm oil (800 mg / kg of total vitamin e, α -tocopherol of 152 and 600 mg / kg tocotrienols ) and olive oil ( 46 to 224 mg / kg Gesamttocopherol with 89-100 % α -tocopherol) on. The dose-and matrix- dependent absorption rate is an average of 30%.

Vitamin E is also synthetically ( inter alia by BASF, E. Merck ( India) and DSM Nutritional Products) as a racemic mixture. Synthetic tocopherol is relatively unstable and is therefore usually also provided with an acetyl group ( see also dl- α -tocopheryl acetate ). This does not have antioxidant properties. However, it can be converted to natural vitamin E in the body to the extent of up to 50 %.

In palm oil and α - Tocomonoenol was detected, while some contain marine organisms called marine tocopherol (marine -derived tocopherol, MDT).

Stability

Vitamin E is relatively stable to heat. Even after several hours of heating at up to 180 degrees (about the frying ) were losses in the range of 15 % -60 %. All eight vitamin E isomers have here a clear positive influence against the formation of undesirable oxidation products. The lower the temperature and the shorter the heating, the more vitamin E will remain unused.

Demand

The minimum requirement is 4 mg / day plus about 0.4 mg per gram of feed of polyunsaturated fatty acids. To achieve the different authors considered to be protective plasma level, a supply of 20 to 35 mg / d is required. Due to the low toxicity partially doses of 268 mg / d are recommended. The plasma levels should be above 30μmol / l (with a cholesterol of 220mg/dl ).

Vitamin E enhanced by its prostaglandin interaction, the effect of anticoagulants ( anticoagulant ), so the therapy must be carefully monitored during use of oral anticoagulants and vitamin K deficiency in order to avoid an increased risk of bleeding.

In patients with atopic dermatitis led supplementation with 268 mg / d over eight months to a significant improvement of symptoms.

Pharmacoepidemiological studies on tocopherol

To Pharmacoepidemiology of α -tocopherol are extensive data from the National Examination Surveys of the German Cardiovascular Prevention Study (DHP ) and from the National Health Survey for the population of the Federal Republic of Germany. By regularly using α - tocopherolhaltiger preparations occurs after a dose-dependent and statistically significant decrease in the β - and γ -tocopherol in the serum. Health aspects of a possible increased bleeding tendency under co-medication with Acetylsalicylsäurepräparaten are discussed in the literature. Also Tocopheroloxidationsprodukten such as the tocopherolquinone are findings from survey data.

In a large study of 35 533 men ( SELECT) was investigated whether vitamin E protects against prostate cancer. Used were 400 IU / d of all rac- α - tocopheryl acetate ( synthetically manufactured dl- α -tocopheryl acetate ). As a result, prostate cancer approached 17 percent more often than the control group. Contrast, has been in several in vitro studies with the gamma -isomer (GTP or GTE) an apoptotic effect on prostate cancer cells was observed.

Deficiency ( hypovitaminosis )

Deficiency symptoms in humans are very rare nowadays in Europe, as tocopherol may very well be stored in the liver and adipose tissue. Proven deficiency symptoms usually occur only in connection with diseases in which simultaneously the intake of fats is distorted. Consequences of hypovitaminosis are:

• Dry, wrinkled skin
• Concentration problems
• Inefficiency
• Fatigue
• Irritability
• Poorly healing wounds
• Favoring of atherosclerosis
• Dystrophy

Overdose ( hypervitaminosis )

As well as the fat soluble vitamins Vitamin A, Vitamin D and Vitamin K enriched RRR - α -tocopherol, and the 2R stereoisomers ( RSR, RSS, and RRS - α -tocopherol) in the adipose tissue or blood plasma of the body. The synthetic 2S- stereoisomers ( SRR, SSR, SRS and SSS - α -tocopherol) will not be saved in the blood plasma.

The European Authority for Food Safety Authority (EFSA ) defined 300 mg ( ~ 450 IU) of α -tocopherol or its equivalents as maximum tolerable intake ( Tolerable Upper Intake Level, UL ), ie the amount that can consume without any health risks for life every day a healthy adult.

For children, a study amounts of 25 mg per kilogram of body weight per day as non-toxic and 10 mg per 100 kcal of food has called for oral administration as a sure guide.

In three meta-analyzes, however, found against, increased mortality was found (all causes) for doses > 400 IU.

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

Use

Tocopherols found in the food industry as antioxidant use. You are in the EU as food additives of the numbers E 306 ( Tocopherol-rich extracts ), E 307 ( alpha ), E 308 ( gamma ) and E 309 (delta -tocopherol) for all foods approved for food additives, in part ( in form of tocopherol extracts from natural origin ) for "organic" foods ( e 306 ), approved.

Besides food, vitamin E is also cosmetics ( sunscreens ) and paints added. Condoms in a vitamin - E coating to, inter alia, increase the tear strength.

Sebacic acid and esterified with polyethylene glycol, the nonionic surfactant is obtained Polyoxyethanyl α - tocopheryl sebacate (PTS), which can be used to assist in the phase transfer catalysis.

Analysis

The methods used nowadays almost entirely for the reliable qualitative and quantitative determination of individual tocopherols are HPLC, gas chromatography, and the coupling method of HPLC-MS and GC / MS. Both methods are used in both the food chemical analysis as well as in pharmaceutical and physiological issues. As a function of the matrices to be examined to recommend appropriate sample preparation techniques, such as extraction techniques, including the use of solid phase extraction columns, or other extraction tools, such as the Extrelut made ​​of diatomaceous earth. The photometric method formerly often used found almost no use, as they do not allow differentiation of the individual tocopherols in general.