Vitamin E

Even in the experiments of it was shown that a semi-purified diet containing vitamins A , B , C and D also supports growth ^[1] .

However, the discovery of vitamin E itself occurred in 1922 by and Catherine Scott Bishop. In their experiments, they showed that rats that fed only a mixture of casein , lard, milk fat, salt and yeast were infertile. Reproductive function could be restored by adding lettuce leaves or wheat germ oil. The addition of fish oil or flour did not lead to any improvement. From this it was concluded that the “factor X” contained in certain vegetable oils was a very important component of food ^{[2] [3] [4]} .

In 1931, Mattill and Alcott described the antioxidant function of vitamin E. In the same year, it was found that vitamin E deficiency causes muscle failure and encephalomalacia ^[1] .

In 1936, α-tocopherol was first isolated by Evans. The name “tocopherol” (from other Greek. Τόκος - “offspring, procreation”, and φέρω - “bear”) was proposed by George Calhoun, professor of Greek at the University of California, California ^{[2] [1]} .

In 1938, the chemical structure of α-tocopherol was described, and Paul Carrer was able to synthesize it ^[1] .

The first therapeutic use of vitamin E was in 1938 by Wiedenbauer, who used wheat germ oil as an additive for 17 premature newborn babies suffering from growth disorders. Eleven of them recovered and were able to resume normal growth rates ^[1] .

The compounds of the vitamin E group are light yellow viscous liquids. Insoluble in water, soluble in chloroform , ethers , hexane , worse in acetone and ethanol .

Solutions intensely fluoresce (maximum absorption 295 nm , maximum radiation - 320 - 340 nm ).

Resistant to mineral acids and alkalis . When interacting with O ₂ and other oxidizing agents, they turn into quinones .

Esters of these substances are much more resistant to oxidation. Decomposed by ultraviolet radiation . In an inert gas atmosphere, they are stable when heated to 100 ° C ^[5] .

The most important biologically active compounds belonging to the vitamin E group are tocopherols and tocotrienols .

Tocotrienols are significantly less biologically active and differ from tocopherols in three double bonds in the linear part of the molecule at positions 3 ′, 7 ′ and 11 ′.

All asymmetric centers of natural tocopherols have an R configuration . Natural tocopherol is designated as RRR-α-tocopherol (the name d-α-tocopherol was also used earlier), and the obtained one is synthetically called all-rac-α-tocopherol , it is a mixture of eight stereoisomers , seven of which are not found in nature.

If phytol is used as the starting material for the synthesis, a mixture of RRR-α-tocopherol and 2S, 4′R, 8′R-α-tocopherol (2-epi-α-tocopherol), called 2-ambo-α-tocopherol, is formed (outdated. dl-α-tocopherol ) ^{[2] [5] [6]} .

All isomers of these substances are active antioxidants, however, only isomers with a 2R configuration have high biological activity ^[7] .

Vitamin E enters the gastrointestinal tract as part of oils, the hydrolysis of which by lipase and esterase leads to the release of vitamin. Then it is absorbed and as part of the chylomicrons enters the lymphatic system, and then into the blood. In the liver, the vitamin binds to tocopherol-binding proteins, with RRR-α-tocopherol having the highest affinity. Other tocopherols are secreted from the liver with bile acids. These proteins deliver the vitamin to the blood as part of VLDL . In plasma, an exchange of tocopherol occurs between VLDL and other blood lipoproteins. The exchange between fractions of lipoproteins (especially between LDL and HDL) and red blood cells provides an equilibrium concentration of tocopherol in the blood ^[2] .

Vitamin B enters the extrahepatic tissues as part of LDL, which are captured by the corresponding receptors. In addition to such a receptor-mediated mechanism, there is another, depending on the activity of lipoprotein lipase: the enzyme releases tocopherol from chylomicrons and VLDL, after which the vitamin enters the tissue by passive diffusion. Due to passive diffusion through the cell membrane, the concentration of RRR-a-tocopherol increases in all body tissues, especially in the brain. The structural organization of phospholipids in cell membranes is able to recognize the chiral form of RRR-a-tocopherol, due to which the vitamin is retained in the membrane, where it performs its function (synthetic tocopherols in the membrane provide less protection against oxidative stress) ^[2] .

Tocopherols that are not absorbed in the intestine are excreted in the feces. Vitamin metabolism products - tocopheric acid and its water-soluble glucuronides - are excreted in the urine ^[2] .

Vitamin E is a universal protector of cell membranes against oxidative damage. It occupies a position in the membrane that prevents the contact of oxygen with unsaturated lipids of the membranes (the formation of hydrophobic complexes). This protects the biomembranes from their peroxide degradation. The antioxidant properties of tocopherol are also due to the ability of the mobile hydroxyl of the chromane nucleus of its molecule to directly interact with free oxygen radicals (O ₂ ·, HO ·, HO ₂ ·), free radicals of unsaturated fatty acids (RO ·, RO ₂ ·) and fatty acid peroxides. The membrane stabilizing effect of the vitamin is manifested and in its ability to protect against oxidation of the SH-group of membrane proteins. Its antioxidant effect also lies in its ability to protect double bonds in carotene and vitamin A molecules from oxidation. Vitamin E (together with ascorbate) promotes the inclusion of selenium in the active center of glutathione peroxidase , thereby activating an enzymatic antioxidant defense (glutathione peroxidase neutralizes lipid hydroperoxides ) ^[2] .

Tocopherol is not only an antioxidant, but also an antihypoxant , due to its ability to stabilize the mitochondrial membrane and save oxygen consumption by cells. It should be noted that of all cellular organelles, mitochondria are most sensitive to damage, since they contain the most easily oxidized unsaturated lipids. Due to the membrane-stabilizing effect of vitamin E in mitochondria, the conjugation of oxidative phosphorylation, the formation of ATP and creatine phosphate increase. It is also important to note that the vitamin controls the biosynthesis of ubiquinone , a component of the respiratory chain and the main mitochondrial antioxidant ^[2] .

The oxidized form of the vitamin can react with hydrogen donors (for example, with ascorbic acid ) and thus again goes into the reduced form ^[7] .

Since oxidized forms are restored in the body, they are usually not found in vivo . The following oxidation products were found in vitro ^[7] :

Tocotrienols exhibit strong neuroprotective, antioxidant properties, reduce the risk of cancer . Micromolar amounts of tocotrienols reduce the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase , which is responsible for the synthesis of cholesterol , thereby reducing its level in the body ^[8] .

Tocopherol controls the synthesis of nucleic acids (at the transcription level), K _{0 of the} enzyme Q, myosin ATPase (necessary for reduction) of calcium ATPase (necessary for the capture of calcium in the sarcoplasmic reticulum during relaxation), catalase and peroxidase (involved in the elimination of peroxides) , as well as heme (thus increasing erythropoiesis ), which is part of cytochromes (P-450, cytochrome-C reductase), hemoglobin and myoglobin. Under its influence, the following proteins are synthesized: collagen in the subcutaneous tissue and bones, contractile proteins in skeletal, smooth muscle and myocardium, proteins of the mucous membranes and placenta, liver enzymes, creatine phosphokinase, vasopressinase and gonadotropic hormones ^{[2] [9]} .

Vitamin E has the ability to inhibit the activity of phospholipase A ₂ lysosomes, which destroys membrane phospholipids . Damage to lysosome membranes leads to the release of proteolytic enzymes into the cytosol , which damage the cell.

Vitamin E is an effective immunomodulator that helps to strengthen the body's immune defense forces ^[2] .

Tocopherol deficiency is a very common occurrence, especially in people living in areas contaminated with radionuclides, as well as exposed to chemical toxicants. Deep hypovitaminosis is rare - mainly in premature babies (manifested by hemolytic anemia ) ^[2] .

With E-vitamin deficiency, partial hemolysis of red blood cells is observed, the activity of antioxidant defense enzymes decreases in them. An increase in the permeability of the membranes of all cells and subcellular structures, the accumulation of lipid peroxidation products in them, is the main manifestation of hypovitaminosis. It is this circumstance that explains the variety of symptoms of tocopherol deficiency - from muscle dystrophy and infertility up to necrosis of the liver and softening of areas of the brain, especially the cerebellum. An increase in the activity of enzymes emerging from damaged tissues in blood serum (creatine phosphokinase, alanine aminotransferase and others) and an increase in the content of lipid peroxidation products in it are observed already in the early stages of E-hypovitaminosis ^[2] .

With vitamin E deficiency in infants and young children with malabsorption, ataxia is much faster than in adults. This means that the nervous system needs a sufficient amount of vitamin for normal development ^[7] .

Deficiency of vitamin E in the body is accompanied by a decrease in the content of immunoglobulins E. After its introduction, the number of T- and B-lymphocytes in the peripheral blood is normalized and the functional activity of T-cells is restored ^[2] .

Vitamin is non-toxic with significant (10-20 times the daily requirement) and long-term excess of its dosage, which is due to the limited ability of specific tocopherol-binding liver proteins to include vitamin in the composition of VLDL . Its excess is excreted from the body with bile . In some cases, prolonged use of megadoses of tocopherol (more than 1 g per day) can lead to hypertriglyceridemia and an increase in blood pressure ^[2] .

The main complications of hypervitaminosis are associated with ^[9] :

• excessive suppression of free radical reactions in neutrophils and other phagocytes (impaired digestion of captured microorganisms, which can manifest as sepsis in very premature infants);
• direct toxic effect on neutrophils , platelets , intestinal epithelium , liver and kidney cells;
• inhibition of the activity of vitamin K-dependent carboxylase.

Possible clinic of α-tocopherol poisoning: sepsis , necrotizing enterocolitis , hepatomegaly , hyperbilirubinemia (more than 20 mg / dl ), azotemia (more than 40 mg / dl ), thrombocytopenia (less than 50 - 60 thousand / μl ), symptoms of renal failure , hemorrhage in retina of the eye or brain, ascites ^[9] .

With intravenous administration of vitamin E, edema, erythrem , and soft tissue calcification occur at the injection site ^[9] .

Nutritional Supplements

At the end of the 20th century, when vitamin E was positioned in the media as a powerful antioxidant that reduces the risk of various diseases, many westerners began to take drugs with a high content of tocopherols. Subsequent studies have shown that regular intake of such supplements is associated with increased mortality ^{[10] [11] [12]} . In 2012, Japanese researchers said that an excess of vitamin A leads to osteoporosis ^[13] . The beneficial effects of vitamin E supplements have been proven only in relation to tocopherol deficiency ^[14] .

Mayo Clinic specialists recommend taking caution when taking preparations containing vitamin E ^[14] . The situation is complicated by the fact that such preparations often also contain vitamin A , which makes it difficult to decide which excess of these vitamins causes a negative effect in a particular case ^[15] .

Acanthocytosis

With this pathology, chylomicrons, LDL and VLDL are absent in the blood plasma due to a violation in the liver of patients with the synthesis of one of the structural proteins of these lipoproteins. Since vitamin E is transported in the blood as part of chylomicrons and LDL, the absence of the latter leads to impaired absorption of tocopherol and its entry into the tissue. Clinically, this is manifested in a sharp decrease in the hemolytic resistance of red blood cells and acanthocytosis, retinitis pigmentosa , muscle weakness and ataxic neuropathy . Treatment comes down to limiting fat intake and additionally introducing water-soluble forms of fat-soluble vitamins (for example, tocopherolpolyethylene glycol succinate) ^[2] .

Congenital dyserythropoietic type II anemia

With this disease, the consumption of vitamin E for the stabilization process and protection against peroxide destruction of defective erythrocyte membranes increases ^[2] .

Congenital Muscular Dystrophy

In some cases, muscular hypotension and muscle dystrophy is caused by a congenital disturbance in the process of tocopherol intake or metabolism in them ^[2] .