Tocopherols vitamin deficiency

Knowledge of the chemical structures of the major vitamins was acquired during the 30 years after 1920, and some were identified as known compounds. They were classified as fat-soluble and water-soluble vitamins. The only heterocyclic compounds in the former class are the tocopherols (vitamin E). They were discovered through their action in preventing sterility in rats, but they appear to play an important part in the metabolism of skeletal muscle. Vitamin E deficiency appears to occur rarely in man, but vitamin E therapy is tried in a number of clinical disorders. The tocopherols may be isolated from vegetable oils, and synthetic a-tocopherol (61) is made by condensing trimethylhydroquinone with phytol or phytyl halides (Scheme 2). For medicinal use they may be converted into their acetates or succinates. 

The predominant form of vitamin E in food is a-tocopherol. This form of the vitamin is also the most biologically potent form (100%), as determined by the rat fertility test. Other forms (and their relative potencies) are P-tocopherol (40%), y-tocopherol (10%), 6-tocopherol (1%), and a-tocotrienol (25%). The rat fertility test is performed as follows. Female rats are fed diets deficient in vitamin E, sufficient in a-tocopherol, or containing a known amount of the test compoimd. The rats are then mated with male rats. The number of living fetuses in the uterus of the female rat is then used to assess the potency of the test compoimd, relative to a-tocopherol. The deficient state results in dead fetuses, spontaneous abortions, and fetal resorptions. 

Tocopherols (vitamin E) occur in many food substances that are consumed as part of the normal diet. The daily nutritional requirement has not been clearly defined but is estimated to be 3.0-20.0 mg. Absorption from the gastrointestinal tract is dependent upon normal pancreatic function and the presence of bile. Tocopherols are widely distributed throughout the body, with some ingested tocopherol metabolized in the liver excretion of metabolites is via the urine or bile. Individuals with vitamin E deficiency are usually treated by oral administration of tocopherols, although intramuscular and intravenous administration may sometimes be used. 

There is reason to conclude that vitamin deficiency might contribute to arteriosclerosis. There is a correlation between elevated homocysteine levels and incidence of cardiovascular disease (59). There is debate as to whether homocysteine contributesto the dam e of cells on the interior of blood vessel or whether homocysteine is a marker of intensive cell repair and formation of replacement cells. Nevertheless, administration of pyridoxine, folic acid, and (yanocobalamin are being recommended along with the two antioxidant vitamins, a-tocopherol and ascorbic acid for arteriosclerosis. Vitamin Bg is required for two of the steps in the catabolism of homocysteine to succinyl CoA (Fig. 8.52). Note in Fig. 8.52 (bottom) that biotin and a coenzyme form of cobalamin also are required for... 

Vitamin E - also called ot-tocopherol. Vitamin E is an antioxidant. It is particularly effective in preventing the attack of peroxides on unsatured fatty acids in membrane lipids. Deficiency of vitamin E also leads to other symptoms, however, so vitamin E probably plays other roles as yet undiscovered. 

Rausch F (1956) Anaphylaktischer Schock nach Folsaure. Ther Ggw 95 53-55 Reuter H, Hellriegel KP (1977) Vitamins. In Side effects of drugs, annual 1. Excerpta Medica, Amsterdam London New York, pp 274-280 Reuter HD, Hellriegel KP (1979) Vitamins. In Side effects of drugs, annual 3. Excerpta Medica, Amsterdam London New York, pp 298-309 Ring J (1978) RIST, PRIST, RAST und so weiter. Dtsch Med Wochenschr 103 365-368 Roe DA (1976) Drug-induced nutritional deficiencies. AVI, Westport, Conn Roed-Petersen J, Hjorth N (1975) Patch test sensitization from D,L-alpha-tocopherol (vitamin E). Contact Dermatitis 1 391-393... 

The therapeutic uses of a-tocopherol, the main active component of vitamin E, can be divided into two distinct groups (1) replacement of a true vitamin deficiency (2) administration in high dosage where no deficiency can be demonstrated. 

Vitamin E was first described ia 1922 and the name was originally applied to a material found ia vegetable oils. This material was found to be essential for fertility ia tats. It was not until the early 1980s that symptoms of vitamin E deficiency ia humans were recognized. Early work on the natural distribution, isolation, and identification can be attributed to Evans, Butt, and Emerson (University of California) and MattiU and Olcott (University of Iowa). Subsequentiy a group of substances (Eig. 1), which fall iato either the family of tocopherols or tocotrienols, were found to act like vitamin E (1 4). The stmcture of a-tocopherol was determined by degradation studies ia 1938 (5). 

The recommended daily allowance for vitamin E ranges from 10 international units (1 lU = 1 mg all-rac-prevent vitamin E deficiency in humans. High levels enhance immune responses in both animals and humans. Requirements for animals vary from 3 USP units /kg diet for hamsters to 70 lU /kg diet for cats (13). The complete metaboHsm of vitamin E in animals or humans is not known. The primary excreted breakdown products of a-tocopherol in the body are gluconurides of tocopheronic acid (27) (Eig. 6). These are derived from the primary metaboUte a-tocopheryl quinone (9) (see Eig. 2) (44,45). 

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

The synergistic effect observed in the presence of all three antioxidants implies that there is an interaction between the individual antioxidant components. The direct interaction of the a-tocopherol radical and ascorbic acid is already well established (Bisby and Parker 1995) and a study by Mayne and Parker (1989) on chicks deficient in vitamin E and selenium showed that the... 

Sleet, R.B. and J.H. Soares, Jr. 1979. Some effects of Vitamin E deficiency on hepatic xanthine dehydrogenase activity, lead, and a-tocopherol concentrations in tissues of lead-dosed mallard ducks. Toxicol. Appl. Pharmacol. 47 71-78. 

Several different tocopherols are known to have vitamin E activity, but a-tocopherol, a trimethyltocol (Figure 12.9) is the most biologically active. Other less potent forms are the /3-, y- and S-tocopherols, which contain fewer methyl groups. They all have antioxidant properties and a deficiency results in a lack of protection of the unsaturated fatty acids in the membrane phospholipids against oxidation by molecular oxygen. 

Further indirect evidence of a role of lipid peroxidation in ozone toxicity has been obtained in studies in which animals deficient in vitamin E were found to be more susceptible to lethal concentrations of ozone and sublethal concentrations led to a more rapid utilization of this antioxidant vitamin. Although vitamin E deficiency potentiates the effects of ozone, it is not completely clear whether supranormal concentrations of vitamin E protect against ozone toxicity. Mice given tocopherol supplements were not protected against lethal concentrations of ozone, and the specific activity of lung hydrolases was found to be unrelated to dietary vitamin E concentration. However, other investigators have reported that additional supplementation with vitamin E above usual dietary concentrations lessens the extent of toxicity in animals that inhale ozone. ... 

Vitamin E, a natural antioxidant, is essential for growth, disease prevention, tissue integrity and reproduction in all fauna. Natural vitamin E, as it occurs in plants, consists mainly of a-tocopherol (III, R = H) with minor amounts of y-tocopherol (IV), although this ratio can vary as for example in the vegetable oil composition shown in Fig. 5a. In animal husbandry, such as dairy farms or cattle feed lots, the stock diets are commonly supplemented with vitamin E, because processed grain-based cereal fodder, hay, and silage are deficient in vitamin This results in higher levels of a-tocopherol... 

Tocopherol is present in adequate amounts in the normal diet and vitamin E deficiency is not known in otherwise healthy children or adults. In man vitamin E also lacks efficacy in the treatment of those diseases that resemble vitamin E deficiency in animals. 

Deficiency of vitamin E is characterized by low serum tocopherol levels and a positive hydrogen peroxide hemolysis test. This deficiency is believed to occur in patients with biliary, pancreatic, or intestinal disease that is characterized by excessive steatorrhea. Premature infants with a high intake of fatty acids exhibit a deficiency syndrome characterized by edema, anemia, and low tocopherol levels. This condition is reversed by giving vitamin E. 

Vitamin E (a-tocopherol) has as its active form any of several tocopherol derivatives. It functions as an antioxidant. Vitamin E deficiency is rarely seen, but can lead to red blood cell fragility that leads to hemolytic anemia. It has no known toxicity. 

Vitamin F, substances are necessary for the normal growth of animals. Without vitamin E, the animals develop infertility, abnormalities of the central nervous system, and myopathies involving both skeletal and cardiac muscle. The antioxidant activity of the tocopherols is in reverse order to that of their vitamin activity. Muscular tissue taken from a deficient... 

Vitamin E is a generic term that represents four tocopherols and four tocotrienols of varying biological potency. The term tocopherol correctly refers to the methyl-substituted derivatives of to-col and is not synonymous with the term vitamin E. The tocopherols and tocotrienols may be referred to collectively as tocochromanols. Many of the diverse deficiency syndromes observed in animals experimentally deprived of vitamin E can be explained by the vitamin s acting as an antioxidant in stabilizing unsaturated lipids in biological membranes. 

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